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Impact of Cross‐Sex Hormone Therapy on Bone Mineral Density and Body Composition in Transwomen
Abstract
Objective
Cross‐sex hormone therapy (CSHT) has been associated with changes in bone and lean/fat mass. This study assessed BMD, appendicular lean mass (ALM), and total fat mass in transwomen undergoing CSHT.
Patients and Design
We evaluated 142 transwomen (mean age: 33.7±10.3 years; BMI: 25.4±4.6; 86.6% with previous CSHT) during the first three months of regular estrogen treatment (with or without anti‐androgens). A reference group including 22 men and 17 cis women was also studied.
Measurements
Clinical and hormonal evaluation and dual energy X‐ray absorptiometry (DXA).
Results
BMD was similar in trans and reference women, and lower at all sites in transwomen vs. men. Low bone mass for age was observed in 18% of transwomen at baseline vs. none of the reference women or men. ALM and total fat mass were positively correlated with L1‐L4 BMD, explaining 14.9% of the observed variation in lumbar spine BMD and 20.6% of the variation in total femur BMD. ALM was similar in trans and reference women, and lower in transwomen vs. men. Total fat mass was lower in trans vs. reference women. Densitometry was repeated after a mean of 31.3±6.5 months in 46 transwomen. There was a significant increase in total fat mass and a significant decrease in ALM. BMD remained stable over time.
Conclusions
The fairly high prevalence of low bone mass in this sample of transwomen from southern Brazil seems to be related to lower ALM. Non‐pharmacological lifestyle‐related strategies for preventing bone loss could be beneficial for transgender women receiving long‐term CSHT.
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... The level of fat percentage generally ranges between 10 and 20% in healthy adult men, whereas a range of 20-30% is more common in healthy adult women (2). Although many papers have reported mean effects of hormonal treatment on body composition, none of these papers report on the distribution and variability of hormonal effects (3,4,5). Such information is relevant, as in clinical practice, doctors are confronted with patients who report no change at all, despite adequate hormone levels. ...
... In 323 transmen and 288 transwomen, the mean relative changes in body fat and LBM during hormone therapy were comparable to previous studies in literature (3,4,5,10,11). While most of the aforementioned studies have reported only data from two different time points (e.g. ...
... First, although BIA measurements correspond highly to DXA measurements in healthy adults (13), the results are not validated in transgender individuals and BIA measurements in obesity must be interpreted with caution. Nevertheless, our study results are comparable to previous studies using DXA to measure body composition (3,4,5), of which one was performed in the current study population (4), suggesting that BIA provides reliable estimates of fat percentage and LBM. Second, we used changes in total body fat as a marker for changes in body composition. ...
Objective
Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step towards individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change.
Design and methods:
Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage.
Results
A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR 1.36, 95% CI 1.01-1.83 per SD increase in LH).
Conclusion
There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individuals effects rather than solely relying on a standardized dosages of hormone therapy.
... Studies have shown a high prevalence of low bone mass in TW when compared with cis men both prior to and while on GAHT. 33, 72,73 The two studies that looked at baseline peripheral quantitative computed tomography (pQCT) found that TW had lower areal BMD (aBMD), smaller cortical bone area and a thinner radial cortex compared with cis men. 74,75 Additionally, these studies showed lower grip strength and muscle mass. ...
... There was a positive correlation between appendicular lean mass and total fat mass that correlated with L1-L4 BMD and explained 14.9% of BMD variation. 72 The question has been raised as to whether some of the improvement in DXA may be artefactual as it is affected by fat mass; however, the correlation between markers of bone turnover and BMD changes shown in some studies 74 would dispute this. ...
... feelings of discrimination)[123][124][125][126] and lifestyle factors.[127][128][129] Studies on the effect of GAHT on weight among TW have revealed no change72,130 or increase in weight;131 however, there has been consistency in body composition findings of decreased lean mass and increased fat mass.72,[130][131][132][133] Klaver and colleagues 132 reported that body composition changes were similar between oral and transdermal oestradiol after adjustment for baseline BMI and age. ...
Transgender (trans) women (TW) were assigned male at birth but have a female gender identity or gender expression. The literature on management and health outcomes of TW has grown recently with more publication of research. This has coincided with increasing awareness of gender diversity as communities around the world identify and address health disparities among trans people. In this narrative review, we aim to comprehensively summarize health considerations for TW and identify TW-related research areas that will provide answers to remaining unknowns surrounding TW’s health. We cover up-to-date information on: (1) feminizing gender-affirming hormone therapy (GAHT); (2) benefits associated with GAHT, particularly quality of life, mental health, breast development and bone health; (3) potential risks associated with GAHT, including cardiovascular disease and infertility; and (4) other health considerations like HIV/AIDS, breast cancer, other tumours, voice therapy, dermatology, the brain and cognition, and aging. Although equally deserving of mention, feminizing gender-affirming surgery, paediatric and adolescent populations, and gender nonbinary individuals are beyond the scope of this review. While much of the data we discuss come from Europe, the creation of a United States transgender cohort has already contributed important retrospective data that are also summarized here. Much remains to be determined regarding health considerations for TW. Patients and providers will benefit from larger and longer prospective studies involving TW, particularly regarding the effects of aging, race and ethnicity, type of hormonal treatment (e.g. different oestrogens, anti-androgens) and routes of administration (e.g. oral, parenteral, transdermal) on all the topics we address.
... Another study on long-term testosterone therapy reported larger cortical bone size in trans men vs. natal females (11). Conversely, trans women receiving estrogen therapy may lose lean mass in association with androgen deprivation, which over time can lead to smaller bones (12) and higher prevalence of low bone mass (13,14). ...
... Of these, 19 were included in the qualitative review ( Figure 1) and also in the meta-analyses (10-13, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Three studies presented both cross-sectional and before-after data (13,21,29); one of them was considered in the meta-analyses of both designs (13). The other two were included only in before-after analyses, because participants were not using CSHT at the baseline evaluation (21, 29). ...
... Of these, 19 were included in the qualitative review ( Figure 1) and also in the meta-analyses (10-13, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Three studies presented both cross-sectional and before-after data (13,21,29); one of them was considered in the meta-analyses of both designs (13). The other two were included only in before-after analyses, because participants were not using CSHT at the baseline evaluation (21, 29). ...
Context
The impact of long-term cross-hormone therapy (CSHT) in transgender men and women is still uncertain.
Objective
To perform a systematic review and metanalysis and update the evidence regarding the effects of CSHT on bone mass density (BMD) in transgender men and women.
Data sources
MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE were searched for studies published until August 2018.
Study selection
Of 10,849 studies, 19 were selected for systematic review. All included individuals were aged >16 years and received CSHT with BMD assessment by dual energy X-ray absorptiometry (DXA).
Data extraction
Data on BMD, CSHT, and clinical factors affecting bone mass were collected. A National Institutes of Health Scale was used to assess the quality of studies.
Data synthesis
Nineteen studies were meta-analyzed (487 trans men and 812 trans women). In trans men, mean BMD difference vs. natal women was not significant in any site in either cross-sectional and before-after studies. In trans women, mean BMD difference was not significant vs. natal men at femoral neck, total femur, and lumbar spine in cross-sectional studies; before-after studies reported a slight, but significant increase in lumbar spine BMD after 12 and ≥ 24 months of treatment.
Conclusions
Long-term CSHT had a neutral effect on BMD in transgender men. In transgender women, only lumbar spine BMD seemed to be affected after CSHT. This evidence is of low to moderate quality as a result of the observational design of studies, small sample sizes, and variations in hormone therapy protocols.
... Prima del trattamento ormonale di affermazione di genere, le donne transgender risultano avere una massa ossea sensibilmente ridotta rispetto ai maschi cis-gender [9][10][11], indipendentemente dallo stato ormonale, associata a un'alta prevalenza di ipovitaminosi D e a una minor massa magra. Questi risultati potrebbero derivare da uno stile di vita poco attivo, anche come esito di un certo grado di isolamento sociale [11]. ...
... Dagli studi condotti emerge un effetto neutro [10] o lievemente positivo [12,13] sulla BMD della terapia ormonale femminilizzante nel breve termine, associato positivamente ai livelli medi di estrogeni e alla supplementazione di vitamina D [12], con una riduzione dei markers di turnover osseo (fosfatasi alcalina, Ctx, P1NP e sclerostina) [14]. Non sono state riscontrate differenze significative in base all'età dei soggetti. ...
Sommario
Gli individui transgender sperimentano un’identità di genere incongruente con le caratteristiche proprie del sesso assegnato alla nascita e possono richiedere, pertanto, un trattamento ormonale di affermazione di genere. Queste terapie, in considerazione dell’importante ruolo metabolico degli ormoni sessuali, possono potenzialmente influire sulla salute ossea. Attualmente non emergono evidenze suggestive per un rischio aggiuntivo dal punto di vista osseo nei soggetti transgender in trattamento.
... Fighera et al. [17] also found that transwomen had BMD (g/cm 2 ) of spine and femoral neck region lower than female and male controls and that total femoral BMD was lower when compared to males. The prevalence of low bone mass in this study was of 18%. ...
... Also, a metanalysis and systematic review including 19 other studies and 812 transwomen concluded that hormone therapy had a neutral result on BMD at all sites evaluated, except the lumbar spine where a small increase in bone mass was detected. [22] A study on serum hormonal levels of transwomen on hormonal treatment has shown that they had lower estrogen levels than women and lower testosterone levels than men [17] and such disbalance may put them at disadvantage regarding bone mass. Different degrees of this Another given explanation for low bone mass in this context is that the transwomen group have lower levels of physical activity. ...
Objectives
Transgender individuals submitted to hormone or surgical treatment may have alterations in their bone metabolism as these elements are important players in bone remodeling. We aimed to study bone mineral density (BMD) and body composition in transwomen undergoing cross-sex hormonal treatment (CSHT) from Brazil for over 3 years, comparing them with female and male controls.
Methods
Ninety-three individuals (31 transwomen, 31 females and 31 males paired for age and body mass index) were studied for bone mass, and body composition by densitometry (by DXA). Epidemiological and clinical data were collected through direct questioning.
Results
Low bone mass (T score ≤2) was found in 12.9% of transwomen; in 3.2% of females and 3.3% of males. Transwomen individuals had lower spine Z score (0.26 ± 1.42 vs 0.50 ± 1.19) and femur Z score (−0.41 ± 0.95 vs 0.29 ± 1.04) than females. They had lower total femur Z score than males (−0.41 ± 0.95 vs 0.20 ± 0.83). Lean mass values correlated positively with total femur BMD (rho = 0.40; 95% CI = 0.009–0.68; p = 0.04) and BMD in femoral neck (rho = 0.48; 95%CI = 0.11–0.74; p = 0.01) but neither the type of therapy received nor the time that they were used, impacted bone mass.
Conclusion
Low bone mineral density is found frequently in transwomen and it is correlated with lean body mass.
Advances in knowledge
There are few studies of the effects of hormone therapy on the bones and muscles of transwomen. This study demonstrated that significant changes occur, and that the population studied needs greater care in musculoskeletal health.
... An additional study of 50 trans women, average age of 43 ± 10 years and all post-orchiectomy on a variety of types of estrogen, found that 23.4% had T-scores of < −2.5 at the lumbar spine and overall average Z-scores were − 1.0 ± 1.4 [28]. A recent study of 142 trans women in Brazil on GAHT for a variable amount of time found 18% had low bone mass for age while none of the reference men and women did [29]. ...
... Body composition changes also occur with GAHT that likely influence bone health. A study of 142 trans women in Brazil assessed appendicular lean mass, as an approximation of muscle mass, derived by DXA measurements [29]. The mean age in the study was 33.7 ± 10.3 years with mean BMI 25.4 ± 4.6 kg/m 2 . ...
It is well known that sex steroids, particularly estrogen, play a crucial role in the attainment and maintenance of peak bone density in all people. Transgender (trans) have been frequently observed to have low bone density prior to initiation of gender-affirming hormone therapy, while trans men generally do not. With pharmacologic estrogen, many studies show improving bone density in trans women. With pharmacologic testosterone, bone density in trans men remains largely unchanged although androgens have indirect effects on bone health via changes in fat and lean mass. Much remains unknown about best practices to optimize bone health, interpret DXA scans and assess fracture risk in trans adults.
... Transgender women have lower bone density prior to starting GAHT when compared to cisgender men [70,71]. In fact, the bone density of transgender women has been noted to be closer to that of cisgender women than to cisgender men [72]. Lower bone mineral density (BMD) in transgender women may be secondary to lower mean muscle mass and lower muscle strength [70], which would put transgender women at increased risk of bone loss with restrictive eating. ...
Transgender and gender diverse (TGD) individuals are at increased risk for the development of eating disorders, but very little has been published with regards to the unique aspects of their medical care in eating disorder treatment. Providing gender affirming care is a critical component of culturally competent eating disorder treatment. This includes knowledge of gender affirming medical and surgical interventions and how such interventions may be impacted by eating disordered behaviors, as well as the role of such interventions in eating disorder treatment and recovery. TGD individuals face barriers to care, and one of these can be provider knowledge. By better understanding these needs, clinicians can actively reduce barriers and ensure TGD individuals are provided with appropriate care. This review synthesizes the available literature regarding the medical care of TGD patients and those of patients with eating disorders and highlights areas for further research.
... Moreover, other longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in TW athletes show very modest changes after 12 months of treatment (approximately 5 %), in terms of lean body mass and muscle size, suggesting that the muscle advantage enjoyed by TW athletes is only minimally reduced when testosterone is suppressed. In fact, given the large baseline differences in muscle mass between males and females (approximately 40 %), the reduction achieved by 12 months of testosterone suppression can reasonably be assessed as small relative to the initial superior mass [83,[110][111][112][113][114][115][116][117][118]. ...
In the female athletic community, there are several endogenous and exogenous variables that influence the status of the hypothalamus-pituitary-ovarian axis and serum sex steroid hormones concentrations (e. g., 17β-estradiol, progesterone, androgens) and their effects. Moreover, female athletes with different sex chromosome abnormalities exist (e. g., 46XX, 46XY, and mosaicism). Due to the high variability of sex steroid hormones serum concentrations and responsiveness, female athletes may have different intra- and inter-individual biological and functional characteristics, health conditions, and sports-related health risks that can influence sports performance and eligibility. Consequently, biological, functional, and/or sex steroid differences may exist in the same and in between 46XX female athletes (e. g., ovarian rhythms, treated or untreated hypogonadism and hyperandrogenism), between 46XX and 46XY female athletes (e. g., treated or untreated hyperandrogenism/disorders of sexual differentiation), and between transgender women and eugonadal cisgender athletes. From a healthcare perspective, dedicated physicians need awareness, knowledge, and an understanding of sex steroid hormones’ variability and related health concerns in female athletes to support physiologically healthy, safe, fair, and inclusive sports participation. In this narrative overview, we focus on the main clinical relationships between hypothalamus-pituitary-ovarian axis function, endogenous sex steroids and health status, health risks, and sports performance in the heterogeneous female athletic community.
... Current literature shows that low bone mass (Z-score that matches gender assigned at birth) has been observed in 12.9-40% of transwomen during GAHT and is related to lower basal BMD, lower lean body mass, lower estradiol levels and lower compliance to GAHT. 49,50,59,62,63 The prevalence of osteoporosis (according to male reference) is around 20% in transwomen after more than 10 years of GAHT. 45,51,64 The direct consequence of a weak bone is an increased risk of fracture but transwomen do not seem to experience this. ...
Bone health in transmen and transwomen is an important issue that needs to be evaluated by clinicians. Prior to gender-affirming hormone treatment (GAHT), transwomen have lower bone mineral density (BMD) and a higher prevalence of osteopenia than cismen probably related to external factors, such as hypovitaminosis D and less physical activities. Gonadotropin-releasing hormone (GnRH) analogues in transgender youth may cause bone loss; however, the addition of GAHT restores or at least improves BMD in both transboys and transgirls. The maintenance or increase in BMD shown in short-term longitudinal studies emphasizes that GAHT does not have a negative effect on BMD in adult transwomen and transmen. Gonadectomy is not a risk factor if GAHT is taken correctly. The prevalence of fractures in the transgender population seems to be the same as in the general population but more studies are required on this aspect. To evaluate the risk of osteoporosis, it is mandatory to define the most appropriate reference group not only taking into consideration the medical aspects but also in respect of the selected gender identity of each person.
... In a study by Fighera et al., transgender women on varying forms of estrogen and androgen suppression therapy were found to have a decrease in appendicular lean mass after a 31-month followup period. [40] The changes in VAT and lean body mass seen among transgender women after GAHT are thought to be due in part to androgen suppression. Among cisgender men with prostate cancer, androgen deprivation therapy, for example, leads to analogous increases in VAT and a reduction in lean body mass. ...
Purpose of Review
Transgender individuals are at disproportionate risk for HIV infection, with prevalence rates highest among transgender women of color. Antiretroviral therapy (ART)-treated people with HIV (PWH) are at increased risk for cardiovascular disease (CVD), in relation to persistent systemic immune activation and metabolic dysregulation. The purpose of this review is to examine parameters which may affect CVD risk among transgender PWH.
Recent Findings
Among transgender women and men, prospective longitudinal studies have shown that gender-affirming hormonal therapy (GAHT) is associated with select deleterious cardiometabolic effects such as increases in visceral adipose tissue. Retrospective studies among transgender women and men suggest an increase in CVD risk, such as venous thromboembolism, cerebrovascular accidents, and myocardial infarction. Studies among transgender PWH adhering to GAHT and ART suggest heightened systemic immune activation/inflammation.
Summary
Prospective longitudinal studies assessing factors associated with increased CVD events among transgender PWH are needed to guide the development of CVD prevention strategies in this at-risk population.
... 23 However, studies have shown low BMD in transgender women (up to 18-22% reported to have low BMD), often prior to GAHT initiation. 24,25 Questions have been raised as to whether lower physical activity, vitamin D deficiency, and tobacco use could contribute to lower baseline BMD in transgender women. After GAHT initiation, BMD increases despite increased fat mass and decreased muscle mass. ...
Despite the growing number of adult transgender and gender diverse (TGD) patients seeking health services, there are many unknowns regarding how routine screening recommendations should be applied to TGD persons receiving gender-affirming hormone therapy (GAHT). Patients taking GAHT may have disease risks that differ from what is expected based on their sex assigned at birth or affirmed gender identity. We discuss two patient cases, one transgender man and one transgender woman who present for routine medical care, to review several conditions that may be impacted by the hormones utilized in masculinizing and feminizing GAHT and for which screening recommendations are available for TGD adults: cardiovascular risk factors, osteoporosis, breast cancer, cervical cancer, and prostate cancer. We reviewed the TGD-specific screening recommendations from several major medical organizations and programs and found them to be largely based upon expert opinion due to a lack of evidence. The goal of this narrative review is to assist healthcare professionals in counseling and screening their TGD patients when and where appropriate. Not all TGD adults have the ability or need to receive routine medical care from a specialized TGD health clinic; therefore, it is essential for all healthcare professionals involved in routine and gender-affirming care to have knowledge about these conditions and screenings.
... These results are in line with previous studies that have evaluated body composition using DXA in trans women. 29,30,41,[44][45][46][47][48][49][50] Only four studies have also previously looked specifically at android and gynoid fat mass regions, either using DXA or magnetic resonance imaging, and, like this study, found an increase in fat mass in both regions. 41,34,45,51 These findings support the theory that activation of oestrogen receptors can lead to stimulation of adipocyte proliferation as well as lipoprotein lipase activity. ...
Background
Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance.
Aims
To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT.
Methods
Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported.
Results
Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5), p < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3), p < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of −6.9 kg (–10.6, –3.1), p < 0.001, fat mass of +9.8 kg (3.9, 14.5), p = 0.001, lower android:gynoid fat ratio −0.1 (–0.2,–0.0), p < 0.05), and higher insulin resistance 1.6 (1.3–1.9), p < 0.001). Higher HOMA2-IR correlated with higher android ( r ² = 0.712, p < 0.001) and gynoid ( r ² = 0.572, p < 0.001) fat mass in both trans men and trans women.
Conclusion
Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.
... Further, clinical bone turnover laboratory measures were not reported and long-term fracture outcome data were unavailable. Recent retrospective data suggest trans women taking nonstandardized long-term GAHT have modestly increased fracture risk compared with age-matched cisgender (nontransgender) controls (7), and several studies suggest trans women have lower BMD before initiating GAHT compared with cisgender controls (8)(9)(10). Thus, clinicians must balance patient priorities and unique risk factors when prescribing GAHT, addressing ease of hormone administration, effectiveness, follow-up monitoring, and medication costs, while ensuring selected GAHT regimens are appropriate to protect long-term bone health in all trans patients. ...
Background
Gender-affirming hormone therapy (GAHT) influences bone health in transgender individuals. Several hormone preparations and administration routes are available for GAHT, but no studies have compared clinical and laboratory bone health measures across different GAHT regimens.
Content
We searched PubMed (MEDLINE), Embase, and Google Scholar for studies measuring bone turnover markers and bone mineral density before and during GAHT in transgender adults. We summarized bone health data by hormone type and administration route (estrogen or testosterone; oral, transdermal/percutaneous, intramuscular). Among trans women, we also examined outcomes among regimens containing different adjunctive agents (antiandrogens or gonadotropin-releasing hormone analogs).
Summary
Most hormone preparations maintained or increased areal bone mineral density among trans adults taking GAHT for at least 12 months from baseline. Different bone turnover markers were measured across studies, and we were unable to compare or comment on the direct influence of selected hormone preparations on these clinical laboratory measures. Larger and uniformed studies are needed to measure volumetric bone mineral density and biomarkers of bone metabolism in trans adults taking standardized GAHT regimens.
... This could be due to lower baseline estrogen levels or undertreatment with exogenous estrogen after surgical or medical treatment with testosteronelowering effects. Indeed, the small number of studies noting lower BMD in transgender women have generally showed below-average baseline values before GAHT initiation or have not described baseline BMD values at all 18,19 . ...
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A transgender person is defined as one whose gender identity is incongruent with their biological sex assigned at birth. This highly marginalized population numbers over 1.4 million individuals in the U.S.; this prevalence skews more heavily toward younger generations and is expected to increase considerably in the future.
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Gender-affirming hormone therapy (GAHT) has physiologic effects on numerous aspects of the patient's health that are pertinent to the orthopaedic surgeon, including bone health, fracture risk, and perioperative risks such as venous thromboembolism and infection.
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Language and accurate pronoun usage toward transgender patients can have a profound effect on a patient's experience and on both objective and subjective outcomes.
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Gaps in research concerning orthopaedic care of the transgender patient are substantial. Specific areas for further study include the effects of GAHT on fracture risk and healing, outcome disparities and care access across multiple subspecialties, and establishment of perioperative management guidelines.
... While estrogen plays a significant role in bone metabolism and attaining peak bone density in females and males (Khosa et al. 2012;Rothman & Iwamoto 2019), studies on its inhibition or administration during GAHT have produced variable results. Some studies have demonstrated that trans women may have lower bone mass (Fighera et al. 2018;T'Sjoen et al. 2009;Wierckx et al. 2012), while others report increased bone mineral density in both trans women and men (Fighera et al. 2019;Singh-Ospina et al. 2017;Wiepjes et al. 2017). While the goal of GAHT is to reduce the prevalence of innate secondary sex characteristics and increase those of the transitioned sex (Berli et al. 2017), the long-term effects of GAHT on the skeleton and the landmarks used to estimate sex remain largely unknown (Mackenzie & Wilkinson 2017). ...
Due to disproportionate violence impacting the transgender community, forensic anthropologists may encounter the remains of trans individuals; however, it is unknown how often trans individuals are represented in casework and if practitioners have sufficient knowledge about trans bodies. After contextualizing forensically relevant demographics for the trans community, this study uses survey data of forensic anthropologists to critically explore the collective knowledge of and experience working with trans individuals; practitioners’ perceptions of sex and gender; and potential opportunities for trans-oriented research. The results indicate that 28.9% of respondents have worked with trans individuals in casework, but 75.0% of forensic anthropologists were unfamiliar with forms and evidence of gender affirming procedures. Additionally, the survey indicates that forensic anthropologists struggle with the binary nature of forensic sex estimation, with 42.4% agreeing that sex is binary and 56.2% disagreeing. Similar opposition was found with reporting gender: 39.5% indicated that gender should be reported in casework and 31.0% disagreed. Moreover, current sex estimation methods are: rigidly binary; not reflective of human biological variation; and inadequate for trans individuals as they are based on assigned sex. To dismantle rigidly binary sex categorization, we propose the adoption
of a biocultural and queer theoretical approach to forensic sex estimation and in sexual
dimorphism research that challenges heteronormative assumptions, questions typological two-sex categorization, and combats the presumptions that gender and sex are stable, independent entities that convey universal meaning. Relatedly, the expansion of trans-oriented research, which is supported by 95.8% of respondents, will further improve methodological accuracies.
... Including Gooren and Bunck [62], 12 longitudinal studies [53,[63][64][65][66][67][68][69][70][71][72][73] have examined the effects of testosterone suppression on lean body mass or muscle size in transgender women. The collective evidence from these studies suggests that 12 months, which is the most commonly examined intervention period, of testosterone suppression to femaletypical reference levels results in a modest (approximately − 5%) loss of lean body mass or muscle size (Table 4). ...
Males enjoy physical performance advantages over females within competitive sport. The sex-based segregation into male and female sporting categories does not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee (IOC) determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been scrutinized. Here, we review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage and thus delivers fair and safe competition. We report that the performance gap between males and females becomes significant at puberty and often amounts to 10–50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and explosive strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 12 months of treatment. Thus, the muscular advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations should consider this evidence when reassessing current policies regarding participation of transgender women in the female category of sport.
... Masculinizing hormone therapy is typically testosterone alone, which induces significant gains in muscle mass, decrease in fat mass and fat redistribution as well as deepening of the voice, facial and body hair growth (7,8). Feminizing hormone therapy is usually estradiol and an anti-androgen such as spironolactone or cyproterone acetate which will induce body fat redistribution to a more gynoid pattern with increases in fat mass, decreases in muscle mass as well as skin softening, decrease in libido and breast growth (7,9). Target sex steroid reference ranges on gender-affirming hormone therapy are generally the normal reference ranges of an individual"s affirmed gender, rather than the gender presumed for them at birth (10)(11)(12). ...
Context
As the number of transgender (trans) people (including those who are binary and/or non-binary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation.
Cases
Case scenarios discussed include 1) hemoglobin and hematocrit in a non-binary person undergoing masculinizing hormone therapy; 2) estimation of glomerular filtration rate in a trans woman at risk of contrast-induced nephropathy; 3) prostate-specific antigen (PSA) in a trans woman; and 4) chest pain in a trans man with a cardiac troponin concentration in-between the reported male and female reference ranges.
Conclusions
The influence of exogenous gender-affirming hormone therapy on fat and muscle distribution and other physiological changes determines interpretation of laboratory tests which have sex-specific differences. In addition to affirmative practice to ensure a patient’s name, gender and pronoun are used appropriately, we propose that once individuals have commenced gender-affirming hormone therapy, the reference range of the affirmed gender be reported (and specified by treating clinicians) except for PSA or cardiac troponin which is dependent on organ size. Whilst suggestions may be challenging to implement, they also represent an opportunity to lead best practice to improve the quality of care and experiences of healthcare for all trans people.
... The association between therapy duration and low bone mass could be due to sustained low compliance leading to a lower exposure to the beneficial effects of estradiol on BMD over many years, along with age-related bone loss. Compliance to estrogen therapy has known to be reduced after GCS: in fact, TW are almost completely feminized and they sometimes stop taking estrogens regularly [5,21,22]. Perhaps, the availability of depot estrogen pharmaceutical preparations could improve patients' compliance. ...
Introduction:
Bone health is a critical issue in transgender women (TW) health care. Conflicting results have been reported on bone status after gender-confirming surgery (GCS). No recent data in Italian TW are available.
Materials and methods:
The aim of this cross-sectional study was to evaluate fracture risk, lumbar spine BMD and 25OH vitamin D (25OHD) levels in a population of TW on estrogen replacement therapy (ERT) after GCS. We retrospectively analyzed a group of 57 TW, aged 45.3 ± 11.3 years, referred to our Gender Dysphoria Clinic, at least 2 years after GCS. Anthropometric parameters, patient compliance to ERT, biochemical and hormonal assessment, lumbar spine BMD and fracture risk were evaluated.
Results:
Prevalence of low bone mass (Z-score ≤ -2) was 40% according to the natal gender. In this group, 17β-estradiol levels were significantly lower (median 21 pg/ml [25th-75th percentile 10.6-48.5] vs 63 pg/ml [38.5-99.5]; p < 0.001) and a higher prevalence of low compliance to ERT was recorded (83% vs 29%; p < 0.0001) compared to those with higher bone mass. An intermediate-high fracture risk was found in 14% of the sample. A high percentage (93%) of hypovitaminosis D was present.
Conclusions:
TW on ERT have a high prevalence of low bone mass, significantly associated with low estradiol levels and low compliance to ERT. A high prevalence of hypovitaminosis D was highlighted. Considering that one out of seven TW showed an intermediate-high 10-year fracture risk, such risk assessment may be considered to prevent and manage osteoporosis in this clinical setting.
... Another longitudinal cohort study in transgender girls in Europe also reported found a significant increase in BMI from the start of GAHT from a mean age of 15 years up to the age of 22 years[40]. However, other studies have not reported increases in BMI over a similar period of time[8,10,41], although they have reported an increase in total body fat along with a significant decrease in lean body mass. The European Network for the Investigation of Gender Incongruence (ENIGI) study reported that the BMI at the initiation of GAHT appears to be a determinant of changes in body composition. ...
Introduction
Many transgender people take hormone therapy to affirm their gender identity. One potential long-term consequence of gender affirming hormone therapy is increased body mass index (BMI), which may be associated with metabolic syndrome, cardiovascular disease and higher mortality. Only a few published studies explored changes in BMI in transgender people taking gender affirming hormone therapy (GAHT).
Objective
To examine the changes in BMI longitudinally in response to GAHT in transgender women and men.
Methods
We conducted a retrospective cohort study of transgender individuals who received GAHT from the endocrinology clinic between January 1, 2000 and September 6, 2018. Subjects who sought GAHT were included if they had two separate measurements of BMI and were excluded if they had a BMI greater than 35 kg/m² or were missing demographic data at entry. We used a linear mixed model to analyze the longitudinal change in BMI.
Results
There were a total of 227 subjects included in this cohort. Among subjects already on GAHT, transgender women were receiving GAHT longer than transgender men (6.59 ± 9.35 vs 3.67 ± 3.43 years, p-value = 0.04). Over the period of 7 years, there was a significant increase in BMI in transwomen who newly initiated GAHT (p-value 0.004). There were no changes in BMI in transgender men and women already on GAHT or in transgender men who newly initiated GAHT in the study.
Conclusion
We conclude that BMI significantly increases in transwomen but not in transmen after initiation of GAHT in a single center based in the United States. In transwomen and transmen, BMI appears to be stable following 3 to 6 years of GAHT. Future investigations should examine the causes for increased BMI in transgender women including type of GAHT, diet and lifestyle, and association with risk of metabolic syndrome and cardiovascular disease.
... 21 ...
Purpose of review:
Hormonal treatment in trans persons can affect bone health. In this review, recent studies published on this topic in adults are discussed.
Recent findings:
Before starting hormonal treatment, trans women were found to have lower bone mineral density than cis men, which seems to be related to lower vitamin D concentrations and lower lean body mass, whereas this was not found in trans men. Short-term and long-term studies show that hormonal treatment does not have detrimental effects on bone mineral density in trans women and trans men. Low estradiol concentrations were associated with a decrease in bone mineral density in trans women.
Summary:
Based on the reassuring findings in these studies, regularly assessing bone mineral density during hormonal treatment does not seem necessary. This confirms the Endocrine Society Guideline stating that bone mineral density should be measured only when risk factors for osteoporosis exist, especially in people who stop hormonal treatment after gonadectomy. The relationship with estradiol concentrations indicate that hormone supplementation should be adequate and therapy compliance should be stimulated. As vitamin D deficiency frequently occurs, vitamin D supplementation should be considered. Future research should focus on fracture risk and long-term changes in bone geometry.
... So if transgender women have a lower BMD than that of cisgender men, the question arises: Is their BMD more comparable to that of cisgender women? Fighera et al (3) described that transgender women who had <3 mo of gender-affirming hormone therapy had a mean total hip BMD of 1.010 g/cm 2 , significantly closer to the mean BMD of cisgender women (0.990 g/cm 2 ) than to that of cisgender men (1.140 g/cm 2 ). Similarly, mean total spine BMD of 1.150 g/cm 2 in transgender women was significantly closer to that of cisgender women (1.210 g/cm 2 ) than to that of cisgender men (1.250 g/cm 2 ). ...
The indications for initial and follow-up bone mineral density (BMD) in transgender and gender nonconforming (TGNC) individuals are poorly defined, and the choice of which gender database to use to calculate Z-scores is unclear. Herein, the findings of the Task Force are presented after a detailed review of the literature. As long as a TGNC individual is on standard gender-affirming hormone treatment, BMD should remain stable to increasing, so there is no indication to monitor for bone loss or osteoporosis strictly on the basis of TGNC status. TGNC individuals who experience substantial periods of hypogonadism (>1 yr) might experience bone loss or failure of bone accrual during that time, and should be considered for baseline measurement of BMD. To the extent that this hypogonadism continues over time, follow-up measurements can be appropriate. TGNC individuals who have adequate levels of endogenous or exogenous sex steroids can, of course, suffer from other illnesses that can cause osteoporosis and bone loss, such as hyperparathyroidism and steroid use; they should have measurement of BMD as would be done in the cisgender population. There are no data that TGNC individuals have a fracture risk different from that of cisgender individuals, nor any data to suggest that BMD predicts their fracture risk less well than in the cisgender population. The Z-score in transgender individuals should be calculated using the reference data (mean and standard deviation) of the gender conforming with the individual's gender identity. In gender nonconforming individuals, the reference data for the sex recorded at birth should be used. If the referring provider or the individual requests, a set of "male" and "female" Z-scores can be provided, calculating the Z-score against male and female reference data, respectively.
... Body composition. In general, most of the studies describe a status quo or increase in BMI in transgender people (66, 72, 75-77, 80 -82, 94 -97 ), although transgender people taking HT are not more likely to be obese compared with cisgender age-matched controls (54,63,94 ) (Supplemental Table 2). WHR tends to change toward the desired gender (81,98 ), which is also reflected in a decrease in subcutaneous fat area and an increase in visceral fat in TM (75,76,98,99 ) and an increase in subcutaneous fat in TW (75,76,98 ) after initiation of HT. ...
Background:
Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised.
Content:
A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles.
Summary:
Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.
Background:
In addition to the familiar sports-related injuries and conditions experienced by cisgender athletes, transgender athletes may also face unique challenges to maintaining their musculoskeletal health. Encouraging sports medicine professionals to become familiar with accepted nomenclature and terminology related to transgender athletes will enable open communication on the field, in the athletic training facility, and office.
Objective:
Understanding contemporary medical and surgical gender-affirming treatments and the unique ways in which the musculoskeletal system might be affected by each - such as impairments in bone health, changes in ligamentous function and the potential increased risk for deep venous thromboembolism - is essential for provision of optimal musculoskeletal care to transgender athletes. Knowledge of the existing participation policies for transgender athletes is also key for enabling sports medicine professionals to effectively counsel athletes about the need for specialized protective equipment. Additionally, this knowledge is important for appropriately managing therapeutic use exemptions in the competitive sports setting.
Conclusion:
This article provides an overview of the current accepted nomenclature, common gender-affirming medical and surgical treatments, unique musculoskeletal health considerations, and participation policies for transgender athletes.
Introduction/Background: Transgender and gender non-conforming (TGNC) individuals face numerous barriers to healthcare, which contribute to many health disparities. TGNC persons may choose gender-affirming therapies with surgery and/or hormone replacement therapy (HRT) to manage gender incongruence. Despite the expanding use of HRT, the long-term outcomes on bone health and metabolism, are still relatively unknown in the TGNC population. In 2019, the International Society of Clinical Densitometry (ISCD) released an official position statement on the appropriate use of dual energy x-ray absorptiometry (DXA) to measure bone density in the TGNC population [1]. In this study, we reviewed which “sex” is currently utilized among providers when performing DXA scans to calculate T- and Z-scores for TGNC persons and how this compares to the positions published by the ISCD.
Methodology: A retrospective analysis was performed utilizing HERON queries and subsequent chart review [2,3]. HERON is a type of Informatics for Integrating Biology and the Bedside software that was utilized to find sets of patients of interest from electronic medical record data while preserving patient privacy through a query interface tool [2]. Project specific sets including patient demographics, medications, gonadectomy, and DXA scan information was created in HERON to make this highly detailed data of specific patients available to the investigators on the platform, as reviewed and retrieved by the Institutional Review Board. The qualitative DXA data obtained from chart review was determined as "correct" or "incorrect" based on positions provided from the ISCD.
Results: 10 DXA scans that met inclusion criteria were obtained between 9 TGNC patients. In total, 18 T-scores and Z-scores of the 10 DXAs were reviewed and scored. Based on ISCD positions, 67% of the T-score and Z-scores were calculated incorrectly; using the erroneous “sex” based standard to compare scores.
Conclusions: Like DXA scans, many current healthcare standards and protocols are based on a patient's sex or gender, which may cause confusion amongst healthcare personnel who have not received proper training regarding the TGNC population. In this study, 67% of T-scores and Z-scores were calculated incorrectly based on ISCD recommendations. An additional prospective research design is required to determine the consequences of incorrectly calculated DXA scans for TGNC patients. Furthermore, future research is needed to determine HRT's effects on bone mineral density in the TGNC population in the United States.
Para adequação de características que atendam ao gênero pertencente, ocorrem transformações corporais e psicossociais que implicam na saúde do transgênero. Diante disto, o presente artigo, tem como questão norteadora: como a nutrição pode estar envolvida na saúde do transgênero? O objetivo deste estudo é analisar o papel da nutrição sobre a saúde dos transgêneros, através do levantamento da literatura que aborde o assunto, para assim, vislumbrar caminhos e apontar as lacunas a serem preenchidas que permitam um atendimento mais abrangente e de qualidade a esta população, com ênfase na atuação do nutricionista. Como metodologia foi utilizada a revisão narrativa da literatura; utilizando-se as palavras-chave "transgênero e nutrição" e "transexual e nutrição" em busca nas bibliotecas virtuais científicas, sites e documentos envolvendo o tema e incorporado trabalhos em língua estrangeira. Como
In line with increasing numbers of transgender (trans) and gender non-binary people requesting hormone treatment, the body of available research is expanding. More clinical research groups are presenting data, and the numbers of participants in these studies are rising. Many previous review papers have focused on all available data, as these were scarce, but a more recent literature review is timely. Hormonal regimens have changed over time, and older data may be less relevant for today's practice.
In recent literature, we have found that even though mental health problems are more prevalent in trans people compared to cisgender (cis) people, less psychological difficulties occur, and life satisfaction increases with gender-affirming hormone treatment (GAHT) for those who feel this is a necessity. With GAHT, body composition and contours change towards the affirmed sex. Studies in bone health are reassuring, but special attention is needed for adolescent and adult trans women, aiming at adequate dosage of hormonal supplementation and stimulating therapy compliance. Existing epidemiological data suggest that the use of (certain) estrogens in transgender women induces an increased risk of myocardial infarction and stroke, the reason that lifestyle management can be an integral part of trans health care. The observed cancer risk in trans people does not exceed the known cancer-risk differences between men and women.
Now it is time to integrate the mostly reassuring data, to leave the overly cautious approach behind, to not copy the same research questions repeatedly, and to focus on longer follow-up data with larger cohorts.
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Abstract
There are no guidelines currently that specifically address medical issues specific in older transgender adults, but this is an active area of research. For transfeminine patients who initiate gender-affirming hormone therapy at an older age, there may be additonal and/or earlier screening and testing indicated for cardiovascular risk factor reduction. Bone density testing for osteoporosis as well as screening for age-related cancers should be done. While the usual feminizing regimens which combine estrogens and adjunct antiandrogens are typically indicated, transdermal estrogen may be the most appropriate route of adminsitration for older adults as it is thought to be the least thrombogenic. Transfeminine patients may present to medical providers at any age and deserve patient-centered, well-informed, and affirming healthcare.
Over the past 15 years, there has been a growing interest in the field of transgender medicine in general and bone heath in particular. Searching the PubMed keyword text for “transgender” or the older term “transsexual” yielded less than 50 entries prior to 2004. However, there has been a steady increase in publications since the year 2005. By the year 2018, the number of publications reached over 1000 per year. The interest in the relatively new medical field have been largely attributed to increased awareness of the medical needs of transgender and gender nonconforming people not only by the medical community but also by the lay public. Guidelines covering various aspects of the medical and mental health needs of the transgender people have been published in 2009 by the Endocrine Society and in 2012 by the World Professional Association of Transgender Health (WPATH), (updated in 2017). These guidelines have stimulated much of the recent interest in this field and approaches to management. Many healthcare professionals have not received formal training in dealing with transgendered patients and may not be comfortable in interacting with and providing care for them. This chapter will review on the current data available regarding bone health in adult transgender men and women as well as adolescents. It will expand to discuss guidelines for transgender hormone treatment, osteoporosis risk in transgender individuals, as well as approaches toward screening for osteoporosis in transgender individuals. It will conclude by discussing clinical implications for bone health management of transgender people in standard clinical practice.
Background
Spironolactone and cyproterone acetate are commonly used in feminizing hormone therapy to achieve the goal of female range testosterone level; however, the data on the efficacy comparing between these two anti-androgens are scarce.
Aim
To compare the anti-androgenic effects between spironolactone and cyproterone acetate as the component of feminizing hormone therapy among transgender women population.
Methods
The study was single-blinded randomized controlled trial involved 52 transgender women from two transgender health clinics. Each participant received oral estradiol valerate 4 mg/day combined with anti-androgen, spironolactone 100 mg/day or cyproterone acetate 25 mg/day, depending on which group they were randomized to. Clinical and biochemical variables were obtained at baseline and at 12 weeks of feminizing hormone therapy.
Main Outcome Measures
The change of testosterone level from baseline. Other changes including free testosterone, estradiol, prolactin and lipid profile after the therapy.
Results
After a 12 weeks of feminizing hormone therapy, the change of testosterone level in the cyproterone acetate group [558.0 ng/dL (IQR 352.0 to 783.3)] was significantly higher than the spironolactone group [226.2 ng/dL (IQR,-4.3 to 480.1)](p value <0.001). Testosterone and calculated free testosterone in the cyproterone acetate group were significantly lower than the spironolactone group. Consequently, a proportion of the participants who achieved the female range testosterone (<50 ng/dL) was significantly higher in cyproterone acetate group (90%) compared to the spironolactone group (19%). Serious adverse effects observed in cyproterone acetate users were drug-induced liver injury and asymptomatic hyperprolactinemia.
Clinical Implications
The data on the differences between the two anti-androgen could be benefit for the transgender health-care providers in medication selection and adverse-effects counseling.
Strengths & Limitations
The study design was randomized controlled trial and controlled the estrogen component by prescribed the same type and dose for each participant. However, the study was suffered from the confound feminizing effects from previous hormone therapy and the high drop-out rate.
Conclusion
For feminizing hormone therapy, cyproterone acetate had a higher testosterone suppression efficacy than spironolactone.
Burinkul S, Panyakhamlerd K, Suwan A, et al. Anti-Andorgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial. J Sex Med 2021;18:1299–1307.
Objective
To examine the effect of gender affirming hormones on athletic performance among transwomen and transmen.
Methods
We reviewed fitness test results and medical records of 29 transmen and 46 transwomen who started gender affirming hormones while in the United States Air Force. We compared pre- and post-hormone fitness test results of the transwomen and transmen with the average performance of all women and men under the age of 30 in the Air Force between 2004 and 2014. We also measured the rate of hormone associated changes in body composition and athletic performance.
Results
Participants were 26.2 years old (SD 5.5). Prior to gender affirming hormones, transwomen performed 31% more push-ups and 15% more sit-ups in 1 min and ran 1.5 miles 21% faster than their female counterparts. After 2 years of taking feminising hormones, the push-up and sit-up differences disappeared but transwomen were still 12% faster. Prior to gender affirming hormones, transmen performed 43% fewer push-ups and ran 1.5 miles 15% slower than their male counterparts. After 1 year of taking masculinising hormones, there was no longer a difference in push-ups or run times, and the number of sit-ups performed in 1 min by transmen exceeded the average performance of their male counterparts.
Summary
The 15–31% athletic advantage that transwomen displayed over their female counterparts prior to starting gender affirming hormones declined with feminising therapy. However, transwomen still had a 9% faster mean run speed after the 1 year period of testosterone suppression that is recommended by World Athletics for inclusion in women’s events.
Background:
Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called 'transition.' Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition.
Objectives:
We aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition.
Search methods:
We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019.
Selection criteria:
We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control.
Data collection and analysis:
We used standard methodological procedures expected by Cochrane to establish study eligibility.
Main results:
Our database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up.
Authors' conclusions:
We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.
Transgender, including gender diverse and nonbinary, individuals are treated with estradiol with or without antiandrogen to align their physical appearance with their gender identity, improve mental health and quality of life. Consensus guidelines give target ranges for serum estradiol concentration based on premenopausal female reference ranges. However, limited studies have evaluated the relationship between serum estradiol concentrations and clinical outcomes in transgender individuals undergoing feminizing hormone therapy. The available evidence has not found that higher serum estradiol concentrations, together with suppressed testosterone, enhance breast development, or produce more feminine changes to body composition. However, ensuring testosterone suppression appears to be an important factor to maximize these physical changes. Higher serum estradiol concentrations have been associated with higher areal bone mineral density. Although the resultant long-term clinical implications are yet to be determined, this could be a consideration for individuals with low bone mass. The precise serum estradiol concentration that results in adequate feminization without increasing the risk of complications (thromboembolic disease, cholelithiasis) remains unknown. Further prospective trials are required.
The effects of gluteal implants on bone mass remain unclear. Transgender women with ILS presented higher BMD in the hip compared with transgender women without implants, while no difference was observed in other sites. These results may be artifactual and suggest using spine/forearm sites for DXA in individuals with ILS.
Purpose:
The inappropriate use of industrial liquid silicone (ILS) injections for cosmetic purposes is practiced by some transgender women. The aim of this study was to evaluate the impact of gluteal ILS on femur BMD in transgender women.
Methods:
A total of 46 trans women with and without ILS injection in the gluteal region were selected. All patients underwent clinical and hormonal evaluation, and bone mass was assessed by DXA.
Results:
Bone mineral density (BMD) values were significantly higher in trans women with ILS (n = 23) in femoral neck and total femur when compared with trans women without implants (n = 23). Similar BMD was observed in other sites, such as lumbar spine and forearm. Good agreement was found in the evaluation of low BMD using spine/forearm or spine/femur in patients without implants (k = 0.744 and 1.000 for male and female reference database, respectively), but poor to fair index was found in patients with ILS implants (k = 0.330 and 0.646 for male and female reference database, respectively).
Conclusions:
In transgender women with ILS implants, poor to moderate agreement was found on BMD when comparing lumbar spine/femur DXA with an alternative site to the femur, depending on using male or female database. These results may be artifactual and suggest using spine/forearm sites for more accurate DXA assessments in trans women with ILS gluteal implants.
Objective
The objective of this scoping review is to describe the extent, range, and nature of available literature examining nutrition-related intermediate and long-term health outcomes in individuals who are transgender. Specific sub-topics examined include 1) dietary intake, 2) nutrition-related health disparities, 3) validity and reliability of nutrition assessment methods, 4) the effects of nutrition interventions/exposures, and 5) hormone therapy.
Methods
A literature search was conducted using MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and other databases for peer-reviewed articles published from January 1999 until December 5, 2019 to identify studies addressing the research objective and meeting eligibility criteria. Conference abstracts and registered trials published or registered in the five years prior to the search were also included. Findings were reported in a study characteristics table, a bubble chart and heat maps.
Results
The search of the databases identified 5403 studies, including full peer-reviewed studies, systematic reviews, conference abstracts and registered trials. Following title/abstract screening, 189 studies were included in the narrative analysis. Ten studies reported dietary intake in transgender individuals, 64 studies reported nutrition-related health disparities in transgender compared to cisgender individuals, one study examined validity and reliability of nutrition assessment methods, two studies reported nutrition interventions, and 127 studies reported on the intermediate and health effects of hormone therapy.
Conclusion
Individuals who are transgender have unique nutrition needs, which may vary according to the stage and type of gender-affirmative therapy that they are undergoing. There is scant research examining effective nutrition therapy methods for nutrition professionals working with transgender individuals. More research is needed in order to inform evidence-based clinical practice guidelines for nutrition practitioners working with transgender individuals.
Sex steroids are important regulators of bone development before puberty and of bone homeostasis throughout adulthood. Gender-affirming therapies with sex steroids are used in transgender and gender diverse persons for treatment of gender dysphoria, which may have profound impacts on their bone metabolism. Many studies have described variable changes in bone density and geometry in transgender cohorts. In order to provide informed guidance on the effect of gender-affirming therapy, the International Society of Clinical Densitometry issued official position statements in 2019 for the performance and interpretation of dual-energy x-ray absorptiometry in transgender and gender-diverse patients. We review the effects of gender-affirming hormone therapy on bone physiology and the changes in bone modulation that have been reported in the literature in transgender patients who have received gender-affirming therapy. We also summarize the recent guidelines for interpretation of dual energy x-ray absorptiometry as an update for the radiologist.
Objectives
To describe the extent, range and nature of literature examining the nutrition-related intermediate and long-term health outcomes in individuals who are transgender. Specific sub-topics include dietary intake, nutrition-related health disparities, validity and reliability of nutrition assessment methods, and the effects of nutrition interventions/exposures and hormone therapy.
Methods
A literature search was conducted of Medline, Embase, PsycINFO, CINAHL, Web of Science, and other databases from 1999 though 2019 to identify peer-reviewed articles published in English that addressed the research objective. Conference abstracts and registered trials were eligible if they were published in 2015 or later. Each title/abstract and eligible full-text article was screened by two reviewers and discrepancies were determined by consensus. Data was extracted by one reviewer and confirmed by a second reviewer.
Results
The literature search identified 3020 original studies, abstracts or registered trials, 424 full-text articles were reviewed for inclusion and 188 were included in qualitative analysis, including 17 systematic reviews. Populations examined included adults (n = 159), adolescents (n = 61) and children (n = 11). The vast majority of included articles examined the effects of hormone therapy on intermediate outcomes (n = 118) such as anthropometric, bone density and laboratory measures, or health outcomes (n = 18) such as cardiovascular disease events or quality of life. There was also considerable research examining the prevalence of health outcomes, such as eating disorders, malnutrition status, or diabetes, in transgender compared to cisgender populations. However, there was a paucity of data describing dietary intake (n = 10), validity and reliability of nutrition assessment methods (n = 1) or the effects of nutrition interventions on nutrition-related outcomes (n = 3) in transgender individuals. Nearly all evidence, except for three hormone trials, was observational in nature.
Conclusions
There is a need for research that examines medical nutrition therapy to promote health and prevent or treat adverse health outcomes that are prevalent in individuals who are transgender.
Funding Sources
Academy of Nutrition and Dietetics.
Sex dimorphism starts during early embryogenesis and is further manifested in response to hormones during puberty. As this leads to physical divergence that is measurably different between sexes, males enjoy physical performance advantages over females within competitive sport. While this advantage is the underlying basis of the segregation into male and female sporting categories, these sex-based categories do not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been collectively scrutinized. Here, we aim to review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage. In this review, we report that the performance gap between males and females amounts to 10-50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 1 year of treatment. Thus, current evidence shows that the biological advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations may therefore be compelled to reassess current policies regarding participation of transgender women in the female category of sport.
Background:
Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.
Aim:
To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk.
Methods:
We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance.
Results:
The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants.
Conclusion:
Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.
This article focuses on the provision of gender‐affirming care and preventive care for transfeminine individuals—those assigned male at birth who identify as female or on the feminine spectrum. To meet the learning needs of health care providers less familiar with gender‐affirming care, this article begins with an overview of gender identity concepts. Initiation and management of feminizing gender‐affirming hormone therapy is then covered in detail, including common gender‐affirming medications and their adverse effects, diagnostic criteria, psychosocial evaluation, initial physical examination and laboratory work, and recommendations for follow‐up visits and laboratory monitoring. Lastly, the article briefly reviews health care of transfeminine individuals before and after surgical gender‐affirming interventions and details best practices for transfeminine preventive care.
Context:
The impact of gender-affirming hormone therapy (HT) on cardiometabolic parameters is largely unknown.
Objective:
The effects of 1 year of treatment with oral or transdermal administration of estrogen (plus cyproterone) and transdermal or IM application of testosterone on serum lipid levels and blood pressure (BP) were assessed in transgender persons.
Design and methods:
In this prospective, observational substudy of the European Network for the Investigation of Gender Incongruence, measurements were performed before and after 12 months of HT in 242 transwomen and 188 transmen from 2010 to 2017.
Results:
Mean values are reported. In transmen, HT increased diastolic BP (2.5%; 95% CI, 0.6 to 4.4) and levels of total cholesterol (TC; 4.1%; 95% CI, 1.5 to 6.6), low-density lipoprotein-cholesterol (LDL-C; 13.0%; 95% CI, 9.2 to 16.8), and triglycerides (36.9%; 95% CI, 29.8 to 44.1); high-density lipoprotein-cholesterol levels decreased (HDL-C; 10.8%; 95% CI, -14.0 to -7.6). In transwomen, HT slightly decreased BP (systolic BP, -2.6%, 95% CI, -4.2 to -1.0; diastolic BP, -2.2%, 95% CI, -4.0 to -0.4) and decreased levels of TC (-9.7%; 95% CI, -11.3 to -8.1), LDL-C (-6.0%; 95% CI, -8.6 to 3.6), HDL-C (-9.3%; 95% CI, -11.4 to -7.3), and triglycerides (-10.2%; 95% CI, -14.5 to -5.9).
Conclusion:
Unfavorable changes in lipid profile were observed in transmen; a favorable effect was noted in transwomen. HT effects on BP were negligible. Long-term studies are warranted to assess whether and to what extent HT in trans individuals results in a differential effect on cardiovascular disease outcomes.
: Transgender women have recently been acknowledged as a unique and important risk group in HIV research and care. Although transgender men also face specific problems related to HIV infection, less is known about the risk behaviours and HIV prevalence of this important population. This article highlights key issues relating to the epidemiology, prevention, treatment and management of complications of HIV infection in transgender adults living with HIV, and explores future areas for HIV-related research, with the ultimate goal of improving healthcare provision and quality of life for transgender persons worldwide.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objective of this proposed systematic review and meta-analysis is to assess the efficacy and safety of hormone replacement therapy with antiandrogens or estradiol or both in transitioning transgender women.
Objective
To update the “Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline,” published by the Endocrine Society in 2009.
Participants
The participants include an Endocrine Society–appointed task force of nine experts, a methodologist, and a medical writer.
Evidence
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
Consensus Process
Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines.
Conclusion
Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person’s genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person’s affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments—appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)—should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.
To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20–89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.
Obesity is associated with increased risk of fractures, especially at skeletal sites with a large proportion of cortical bone, such as the humerus and ankle. Obesity increases fracture risk independently of BMD, indicating that increased adipose tissue could have negative effects on bone quality. Microindentation assesses bone material strength index (BMSi) in vivo in humans. The aim of this study was to investigate if different depots of adipose tissue were associated with BMSi and cortical bone microstructure in a population based group of 202 women, 78.2 ± 1.1 (mean ± SD) years old. Bone parameters and subcutaneous(s.c.) fat were measured at the tibia with an XtremeCT. BMSi was assessed using the Osteoprobe® device, and based on at least 11 valid reference point indentations at the midtibia. Body composition was measured with dual x-ray absorptiometry. BMSi was inversely correlated to body mass index (r = -0.17, p = 0.01), whole body fat mass (r = -0.16,p = 0.02) and, in particular, to tibia s.c. fat (r = -0.33, p < 0.001). Tibia s.c. fat was also correlated to cortical porosity (Ct.Po;r = 0.19, p = 0.01) and cortical volumetric BMD (Ct.vBMD;r = -0.23, p = 0.001). Using linear regression analyses, tibia s.c. fat was independently of covariates (age, height, log weight, bisphosphonates or glucocorticoid use, smoking, calcium intake, walking speed, and BMSi operator) associated with BMSi (β = -0.34,p < 0.001), Ct.Po (β = 0.18,p = 0.01), and Ct.vBMD (β = -0.32,p < 0.001). BMSi was independently of covariates associated with cortical porosity (β = -0.14,p = 0.04) and cortical volumetric BMD (β = 0.21,p = 0.02) at the distal tibia, but these bone parameters could only explain 3.3% and 5.1%, respectively, of the variation in BMSi. In conclusion, fat mass was independently and inversely associated with BMSi and Ct.vBMD, but positively with Ct.Po, indicating a possible adverse effect of adipose tissue on bone quality and bone microstructure. Local s.c. fat in tibia was most strongly associated with these bone traits, suggesting a local or paracrine, rather than systemic, negative effect of fat on bone. This article is protected by copyright. All rights reserved.
The role of the gynaecologist in the treatment of female-to-male transsexual patients is largely confined to hysterectomy and vaginectomy. We showed that laparoscopic hysterectomy is feasible and safe in this group. When surgery is not performed completely, follow-up of the remaining organs is necessary.
The major part of this thesis deals with the necessity and acceptability of gynaecological follow-up in male-to-female (MTF) transsexual patients. These patients function well on a physical, emotional, psychological and social level. Sexual function was less satisfactory, especially concerning arousal, lubrication and pain.
Typical gynaecological exams proved to be feasible and well accepted. Transvaginal palpation of the prostate is of poor clinical value, in contrast to transvaginal ultrasound. Mammography was judged almost painless and 98% of transsexual women intend to return for screening. Since there is uncertainty about breast cancer risk in transsexual women, we conclude that breast screening in this population should not differ from that in biological women.
Microflora and cytology of the penile skin-lined neovagina of transsexual women were described for the first time. Vaginal lactobacilli were largely lacking. A mixed microflora of aerobe and anaerobe species, usually found on skin, in bowel or in bacterial vaginosis microflora, was encountered. No high-grade cervical lesions were found, however, one patient displayed a low-grade lesion (positive for HR-HPV with koilocytes).
Finally, low bone mass was highly prevalent in our study group. This finding appeared to be largely determined, in comparison to healthy males, by smaller bone size and a strikingly lower muscle mass.
Context:
Body weight is the most important anthropometric determinant of bone mineral density (BMD). Body weight is mainly made up of lean mass (LM) and fat mass (FM), and which component is more important to BMD has been a controversial issue.
Objective:
This study sought to compare the magnitude of association between LM, FM, and BMD by using a meta-analytic approach.
Data source:
Using an electronic and manual search, we identified 44 studies that had examined the correlation between LM, FM, and BMD between 1989 and 2013. These studies involved 20,226 men and women (4966 men and 15,260 women) aged between 18 and 92 years. We extracted the correlations between LM, FM, and BMD at the lumbar spine, femoral neck, and whole body. The synthesis of correlation coefficients was done by the random-effects meta-analysis model.
Results:
The overall correlation between LM and femoral neck BMD (FNBMD) was 0.39 (95% confidence interval, 0.34 to 0.43), which was significantly higher than the correlation between FM and FNBMD (0.28; 95% confidence interval, 0.22 to 0.33). The effect of LM on FNBMD in men (r=0.43) was greater than that in women (r=0.38). In premenopausal women, the effect of LM on BMD was greater than the effect of FM (r=0.45 vs r=0.30); however, in postmenopausal women, the effects of LM and FM on BMD were comparable (r=0.33 vs r=0.31).
Conclusion:
LM exerts a greater effect on BMD than FM in men and women combined. This finding underlines the concept that physical activity is an important component in the prevention of bone loss and osteoporosis in the population.
Introduction. Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known.
Aim. The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women.
Main Outcome Measures. Hormone levels were measured by immunoassays. Physical health was assessed by physical examination and questionnaires on general health and specific side effects, areal bone parameters by dual energy X-ray absorptiometry.
Methods. Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy.
Results. Transsexual men did not experience important side effects such as cardiovascular events, hormone-related cancers, or osteoporosis. In contrast, a quarter of the transsexual women had osteoporosis at the lumbar spine and radius. Moreover, 6% of transsexual women experienced a thromboembolic event and another 6% experienced other cardiovascular problems after on average 11.3 hormone treatment years. None of the transsexual women experienced a hormone-related cancer during treatment.
Conclusion. Cross-sex hormone treatment appears to be safe in transsexual men. On the other hand, a substantial number of transsexual women suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management. Wierckx K, Mueller, S, Weyers S, Van Caenegem E, Roef G, Heylens G, and T'Sjoen G. Long-term evaluation of cross-sex hormone treatment in transsexual persons. J Sex Med **;**:**–**.
Background
The impact of sex steroids on bone health in transgender individuals is unclear.
Methods
A comprehensive search of several databases to April 7th 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CI).
Results
Thirteen studies evaluating 639 transgender individuals were identified (392 male to female [MTF], 247 female to male [FTM]). In FTM individuals and compared to baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck or total hip BMD when assessed at 12 and 24 months. In MTF individuals and compared to baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm²; 95% CI, 0.03, 0.06 g/cm²) and 24 months (0.06 g/cm²; 95% CI, 0.04, 0.08 g/cm²). Fracture rates were evaluated in a single cohort of 53 MTF/53FTM individuals with no events at 12 months. The body of evidence is mostly derived from observational studies at moderate risk of bias.
Conclusion
In FTM individuals, masculinizing hormone therapy does not seem to be associated with significant changes in BMD whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient important outcomes such as fracture risk is uncertain.
Purpose of review:
To give an overview of recent research findings and insights on the role of body composition assessment in fracture risk prediction.
Recent findings:
While there is to date little doubt that bone mineral density (BMD) is a main pathogenic factor of osteoporotic fractures, recent studies have emphasized the independent contribution of body composition components, especially lean mass, to fracture risk. In this article, we address body composition changes with aging, before to focus on recent studies addressing the contribution of lean and fat mass to fracture risk, together with some hypothesized mechanisms and clinical implications.
Summary:
Recent compelling evidence suggest that clinicians should recognize the potential role of muscle wasting in determining fracture risk among older adults and that measures of lean mass, especially appendicular lean mass - which can be assessed simultaneously with the BMD measurement - should be considered in fracture risk assessment beyond BMD and clinical risk factors. More evidence is needed to support certain fat-related indicators in fracture risk prediction, but regional adiposity measures appear promising. Further studies in the field should help to elucidate whether interventions effective at attenuate, prevent, or ultimately reverse skeletal lean mass loss or fat accumulation, may prevent fractures.
Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study is to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol, transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after one year CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval (CI) 3.20 to 4.13%, p?<?0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p?<?0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p?<?0.001) BMD was found. In transmen, TH BMD increased after one year CHT (+1.04%, 95% CI 0.64 to 1.44%, p?<?0.001). No changes were observed in FN BMD (-0.46%, 95% CI -1.07 to 0.16%, p?=?0.144). The increase in LS BMD was larger in transmen ?50 years (+4.32%, 95% CI 2.28 to 6.36%, p?=?0.001) compared with transmen <50 years (+0.68%, 95% CI 0.19 to 1.17%, p?=?0.007). In conclusion, BMD increased in transgender persons after one year CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. This article is protected by copyright. All rights reserved.
Whether low muscle mass predisposes to fracture is still poorly understood. In the diagnosis of sarcopenia, different thresholds for low lean mass have been proposed but comparative data for these criteria against hard outcomes like fractures are lacking. This study aimed to investigate the prevalence of low lean mass according to different thresholds used in operational definitions of sarcopenia and their association with 3-year fracture incidence in a cohort of healthy 63-67 years old community-dwellers. In a longitudinal analysis of 913 participants (mean age 65.0 ± 1.4 years) enrolled in the Geneva Retirees Cohort (GERICO) study, lean mass was assessed by dual-energy X-ray absorptiometry, and low trauma clinical fracture incidence was recorded over a 3-year period. Prevalence of low lean mass ranged from 3.5% to 20.2% according to the threshold applied. During a follow-up of 3.4 ± 0.9 years, 40 (4.4%) participants sustained at least one low trauma fracture. After multivariate adjustment including FRAX® probability with femoral neck BMD, low lean mass, as defined by Baumgartner thresholds, was associated with higher fracture risk (odds ratio, 2.32; 95% CI, 1.04 to 5.18; p = 0.040). It also added significant predictive value beyond FRAX® (likelihood ratio test for nested models, 4.28; p < 0.039). No significant association was found for other definition thresholds. The co-existence of sarcopenia and a T-score < -2.5 at spine or hip was associated with a 3.39 (95% CI, 1.54 to 7.46; p = 0.002)-fold increase in low trauma fracture risk. In conclusion, low lean mass, as defined by the Baumgartner thresholds, is a predictor of incident fractures in a large cohort of healthy 65-year old community-dwellers, independently of FRAX® probability. The increased risk is related to the threshold for low lean mass selected. These findings suggest that identification of sarcopenia should be considered in fracture risk assessment beyond usual risk factors. This article is protected by copyright. All rights reserved.
Purpose of review:
We provide an update of bone health in trans persons on cross-sex hormonal therapy. This drastic hormonal reversal will have direct but also indirect effects on bone, through body composition changes.
Recent findings:
Recent evidence suggests that trans women, even before the start of any hormonal intervention, already have a lower bone mass, a higher frequency of osteoporosis, and a smaller bone size vs. natal men. During cross-sex hormonal treatment, bone mass was maintained or gained in trans women. In trans men, bone metabolism seemed to increase during short-term testosterone therapy, but no major changes have been found in bone density. On long-term testosterone therapy, larger cortical bone size was observed in trans men vs. natal women.
Summary:
Follow-up of bone health and osteoporosis prevention in trans persons is important. We advise active assessment of osteoporosis risk factors including the (previous) use of hormonal therapy. Based on this risk profile and the intended therapy, bone densitometry may be indicated. Long-term use of antiandrogens or gonadotropin-releasing hormone agonists alone should be monitored as trans women may have low bone mass, even prior to treatment. Therapy compliance with the cross-sex hormones is of major concern, especially after gonadectomy. Large-scaled, multicenter, and long-term research is needed to determine a well tolerated dosage of cross-sex hormonal treatment, also in elderly trans persons.
Obesity is associated with greater areal BMD (aBMD) and considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site-specific differences in BMD, bone structure or strength between obese and normal weight adults. We studied 100 individually-matched pairs of normal (BMI 18.5-24.9 kg/m2) and obese (BMI>30 kg/m2) men and women, aged 25-40 or 55-75 years. We assessed aBMD at the whole body (WB), hip (TH) and lumbar spine (LS) with DXA, LS Tb.vBMD by QCT and vBMD, and microarchitecture and strength at the distal radius and tibia with HR-pQCT and micro-finite element analysis. Serum PINP and βCTX were measured by automated ECLIA. Obese adults had greater WB, LS and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p<0.01). Obese adults had greater vBMD than normal adults at the tibia (p<0.001 both ages) and radius (p<0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD and greater trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p<0.05) and tibia (p<0.01). Differences in HR-pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than normal adults. Greater BMD in obesity is not an artefact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest obesity may protect against age-related bone loss, and also increase peak bone mass. This article is protected by copyright. All rights reserved
Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton.
The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy.
In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-beta estradiol 100 mu g/24 h for patients > 45 years old), both combined with oral cyproterone acetate 50 mg daily.
Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05).
Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.
Background: Cross-sex hormone treatment in male-to-female (M2F) transsexuals appears reasonably safe. Little is known about its long-term use. The aim of our study was to evaluate the effect of long-term high dose estrogens, plus the antiandrogen cyproterone acetate, on bone composition and on biochemical/hormonal parameters in M2F transsexuals. Methods: A retrospective analysis was performed on 45 young M2Fs (mean age 39.5 years; body mass index (BMI) = 22) receiving estrogens (previously 100 μg ethinyl estradiol, now 2-4 mg oral estradiol valerate/day or 100 μg transdermal estradiol/day) plus the antiandrogen cyproterone acetate 100 mg/day. Data were retrieved from 20 subjects after reassignment surgery (mean hormonal treatment duration 15.6 years). A complete hormonal and biochemical assessment, as well as bone biochemical markers (parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase and plasma pyridinoline crosslinks), were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Results: All subjects had suppressed serum testosterone levels (mean = 0.57 nmol/l), whereas serum estradiol levels were within the supraphysiological range (mean = 880 pmol/l). A mild osteopenia at both lumbar spine and femoral neck was observed in 15 out of the 20 (75%) M2Fs (BMD = 0.89 ± 0.14 (mean ± standard deviation (SD)) g/cm2 versus 1.1 ± 0.09, p < 0.001; lumbar T-score = -1.39 ± 0.84 versus 0.5 ± 1.10, p < 0.0005; femoral T-score = -1.12 ± 0.76 versus 0.08 ± 1.00, p < 0.05, respectively). No differences in plasma crosslink levels or in hormonal and biochemical parameters were found between subjects. Conclusions: Our results indicate that cross-sex hormone treatment of M2Fs, independently of serum testosterone levels, seems acceptably safe over a median treatment period of 15 years in a consistent population of subjects. A protective role for estrogens on bone seems to be present in a minority of subjects.
Objective:
Cross-sex hormonal therapy and sex reassignment surgery (including gonadectomy) in transsexual persons has an impact on body composition and bone mass and size. However, it is not clear whether baseline differences in bone and body composition between transsexual persons and controls before cross-sex hormonal therapy play a role.
Design:
A cross-sectional study with 25 male-to-female transsexual persons (transsexual women) before cross-gender sex steroid exposure (median age 30 years) in comparison with 25 age-matched control men and a male reference population of 941 men.
Main outcome measures:
Areal and volumetric bone parameters using respectively dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), body composition (DXA), grip strength (hand dynamometer), Baecke physical activity questionnaire, serum testosterone and 25-OH vitamin D.
Results:
Transsexual women before cross-sex hormonal therapy presented with less muscle mass (p≤0.001) and strength (p≤0.05) and a higher prevalence of osteoporosis (16%) with a lower aBMD at the hip, femoral neck, total body (all p<0.001) and lumbar spine (p=0.064) compared with control men. A thinner radial cortex (p≤0.01) and lower cortical area at the radius and tibia (both p<0.05) was found in transsexual women vs. control men. Serum testosterone was comparable in all 3 groups, but 25-OH vitamin D was lower in transsexual women (p≤0.001).
Conclusions:
Transsexual women before the start of hormonal therapy appear to have lower muscle mass and strength and lower bone mass compared with control men. These baseline differences in bone mass might be related to a less active lifestyle.
It is unknown whether long term cross-sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28–63 months in 20 male-to-female transsexuals (M → F) treated with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F → M) treated with androgens. They underwent gonadectomy 13–35 months after the start of cross-sex hormone administration.
Bone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28–63 months of cross-sex hormone administration.
In oestrogen-treated M → F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28–63 months of cross-sex hormones.
In F → M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28–63 months following ovariectomy. In both M → F and F → M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long-term LH levels were more elevated in testosterone-treated F → M than in oestrogen-treated M → F transsexuals.
In M → F, oestrogen treatment prevented bone loss after testosterone deprivation. In F → M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non-compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.
Estrogen is the major hormonal regulator of bone metabolism in women and men. Therefore, there is considerable interest in unraveling the pathways by which estrogen exerts its protective effects on bone. Although the major consequence of the loss of estrogen is an increase in bone resorption, estrogen deficiency is associated with a gap between bone resorption and formation, indicating that estrogen is also important for maintaining bone formation at the cellular level. Direct estrogen effects on osteocytes, osteoclasts, and osteoblasts lead to inhibition of bone remodeling, decreased bone resorption, and maintenance of bone formation, respectively. Estrogen also modulates osteoblast/osteocyte and T-cell regulation of osteoclasts. Unraveling these pleiotropic effects of estrogen may lead to new approaches to prevent and treat osteoporosis.
The potential beneficial effects of increased body weight on bone mineral density (BMD) conflict with the adverse effects of obesity on various health outcomes, necessitating more specific evaluations of the association between each body component and BMD. In the present study, we evaluated associations of lean mass (LM) and fat mass (FM) with BMD in a Korean sample consisting of a total of 1782 men and women whose mean (standard deviation) age was 43.2 (12.6) years. They were selected from the Healthy Twin Study, a nationwide Korean twin and family study. BMD, FM and LM were measured using dual-energy X-ray absorptiometry. Quantitative genetic analysis and linear mixed analysis were performed with respect to familial relationships and a wide range of probable covariates. Linear mixed analysis revealed that BMD was positively associated with both FM and LM at each region of BMD measurement (whole body, spine, arms, and legs) in men, premenopausal women, and postmenopausal women. However, the association with BMD was stronger for LM than FM. Both LM and FM had positive genetic correlations with BMD at each region, although the correlation with BMD tended to be stronger for LM than FM. Together, these findings suggest that increased LM, rather than FM, is more beneficial for BMD in the Korean population and warrants further study of the common genetic determinants of BMD and body composition.
The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.
GUNTER, K. B., H. C. ALMSTEDT, and K. F. JANZ. Physical activity in childhood may be the key to optimizing lifespan skeletal health. Exerc. Sport Sci. Rev., Vol. 40, No. 1, pp. 13-21, 2012. Physical activities undertaken in childhood, particularly activities, which apply large forces quickly convey optimal benefits to bone mass, size, and structure. Evidence is accumulating that benefits persist well beyond activity cessation. This review examines the potential for early childhood activity to improve bone mineralization and structure and explores childhood activity as prevention for osteoporosis in later life.
We aimed at evaluating the relationship of lean and fat mass to bone mass in osteoporotic postmenopausal women. We invited 65 women who were being treated at the São Paulo Hospital osteoporosis outpatients' clinic to participate. Body composition and bone mineral density (BMD) measurements were performed using Dual-energy X-ray absorptiometry methodology (DXA). The mean age and weight were 69.7±6.4 years and 56.3±7.6 kg, respectively. Accordingly to the body mass index (BMI), 52.8% were of normal weight and 47.1% of the patients were overweight. Overweight women had significantly higher bone mass. Similarly, skeletal muscle index (SMI) showed a positive effect on BMD measurements and women with sarcopenia had significantly lower BMD measurements in total femur and femoral neck. In multiple regression analysis only lean mass and age, after adjustments to fat mass and BMI, were able to predict total body bone mineral content (BMC) (R(2)=28%). Also lean mass adjusted to age and BMI were able to predict femoral neck BMD (R(2)=14%). On the other hand, none of the components of the body composition (lean mass or fat mass) contributed significantly to explaining total femur BMD and neither body composition measurements were associated with spine BMD. These findings suggest that lean mass has a relevant role in BMC and BMD measurements. In addition, lower BMI and lean mass loss (sarcopenia) is associated to lower BMC and BMD of femoral neck and total femur and possible higher risk of osteoporotic fracture.
Bone health is a parameter of interest in the daily follow-up of male-to-female (M --> F) transsexual persons both before and after sex reassignment surgery (SRS) due to an intensely changing hormonal milieu. We have studied body composition, areal, geometric, and volumetric bone parameters, using DXA and peripheral quantitative computed tomography at different sites in 50 M --> F transsexual persons, at least 3 yr after the start of the hormonal treatment and 1 yr after SRS. In this cross-sectional study, hormone levels and markers of bone metabolism were assessed using immunoassays. Prevalence of low bone mass as defined by a Z-score < or = -2.0 according to DXA criteria was 26% at lumbar spine and 2% at the total hip. We found no major differences in hormonal parameters between participants with a Z-score < or = or > -2.0. Markers of bone turnover were comparable between subjects with or without low bone mass, indicating a stable bone turnover at the time of investigation. No significant differences in bone size or density were observed between patients on transdermal vs. oral estrogens. Low bone mass is not uncommon in M --> F transsexual persons. Smaller bone size, and a strikingly lower muscle mass compared with men appear to underlie these findings.
Male-to-female (M-->F) transsexual persons undergo extreme changes in gonadal hormone concentrations, both by pharmacological and surgical interventions. Given the importance of sex steroids for developing and maintaining bone mass, bone health is a matter of concern in daily management of these patients.
To provide data on bone metabolism, geometry and volumetric bone mineral density in M-->F transsexual persons.
Twenty-three M-->F transsexual persons, recruited from our gender dysphoria clinic and at least 3 yrs after sex reassignment surgery, together with 46 healthy age- and height-matched control men were included in this cross-sectional study.
Body composition, areal and volumetric bone parameters determined using DXA and peripheral quantitative computed tomography. Hormone levels and markers of bone metabolism assessed using immunoassays. Peak torque of biceps and quadriceps muscles and grip strength assessed using an isokinetic and hand dynamometer, respectively.
M-->F transsexual persons presented lower total and regional muscle mass and lower muscle strength as compared to controls (all P<0.001). In addition, they had higher total and regional fat mass (P<0.010) and a lower level of sports-related activity index (P<0.010). Bone mineral content and areal density (aBMD) of the lumbar spine, total hip and distal radius, as well as trabecular vBMD of the distal radius was lower as compared to controls (P<0.010). At cortical sites, no differences in cortical vBMD were observed, whereas M-->F transsexual persons were characterized by smaller cortical bone size at both the radius and tibia (P<0.010). Lower levels of biochemical markers of bone formation and resorption (P<0.010) suggested decreased bone turnover.
M-->F transsexual persons have less lean mass and muscle strength, and higher fat mass. In addition, they present lower trabecular vBMD and aBMD at the lumbar spine, total hip and distal radius, and smaller cortical bone size as compared to matched controls. Both the lower level of sports-related physical activity as well testosterone deprivation could contribute to these findings. These results indicate that bone health should be a parameter of interest in the long-term follow-up care for M-->F transsexual persons.
A deficiency of sex hormones leads in both sexes to increased bone loss, and hormonal substitution can prevent this. The effect of the change of hormonal environment on bone metabolism in transsexuals is unknown. Transilial bone biopsies were obtained from 23 male-to-female transsexuals (mean age +/- SD, 38.0 +/- 11.7 years) after estrogen (ethinylestradiol, 100 micrograms/day) and antiandrogen treatment (cyproterone acetate, 100 mg/day) for 8-41 months. Histomorphometric data were compared with those from 11 healthy men (39.6 +/- 9.4 years). There was no difference in bone volume, bone surface, or trabecular thickness between transsexuals and controls. Eroded surface and osteoclast number were not different between the groups. The osteoid volume, surface, and thickness were significantly lower in the transsexuals than in the controls. The mineral apposition rate and adjusted apposition rate were normal, but mineralizing surface and bone formation rate were suppressed in the transsexuals compared with data reported from the literature. The results indicate that antiandrogen and estrogen treatment in male-to-female transsexuals may suppress bone turnover and is not associated with bone loss.
Sunlight has long been recognized as a major provider of vitamin D for humans; radiation in the UVB (290-315 nm) portion of the solar spectrum photolyzes 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted by a thermal process to vitamin D3. Latitude and season affect both the quantity and quality of solar radiation reaching the earth's surface, especially in the UVB region of the spectrum, but little is known about how these influence the ability of sunlight to synthesize vitamin D3 in skin. A model has been developed to evaluate the effect of seasonal and latitudinal changes on the potential of sunlight to initiate cutaneous production of vitamin D3. Human skin or [3 alpha-3H]7-dehydrocholesterol exposed to sunlight on cloudless days in Boston (42.2 degrees N) from November through February produced no previtamin D3. In Edmonton (52 degrees N) this ineffective winter period extended from October through March. Further south (34 degrees N and 18 degrees N), sunlight effectively photoconverted 7-dehydrocholesterol to previtamin D3 in the middle of winter. These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.
The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500-3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100-300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate "setpoints" of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.
It is unknown whether long term cross-sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28-63 months in 20 male-to-female transsexuals (M-->F) treated with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F-->M) treated with androgens. They underwent gonadectomy 13-35 months after the start of cross-sex hormone administration.
Bone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28-63 months of cross-sex hormone administration.
In oestrogen-treated M-->F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28-63 months of cross-sex hormones. In F-->M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28-63 months following ovariectomy. In both M-->F and F-->M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long-term LH levels were more elevated in testosterone-treated F-->M than in oestrogen-treated M-->F transsexuals.
In M-->F, oestrogen treatment prevented bone loss after testosterone deprivation. In F-->M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non-compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.
The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men.
Cross-sectional study of BMD in male to female transsexuals.
Subjects consisted of two groups of transsexual male dancers aged 16-34 years who did not receive transsexual operations (n = 28). Group 1 (n = 11) and group 2 (n = 17) had used oestrogen for 2 years or less and more than 2 years, respectively. Twenty-four healthy adult males served as controls.
Signs of feminization were presented in both group 1 and group 2, with Tanner's stage II-III breast development. BMD at various sites were correlated only to body weight and not to smoking or milk consumption. After controlling for body weight, it was found that group 2 had significantly higher BMD at L2-4 than controls (1.22 +/- 0.03 vs. 1.14 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.22 +/- 0.03 vs. 1.08 +/- 0.04 g/cm2, P < 0.05). BMD at femoral neck was also higher in group 2 compared to controls (1.10 +/- 0.03 vs. 1.01 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.10 +/- 0.03 vs. 0.95 +/- 0.04 g/cm2, P < 0.05). Group 1 subjects had lower BMD compared to controls at femoral trochanter (0.70 +/- 0.04 vs. 0.83 +/- 0.03 g/cm2, P < 0.05) and total femur (0.96 +/- 0.05 vs. 1.07 +/- 0.03 g/cm2, P < 0.05).
Long-term oestrogen exposure transsexual men result in an increase in bone mineral density despite signs of feminization. This suggests that oestrogen has positive effects on bone density in males. The finding of the trend towards reduced bone density in group 1 remains unexplained.
The effect of chronic administration of estrogens on bone and mineral metabolism in men is not known. We have studied the effect of chronic administration of estrogens on bone mineral metabolism in a group of transsexual (TS) Canarian men, who were taking estrogens for a minimum of 3 years. This is a cross-sectional study of cases and controls and we studied biochemical markers of bone remodeling, bone mineral density (BMD), and selected biochemical and hormonal features. TS subjects had shorter stature than controls, and after adjusting for height and weight, we found that they had lower values for serum-free testosterone and higher values for BMD, both in the lumbar spine and in femoral neck. Biochemistry, bone remodeling markers, and calcitropic hormone values were similar in both groups. Finally, the distributions of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba) polymorphisms were also similar in both groups. We conclude that the chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD-both in lumbar spine and in femoral neck. We found no association between the transsexual phenotype and the distribution of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba).
The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.
In this population-based study, amount of PA was associated with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones in young men. The lowest effective amount of PA was > or = 4 h/week.
Physical activity (PA) is believed to have positive effects on the skeleton and possibly help in preventing the occurrence of osteoporosis. Neither the lowest effective amount of PA needed to induce an osteogenic response nor its effect on the BMD and size of the different bone compartments (i.e., trabecular and cortical bone) has yet been clarified.
In this population-based study, we investigated the amount of all types of PA in relation to areal BMD (aBMD), trabecular and cortical volumetric BMD (vBMD), and cortical bone size in 1068 men (age, 18.9 +/- 0.02 years), included in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. aBMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT.
The amount of PA was associated with aBMD of the total body, radius, femoral neck, and lumbar spine, as well as with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones. The lowest effective amount of PA was > or = 4 h/week. aBMD, cortical bone size, and trabecular vBMD were higher in subjects who started their training before age 13 than in subjects who started their training later in life. Our data indicate that > or = 4 h/week of PA is required to increase bone mass in young men and that exercise before and during the pubertal growth is of importance. These findings suggest that PA is imperative for the augmentation of cortical bone size and trabecular vBMD but does not affect the cortical vBMD in young men.
The relative importance of AR and ER activation has been studied in pubertal male AR knockout and WT mice after orchidectomy and androgen replacement therapy, either with or without an aromatase inhibitor. AR activation dominates normal trabecular bone development and cortical bone modeling in male mice. Moreover, optimal periosteal bone expansion is only observed in the presence of both AR and ER activation.
Androgen receptor (AR)-mediated androgen action has traditionally been considered a key determinant of male skeletal growth. Increasing evidence, however, suggests that estrogens are also essential for normal male bone growth. Therefore, the relative importance of AR-mediated and estrogen receptor (ER)-mediated androgen action after aromatization remains to be clarified.
Trabecular and cortical bone was studied in intact or orchidectomized pubertal AR knockout (ARKO) and male wildtype (WT) mice, with or without replacement therapy (3-8 weeks of age). Nonaromatizable (dihydrotestosterone [DHT]) and aromatizable (testosterone [T]) androgens and T plus an aromatase inhibitor (anastrazole) were administered to orchidectomized ARKO and WT mice. Trabecular and cortical bone modeling were evaluated by static and dynamic histomorphometry, respectively.
AR inactivation or orchidectomy induced a similar degree of trabecular bone loss (-68% and -71%, respectively). Both DHT and T prevented orchidectomy-induced bone loss in WT mice but not in ARKO mice. Administration of an aromatase inhibitor did not affect T action on trabecular bone. AR inactivation and orchidectomy had similar negative effects on cortical thickness (-13% and -8%, respectively) and periosteal bone formation (-50% and -26%, respectively). In orchidectomized WT mice, both DHT and T were found to stimulate periosteal bone formation and, as a result, to increase cortical thickness. In contrast, the periosteum of ARKO mice remained unresponsive to either DHT or T. Interestingly, administration of an aromatase inhibitor partly reduced T action on periosteal bone formation in orchidectomized WT mice (-34% versus orchidectomized WT mice on T), but not in ARKO mice. This effect was associated with a significant decrease in serum IGF-I (-21% versus orchidectomized WT mice on T).
These findings suggest a major role for AR activation in normal development of trabecular bone and periosteal bone growth in male mice. Moreover, optimal stimulation of periosteal growth is only obtained in the presence of both AR and ER activation.
Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.
To assess the relationship of total fat mass (TFM) and total lean mass (TLM) with bone mineral density (BMD) and bone mineral content (BMC), we studied 770 postmenopausal white women after total body measurements by dual-energy X-ray absorptiometry. Height-independent bone mineral density (HIBMD) was also tested. The effects of TFM and TLM on the dependent variables HIBMD, BMD, and BMC were assessed by the univariate general linear model (UGLM). Age, age at menopause, height, and bone area were entered in the models as controlling variables when appropriate. In the total population, TLM and TFM were associated with BMD, BMC, and HIBMD (P < 0.001). Taking the T-score cut-off as -2.5, women without (463) and with (307) osteoporosis were then tested separately. In nonosteoporotic women, TLM was significantly associated with BMD, BMC, and HIBMD (P < 0.001), while TFM was not. In osteoporotic women, both TLM and TFM were associated with BMD to the same extent (P < 0.05), but not with HIBMD. Women without osteoporosis were then tested according to whether their TFM/TLM fraction was less than or greater than 1. In those with TFM/TLM less than 1, both TLM (P < 0.001) and TFM (P < 0.01), tested separately, were associated with BMD and BMC, but not with HIBMD. When TLM and TFM were tested at the same time and assessed by the same UGLM, only TLM (P < 0.001) still affected these three bone parameters. In women with TFM/TLM greater than 1, testing the body components both separately and at the same time and using the UGLM showed that TFM affected both BMC and BMD (P < 0.05), while TLM did not. In conclusion, our data indicate that both TFM and TLM affect bone density, with different physiological/pathological conditions modulating this relationship.
Bone in trans persons
- E Van Caenegem
- G T'Sjoen