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Concomitant Psychiatric Problems And Hormonal Treatment Induced Metabolic Syndrome In Gender Dysphoria Individuals: A 2 Year Follow-Up Study

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... Transgender Clinical Chemistry Reference Intervals has been mostly from retrospective analyses (11)(12)(13)(14)(15)(16)(17) or observational studies that followed transgender people for a variety of physiologic and laboratory parameters after initiation of gender-affirming therapies (18)(19)(20)(21)(22)(23)(24). Both approaches have been useful in identifying relative changes in laboratory tests; however, these cohorts include some people with pathophysiology that make it difficult to define normative laboratory ranges. ...
... In the present study, we determine reference intervals in the adult transgender population for common clinical chemistry analytes including electrolytes, enzymes, lipids, and creatinine. In Supplemental Tables 3 and 4, we compare the results of our study with the findings in prior retrospective and observational (including longitudinal) studies in the transgender population (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). In comparing between the present and prior studies, it is important to point out that conditions that were exclusions in our study (e.g., severe cardiovascular disease, diabetes, obesity, cigarette smoking) were The enzymes analyzed in the present study (ALK, ALT, AST, and GGT), often used to assess liver and biliary tract function, showed relative increases in transgender men compared to cisgender women. ...
... The impact of gender-affirming hormones on lipids has shown variable results across prior retrospective and observational studies, especially with LDL, TRIG, and total cholesterol (summarized in Supplemental Tables 3 and 4). The most robust trend across studies has been a decrease in HDL in transgender men (11,13,16,18,19,21,22,24), a finding also observed in the present study. The impact of these lipid concentration changes on overall health in the transgender population has not yet been determined. ...
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Background: Gender-affirming hormone therapy with either estradiol or testosterone is commonly prescribed for transgender individuals. Masculinizing or feminizing hormone therapy may impact clinical chemistry analytes, but there is currently a lack of published reference intervals for the transgender population. Methods: Healthy transgender and nonbinary individuals who had been prescribed either estradiol (n = 93) or testosterone (n = 82) for at least 12 months were recruited from primary care and internal medicine clinics specializing in transgender medical care. Electrolytes, creatinine, urea nitrogen, enzymes (alkaline phosphatase, ALK; alanine aminotransferase, ALT; aspartate aminotransferase, AST; gamma-glutamyltransferase, GGT), hemoglobin A1c, lipids [total cholesterol, high-density lipoprotein (HDL), triglycerides], and high-sensitivity C-reactive protein (hsCRP) were measured on 2 clinical chemistry platforms. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. Results: There was minimal impact of gender-affirming hormone therapy on electrolytes, urea nitrogen, hemoglobin A1c, and hsCRP. In general, the enzymes studied shifted toward affirmed gender. Creatinine values for both transgender cohorts overlaid the reference interval for cisgender men, with no shift toward affirmed gender for the estradiol cohort. The effects on lipids were complex, but with a clear shift to lower HDL values in the testosterone cohort relative to cisgender women. Conclusions: Transgender individuals receiving either masculinizing or feminizing hormone therapy showed significant changes in some analytes that have sex-specific variation in the cisgender population. The clearest shifts toward affirmed gender were seen with enzymes for the estradiol and testosterone cohorts and with creatinine and HDL in the testosterone cohort.
... In contrast, a prospective observational study showed that GAHT in transgender women was associated with deleterious alteration in lipid prolife: TC, TG, LDL-C increased and HDL-C decreased after 1 year and 2 years of GAHT compared with baseline [13]. The study also demonstrated alteration in glyco-insulinemic profile in transgender women with homeostatic model assessment-insulin resistance index (HOMA-IR index) of 6.57 (SD 2.69) after 2 years of GAHT compared with baseline HOMA-IR index of 3.63 (SD 0.77) [13]. ...
... In contrast, a prospective observational study showed that GAHT in transgender women was associated with deleterious alteration in lipid prolife: TC, TG, LDL-C increased and HDL-C decreased after 1 year and 2 years of GAHT compared with baseline [13]. The study also demonstrated alteration in glyco-insulinemic profile in transgender women with homeostatic model assessment-insulin resistance index (HOMA-IR index) of 6.57 (SD 2.69) after 2 years of GAHT compared with baseline HOMA-IR index of 3.63 (SD 0.77) [13]. A higher prevalence of diabetes was observed in transgender women receiving estrogen compared with both sex assigned at birth men and sex assigned at birth women in a case-control study [8]. ...
... In contrast, an observational study of 79 transgender women showed an increase in blood pressure (both systolic and diastolic) after 1 year and 2 years of GAHT compared with baseline [13]. A similar increase in blood pressure was seen in another prospective observational study of 20 transgender women [16]. ...
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Approximately 1.5 million people in the United States currently identify as transgender. The use of gender affirming hormone therapy is integral to routine clinical care of transgender individuals, yet our understanding of the effects of this therapy is limited. There are reasons to believe that gender affirming hormone therapy may have important effects on cardiovascular risk and bone health in transgender individuals. The purpose of this review article is to summarize the evidence for the cardiovascular effects (including coronary artery disease, hypertension and stroke) as well as the effects on bone metabolism associated with gender affirming hormone therapy in both transgender men and transgender women.
... Our findings of higher lean mass (median 7.8 kg) and a higher android:gynoid fat ratio are consistent with previous studies investigating masculinising hormone therapy in trans men. [27][28][29][30][31][32][33][34][35][36][37][38][39] Testosterone is known to increase the synthesis of muscle tissue by promoting differentiation of cells of the myogenic lineage and to inhibit the differentiation of adipocyte precursor cells. 40 Moreover, testosterone also inhibits lipoprotein lipase activity in adipocytes, an enzyme that increases fat deposition by decreasing adipose tissue lipolysis. ...
... 40 Moreover, testosterone also inhibits lipoprotein lipase activity in adipocytes, an enzyme that increases fat deposition by decreasing adipose tissue lipolysis. 14 We found no significant difference in insulin resistance between trans men and cisgender female controls, in keeping with all but one prior study in transgender men that showed either no cha nge [27][28][29][31][32][33][34][35][36][37]41 or a decrease 30,39 in insulin resistance. All these studies were prospective longitudinal in design but only one had a control group. ...
... Nine studies have previously looked at insulin resistance in trans women on feminising hormone therapy and, of these, six similarly showed worsening insulin resistance. 29,30,32,34,38,41 Three did not detect a significant change -one showed a trend towards increase insulin resistance but failed to reach statistical significance, 55 another had a sample size of only six participants 27 and the remaining study did not measure body composition changes so it is unclear whether changes to this occurred. 39 All but one study 55 was prospective longitudinal in design but none had a control group. ...
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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.
... Of the included studies, all studies were pre-post observational studies without control groups. Only one study provided the device used to measure BP (BP-8800; Colin Corporation, Hayashi, Japan) [19], the position of measurement was acknowledged in four studies [19][20][21], and the use of multiple BP measurements mentioned in three studies [19,20,22]. ...
... Of the included studies, all studies were pre-post observational studies without control groups. Only one study provided the device used to measure BP (BP-8800; Colin Corporation, Hayashi, Japan) [19], the position of measurement was acknowledged in four studies [19][20][21], and the use of multiple BP measurements mentioned in three studies [19,20,22]. ...
... As demonstrated in Table 1, the effect of testosterone GHT on BP varies considerably between these studies. The majority of these studies did not demonstrate a significant change in SBP (n ¼ 9), whereas three studies reported a significant increase in SBP ranging between 4.3 and 13.3 mmHg [20,25,27] and only one study reported a significant decrease in SBP (4.6 mmHg) [22]. Most studies (n ¼ 10) did not report a significant change in DBP. ...
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Objectives: Gender-affirming hormone therapy (GHT) is utilized by people who are transgender to align their secondary sex characteristics with their sex identity. Data relating to cardiovascular outcomes in this population are limited. We aimed to review the impact of GHT on the blood pressure (BP) of transgender individuals. Methods: We searched PubMed/MEDLINE, SCOPUS and Cochrane Library databases for articles published relating to the BP of transgender adults commencing GHT. Methodological quality was assessed via the 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group'. Results: Six hundred articles were screened, of which 14 studies were included in this systematic review encompassing 1309 individuals (∼50% transgender men and women) treated with GHT between 1989 and 2019. These articles were all pre-post observational studies without control groups. Mean ages ranged between 23.0-36.7 years (transgender men) and 25.2-34.8 years (transgender women). Interventions were diverse and included oral, transdermal and injectable hormonal preparations with 4 months to 5 years follow-up. Most studies in transgender men did not demonstrate a change in BP, whereas transgender women on GHT demonstrated an increase in SBP but not DBP. These studies were heterogenous with significant methodological limitations and only two were determined to have a good quality rating. Conclusion: There is currently insufficient data to advise the impact of GHT on BP in transgender individuals. Better quality research is essential to elucidate whether exogenous sex hormones modulate BP in transgender people and whether this putative alteration infers poorer cardiovascular outcomes.
... 22 After 2 years of GHT in 79 TGFs and 43 TGMs, the mean of 3 consecutive systolic BPs increased significantly by 17.8 mm Hg and 13.4 mm Hg, respectively. 23 The TGF group also demonstrated a 3.17 mm Hg increase in diastolic BP, which was not noted in the TGM group. 23 Lastly, selfreported hypertension in 369 TGFs and 239 TGMs was no higher when compared with cisgender populations. ...
... 23 The TGF group also demonstrated a 3.17 mm Hg increase in diastolic BP, which was not noted in the TGM group. 23 Lastly, selfreported hypertension in 369 TGFs and 239 TGMs was no higher when compared with cisgender populations. 18 Furthermore, prospective studies demonstrated alteration in BP following GHT initiation. ...
... Increases in homeostatic model assessment for insulin resistance index in TGFs has been demonstrated after 2 years of transdermal estrogen, but not after 1 year or in TGM. 23,31 Fasting blood glucose in TGF is higher with transdermal estrogen but not oral ethinylestradiol. 23,24 Studies using the self-reporting Behavioral Risk Factor Surveillance system with no GHT confirmation did not demonstrate a higher risk of diabetes mellitus. ...
Article
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Gender-affirming or cross-sex hormone therapy is integral to the management of transgender individuals yet our appreciation of the effects of such hormones on cardiovascular health is limited. Insights into vascular pathophysiology and outcomes in transgender people receiving sex steroids could be fundamental in providing better care for this population through the management of cardiovascular risk and more broadly advance our understanding of the role of sex and gender in vascular health and disease. In addition, there is a need to understand how gender-affirming hormone therapy impacts cardiovascular disease risk and events as transgender individuals age. This review explores the available evidence on the associations between gender-affirming hormones and cardiovascular events such as coronary artery disease, stroke, hypertension, thrombosis, lipid abnormalities, and diabetes mellitus. Current research about vascular outcomes in adults receiving hormonal therapy is limited by the absence of large cohort studies, lack of appropriate control populations, and inadequate data acquisition from gender identity services. Existing epidemiological data suggest that the use of estrogens in transgender females confers an increased risk of myocardial infarction and ischemic stroke. Conversely, transgender males receiving testosterone lack any consistent or convincing evidence of increased risk of cardiovascular or cerebrovascular disease. Further studies are required to confirm whether such risk exists and the mechanisms by which they occur.
... Our results demonstrate changes in several laboratory analytes, including creatinine, calcium, albumin, triglycerides, and HDL concentrations, during gender transition with HT. Changes in hemoglobin concentration and hematocrit during HT are well documented, and our findings are consistent with previous studies of TM (11)(12)(13) and TW (5,12,14 ). Androgens are known to stimulate erythropoiesis, and low testosterone concentration is associated with lower hematocrit. ...
... This is an area of relative controversy with several studies having inconsistent results. For instance, HDL has been described to decrease with estrogen (12,14 ), increase (11,24 ), or not change (5,6 ). LDL has also been found to be increased (14 ), decreased (5, 12 ), or not changed (6,24 ). ...
... For instance, HDL has been described to decrease with estrogen (12,14 ), increase (11,24 ), or not change (5,6 ). LDL has also been found to be increased (14 ), decreased (5, 12 ), or not changed (6,24 ). Similar differences are reported for triglycerides and total cholesterol. ...
Article
Background: For transgender individuals taking hormone therapy (HT), data on laboratory values are limited, and the effects on laboratory values cannot be easily predicted. We evaluated the impact on common laboratory analytes in transgender individuals before and after initiation of HT. Methods: We conducted a retrospective chart review of transgender patients identified at transgender-specific clinics at an urban county hospital and community clinic. Laboratory data were collected on hormone concentrations, hematologic parameters, electrolytes, lipids, and liver and renal markers before and after initiation of HT. Results: We identified 183 transgender women (TW) and 119 transgender men (TM) for whom laboratory data were available. In all, 87 TW and 62 TM had baseline laboratory data, and data were also available for 133 TW and 89 TM on HT for >6 months. The most significant changes were seen in red blood cell count, hemoglobin concentration, hematocrit, and creatinine levels after >6 months of HT, which increased in TM and decreased in TW after HT (P < 0.005; d index > 0.6). Alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels increased in TM; however, the effect size was small (d index < 0.5). Calcium, albumin, and alkaline phosphatase levels significantly decreased in TW (P < 0.001; d > 0.6). Additionally, TM were found to have increased triglycerides and decreased HDL levels (P < 0.005; d > 0.6). Conclusions: Changes occur in several common laboratory parameters for patients on HT. Some laboratory values changed to match the gender identity, whereas others remained unchanged or were intermediate from the baseline values. These findings will help guide interpretation of laboratory test results in transgender patients taking HT.
... As stated above, prospectively derived reference ranges have yet to be reported for the transgender population (1,5). However, some other studies have reported on the influence of hormone therapy on clinical chemistry and hematology parameters (18)(19)(20)(21)(22)(23)(24)(25). Table 3 shows a comparison of the significant results of the present study compared with other reports. ...
... The data are more consistent with HDL and LDL in transgender individuals receiving masculinizing hormones. For HDL, except for 1 study (21), 5 reports, including the present study, show a decrease in HDL in transgender individuals receiving masculinizing hormones (19,20,22,23,25). For LDL, the present study and 2 others showed no significant changes in transgender individuals receiving masculinizing hormones (20,21). ...
... No change (24) Cholesterol, total No Increased (19,22,25) No Increased (19) No change (20,21,23) Decreased (25) No change (20,21,24) HDL Decreased Decreased (19,20,22,23,25) Increased Increased (20,21) No change (21) Decreased (19,25) ...
Article
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Background: Many laboratory tests are reported and interpreted with sex-specific reference intervals. However, transgender individuals receiving masculinizing or feminizing hormone therapy experience physiological changes predisposing some laboratory tests to shift outside of existing reference intervals. In this study, we review laboratory testing of a large cohort of transgender individuals who were prescribed hormone therapy for at least 6 months at an academic medical center. Methods: Transgender patients were identified using a search function within the electronic health record with gender identity status verified by chart review. Patients were grouped based on type of hormone therapy administered. All laboratory studies were ordered for medical purposes as part of clinical care; as a result, the exact laboratory tests differed among the patients. Some of the patients had sufficient data for both 6- and 12-month comparisons with baseline laboratory values. Results: Statistically significant changes were observed at 6- and 12-month comparisons in basic chemistry, endocrine, and hematologic parameters for transgender individuals receiving masculinizing or feminizing hormones. Chart review demonstrated variation in route of administration of hormone therapy and frequency of gender-affirming surgery within the study population. Conclusions: Transgender individuals receiving hormone therapy experienced significant changes in components of basic chemistry, endocrine, and hematologic parameters following administration of hormone therapy. Variability in hormone dosing and route of administration for gender-affirming treatment warrants further investigation.
... In trans women, effects of estrogen therapy on systolic blood pressure (SBP) are inconsistent, with most studies showing an increase [28,29,35,36]. Studies showed either no change or an increase in diastolic blood pressure (DBP) [28,29,35,36]. ...
... In trans women, effects of estrogen therapy on systolic blood pressure (SBP) are inconsistent, with most studies showing an increase [28,29,35,36]. Studies showed either no change or an increase in diastolic blood pressure (DBP) [28,29,35,36]. In the prospective ENIGI study of 53 trans women treated for 12 months, the mean SBP decreased from 125.1 to 118.8 mmHg in subjects on oral estradiol 4 mg/day + CPA and was unchanged in subjects on transdermal estradiol + CPA [28]. ...
... In a study of 20 trans women treated for 12 months with ethinyl estradiol + CPA, the mean SBP increased from 127 to 134 mmHg and the DBP increased from 70 to 76 mmHg [35]. In a study of 79 trans women treated for 2 years with transdermal estradiol + CPA, the mean SBP increased from 111 to 129 mmHg and the DBP increased from 76 to 79 mmHg [36]. In a retrospective study of 150 trans women treated for 2 years with oral or transdermal estradiol + CPA, the mean SBP increased from 115.5 to 121.9 mmHg and the DBP increased from 72.9 to 76.6 mmHg [29]. ...
Article
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This review examines the relationship between exogenous sex steroids and cardiovascular events and surrogate markers in trans (transgender) people. Data from trans populations is compared to data from postmenopausal women and hypogonadal men when appropriate. In an age-adjusted comparison with cisgender people, trans people appear to have an increased risk for myocardial infarction and death due to cardiovascular disease. It is uncertain whether hormone therapy in trans people affects their risk of stroke. In studies that followed trans people on hormone therapy, the rates of myocardial infarction and stroke were consistently higher in trans women than trans men. There is strong evidence that estrogen therapy for trans women increases their risk for venous thromboembolism over 5 fold. Extrapolating from studies of hormone therapy in postmenopausal women, transdermal estrogen likely carries a lower risk for venous thromboembolism than oral estrogen. Regarding red blood cells, testosterone therapy increases hemoglobin in trans men, and lowering testosterone in trans women has the opposite effect. Regarding blood pressure, the effects of hormone therapy on systolic blood pressure in trans women are inconsistent, with most studies showing an increase. In trans men, testosterone therapy consistently increases systolic blood pressure and may increase diastolic blood pressure. For lipids, hormone therapy may increase triglycerides in both trans women and men. In trans men, testosterone therapy also may increase LDL-cholesterol and decrease HDL-cholesterol.
... Testosterone supplementation in transmen can increase LDL. There is some speculation connecting insulin resistance, metabolic syndrome, and hormonal treatment, but this research is still in its infancy (33 ). Both testosterone and estrogen therapy are associated with weight gain, but not to a degree that justifies more than routine diabetes screening. ...
... By contrast, reference interval studies specific to the transgender population are strikingly absent within the literature (9 ). There are, however, select publications that look at the influence of hormone therapy on these analytes (Table 4) (25,31,33,35,(53)(54)(55)(56). These studies do not correlate laboratory values to clinical phenotype and instead just look for global changes in concentration from baseline after initiation of hormone therapy. ...
... Decision points for basic lipid panels are outcome based and set equivalent between sexes, but if combined with other assessments of cardiac risk can be complicated by sex-specific variations in homocystine and highsensitivity C-reactive protein (52 ). Several studies have shown that in transmen LDL is increased and HDL decreased compared to baseline concentrations, while transwomen showed a decreased LDL and increased HDL, but other studies showed no change in these parameters or the inverse effect in transwomen (Table 4) (25,31,33,35,53,55,56 ). Similarly, these studies show that triglyceride concentrations either increase or are unchanged in transmen; publications document overall increases, decreases, and no change in triglyceride concentration in transwomen. ...
Article
Background: Transgender is an umbrella term used to describe individuals who identify with a gender incongruent to or variant from their sex recorded at birth. Affirming gender identity through a variety of social, medical, and surgical interventions is critical to the mental health of transgender individuals. In recent years, awareness surrounding transgender identities has increased, which has highlighted the health disparities that parallel this demographic. These disparities are reflected in the experience of transgender patients and their providers when seeking clinical laboratory services. Content: Little is known about the effect of gender-affirming hormone therapy and surgery on optimal laboratory test interpretation. Efforts to diminish health disparities encountered by transgender individuals and their providers can be accomplished by increasing social and clinical awareness regarding sex/gender incongruence and gaining insight into the physiological manifestations and laboratory interpretations of gender-affirming strategies. This review summarizes knowledge required to understand transgender healthcare including current clinical interventions for gender dysphoria. Particular attention is paid to the subsequent impact of these interventions on laboratory test utilization and interpretation. Common nomenclature and system barriers are also discussed. Summary: Understanding gender incongruence, the clinical changes associated with gender transition, and systemic barriers that maintain a gender/sex binary are key to providing adequate healthcare to transgender community. Transgender appropriate reference interval studies are virtually absent within the medical literature and should be explored. The laboratory has an important role in improving the physiological understanding, electronic medical system recognition, and overall social awareness of the transgender community.
... Observational studies of transgender women on various estrogen and androgen blockers show inconsistent associations with blood pressure. In two studies in which CPA was used as the androgen blocker and the estrogen regimen consisted of ethinyl estradiol or transdermal estradiol, both SBP and DBP increased significantly from baseline to 1 or 2 years after starting hormones [42,43]. We recommend regular BP monitoring of all transgender adults and suggest closer monitoring in transgender men initiating GAHT, particularly for patients with concomitant cardiovascular comorbidities. ...
... The effect of GAHT on the lipid profile of transgender women is ambiguous, as several studies have shown inconsistent results. LDL has been variously described to be increased [42], decreased [40,47], or unchanged [46,48] with estrogen, as is the case for HDL [43,47,49]. However, results in transgender women may have been affected by progesterone use, which was variably reported. ...
Article
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Purpose of Review Transgender individuals represent a growing part of our population with current trends indicating that clinicians will be treating more transgender patients in both the inpatient and outpatient setting. Current cardiovascular guidelines lack recommendations for transgender care secondary to limited data in this population. As we await future guideline recommendations, we provide a comprehensive review of the literature and practical management strategies related to transgender cardiovascular health. Recent Findings Transgender individuals are at higher risk for some cardiovascular diseases compared to their cisgender counterparts. Gender-affirming hormone therapy, concomitant health conditions, lifestyle habits, access to services, and quality of care all contribute to this finding. Summary While it is likely both safe and appropriate to apply current CVD guidelines to the care of transgender men and women, clinicians should consider additional factors in risk assessment and address unique aspects of care at every visit.
... The results are displayed in Table 5. Moreover, patients showed higher levels of fasting blood insulin, linked to insulin resistance (76). As already stated, metabolic syndrome is a cluster of conditions that are deregulated. ...
... The treatment used for psychotherapeutic assistance could worsen patients' health because it raises the risk of suffering metabolic syndrome. Some medication that increases BMI and waist circumference are second-generation antipsychotics, such as olanzapine and clozapine, or atypical antipsychotics, alongside antidepressant medication tricyclic antidepressants and selective serotonin reuptake inhibitors (76). ...
Article
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Transgender people do not identify with their assigned gender causing them to feel distressed and suffer gender dysphoria. To diminish gender dysphoria, they could endure hormonal treatment or gender confirming-surgery. Transgender women are persons whose assigned gender was male, but they identify as women. Patients who decide to start hormonal treatment will be examined by an endocrinologist who will select the therapy more suitable for their age and conditions. The treatment comprises gonadotropin-releasing hormone agonists (GnRHa), antiandrogens and estradiol. The medication is worthwhile, provided it diminishes secondary birth sex characteristics, decreases androgens, and increases feminine attributes. Nevertheless, various studies have explored the possibilities that hormonal treatment could affect transgender women’s well-being. After conducting bibliographical research, the results showed that patients are more susceptible to develop illnesses due to their hormonal treatment. Estradiol increases the possibility of suffering hyperprolactinemia, metabolic syndrome and type 2 diabetes mellitus (T2DM). Moreover, if patients have prior cardiovascular risks, there are an increase in myocardial infarction (MI) cases. The use of ethinylestradiol is not recommended because it raises the incidence of MI, venous thromboembolism and T2DM. Another treatment used is triptorelin, a GnRHa, associated with developing arterial hypertension in older patients. Despite this, hormonal therapy does not increase breast and prostate cancer cases in the transgender female population. However, several studied patients had previously risk factors, including smoking and hypercholesterolemia, which could influence cardiometabolic diseases’ progression.
... Therefore, it is important during HT to evaluate biomarkers and risk factors that predict cardiovascular disease later in life. Importantly, even in these younger trans men cohorts, HT is associated with increased systolic blood pressure in some [70][71][72] but not all studies [73,74], and is also associated with increased triglycerides (TG) [72,74], LDL-cholesterol and decreased HDLcholesterol [66,71]. A recent meta-analysis revealed that in a female-to-male transgender population, testosterone administration increased serum TG and LDL-cholesterol and decreased HDL-cholesterol at 3, 6, and 24 months [66]. ...
... Therefore, it is important during HT to evaluate biomarkers and risk factors that predict cardiovascular disease later in life. Importantly, even in these younger trans men cohorts, HT is associated with increased systolic blood pressure in some [70][71][72] but not all studies [73,74], and is also associated with increased triglycerides (TG) [72,74], LDL-cholesterol and decreased HDLcholesterol [66,71]. A recent meta-analysis revealed that in a female-to-male transgender population, testosterone administration increased serum TG and LDL-cholesterol and decreased HDL-cholesterol at 3, 6, and 24 months [66]. ...
Article
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Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences in cardiovascular disease states. This review focuses on how the effects of testosterone on arterial vessels impact the female vasculature. In women with androgen-excess polycystic ovary syndrome, and in transgender men, testosterone exposure is associated with high blood pressure, endothelial dysfunction, and dyslipidemia. These relationships suggest that androgens may exert pathophysiological effects on the female vasculature, and these effects on the female vasculature appear to be independent from other co-morbidities of cardiovascular disease. There is evidence that the engagement of androgens with androgen receptor induces detrimental outcomes in the female cardiovascular system, thereby representing a potential causative link with sex differences and cardiovascular regulation. Gender affirming hormone therapy is the primary medical intervention sought by transgender people to reduce the characteristics of their natal sex and induce those of their desired sex. Transgender men, and women with androgen-excess polycystic ovary syndrome both represent patient groups that experience chronic hyperandrogenism and thus lifelong exposure to significant medical risk. The study of testosterone effects on the female vasculature is relatively new, and a complex picture has begun to emerge. Long-term research in this area is needed for the development of more consistent models and controlled experimental designs that will provide insights into the impact of endogenous androgen concentrations, testosterone doses for hormone therapy, and specific hormone types on function of the female cardiovascular system.
... 9,11 It is therefore logical that the HT for TGM may increase their cardiovascular risk, and these risks may be compounded by other medical or surgical interventions. Even in young TGM cohorts, testosterone therapy consistently increases systolic blood pressure, [12][13][14][15][16] triglycerides 15,16 LDL-cholesterol and decreases HDL-cholesterol. 14,17 Testosterone exposure can begin in many TGM at an age when the overall risk for cardiovascular events is still low. ...
... 9,11 It is therefore logical that the HT for TGM may increase their cardiovascular risk, and these risks may be compounded by other medical or surgical interventions. Even in young TGM cohorts, testosterone therapy consistently increases systolic blood pressure, [12][13][14][15][16] triglycerides 15,16 LDL-cholesterol and decreases HDL-cholesterol. 14,17 Testosterone exposure can begin in many TGM at an age when the overall risk for cardiovascular events is still low. ...
Article
Context: Transgender men (TGM) are persons assigned female gender at birth with a male gender identity and are routinely treated with testosterone. Androgen excess is associated with endothelial dysfunction among cisgender females (CGF) and is an early sign of atherosclerosis and hypertension. Objective: To determine the effect of testosterone treatment on endothelial function in TGM. Setting: The John B. Pierce Laboratory and Yale School of Medicine. Subjects: Eleven TGM (age 27 ± 5 y; BMI 24.4 ± 3.7 kg/m2 ) receiving testosterone (T) and 20 CGF (28 ± 5 y; BMI 26.0 ± 5.1 kg/m2 ) during the early follicular phase of their menstrual cycle. Design and outcome measures: We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 3-min occlusion to determine endothelial function (flow mediated vasodilation, FMD). Results: Total T was greater in the TGM compared to CGF (484.6 ± 122.5 vs. 1.5 ± 0.7 ng/dL), as was free T (83.9 ± 32.4 vs. 1.9 ± 0.8 pg/dL). FMD was markedly lower in the TGM (4.5 ± 2.7%) compared to the CGF (8.1 ± 2.9%, P=0.002) indicating significantly diminished endothelial function in TGM. Conclusions: We have shown for the first time that in TGM the androgen-dominant hormonal milieu was associated with impaired endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaque in the coronary arteries, so is an important marker for clinical cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.
... Some studies identified older age, secondary transsexualism, late onset or gynephilic transgender women as risk factors (Landén et al., 1998b;Blanchard et al., 1987;De Cuypere et al., 2006;Eldh et al., 1997;Lindemalm et al., 1987;Lothstein, 1979;Pfäfflin & Junge, 1992;Smith et al., 2005;Sørensen, 1981;Wålinder et al., 1978). Later studies have not confirmed any differences in outcome related to gender, sexual orientation or age of onset (Colizzi et al., 2013;Colizzi et al., 2015;Gorin-Lazard et al., 2013;Heylens, et al., 2014;Johansson et al., 2010;Ruppin & Pfäfflin, 2015). ...
... The results are conflicting with regard to gender differences. Some found more psychopathology in transgender womenDuisin et al., 2014;Simon et al 2011) and others found no differences between the gender groups(Colizzi et al., 2015; Fisher et al., 2013; Heyelens et al 204a). Some studies used cisgender control groups(Auer et al., 2013;Davey, Bouman, Meyer & Arcelus, 2014;Duisin et al., 2014) compared with normative data(Gomez-Gil, Vidal-Hagemeijer, & Salamero, 2008;Haraldsen & Dahl, 2000;Kersting et al., 2003; Kim et al., 2006;Simon et al., 2011), or compared hormone treated or non-hormone treated transgender groups(Fisher et al., 2014; Gorin-Lazard et al., 2013), but most used no comparison group. ...
... Different authors have pointed out the need for specific reference ranges for laboratory test results in trans persons (Roberts et al., 2014;Colizzi et al., 2015;Kandhro, 2016). Although it has not been established yet whether totally new reference ranges should be developed or whether the reference ranges of the perceived gender should be applied, to avoid major errors, it seems important that there should be at least some guidance for clinicians about what to expect in their patients. ...
... For example, apart from changes in hematocrit, gender-affirming hormonal treatment also has an impact on a range of other factors that are associated with cardiovascular health, such as changes in body fat composition (Elbers et al., 1997), cholesterol levels, and glucose metabolism (Elbers et al., 2003). As these changes primarily occur during the first year of hormonal treatment, this period should receive particular attention (Colizzi et al., 2015). As shown in Fig. 2a, our results show that serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender-affirming hormonal treatment. ...
Article
In trans persons on gender‐affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone‐naïve trans persons. Gender‐affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82–5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94–3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50–4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender‐affirming hormonal treatment.
... In society, an individual with FtM GD displaying masculine features is generally more accepted than an individual with MtF GD displaying feminine features (Turan et al., 2015b;van de Grift et al., 2016a). Some studies have reported that persons with GD have higher depersonalization scores Fisher et al., 2013) and that depersonalization scores decrease after CHT administration (Colizzi, Costa, & Todarello, 2015a) and SRS (Kersting et al., 2003;Wolfradt & Neumann, 2001). Further, in their longitudinal study, Colizzi et al. (2015a) reported no significant differences in depersonalization/derealization scores between GD individuals who had received CHT and those who had undergone SRS. ...
... Some studies have reported that persons with GD have higher depersonalization scores Fisher et al., 2013) and that depersonalization scores decrease after CHT administration (Colizzi, Costa, & Todarello, 2015a) and SRS (Kersting et al., 2003;Wolfradt & Neumann, 2001). Further, in their longitudinal study, Colizzi et al. (2015a) reported no significant differences in depersonalization/derealization scores between GD individuals who had received CHT and those who had undergone SRS. Our finding regarding a decrease in depersonalization scores after CHT may be associated with the psychological effects of CHT, in that it helps to reduce feelings of alienation from their own body among persons with GD. ...
Article
Full-text available
Body dissatisfaction plays an important role in the development of psychiatric problems such as eating disorders as well as gender dysphoria (GD). Cross-sex hormonal treatment (CHT) alleviates the dissatisfaction by making various changes in the body. We examined the alteration of body uneasiness, eating attitudes and behaviors, and psychological symptoms longitudinally in Turkish participants with female-to-male gender dysphoria (FtM GD) after CHT. Thirty-seven participants with FtM GD and 40 female controls were asked to complete the Body Uneasiness Test to explore different areas of body-related psychopathology, the Eating Attitudes Test to assess eating disturbances, and the Symptom Checklist-90 Revised to measure psychological state, both before CHT and after 6 months of CHT administration. The baseline mean body weight, BMI scores, body uneasiness scores, and general psychopathological symptoms of participants with FtM GD were significantly higher than female controls, whereas baseline eating attitudes and behaviors were not significantly different. Over time, FtM GD participants’ mean body weight and BMI scores increased, body uneasiness and general psychopathological symptoms decreased, and eating attitudes and behaviors had not changed at 24th weeks following CHT administration compared to baseline. CHT may have a positive impact on body uneasiness and general psychopathological symptoms in participants with FtM GD. However, CHT does not have an impact on eating attitudes and behaviors.
... The use of cross-sex hormones exposes the individual to the risk of a metabolic abnormality in about 15% of cases, but the significance of this finding is not clear and it does not seem a contraindication to their use. 36 Further research is required on the nature of possible metabolic abnormalities arising from the use of cross-sex hormones. ...
Article
Full-text available
The development of gender identity in children from around the age of 3 years is described. Wishes for transgender identity are distinguished from gender-atypical behaviour. Reasons for the recent rise in transgender referrals in the early teen years are discussed. The now widely used protocol developed by the Amsterdam group for assessing transgender children and young people and, where appropriate, offering them puberty blockers, cross-sex hormones and sex reassignment surgery is described. Evidence for the effectiveness of this approach is considered. The competence of young people to give consent to these procedures is discussed. Finally, proposals are made for topics urgently requiring further research.
... Previous reports demonstrated higher total cholesterol, triglycerides and LDL-C in TF receiving hormone therapy. 12,35 The finding of higher total cholesterol and LDL-C in TM was also described in a 2017 meta-analysis of cardiovascular outcomes. 36 In a dynamic study on the impact of hormone therapy on laboratory values, Allen et al. found increased LDL and decreased HDL in TM and increased HDL in TF. 15 The changes seen in the lipid fractions are inconsistent, and it is most prudent to interpret each person and provide the necessary risk modification therapy while being cognisant that alterations are likely in these groups of patients. ...
Article
Background Hormone therapy in transgender individuals may impact processes that lead to changes in biochemical analytes, and therefore reference intervals. Currently, few reference interval studies are available for the transgender population. We determined biochemical reference intervals for transgender individuals receiving hormone therapy. Methods Our retrospective, laboratory-based, observational study included healthy transgender males ( N = 24) and transgender females ( N = 84) on hormone therapy. Various biochemical reference intervals were established for each cohort and compared to their cisgender counterparts. Results We detected significant differences in reference intervals for sodium, 139–142 mmol/L vs. 136–145 mmol/L when comparing transgender males (TM) with cisgender males (CM). The following significant changes in upper reference limits (URL) for TM versus CM were detected, ALP (URL: 96 U/L vs. 128 U/L), GGT (URL: 27 U/L vs. 67 U/L) and testosterone (URL: 46.7 nmol/L vs. 29.0 nmol/L), respectively. Moreover, when comparing transgender female (TF) to cisgender female (CF), significant differences in creatinine (URL: 117 μmol/L vs. 90 μmol/L), albumin (lower reference limit: 41 g/L, vs. 35 g/L), AST (URL: 50 U/L vs. 35 U/L), ALP (URL: 118 U/L vs. 98 U/L) and oestradiol (URL: 934 pmol/L vs. 213 pmol/L) were noted, respectively. Significantly higher LDL-C was observed for TM on hormone treatment, compared to baseline (2.9 mmol/L vs. 2.2 mmol/L, p <0.01). Conclusions Biochemical results for TM and TF receiving hormone therapy can be evaluated against our transgender-specific reference intervals for some analytes, while others can be compared to their identified gender reference intervals.
... En primer lugar, dado el número limitado de individuos analizados, sería necesario la inclusión de una muestra mayor para lograr un mayor peso estadístico. Sin duda, un estudio de seguimiento más prolongado (a los 12 y 18 meses de tratamiento) aportaría información adicional importante, aunque Colizzi et al (2015) advierten que los cambios metabólicos son más notorios durante los primeros 12 meses de tratamiento. Además, aumentar el número de regiones analizadas de la región promotora del ESR1 y aumentar el número de tejidos analizados proporcionaría una mejor comprensión de la variación en el patrón de metilación. ...
Thesis
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La incongruencia de género en el CIE-11 (Clasificación Internacional de Enfermedades- 11) se caracteriza por “una incongruencia persistente entre la experiencia individual de género y el sexo asignado al nacer”. Su origen es complejo y multifactorial. La primera parte de la investigación se centró en el análisis retrospectivo CpG (citosina-fosfato-guanina) del fragmento III (RIII) de la región promotora del receptor de estrógenos α, en una población de hombres y mujeres con incongruencia de género, antes vs. después de seis meses de tratamiento hormonal de afirmación de género (GAHT). La segunda parte de la investigación se centró en el análisis de la metilación global CpG utilizando el BeadChip de metilación de 850k de Illumina© Infinium. El análisis del perfil de metilación del RIII se realizó mediante secuenciación por bisulfito en 20 personas cisgénero y 20 personas transgénero antes vs. después del GAHT. Los ADNs se trataron con bisulfito, se amplificaron, clonaron y secuenciaron. El análisis estadístico se realizó con el programa QUMA (QUantification tool for Methylation Analysis). El análisis global de metilación se realizó en 16 personas cisgénero y 16 personas transgénero con el BeadChip de metilación de 850K de Illumina© Infinium, después de la conversión con bisulfito. Los perfiles de metilación se analizaron con el programa Partek® Genomics Suite® mediante un ANOVA de 3 vías comparando las poblaciones según grupo, sexo y tratamiento. Finalmente se realizó un análisis de enriquecimiento con el programa Partek® Pathway y la WebGestalt. La primera parte del estudio mostró (i) que en ambas poblaciones, cis y trans, los hombres y las mujeres presentan patrones de metilación diferentes del RIII; (ii) que antes del tratamiento GAHT, ambos grupos trans (hombres y mujeres) presentaban grados de metilación intermedios, no coincidentes con las poblaciones cis; (iii) que el GAHT modificó el patrón de metilación del RIII hacia perfiles más similares al género sentido. En cuanto al estudio de metilación global CpG, el principal resultado es que las poblaciones cis y trans difieren en el grado de metilación antes del tratamiento GAHT. En la población masculina (según el sexo natal asignado), se encontraron 22 islas CpGs que pasaron los criterios estadísticos (FDR p <0.05; fold change o incremento del cambio ≥ ± 2). Los CpGs más significativos se relacionaron con los genes WDR45, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP y NCOA6. En cuanto a la población femenina (según el sexo natal asignado), se encontraron 2 CpGs que pasaron los criterios estadísticos, pero ninguno de ellos se ubicaba en islas. Uno de estos CpGs, el relacionado con el gen MPPED2, es compartido por hombres y mujeres trans. El análisis de enriquecimiento mostró que estos genes están involucrados en funciones importantes como la regulación negativa de la expresión génica (GO: 0010629), el desarrollo del sistema nervioso central (GO: 0007417), el desarrollo del cerebro (GO: 0007420), la unión de ribonucleótidos (GO: 0032553) y la unión de ARN (GO: 0003723). Además, seis meses de tratamiento GAHT produjo una disminución significativa en el grado de metilación en ambas poblaciones trans, respecto a la población cis. Los hombres trans mostraron variaciones en 95 islas CpG, de las cuales el 72,63% disminuyó el grado de metilación después del tratamiento. En cuanto a las mujeres trans, seis meses de GAHT modificaron la metilación en 78 islas CpG, de las cuales el 85,9% estaban hipometiladas tras el tratamiento. Por tanto, en ambas poblaciones trans, el tratamiento GAHT indujo una reducción significativa de la metilación.
... En primer lugar, dado el número limitado de individuos analizados, sería necesario la inclusión de una muestra mayor para lograr un mayor peso estadístico. Sin duda, un estudio de seguimiento más prolongado (a los 12 y 18 meses de tratamiento) aportaría información adicional importante, aunque Colizzi et al (2015) advierten que los cambios metabólicos son más notorios durante los primeros 12 meses de tratamiento. Además, aumentar el número de regiones analizadas de la región promotora del ESR1 y aumentar el número de tejidos analizados proporcionaría una mejor comprensión de la variación en el patrón de metilación. ...
Thesis
Full-text available
La incongruencia de género en el CIE-11 (Clasificación Internacional de Enfermedades- 11) se caracteriza por “una incongruencia persistente entre la experiencia individual de género y el sexo asignado al nacer”. Su origen es complejo y multifactorial. La primera parte de la investigación se centró en el análisis retrospectivo CpG (citosina-fosfato-guanina) del fragmento III (RIII) de la región promotora del receptor de estrógenos α, en una población de hombres y mujeres con incongruencia de género, antes vs. después de seis meses de tratamiento hormonal de afirmación de género (GAHT). La segunda parte de la investigación se centró en el análisis de la metilación global CpG utilizando el BeadChip de metilación de 850k de Illumina© Infinium. El análisis del perfil de metilación del RIII se realizó mediante secuenciación por bisulfito en 20 personas cisgénero y 20 personas transgénero antes vs. después del GAHT. Los ADNs se trataron con bisulfito, se amplificaron, clonaron y secuenciaron. El análisis estadístico se realizó con el programa QUMA (QUantification tool for Methylation Analysis). El análisis global de metilación se realizó en 16 personas cisgénero y 16 personas transgénero con el BeadChip de metilación de 850K de Illumina© Infinium, después de la conversión con bisulfito. Los perfiles de metilación se analizaron con el programa Partek® Genomics Suite® mediante un ANOVA de 3 vías comparando las poblaciones según grupo, sexo y tratamiento. Finalmente se realizó un análisis de enriquecimiento con el programa Partek® Pathway y la WebGestalt. La primera parte del estudio mostró (i) que en ambas poblaciones, cis y trans, los hombres y las mujeres presentan patrones de metilación diferentes del RIII; (ii) que antes del tratamiento GAHT, ambos grupos trans (hombres y mujeres) presentaban grados de metilación intermedios, no coincidentes con las poblaciones cis; (iii) que el GAHT modificó el patrón de metilación del RIII hacia perfiles más similares al género sentido. En cuanto al estudio de metilación global CpG, el principal resultado es que las poblaciones cis y trans difieren en el grado de metilación antes del tratamiento GAHT. En la población masculina (según el sexo natal asignado), se encontraron 22 islas CpGs que pasaron los criterios estadísticos (FDR p <0.05; fold change o incremento del cambio ≥ ± 2). Los CpGs más significativos se relacionaron con los genes WDR45, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP y NCOA6. En cuanto a la población femenina (según el sexo natal asignado), se encontraron 2 CpGs que pasaron los criterios estadísticos, pero ninguno de ellos se ubicaba en islas. Uno de estos CpGs, el relacionado con el gen MPPED2, es compartido por hombres y mujeres trans. El análisis de enriquecimiento mostró que estos genes están involucrados en funciones importantes como la regulación negativa de la expresión génica (GO: 0010629), el desarrollo del sistema nervioso central (GO: 0007417), el desarrollo del cerebro (GO: 0007420), la unión de ribonucleótidos (GO: 0032553) y la unión de ARN (GO: 0003723). Además, seis meses de tratamiento GAHT produjo una disminución significativa en el grado de metilación en ambas poblaciones trans, respecto a la población cis. Los hombres trans mostraron variaciones en 95 islas CpG, de las cuales el 72,63% disminuyó el grado de metilación después del tratamiento. En cuanto a las mujeres trans, seis meses de GAHT modificaron la metilación en 78 islas CpG, de las cuales el 85,9% estaban hipometiladas tras el tratamiento. Por tanto, en ambas poblaciones trans, el tratamiento GAHT indujo una reducción significativa de la metilación.
... HDL has been reported to decrease (15,38), increase (36,37), and not change (6) in response to estrogen. Our previous study showed no difference in lipid profiles of TW receiving HT (5). ...
Article
Full-text available
Background Known physiological changes occur while transgender patients are taking hormone therapy (HT). However, knowledge is limited about when laboratory values stabilize and if there are any long-term impacts, making it challenging for physicians to provide adequate gender-affirming care. We aim to analyze laboratory values with HT use over 5 years and after discontinuation of HT to define when values achieve stability. Methods We performed a multicenter retrospective analysis of 126 transgender women (TW) and 91 transgender men (TM) at consecutive clinic visits. Labs included complete metabolic panel, complete blood count, lipids, and hormone levels and were monitored for 5 years. Absolute measurement and percentage change from baseline were calculated for each analyte value. We collected the laboratory studies described from patients off HT and the duration of discontinuation to determine the time to return to baseline levels. Results During HT, red blood cell (RBC; erythrocyte) indexes reach stable levels within 6 months (P < 0.001) and are unchanged long term. Some analytes such as HDL and platelets showed increases beyond the first year of HT in TW (P = 0.001 and P < 0.001, respectively). LDL and alanine aminotransferase increased beyond 1 year in TM (P < 0.005 and P < 0.001, respectively), whereas HDL decreased beyond 1 year (P < 0.001). Time for laboratory values to return to baseline occurred around 10 weeks. Conclusions Most analytes reach stable levels within 6 months (RBC and creatinine), whereas others change in the long term (LDL, HDL, platelets). This information can be used to guide physicians as they monitor their transgender patients in all stages of their progress through HT.
... Adequate controls are missing. Interventions are not clearly defined Colizzi 2015 Increased prevalence of metabolic syndrome among individuals with gender dysphoria treated by cross-sex hormonal treatment. Study without adequate comparator group. ...
Article
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.
... Triglycerides and LDL showed no significant changes. The results from the CPA+E group extend and confirm most of the previously published data by us and others that showed similar effects on cholesterol even if after shorter follow-ups (11,21,22,23). These variations may be related to the residual androgenic effect of CPA (24). ...
Article
Objective: The impact of different combinations of long-term gender-affirming hormone therapy (GAHT) in transwomen (TW) is largely unknown. To assess the effects of 5-year administration of cyproterone acetate (CPA) or leuprolide acetate (Leu) plus transdermal or oral estradiol (E). Design: Cohort study based on prospectively collected data. Fifty TW received 50 mg CPA daily orally (n = 25; CPA+E group) or 3.75 mg Leu i.m. monthly (n = 25; Leu+E group) with 1 or 2 mg E daily for 5 years. Reproductive hormones, biochemical and anthropometric parameters, body composition and bone mineral density (BMD) were assessed. Results: LH, FSH and total testosterone levels were similarly and significantly suppressed in both groups. Prolactin increased only in the CPA+E group (P = 0.002). Fasting insulin resistance and glucose progressively increased in the CPA+E group only (treatment × time effect P = 0.002 and P = 0.043, respectively). Total cholesterol increased more in the Leu+E group than in the CPA+E group and HDL-cholesterol decreased in the CPA+E group (time × treatment interaction effect, P = 0.007). Lumbar and total body BMD increased in both groups after 3 years. No serious adverse events were recorded. Conclusions: Both regimens were effective in suppression of T production. CPA+E worsened the metabolic profile with a slight increase in PRL levels. All subjects presented an increase in BMD regardless of treatment. These preliminary data could have clinical implications in the choice of GAHT, in particular for those TW not requiring gender-affirming surgery.
... Androgens are known to stimulate erythropoiesis whilst the impact of estrogens are not as well understood. In trans people who have been on established and full-dose feminizing hormone therapy (estradiol and anti-androgen) for at least 6 months, there is a significant decrease in hemoglobin, hematocrit and red blood cell count to the female reference range (16,(23)(24)(25). Conversely after 6 months of masculinizing testosterone therapy, trans people demonstrate an increase in hemoglobin, hematocrit and red blood cell count to the male reference range (16,20,23,26). ...
Article
Full-text available
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.
... Berra and colleagues 81 observed a decrease in adiponectin levels in TM 6 months after the initiation of HT. On the other hand, 1 prospective study reported an increased incidence of metabolic syndrome after 1 and 2 years of HT. 82 In addition, hyperinsulinemic-euglycemic clamp studies (a measure for peripheral insulin resistance) in TM after 4 months of HT showed a decrease in glucose utilization. 83 Elbers and colleagues 61 reported no change in fasting insulin levels or insulin sensitivity after 12 months of testosterone administration in the physiologic range in TM, although administration of supraphysiological levels of testosterone resulted in a reduced glucose uptake during a clamp test. ...
Article
Prescribing gender-affirming hormonal therapy in transgender men (TM) not only induces desirable physical effects but also benefits mental health. In TM, testosterone therapy is aimed at achieving cisgender male serum testosterone to induce virilization. Testosterone therapy is safe on the short term and middle term if adequate endocrinological follow-up is provided. Transgender medicine is not a strong part of the medical curriculum, although a large number of transgender persons will search for some kind of gender-affirming care. Because hormonal therapy has beneficial effects, all endocrinologists or hormone-prescribing physicians should be able to provide gender-affirming hormonal care.
... The results of the studies within this meta-analysis (11) are conflicting. For example, the largest English study reported increased levels of LDL-C, triglycerides, and total cholesterol (TC), and decreased levels of HDL-C in 79 transwomen treated with transdermal estradiol gel and cyproterone acetate (CPA) for 2 years (12). The second largest study reported a decrease in levels of HDL-C and triglycerides in 15 transwomen treated with transdermal 17Bestradiol and CPA, but an increase in levels of HDL-C and triglycerides in 15 transwomen treated with oral ethinyl estradiol and CPA (13). ...
Article
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.
... Adequate controls are missing. Interventions are not clearly defined Colizzi 2015 Increased prevalence of metabolic syndrome among individuals with gender dysphoria treated by cross-sex hormonal treatment. Study without adequate comparator group. ...
Article
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.
... informaci?n adicional, aunque los trabajos de Colizzi et al., (2015) sugieren que las variaciones metab?licas en la poblaci?n con DG en tratamiento hormonal son m?s pronunciadas en el primer a?o de tratamiento. Por otro lado, aumentar el n?mero de regiones analizadas en la regi?n promotora del gen ESR1 habr?a permitido una mejor comprensi?n ...
Thesis
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Epigenetics offers a new vision to understand how the environment affects the gene expression and is considered one of the mechanisms implicated in the etiology of Gender Dysphoria (GD). GD is defined as the discrepancy between genetic sex and gender, manifesting the discomfort with biological sex and the feeling of belonging to the opposite sex (American Psychiatric Association, 2013). DNA methylation is one of the main epigenetic mechanisms and, according to recent scientific evidence, it could be related to the silencing of the estrogen receptor α gene (ERα) (Berger and Daxenbichler, 2002). The objective of the study was to analyze the methylation level of the fragment RIII (Asada et al., 2008) of the α estrogen receptor gene (ESR1) promoter region in a GD population. To this end, the methylation level of the RIII fragment was analyzed in a population of 14 GD subjects (7FtMs and 7MtFs), before and after six months of cross-hormone treatment (THC), and was compared to a control population without GD. The DNA of each subject was treated with bisulfite, the region RIII was amplified by PCR, cloned and sequenced. The statistical analysis was carried out with the specific program QUMA (http://quma.cdb.riken.jp/). Our results showed that the THC increased the methylation level of the ERα promoter region only in the FtM population. Keywords: Cerebral dimorphism, epigenetics, ERα, ESR1, FtM, Gender Dysphoria, methylation, MtF.
... Furthermore, sexual orientation was often generally categorized based on the sex assigned at birth, instead of defining sexual orientation in relation to the self-identification of trans people (Bockting, Benner, & Coleman, 2009). In sum, in most transgender-related research and diagnostics, sexual orientation was, and still is, assessed in a somehow one-dimensional and reductionist manner, relying on one factor only -identity (e.g., Colizzi, Costa, Scaramuzzi, Palumbo, Tyropani, Pace, Quagliarella, Brescia, Natilla, Loverro, & Todarello, 2015;Gorin-Lazard, Baumstarck, Boyer, Maquigneau, Penochet, Pringuey, Albarel, Morange, Bonierbale, Lancon, & Auquier, 2013). Against this background, transgender individuals historically feared that certain information would be used to deny them access to TRMI. ...
... A higher number of participants would have allowed a stronger statistical power, but inclusion was restricted by stringent exclusion criteria. A longer follow-up would have also given us additional information, although other work such as Colizzi et al., suggested that metabolic variations in gender dysphoria are more pronounced in the first year of CHT, although they did not address methylation or gene expression in this study [26]. The lack of good correlation between changes in methylation and expression patterns after CHT may be due to several reasons. ...
Article
Cross-sex hormone therapy (CHT) is critical for phenotypical and physiological transition in adults with gender dysphoria (GD). However, the impact of the CHT onto the molecular level/epigenetic regulation has not been comprehensively addressed. We postulate that CHT in GD could drive changes at the androgen receptor (AR), estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2), affecting their DNA methylation pattern and mRNA expression that may influence in the phenotypical changes associated to CHT.
... However, in most trans-related research and diagnostics sexual orientation is assessed in a rather one-dimensional and reductionist manner, relying on one item only -identity (e.g. Colizzi, Costa, Scaramuzzi et al., 2015;Gorin-Lazard et al., 2013). ...
Article
As the number of transgender and gender-diverse (TGD) people accessing gender-affirming care increases, the need for healthcare professionals (HCPs) providing gender-affirming hormonal therapy (GAHT) also increases. This chapter provides an overview of the HCPs interested in getting involved in providing GAHT.
Article
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Background The effects of gender-affirming hormone therapy on lipid profiles among transgender adults have been inconsistent and incompletely characterized. Objective To longitudinally assess changes to lipid profiles following hormone therapy and to establish prevalence rates of hyperlipidemia/low HDL-cholesterol. Methods This longitudinal study followed lipid profiles of 366 transgender and gender-diverse adult patients (170 transfeminine and 196 transmasculine; mean age, 28 years) in Washington DC USA. Lipid profiles were measured at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of hormone therapy. Results Within 2-10 months of starting gender-affirming hormone therapy, mean levels of HDL-cholesterol decreased by 16% in transmasculine individuals and increased by 11% in transfeminine individuals. Over the study, mean triglyceride levels increased by 26-37% in the transmasculine group. Over the study, the prevalence of moderate hypertriglyceridemia (175-499 mg/dL) ranged from 11-32% in the transfeminine group and 6-19% in the transmasculine group. Severe hypertriglyceridemia (≥500 mg/dL) was only observed in one individual. On hormone therapy, 24-30% of the transfeminine group had a HDL-cholesterol < 50 mg/dL and 16-24% of the transmasculine group had a HDL-cholesterol < 40 mg/dL. LDL-cholesterol levels ≥160 mg/dL were rare among both groups. Conclusions In a gender-diverse population on hormone therapy, low HDL-cholesterol and moderate hypertriglyceridemia were relatively common. HDL-cholesterol decreased with testosterone therapy and increased with a combination of oral estrogen and spironolactone. Testosterone use was associated with an increase in triglycerides. Our data support the recommendation to routinely monitor lipid profiles in gender-diverse patients on GAHT.
Article
In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with <30 years of age and had a follow-up >5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p < 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered.
Article
New findings: What is the topic of this review? This review discusses the current status of the literature in sex differences in exertional heat stroke. What advances does this review highlight? We utilize a translational model to explore possible physical and physiological differences with respect risk and treatment of exertional heat stroke. Abstract: Exertional heat stroke (EHS) is a potentially fatal condition brought about by a combination of physical activity and heat stress and resulting in central nervous system dysfunction and organ damage. EHS impacts several hundred individuals each year ranging from military personnel, athletes, to occupational workers. Understanding the pathophysiology and risk factors can aid in reducing EHS across the globe. While we know there are differences between sexes in mechanisms of thermoregulation, there is currently not a clear understanding if/how those differences impact EHS risk. The purpose of this review is to assess the current status of the literature surrounding EHS from risk factors to treatment using both animal and human models. We use a translational approach, considering both animal and human research to elucidate the possible influence of female sex hormones on temperature regulation and performance in the heat and highlight the specific areas with limited research. While more work is necessary to comprehensively understand these differences, the current research presented provides a good framework for future investigations. This article is protected by copyright. All rights reserved.
Article
Background Risk of type 2 diabetes mellitus (T2DM) in transgender and gender diverse (TGD) persons, especially those receiving gender affirming hormone therapy (GAHT) is an area of clinical and research importance. Methods We used data from an electronic health record-based cohort study of persons 18 years and older enrolled in three integrated health care systems. The cohort included 2869 transfeminine members matched to 28,300 cisgender women and 28,258 cisgender men on age, race/ethnicity, calendar year, and site, and 2133 transmasculine members matched to 20,997 cisgender women and 20,964 cisgender men. Cohort ascertainment spanned 9 years from 2006 through 2014 and follow up extended through 2016. Data on T2DM incidence and prevalence were analyzed using Cox proportional hazards and logistic regression models, respectively. All analyses controlled for body mass index. Results Both prevalent and incident T2DM was more common in the transfeminine cohort relative to cisgender female referents with odds ratio and hazard ratio (95% confidence interval) estimates of 1.3 (1.1-1.5) and 1.4 (1.1-1.8), respectively. No significant differences in prevalence or incidence of T2DM were observed across the remaining comparison groups, both overall and in TGD persons with evidence of GAHT receipt. Conclusion Although transfeminine people may be at higher risk for T2DM compared to cisgender females the corresponding difference relative to cisgender males is not discernable. Moreover, there is little evidence that T2DM occurrence in either transfeminine or transmasculine persons is attributable to GAHT use.
Chapter
Gender affirming hormonal treatment (GAHT) in transgender men consists of testosterone treatment in different formulations. The main goal of testosterone treatment is to achieve cisgender male serum testosterone levels in order to induce virilization. The desired effects include increased facial and body hair, deepening of the voice, cessation of menses, fat redistribution and increased lean mass and strength, as well as improvement of psychological well-being. However, testosterone treatment may induce potential undesired effects and risks, such as acne, androgenetic alopecia, increase in systolic blood pressure, haematocrit and changes in lipid profile. GAHT in transgender men is considered safe on the short term and middle term, although several aspects, such as long-term cardiovascular and oncological safety, need to be adequately assessed in the future through long-term prospective studies.
Article
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Gender-diverse people likely suffer from higher rates of cardiovascular disease than cisgender people. Studies on the effects of gender-affirming hormone therapy (GAHT) on blood pressure in adult transgender populations have been inconsistent. We sought to address knowledge gaps on this topic by conducting the largest and longest observational study to date using multiple blood pressure readings from a racially and ethnically diverse sample. We followed the blood pressure of 470 transgender and gender-diverse adult patients (247 transfeminine and 223 transmasculine; mean age, 27.8 years) seen at a Federally Qualified Health Center and an academic endocrinology practice, both in Washington DC. Blood pressure was measured at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of GAHT. Our study found that within 2 to 4 months of starting GAHT, mean systolic blood pressure was lower in the trans feminine group by 4.0 mm Hg ( P <0.0001) and higher in the trans masculine group by 2.6 mm Hg ( P =0.02). These blood pressure changes were maintained during the whole follow-up period. There were no changes to diastolic blood pressure for either group. The prevalence of stage 2 hypertension decreased in the trans feminine group by 47% ( P =0.001) within 2 to 4 months of GAHT. In conclusion, our data support routine blood pressure monitoring after the initiation of GAHT. Further research is needed on the effects of GAHT in older gender-diverse individuals and on optimal formulations of GAHT.
Article
With the growing number of transgender and gender-nonbinary individuals who are becoming visible, it is clear that there is a need to develop a rigorous evidence base to inform care practice. Transgender health research is often limited to HIV/AIDS or mental health research and is typically subsumed in larger studies with general LGBTQ focus. Although the number of knowledgeable health care providers remains modest, the model for the medical approach to transgender health is shifting owing to growing social awareness and an appreciation of a biological component. Gender-affirming medicine facilitates aligning the body of the transgender person with the gender identity; typical treatment regimens include hormone therapy and/or surgical interventions. While broadly safe, hormone treatments require some monitoring for safety. Exogenous estrogens are associated with a dose-dependent increase in venous thromboembolic risk, and androgens stimulate erythropoiesis. The degree to which progressing gender-affirming hormone treatment changes cancer risk, cardiac heart disease risk, and/or bone health remains unknown. Guidelines referencing the potential exacerbation of cancer, heart disease, or other disease risk often rely on physiology models, because conclusive clinical data do not exist. Dedicated research infrastructure and funding are needed to address the knowledge gap in the field.
Chapter
Transgender hormone therapy can play an important role in patients undergoing gender affirmation and results in improved quality of life for transgender individuals. Hormone therapy may be a step on the pathway to gender-affirming surgery, but many patients may choose to remain on hormone therapy without surgery or may not have access to surgical therapy. Basic criteria should be met prior to initiation of hormone therapy. Hormone therapy in transgender women includes estrogen and anti-androgens. Transgender men are treated primarily with exogenous testosterone supplementations. Patients should be made aware of side effects of hormone therapy prior to initiation. Close monitoring is important during the first year of therapy, and it can be less frequent thereafter. Although there is no consensus available, it is generally recommended that estradiol therapy be stopped temporarily before gender affirmation surgeries or other major surgical interventions. It is less clear whether it is necessary to hold testosterone therapy prior to surgery. Usual thromboprophylaxis measures are recommended for any gender-affirming surgeries that require extensive surgery and prolonged immobilization.
Article
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.
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Background Brain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. Aim To analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. Methods We carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. Outcomes The main outcome of this study was RIII analysis using bisulfite genomic sequencing. Results We found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P ≤ .003, P ≤ .026, P ≤ .001, P ≤ .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P ≤ .0001, P ≤ .018, P ≤ .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical Implications Clinical implications in the hormonal treatment of trans people. Strengths & Limitations Increasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. Conclusions Our data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and transmen showed a characteristic methylation profile, different from both the cisgender groups. But the hormonal treatment modified RIII methylation in trans populations, which are now more similar to their gender. Therefore, our results suggest that the methylation of RIII could be involved in gender dysphoria. Fernández R, Ramírez K, Gómez-Gil E, et al. Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen. J Sex Med 2020;XX:XXX–XXX.
Article
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.
Article
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.
Article
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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.
Article
Transgender women often seek hormone therapy to attain feminine physical features congruent with their gender identity. The aim of feminizing hormone therapy (FHT) is to provide suppression of endogenous testosterone and to maintain estradiol levels within the normal female range. Overall, FHT is safe if provided under supervision of an experienced health care provider and has been shown to improve quality of life. Data on care of transgender women are scarce and high-quality evidence-based recommendations are lacking. This article aims to review the published literature on FHT and provide guidance to clinicians caring for transgender women.
Chapter
Since the mid-twentieth century, transgender individuals have become increasingly visible. Strong advocacy group efforts and increasing government support have improved access to medical care for people with gender dysphoria. Physicians should be aware of the unique conditions and challenges affecting this population. Healthcare professional organizations such as the American Medical Association (AMA), the Endocrine Society, and the World Professional Association for Transgender Health have concluded that hormonal and surgical treatment of gender dysphoria is medically necessary to prevent long-term morbidity. Furthermore, physicians caring for transgender persons must have sufficient experience to recognize gender dysphoria as a spectrum of conditions, and should be adept in tailoring therapy to the individual patient. Many, but not all, gender dysphoric individuals presenting for care will ultimately seek endocrine therapy for the modulation of endogenous hormone production and exogenous hormone supplementation, to improve their quality of life.
Article
Gender affirming treatment for transgender people requires a multidisciplinary approach in which endocrinologists play a crucial role. The aim of this paper is to review recent data on hormonal treatment of this population and its effect on physical, psychological and mental health. The Endocrine Society guidelines for transgender women include estrogens in combination with androgen lowering medications. Feminizing treatment with estrogens and anti-androgens has desired physical changes, such as enhanced breast growth, reduction of facial and body hair growth and fat redistribution in a female pattern. Possible side effects should be discussed with patients, particularly those at risk of venous thromboembolism. The Endocrine Society guidelines for transgender men include testosterone therapy for virilization with deepening of the voice, cessation of menses plus increase of muscle mass, facial and body hair. Due to the lack of evidence, treatment for gender non-binary people should be individualized. Young people may receive pubertal suspension, consisting of gonadotrophin-releasing hormone analogs, later followed by sex steroids. Options for fertility preservation should be discussed before any hormonal intervention. Morbidity and cardiovascular risk with cross-sex hormones is unchanged among transgender men and unclear among transgender women. Sex steroid-related malignancies can occur, but are rare. Mental health problems such as depression and anxiety have been found to reduce considerably following hormonal treatment. Future studies should aim to explore the long-term outcome of hormonal treatment in transgender people and provide evidence as to effect of gender affirming treatment in the non-binary population.
Article
Background Transgender individuals receive cross sex hormonal therapy to induce desired secondary sexual characteristics despite limited data of the effects on cardiovascular health. Methods A comprehensive search of several databases to April 7th 2015 was conducted for studies evaluating the effect of sex steroids use on lipids, myocardial infarction, stroke, venous thromboembolism (VTE) and mortality in transgender individuals. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CI). Results We found 29 eligible studies at moderate risk of bias. In female-to-male (FTM), sex steroid therapy was associated with a statistically significant increase in serum triglycerides (TGs) at 3-6 months and at ≥ 24 months (21.4 mg/dl, 95%CI: 0.14, 42.6) and in LDL-C levels at 12 months and ≥ 24 months (17.8 mg/dl, 95%CI: 3.5, 32.1). HDL-C levels decreased significantly across all follow up time periods (highest at ≥ 24 months, -8.5 mg/dl, 95%CI: -13.0, -3.9). In male-to-female (MTF), serum TGs were significantly higher at ≥ 24 months (31.9 mg/dl, CI: 3.9, 59.9) without any changes in other parameters. Few myocardial infarction, stroke, VTE and death events were reported, more frequently in MTF. Conclusions Low quality evidence suggests that sex steroid therapy may increase LDL-C and TG and decrease HDL-C levels in FTM, while oral estrogens may increase TGs in MTF. Data about patient important outcomes remain sparse.
Purpose of review: To explore the medical and surgical clinical dilemmas in the management of trans (transgender) men, a growing population receiving more attention than in the past. Recent findings: Testosterone therapy is commonly prescribed to trans men for masculinization. Nonetheless, the optimal formulations and doses of testosterone therapy for trans men have not been well established. Testosterone therapy has been associated with increased levels of hemoglobin and triglycerides, as well as diabetes. Periodic monitoring of hemoglobin, cholesterol, and fasting glucose is therefore recommended. As compared to non-transgender women, trans men have lower age-specific rates of breast cancer and cervical cancer which can be attributed, in part, to surgeries such as bilateral mastectomies and hysterectomies. The frequency in which to recommend mammograms and Pap smears (in patients with intact cervices) is uncertain in this population because of a lack of evidence-based data. Many trans men desire and undergo bilateral mastectomies with much fewer undergoing metoidioplasty or phalloplasty. Summary: For trans men, most clinicians target serum testosterone concentrations in the normal male reference range. The frequency of screening for breast and cervical cancer should be individualized based upon anatomy, patient age, age of initiation of testosterone therapy, and other factors.
Article
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Associations of cortisol and depression vary at different life-stages, yet population-based, prospective studies are scarce. We aimed to assess associations of morning cortisol with depressive symptoms in mid-life taking account of lifetime psychological health. Participants were 5,403 men and women from the 1958 British Birth Cohort whose salivary cortisol was assessed at 45y (45min after waking (T1) and 3h later (T2)) and who completed the 5-item Mental-Health Index (MHI-5) about depressive symptoms at age 50y. Lifetime psychological health was identified from child and adult measures. For women, higher T2 cortisol at 45y predicted depression (MHI-5 scores ≤52) at 50y (odds ratio [OR]=1.17; 95% confidence intervals [CI] 1.05,1.30 per standard deviation increase in T2 cortisol), attenuating when adjusted for current (45y) and previous (7-42y) psychological health (OR=1.11; 95% CI 0.98, 1.24). Similarly, an association in women of flatter cortisol delta (T2-T1) with depressive symptoms at 50y weakened after adjustment for current (45y) and previous (7-42y) psychological health. For men, lower T2 cortisol at 45y predicted greater depressive symptoms at 50y and the association strengthened when adjusted for lifetime psychological health. Likewise, lower cortisol AUC predicted higher risk of depression for men after adjusting for prior psychological health (OR=0.85; CI 0.72, 1.00). Associations were largely unaltered by control for covariates. In women, higher cortisol in late morning at 45y is prospectively associated with depressive symptoms at 50y through a link with lifetime psychological health. In men, lower cortisol predicts subsequent symptoms, independent of depressive history.
Article
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The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts of the world are necessary. The SOC articulate standards of care while acknowledging the role of making informed choices and the value of harm reduction approaches. In addition, this version of the SOC recognizes that treatment for gender dysphoria i.e., discomfort or distress that is caused by a discrepancy between persons gender identity and that persons sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics) has become more individualized. Some individuals who present for care will have made significant self-directed progress towards gender role changes or other resolutions regarding their gender identity or gender dysphoria. Other individuals will require more intensive services. Health professionals can use the SOC to help patients consider the full range of health services open to them, in accordance with their clinical needs and goals for gender expression.
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This study evaluates the short- and long-term cardiovascular- and cancer-related morbidities during cross-sex hormone therapy in a large sample of trans persons. A specialist centre cross-sectional study compared 214 trans women (male-to-female transsexual persons) and 138 trans men (female-to-male trans persons) to an age- and gender-matched control population (1 to 3 matching). Participants were on cross-sex hormone therapy for an average of 7.4 years. We assessed physical health and possible treatment-related adverse events using questionnaires. Five percent of trans women experienced venous thrombosis and/or pulmonary embolism during hormonal therapy. Five of these adverse events occurred during the first treatment year, while another 3 occurred during sex reassignment surgery. TRANS WOMEN EXPERIENCED MORE MYOCARDIAL INFARCTIONS COMPARED TO CONTROL WOMEN (P=0.001) BUT A SIMILAR PROPORTION COMPARED TO CONTROL MEN. CEREBROVASCULAR DISEASE PREVALENCE WAS HIGHER IN TRANS WOMEN COMPARED TO CONTROL MEN (P=0.03). TRANS MEN HAD SIMILAR RATES OF MYOCARDIAL INFARCTION AND CEREBROVASCULAR DISEASE COMPARED TO CONTROL MALE AND FEMALE SUBJECTS. TYPE 2 DIABETES PREVALENCE WAS HIGHER IN BOTH TRANS MEN AND WOMEN COMPARED TO THEIR RESPECTIVE CONTROLS, WHEREAS CANCER RATES WERE SIMILAR TO CONTROL MEN AND WOMEN.CONCLUSION: Morbidity rate during cross-sex hormone therapy was relatively low, especially in trans men. We observed a higher prevalence of venous thrombosis, myocardial infarction, cerebrovascular disease and type 2 diabetes in trans women compared to control population. Trans men had similar morbidity rates compared to controls aside from increased type 2 diabetes prevalence.
Article
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Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.
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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 **;**:**–**.
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Objective: The aim was to compare the effects of a traditional therapy (an oral estroprogestagen) to those of a novel treatment (a low-dose combination of generics) in adolescent girls with androgen excess. Study design and methods: In an open-label trial over 1 yr, 34 adolescents (age, 16 yr; body mass index, 23 kg/m2) with hyperinsulinemic androgen excess and without pregnancy risk were randomized to receive daily ethinyl estradiol-cyproterone acetate (EE-CA; Diane 35 Diario) or a low-dose combination of pioglitazone 7.5 mg/d, flutamide 62.5 mg/d, and metformin 850 mg/d (PioFluMet). Markers of androgen excess, C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and gene expression in longitudinal biopsies of sc adipose tissue at the abdominal level (RT-PCR) were assessed at baseline and after 1 yr. Results: EE-CA and low-dose PioFluMet reduced androgen excess comparably, but had divergent effects on C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, lean mass, abdominal and visceral fat, and on the expression of CD163, leptin, TNF-like weak inducer of apoptosis receptor, and angiopoietin-like protein 4, respectively, related to macrophage activation, fat accretion, inflammation, and lipoprotein metabolism in adipose tissue. All these divergences pointed to a healthier condition on low-dose PioFluMet. Conclusion: EE-CA and PioFluMet are similarly effective in reversing androgen excess over 1 yr, but low-dose PioFluMet is superior in reversing inflammatory, metabolic, and cardiovascular anomalies that are often associated with androgen excess.
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A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants.
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Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses. In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population. The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.
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Testosterone therapy in men and women results in decreased high-density lipoprotein cholesterol (HDL) and increased low-density lipoprotein cholesterol (LDL). We sought to determine whether testosterone therapy has this same effect on lipid parameters and adipocyte hormones in female-to-male (FTM) transsexuals. Twelve FTM transsexuals provided a fasting lipid profile including serum total cholesterol, HDL, LDL, and triglycerides prior to and after 1 year of testosterone therapy (testosterone enanthate or cypionate 50–125 mg IM every two weeks). Subjects experienced a significant decrease in mean serum HDL (52 ± 11 to 40 ± 7 mg/dL) (P < .001). The mean LDL (P = .316), triglyceride (P = .910), and total cholesterol (P = .769) levels remained unchanged. In a subset of subjects, we measured serum leptin levels which were reduced by 25% but did not reach statistical significance (P = .181) while resistin levels remained unchanged. We conclude that testosterone therapy in FTM transsexuals can promote an increased atherogenic lipid profile by lowering HDL and possibly reduce serum leptin levels. However, long-term studies are needed to determine whether decreases in HDL result in adverse cardiovascular outcomes.
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To investigate visceral fat distribution in patients with schizophrenia. Cross sectional study using CT scanning in patients with drug-naive and drug-free schizophrenia. Fifteen (13 men and two women) subjects with schizophrenia (mean age 33.7 y; mean body mass index (BMI)=26.7 kg/m(2)), and 15 age- and sex-matched controls (mean age 30.5 y; mean BMI=22.8 kg/(2)). Various fatness and fat distribution parameters (by CT scanning and anthropometry) and 16:00 h plasma cortisol. In comparison to controls, patients with schizophrenia had central obesity and had significantly higher levels of plasma cortisol. Furthermore, previous neuroleptic exposure did not appear to influence these findings as both drug-naive and drug-free patients had equally high levels of visceral fat deposition. Central obesity is a well recognized risk factor in developing certain general medical conditions. This study shows that patients with schizophrenia have increased intra-abdominal fat which may provide one explanation for why they die prematurely.
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The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies. The authors' goal was to assess the effects of clozapine, olanzapine, risperidone, and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a randomized double-blind 14-week trial. One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were inpatients at four hospitals were originally included in the study. The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period. Planned assessments included fasting glucose and cholesterol, which were collected at baseline and at the end of the 8-week period and the following 6-week period. One hundred eight of the 157 patients provided blood samples at baseline and at least at one point after random assignment to clozapine, olanzapine, risperidone, or haloperidol during the treatment trial. Seven of these patients had diabetes; their glucose levels were >125 mg/dl at baseline. Data from 101 patients were used for statistical analyses. During the initial 8-week period there was an overall significant increase in mean glucose levels. There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine (N=27) and those given haloperidol (N=25). The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period (N=22). Fourteen of the 101 patients developed abnormal glucose levels (>125 mg/dl) during the trial (six with clozapine, four with olanzapine, three with risperidone, and one with haloperidol). Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine (N=27) and those given olanzapine (N=26); cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine (N=22). In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.
Book
Citation: Pagoto SL. (ed.) (2011). Psychological Co-Morbidities of Physical Illness: A Behavioral Medicine Perspective. Springer. ISBN 978-1-4419-0030-2 (Print) 978-1-4419-0029-6 (Online). DOI 10.1007/978-1-4419-0029-6. Book preview also available via Google Books. Summary: Evidence for the efficacy of behavioral approaches to the treatment and management of physical illness is mounting, as is the evidence for behavioral interventions for psychological disorders. A pressing question that remains is how to effectively treat co-morbid physical and psychological illnesses. Diseases co-occur more often than not, and the co-occurrence of physical and psychological illnesses is associated with greater impairment and healthcare costs. Unfortunately, the treatment literature has traditionally been disease-specific, with fewer insights and discoveries regarding the underlying processes of co-morbid physical and psychological illnesses, and even fewer of approaches to treatment.Research on co-morbidities between physical and psychological illnesses has focused primarily on depression. Quite extensive literatures describe the negative impact of depression on type 2 diabetes, cardiovascular disease, cancer, obesity, pain, and other physical illnesses. More recently, higher rates of physical illness have been documented in individuals with bipolar disorder, anxiety disorders, schizophrenia, and impulse control disorders. Studies emanating from the National Comorbidity Survey-Replication (NCS-R), the only U.S. population-based database that includes diagnostic information on all DSM-IV psychological disorders, have revealed strong links between a number of physical and psychological illnesses. These data draw attention to the prevalence of physical and psychological co-morbidities at the population level, which has stimulated research on the biobehavioral mechanisms of those co-morbidities, with the goal of developing and improving treatment approaches. As this area of research grows, practical resources are needed for clinicians and researchers who encounter individuals with co-morbid physical and psychological illnesses in their work. This book is the first to provide a comprehensive overview of psychological co-morbidities of physical illness, biological and behavioral mechanisms of those co-morbidities, and implications for treatment. Each chapter focuses on a physical condition, such as obesity, type 2 diabetes, HIV infection, tobacco dependence, cardiovascular disease, cancer, asthma, pain, irritable bowel syndrome, autoimmune disorders, and obstetric/gynecological conditions. Chapters are structured to cover 1) the epidemiology of the most prevalent co-morbid psychological disorders within that physical condition (e.g., depression and other mood disorders, anxiety disorders, psychotic disorders, impulse control disorders, and eating disorders; 2) biobehavioral mechanisms of the co-morbidity; 3) a review of the behavioral treatment literature including evidence-based practice guidelines (where available); and 4) treatment considerations including issues of stepped care, evidence-based treatment decisions, treatment sequencing, treatment blending, treatment interactions, and contraindications. Content is guided by available research evidence and relevant theoretical models, and it is presented in such a way as to inform clinical practice, identify important gaps in the research literature, and provide directions for future research. The book serves as a tool for clinicians and researchers who work in the area of behavioral medicine in medical, academic, and/or training settings. Patients with psychological and medical co-morbidities may be encountered by clinicians working in either mental health or medical settings, where the presenting problem could be either the psychological disorder or the medical disorder. As such, assessment and treatment issues are discussed from both perspectives. For the clinician, the book reviews brief assessment tools, provides practical summaries of the treatment outcome literature and treatment considerations (e.g., treatment sequencing, contraindications), and includes treatment decision hierarchies that help the clinician incorporate each facet of evidence-based decisions (the evidence, patient characteristics, and their own expertise). For the researcher, the book brings together the literature for the medical and psychological disorder, highlighting still unanswered research questions relevant to the co-morbidity. Literature relevant to the underlying biobehavioral mechanisms of the co-morbidity as well as treatment are summarized. While a vast literature exists for the treatment of these disorders in isolation, one important purpose of this book is to bring together this literature to uncover specific areas in need of future study that will further our understanding of why different disorders co-occur and the best ways to treat them when they do.
Article
The aim of the present study was to evaluate the presence of psychiatric diseases/symptoms in transsexual patients and to compare psychiatric distress related to the hormonal intervention in a one year follow-up assessment. We investigated 118 patients before starting the hormonal therapy and after about 12 months. We used the SCID-I to determine major mental disorders and functional impairment. We used the Zung Self-Rating Anxiety Scale (SAS) and the Zung Self-Rating Depression Scale (SDS) for evaluating self-reported anxiety and depression. We used the Symptom Checklist 90-R (SCL-90-R) for assessing self-reported global psychological symptoms. Seventeen patients (14%) had a DSM-IV-TR axis I psychiatric comorbidity. At enrollment the mean SAS score was above the normal range. The mean SDS and SCL-90-R scores were on the normal range except for SCL-90-R anxiety subscale. When treated, patients reported lower SAS, SDS and SCL-90-R scores, with statistically significant differences. Psychiatric distress and functional impairment were present in a significantly higher percentage of patients before starting the hormonal treatment than after 12 months (50% vs. 17% for anxiety; 42% vs. 23% for depression; 24% vs. 11% for psychological symptoms; 23% vs. 10% for functional impairment). The results revealed that the majority of transsexual patients have no psychiatric comorbidity, suggesting that transsexualism is not necessarily associated with severe comorbid psychiatric findings. The condition, however, seemed to be associated with subthreshold anxiety/depression, psychological symptoms and functional impairment. Moreover, treated patients reported less psychiatric distress. Therefore, hormonal treatment seemed to have a positive effect on transsexual patients’ mental health.
Article
IntroductionGender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic-pituitary-adrenal system dysregulation and subjective stress. AimThe objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. Methods We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. Main Outcome MeasuresWe used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self-reported perceived stress and the Adult Attachment Interview to determine attachment styles. ResultsAt enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P<0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P<0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P<0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. Conclusion Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be. Colizzi M, Costa R, Pace V, and Todarello O. Hormonal treatment reduces psychobiological distress in gender identity disorder, independently of the attachment style. J Sex Med 2013;10:3049-3058.
Article
BACKGROUND: Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. PURPOSE: To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality, tardive dyskinesia, and a major metabolic syndrome. DATA SOURCES: English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature. STUDY SELECTION: Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events. DATA EXTRACTION: Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole, increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus. LIMITATIONS: All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability. CONCLUSION: Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
Chapter
The association between obesity and psychological disorders has gained attention as the prevalence of obesity has rapidly increased in recent decades. Prevalence of obesity in people with psychological disorders has grown as fast or faster than in the general population (Am J Prev Med 36:341–350, 2009), which points to a growing health disparity in psychological-disordered populations. Not only are people with various psychological disorders disproportionately affected by obesity, but obesity appears to increase risk for various psychological disorders. The aim of this chapter is to provide a comprehensive overview of the associations between obesity and psychological disorders, potential mechanisms underlying these associations, and assessment and treatment of individuals with these comorbidities, including clinical challenges. Gaps in the research literature will be identified and recommendations for future made.