Article

Endocrine care of transpeople Part I. a review of cross-sex hormonal treatments, outcomes and adverse effects in transmen

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Abstract

Gender dysphoria (GD) is characterized by discomfort with the assigned or birth gender and the urge to live as a member of the desired sex. The goal of medical and surgical treatment is to improve the well-being and quality of life of transpeople. The acquisition of phenotypic features of the desired gender requires the use of cross-sex hormonal therapy (CHT). Adult transmen are treated with testosterone to induce virilization. In adolescents with severe and persistent GD, consideration can be given to arresting puberty at Tanner Stage II and if dysphoria persists CHT is generally started after 16 years of age. Currently available short and long-term safety studies suggest that CHT is reasonably safe in transmen. Monitoring of transmen should be more frequent during the first year of cross-sex hormone administration reducing to once or twice per year thereafter. Long-term monitoring after sex reassignment surgery (SRS) includes annual check-ups as are carried out for natal hypodonadal men. In elderly transmen special attention should be paid to hematocrit in particular. Screening for breast and cervical cancer should be continued in transmen not undergoing SRS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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... Intramuscular testosterone esters, namely testosterone cypionate and testosterone enanthate, are the most commonly used masculinizing hormone formulation in the USA (Table 1) [9]. One of the main advantages of parenteral therapy is the ability to achieve higher testosterone levels more easily [5••]. ...
... Mixed testosterone esters containing testosterone propionate, phenylpropionate, isocaproate, and decanoate are also available but not recommended, owing to unpredictable fluctuations in serum testosterone levels [9]. Longer-acting testosterone undecanoate is available in the USA as a parenteral formulation and in Europe as both parenteral and oral formulations [11]. ...
... For this reason, the US Food and Drug Administration (FDA) mandates certification via a Risk Evaluation and Mitigation Strategy to prescribe this drug [5••]. The oral preparation is rarely used as it requires three times daily dosing, results in inconsistent serum testosterone levels [9], and has been found ineffective at suppressing menses [13]. ...
Article
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Purpose of Review The purpose of this review is to provide an up-to-date overview of gender-affirming hormone therapy, including the various hormone regimens available, the efficacy and potential risks of these treatments, and considerations for surveillance and long-term care. Recent Findings Recent studies reaffirm that hormone therapy has positive physical and psychological effects for many transgender individuals. The overall risks of treatment are low. Transgender women may have an increased risk of venous thromboembolism and breast cancer based on recent cohort studies, but these findings have yet to be confirmed with randomized controlled trials. Important long-term considerations include metabolic, cardiovascular, and skeletal health. Summary High-quality, long-term studies on the effectiveness and safety of various gender-affirming hormone treatment regimens are lacking, but the currently available evidence suggests that it is overall safe and effective with appropriate oversight.
... Menses discontinuation, clitoris enlargement, and lower-pitched voice are some of the changes aimed by transgender men (7,51,52). In addition, therapy will enhance a more masculine musculature, body shape with an increase in body weight, a decrease in body fat, and an increase in lean mass as well as grip strength (51)(52)(53)(54)(55). Testosterone therapy has been associated with increases in the Ferryman-Gallwey hirsutism scores. ...
... However, after 12 months, facial and abdominal hair do not reach diameters found in cisgender males. An increase in acne and alopecia is often observed as some of the side effects (51,52,54). ...
... Testosterone therapy increases plasma homocysteine levels in transgender men, which could have a negative impact on CV risk. After one year of hormonal treatment, transgender men presented increased homocysteine and leucocytes levels, with an increase in mean maximum carotid intimal media thickness (36,54). ...
Article
Transgender men and women represent about 0.6 -1.1%% of the general population. Gender affirming hormone therapy (GAHT) helps ameliorate gender dysphoria and promote well-being. However, these treatments’ cardiovascular (CV) effects are difficult to evaluate due to the limited number of extensive longitudinal studies focused on CV outcomes in this population. Furthermore, these studies are mainly observational and difficult to interpret due to a variety of hormone regimens and observation periods, together with possible bias by confounding factors (comorbidities, estrogen types, smoking, alcohol abuse, HIV infection). In addition, the introduction of GAHT at increasingly earlier ages, even before the full development of the secondary sexual characteristics, could lead to long-term changes in CV risk compared to current data. This review examines the impact of GAHT in the transgender population on CV outcomes and surrogate markers of CV health. Furthermore, we review available data on changes in DNA methylation or RNA transcription induced by GAHT that may translate into changes in metabolic parameters that could increase CV risk.
... Estrogen monotherapy does not lead a decrease in testosterone levels in MTF transgenders upto standard female values [25,29] and most studies highlighted the need to prescribe additional antiandrogenic drugs [29,32,33]. It is noteworthy that some progestins, such as cyproterone acetate, may have anti-androgenic properties [26,17,34]. ...
... In addition, single cases of pulmonary artery embolism [42] and cerebral thrombosis [43] have been published. The higher risk of thrombosis is associated with oral administration of ethinyl-estadiol [26,17,33], smoking, and the presence of cardiovascular and thrombophylic diseases [44,20]. By oral route, estrogens undergo active metabolism in the liver that stimulates the production of coagulation factors and triglycerides [25]. ...
... Masculinizing effect can be achieved by using various testosterone pharmacological preparations. [35,29,33]. The aim of cross-sex hormonal replacement therapy in this case is to achieve normal male testosterone blood levels, usually within the range of 320-1000 ng / dl [48]. ...
Chapter
Transsexualism is an emergent medical and legal problem. Discrimination, inaccessibility of medical care, lack of qualified medical specialists, high costs of services, lack of ethical skills, transphobic moods, inadequacy of existing mechanisms of medical care to transgender people with the principles of human rights, and imperfection of the legislative base among other circumstances are actual concerns nowadays. Transsexual subjects need to receive an effective and safe treatment. The purpose of those treatments is to rehabilitate a person as a member of the society in the gender area with which he or she is identified. Options for medical treatment include feminization or masculinization of the body through hormone therapy and/or surgery that are effective enough to alleviate gender dysphoria and are medically necessary for many patients. Despite the improvement in the medical care of transsexuals in countries with advanced human rights protection, there are multifactorial problems around the world that are associated with providing medical care to this group of patients, both in primary and highly specialized institutions. The lack of qualified health professionals and medical information on trans-health care is cited as one of the main reasons for the limitations for patients with gender transition seeking for medical assistance. The result of inaccessibility of qualified medical care can be self-castration, uncontrolled hormone therapy, suicidal mood, and long-term social disadaptation of transsexuals who cannot compensate for their gender discomfort. This review discusses the management of transsexuals, the types, the rationale, the effectiveness of their treatment, the recommendations of clinical centers, and the potential side effects of cross-sex hormonal treatment.
... The Endocrine Society recommends titrating T doses to serum T levels within the typical range of cisgender men, generally 320 to 1000 ng/dL (6), although multiple protocols for T management exist, some with less reliance on serum levels. There are few data to guide clinicians providing T therapy specifically to transgender men, with the majority of protocols being derived from experience with androgen replacement in hypogonadal cisgender men (8). Studies have suggested similar hormone profiles between transgender men and hypogonadal cisgender men taking exogenous T (9); however, the goals of treatment differ between the 2 populations necessitating further research on the most appropriate protocols for the transgender population. ...
... Studies have suggested similar hormone profiles between transgender men and hypogonadal cisgender men taking exogenous T (9); however, the goals of treatment differ between the 2 populations necessitating further research on the most appropriate protocols for the transgender population. The most common route of administration is intramuscular or subcutaneous injections with T enanthate or cypionate, but other options include intramuscular injections of mixed T esters or longer-acting T undecanoate, T implants, or transdermal administration with patches or gel (4,6,8). Studies comparing subcutaneous to intramuscular T injections suggest equivalent effectiveness and safety, with better patient acceptance of subcutaneous injections (10). ...
... Studies comparing subcutaneous to intramuscular T injections suggest equivalent effectiveness and safety, with better patient acceptance of subcutaneous injections (10). Oral preparations of T are rarely used because of required frequent dosing and unpredictability of serum levels (8). Other hormonal agents, such as gonadotropin-releasing hormone agonists (GnRHa) or progestins, are rarely required, and are generally used for menstrual suppression in transgender men who do not achieve amenorrhea with T therapy alone (4,6). ...
Article
Studies show that a subset of transgender men desire children; however, there is a paucity of literature on the effect of gender-affirming testosterone therapy on reproductive function. In this manuscript, we will review the process of gender-affirming hormone therapy for transgender men and what is known about ovarian and uterine consequences of testosterone exposure in transgender men; draw parallels with existing animal models of androgen exposure; summarize the existing literature on parenting experiences and desires in transgender people; discuss considerations for assisted reproductive technologies and fertility preservation; and identify gaps in the literature and opportunities for further research.
... O objectivo é manter níveis séricos de testosterona total média no intervalo de referência para o sexo masculino (400-700 ng/dl), e níveis baixos de estradiol (< 50 pg/ml) (Hembree et al., 2017). Os estrogénios, de uma forma geral, estão associados a um risco acrescido de eventos tromboembólicos, no entanto, vários estudos demonstraram que este efeito parece estar especificamente relacionado com o etinilestradiol (Dittrich et al., 2005;Meriggiola & Gava, 2015;Prior et al., 1989), razão pela qual o seu uso não é recomendado em nenhum plano terapêutico. ...
... Estão disponíveis múltiplas terapêuticas adjuvantes dos estrogénios, como progestativos com atividade antiandrogénica (acetato de ciproterona, espironolactona) e agonistas da GnRH. A terapêutica adjuvante vai potenciar a diminuição dos níveis endógenos de testosterona e possibilitar a diminuição das doses exógenas de estrogénios, permitindo reduzir os efeitos secundários associados a altas doses de estradiol (Gooren, 2011a;Heylens et al., 2014;Meriggiola & Gava, 2015;Moore et al., 2003). ...
Chapter
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Pereira, H. (2022). Relacionamentos em pessoas LGBTQIA+. In S. Neves & M. Correia, Investigação e prática: Abordagens interdisciplinares sobre a saúde e o bem-estar das pessoas LGBTI+ (pp. 14-42). Associação Plano I.
... These fluctuating levels are often perceived by the subjects and may generate mood swings. 23,24 The long-acting intramuscular formulation of T undecanoate maintains more stable T levels and therefore may be preferred because of the lower effect on mood in addition to the advantage of requiring less frequent injections but it is more expensive compared to the short-acting formulations. Transdermal formulations (patch or gel) mimic the physiological male circadian release of T allowing for stable T levels with minimal plasmatic oscillations. ...
... Transdermal formulations (patch or gel) mimic the physiological male circadian release of T allowing for stable T levels with minimal plasmatic oscillations. 24 We do not currently know how different routes of administration or different formulations may affect bone balance. A shortterm study comparing transdermal, short-and long-acting T formulations did not report any difference in BMD after 1 year of administration. ...
Article
Full-text available
Bone health in transmen and transwomen is an important issue that needs to be evaluated by clinicians. Prior to gender-affirming hormone treatment (GAHT), transwomen have lower bone mineral density (BMD) and a higher prevalence of osteopenia than cismen probably related to external factors, such as hypovitaminosis D and less physical activities. Gonadotropin-releasing hormone (GnRH) analogues in transgender youth may cause bone loss; however, the addition of GAHT restores or at least improves BMD in both transboys and transgirls. The maintenance or increase in BMD shown in short-term longitudinal studies emphasizes that GAHT does not have a negative effect on BMD in adult transwomen and transmen. Gonadectomy is not a risk factor if GAHT is taken correctly. The prevalence of fractures in the transgender population seems to be the same as in the general population but more studies are required on this aspect. To evaluate the risk of osteoporosis, it is mandatory to define the most appropriate reference group not only taking into consideration the medical aspects but also in respect of the selected gender identity of each person.
... Recommended dosages are 200 to 400 mg per month, divided weekly to every other week. 2,4 Earlier onset (by 3 months of treatment) of desired effects may be greater in patients receiving higher doses, but these differences disappear at 12 months. 5 IM Tc and Te can produce supraphysiologic levels of T 2 to 3 days after injection and subtherapeutic levels at trough (especially if given every other week rather than weekly). ...
... 5 IM Tc and Te can produce supraphysiologic levels of T 2 to 3 days after injection and subtherapeutic levels at trough (especially if given every other week rather than weekly). Transdermal T patches or gel, with dosages from 2.5 to 10 mg daily, may better mimic physiologic levels of T. 2,4 T can be transmitted to others by skin-to-skin contact; however, the amount transferred is modest. 6 The authors recommend patients not shower for at least 4 hours after application because it can significantly decrease serum T levels. ...
Article
Untreated transgender men face serious negative health care outcomes. Effective medical, surgical, and mental health treatment ameliorates these risks. Although the research is not as robust as would be ideal, hormone treatment is effective and generally well tolerated with few serious medical risks. Surgeries carry serious risks; but for most transgender men, the benefits outweigh the risks. This review describes current evidence-based medical treatments for transgender men and provides an overview of surgical therapy to enable practitioners to discuss these options with their transgender male patients.
... Clinical studies have demonstrated the efficacy of several different androgen preparations to induce masculinization in transgender males (Appendix A) (113,114,(131)(132)(133)(134). Regimens to change secondary sex characteristics follow the general principle of hormone replacement treatment of male hypogonadism (135). ...
... Patients can take estrogen as oral conjugated estrogens, oral 17b-estradiol, or transdermal 17b-estradiol. Among estrogen options, the increased risk of thromboembolic events associated with estrogens in general seems most concerning with ethinyl estradiol specifically (134,140,141), which is why we specifically suggest that it not be used in any transgender treatment plan. Data distinguishing among other estrogen options are less well established although there is some thought that oral routes of administration are more thrombogenic due to the "first pass effect" than are transdermal and parenteral routes, and that the risk of thromboembolic events is dose-dependent. ...
Article
Full-text available
Objective To update the “Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline,” published by the Endocrine Society in 2009. Participants The participants include an Endocrine Society–appointed task force of nine experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person’s genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person’s affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments—appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)—should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.
... Clinical studies have demonstrated the efficacy of several different androgen preparations to induce masculinization in transgender males (Appendix A) (113,114,(131)(132)(133)(134). Regimens to change secondary sex characteristics follow the general principle of hormone replacement treatment of male hypogonadism (135). ...
... Patients can take estrogen as oral conjugated estrogens, oral 17b-estradiol, or transdermal 17b-estradiol. Among estrogen options, the increased risk of thromboembolic events associated with estrogens in general seems most concerning with ethinyl estradiol specifically (134,140,141), which is why we specifically suggest that it not be used in any transgender treatment plan. Data distinguishing among other estrogen options are less well established although there is some thought that oral routes of administration are more thrombogenic due to the "first pass effect" than are transdermal and parenteral routes, and that the risk of thromboembolic events is dose-dependent. ...
... Other transmen require GAS as a mandatory step toward living successfully as individual of the desired gender [12]. Hormonal intervention induces physical changes including amenorrhea, clitoral enlargement, development of male features, facial and body hair growth, deepening of the voice, increase of muscle mass and strength, and fat redistribution [14][15][16]. ...
... There is no evidence that contraindicates combined hormonal contraceptives (CHCs) prescription in transmen, however the associated risk of venous thromboembolism (VTE) should be considered. Although no VTE events have been reported in the literature in transmen treated with T formulations, they have been reported in hypogonal men treated with T. Therefore, possible adverse events due to an increase in hematocrit and estradiol levels should be considered [16,[53][54][55]. CHCs require frequent (daily, weekly, or monthly) application, are less effective in preventing pregnancy compared with LARCs, and contain estrogens, conventionally seen as female hormones by transmen [39]; furthermore, CHCs initiation can cause breast tenderness, perceived as a feminizing effect that may exacerbate gender dysphoria [12]. ...
Article
Sexual and reproductive issues are essential elements of well-being in cisgenders as well as for the transgender population. Gender-affirming hormonal treatments (GAHTs) aim to induce phenotypical changes congruent with the desired gender and subsequent reduction of gender dysphoria. While genital surgical procedures including hysterectomy and/or adenectomy cause permanent loss of ability to conceive, GAHT may induce a varying degree of reversible loss of fertility. For these reasons, transgender men and women need to be counseled concerning contraceptive options and potential effects of treatment on reproductive function before initiating GAHT. The literature reports that sexual activity with genital involvement is performed by less than half of transgender persons who have been sexually active with a partner in the past. Testosterone (T) is the most commonly used compound in transmen and usually leads to amenorrhea within 1–12 months from first administration, however cessation of menses does not mean anovulation. Some studies report cases of unintended pregnancies among transgender men under masculinizing therapy, therefore T treatment cannot be considered a contraceptive option. Currently available contraceptive options have pros and cons in transmen and scarce literature exists on their use. The effects of GAHT on fertility in transwomen are even less well known. Prolonged estrogen exposure induces sperm suppression and morphological changes of the spermatozoa, however the degree of resulting pregnancy protection is unclear. Further research to inform the contraceptive counseling in this population is mandatory.
... O objectivo é manter níveis séricos de testosterona total média no intervalo de referência para o sexo masculino (400-700 ng/dl), e níveis baixos de estradiol (< 50 pg/ml) (Hembree et al., 2017). Os estrogénios, de uma forma geral, estão associados a um risco acrescido de eventos tromboembólicos, no entanto, vários estudos demonstraram que este efeito parece estar especificamente relacionado com o etinilestradiol (Dittrich et al., 2005;Meriggiola & Gava, 2015;Prior et al., 1989), razão pela qual o seu uso não é recomendado em nenhum plano terapêutico. ...
... Estão disponíveis múltiplas terapêuticas adjuvantes dos estrogénios, como progestativos com atividade antiandrogénica (acetato de ciproterona, espironolactona) e agonistas da GnRH. A terapêutica adjuvante vai potenciar a diminuição dos níveis endógenos de testosterona e possibilitar a diminuição das doses exógenas de estrogénios, permitindo reduzir os efeitos secundários associados a altas doses de estradiol (Gooren, 2011a;Heylens et al., 2014;Meriggiola & Gava, 2015;Moore et al., 2003). ...
Chapter
Full-text available
Ferreira, E. (2022). (In)visibilidades LGBTI+. In S. Neves e M. Ferreira (Org.), Investigação e prática: Abordagens interdisciplinares sobre a saúde e o bem-estar das pessoas LGBTI+. (pp. 43-64). Associação Plano I. A legislação de direitos de pessoas LGBTI+ em Portugal teve avanços significativos nos últimos anos. No entanto, a legislação por si só não é suficiente para promover mudanças ao nível da discriminação social. São necessárias políticas de igualdade. E ao nível das políticas de igualdade, só a partir de 2011 os planos de igualdade em Portugal começaram a incluir de forma consistente medidas de combate à discriminação com base na orientação sexual e identidade de género. Embora muitas áreas da vida das pessoas LGBTI+ tenham tido alterações profundas com a adoção de legislação mais inclusiva, a invisibilidade no espaço público em diversos contextos de vida continua a ser uma realidade dominante. A forte pressão da sociedade para confinar e esconder os comportamentos afetivos entre pessoas do mesmo sexo dentro de espaços privados é uma das formas de discriminação social mais comum. A sexualidade não é uma característica da vida privada, é um processo de relações de poder que medeia todas as nossas interações quotidianas, e discursos hegemónicos, como a heteronormatividade, estão literalmente inscritos no espaço. Também ao nível da produção académica em Portugal podemos falar de invisibilidade dos estudos LGBTI+, sendo quase inexistentes as ofertas curriculares nas ciências sociais especificamente focadas nas sexualidades LGBTI+. Refletir sobre futuros possíveis, no contexto social e político mundial atual, também é equacionar os riscos de retrocessos dos direitos LGBTI+. Para uma mudança positiva, consolidação dos aspetos legais e o aprofundar das mudanças sociais, é fundamental a ação conjunta das políticas de igualdade, do ativismo e da academia.
... While a study of long-term and side effects of cross-sex hormone therapy in transgender people did not observe cardiovascular events or deep venous thrombosis in transgender men (Wierckx et al., 2012), increases in hematocrit and hemoglobin related to sex-hormone therapy may represent a concern in older transgender men, in those who are obese, dyslipidemic and/or hypertensive, and therefore at higher risk of cardiovascular events such as thrombosis. Indeed, the goal of cross-sex hormone treatment for transgender men should be to achieve equal or slightly lower male physiological levels of serum testosterone to maintain adequate androgenization (Hembree et al., 2009;Traish & Gooren, 2010;Meriggiola & Gava, 2015). ...
... Transmen who have sex with men have reported inconsistent condom use with partners (Sevelius, 2009). Transmen who use hormones may incorrectly believe they are not at risk of pregnancy due to their using testosterone and thus do not seek out proper sexual health care (Meriggiola & Gava, 2015). Transmen may feel uncomfortable asking for, or receiving, a cervical Pap smear or pelvic examination because of previous negative experiences (Semlyen & Kunasegaran, 2016). ...
Article
Full-text available
People who identify as non-monosexual and transgender experience disparities in engagement with healthcare services relative to monosexual and cisgender persons, respectively. However, little is known about the healthcare utilization of those with intersecting sexual and gender minority identities. We explored the knowledge, attitudes, and health motivation of non-monosexually identified transgender participants regarding preventive care and access to sexual healthcare services. We surveyed 87 ciswomen, 34 transwomen, and 27 transmen, all of whom identified as bisexual, pansexual, or queer (bi+). We assessed their access to health care, health outcome experiences, confidence with talking about anogenital topics, proactivity toward their health, comfort with healthcare providers, and knowledge about HPV and examined differences across groups. The data indicated that bi+ transmen and transwomen were more likely to be uninsured or on a government-sponsored insurance plan relative to bi+ ciswomen. Only a minority of transmen and transwomen had seen an obstetrician/gynecologist compared with ciswomen. Transmen were less likely to have received a pelvic examination or cervical Pap smear in their lifetime. Transgender participants had significantly less correct knowledge about HPV relative to ciswomen. Finally, relative to ciswomen, transgender participants reported lower comfort talking with health providers. Our findings suggest that bi+ transmen and transwomen access care less than bi+ ciswomen and have less health knowledge and comfort with their providers. Implications for intervention include encouraging transgender individuals to seek routine screenings, reducing structural barriers to care based on medical coverage, and improving patient–provider competencies around bi+ and transgender health needs.
... 13 Although there have been no documented cases of VTE in individuals who are on testosterone therapy in the literature, it is reasonable to weigh risks and benefits, particularly for individuals with other VTE risk factors such as smoking, obesity, or age older than 35 years. 11 Despite these 2 considerations, combined hormonal contraceptives have successfully prevented pregnancy within the milieu of testosterone therapy 9 and could be a good option for an individual with a low VTE risk. However, when progestinonly or nonhormonal contraceptive options are acceptable to transmasculine individuals, it is reasonable to use these as first-line contraception before considering methods that contain estrogen. ...
Article
Full-text available
Contraception and fertility‐associated advisement is needed for any individual with a uterus who is engaging in sexual activity with reproductive potential. As greater awareness spreads regarding the health care needs of transgender, nonbinary, and gender‐nonconforming individuals, the research on evidence‐based care for these populations lags behind. Many clinicians may not be well versed in the best practices to support the sexual and reproductive well‐being of individuals who are taking gender‐affirming hormone therapy. This article reviews the use of contraception for individuals who are on testosterone gender‐affirming hormone therapy. Each contraceptive method is individually considered for the risks and benefits that are unique to this population.
... 53 Previous studies involving transsexual individuals have found hormone-sensitive tumors. 16,20,54 Further, in the present study, two deaths were caused by cancer and by leukemia and lung cancer, respectively. However, as in the present study, small samples and the sample design preclude causal inferences regarding relations between treatment of SRS individuals and cancer or cancer-related deaths. ...
Article
Full-text available
Introduction: Studies of mortality and somatic well-being after sex-reassignment surgery (SRS) of transsexual individuals are equivocal. Accordingly, the present study investigated mortality and somatic morbidity using a sample of transsexual individuals who comprised 98% (n = 104) of all surgically reassigned transsexual individuals in Denmark. Aims: To investigate somatic morbidity before and after SRS and cause of death and its relation to somatic morbidity after SRS in Danish individuals who underwent SRS from 1978 through 2010. Methods: Somatic morbidity and mortality in 104 sex-reassigned individuals were identified retrospectively by data from the Danish National Health Register and the Cause of Death Register. Main Outcome Measures: Somatic morbidity and cause of death. Results: Overall, 19.2% of the sample were registered with somatic morbidity before SRS and 23.1% after SRS (P = not significant). In total, 8.6% had somatic morbidity before and after SRS. The most common diagnostic category was cardiovascular disease, affecting 18 individuals, 9 before and 14 after SRS, and 5 of those 14 who were affected after SRS had cardiovascular disease before and after SRS. Ten individuals died after SRS at an average age of 53.5 ± 7.9 years (male to female) and 53.5 ± 7.3 years (female to male). Conclusion: Of 98% of all Danish transsexuals who officially underwent SRS from 1978 through 2010, one in three had somatic morbidity and approximately 1 in 10 had died. No significant differences in somatic morbidity or mortality were found between male-to-female and female-to-male individuals. Despite the young average age at death and the relatively larger number of individuals with somatic morbidity, the present study design does not allow for determination of casual relations between, for example, specific types of hormonal or surgical treatment received and somatic morbidity and mortality.
... Parenteral estradiol valerate (2-10 mg weekly or 5-30 mg every 2 weeks) or estradiol cypionate (1-2.5 mg weekly or 2-5 mg every 2 weeks) intramuscular injections can also be administered, although intramuscular estrogen is not currently available in Europe. Data suggest an increased risk of thromboembolic events with the use of ethinyl estradiol [40][41][42] and the Endocrine Society specifically recommends against its use. Patients may switch among formulations if they suffer from side effects or if their response is inadequate. ...
Introduction: This review summarizes gender affirming medical and surgical care available to transgender individuals, along with proposals to improve medically and culturally appropriate care. Areas covered: Transgender individuals are those whose gender identity differs from that recorded at birth (usually based on visualization of external sexual anatomy). In order to align the body with the patient's gender identity, clinicians can provide hormone therapy (HT) to bring sex hormone levels to the range associated with the patient's gender identity. At steady state, monitoring for maintenance of levels, as well as for known risks and complications, is required. Treating clinicians should have knowledge of trans assessment criteria, hormone therapy, surgical options, primary care, and mental health needs of transgender patients. A narrative literature review was conducted using Pubmed and EMBASE with articles then selected for relevance. The initial search terms were: androgen suppression, antiandrogen, breast development, chest reconstruction, cisgender, estrogen, fertility preservation, gender-affirming surgery, gender identity, gender incongruence, genital reconstruction, hormone replacement, hyperlipidemia, orchiectomy, prolactin, prostate atrophy, spermatogenesis, spironolactone, testosterone, thrombogenesis, transgender, and virilization. Expert opinion: Although guidelines exist and examples of training are available, systematic formal training must be implemented to truly mainstream high-quality gender-affirming health care .
... La masculinisation du corps avec la testostérone amène une augmentation de la satisfaction corporelle qui impacte positivement l'estime de soi et la sexualité (Fisher et al., 2016 ;McGuire et al., 2016). La testostérone entraîne également une augmentation du désir sexuel, de la fréquence, de la masturbation, de l'excitation sexuelle et de la fantasmatique (Kranz et al., 2018 ;Meriggiola et Gava, 2015 ;Nikkelen et Kreukels, 2018 ;Wierckx et al., 2014). Alors qu'avant la prise d'hormone, les hommes trans semblent avoir un rapport difficile avec leur corps et leur sexualité, avec la testostérone et la masculinisation du corps, la sexualité devient un espace d'affirmation de leur identité masculine (Pollock et Eyre, 2012 ;Stephenson et al., 2017). ...
Article
Résumé Objectif Cet article a pour objectif d’apporter une meilleure compréhension de l’expérience de l’hormonothérapie avec testostérone telle que vécue par les personnes trans. Méthode Une analyse des vidéoblogues sur YouTube pour et par des personnes transmasculines abordant leur première année d’hormonothérapie avec testostérone a été effectuée. Au total, 63 vidéoblogues répartis sur cinq chaînes YouTube d’hommes trans et une personne non binaire nord-américains prenant de la testostérone ont été analysés. Résultats Les vidéoblogues des personnes transmasculines abordent la manière dont les personnes vivent au quotidien la prise de testostérone, négocient leurs attentes et les impacts vécus de leur hormonothérapie. Les résultats identifient les éléments à prendre en compte dans l’accompagnement lors de la transition avec testostérone, tant corporels que symboliques, et rendent compte de l’aspect multifacette de l’expérience subjective de la testostérone. Ils montrent que les changements sont envisagés selon trois niveaux d’attente : fortement espérés, attendus et appréhendés. Parmi ceux-ci, la voix semble être le changement le plus important, suivi de la disparition des menstruations et de l’apparition de la pilosité. Conclusions Cette recherche par sa méthodologie souligne l’importance et le caractère précieux et unique de l’éducation et la formation des personnes trans et non binaires par des ressources en ligne pour et par les pairs. Elle souligne aussi l’expérience des modifications corporelles et l’investissement de leurs corps d’hommes trans ne sont pas des copies d’hommes cisgenres mais des constructions nouvelles du corps. Les savoirs produits et consommés par les personnes transmasculines sur internet doivent être reconnus pour leur apport complémentaire à la littérature médicale. Ces vidéoblogues constituent de nouveaux savoirs experts sur la transition avec testostérone.
... Therefore, hormonal therapy is an essential step during the reversible phase of the sexual transition process and must be prolonged for many years even after the SRS [4]. Periodic monitoring of metabolic and hormonal changes during the hormonal treatment allow a determination of the correlation between type and dose of testosterone administered, serum hormonal levels, and the clinical phenotypic changes so as to achieve a personalized adjustment of testosterone dosage [5]. The purpose of this study is to describe how hormone treatment can change metabolic and hematological indices so that periodic clinical monitoring may ensure the safety and efficacy of long-term hormone therapy. ...
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Background: Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations. Methods: Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators. Results: In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant. Conclusion: Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration. Trial registration: Retrospectively registered.
... It requires a multidisciplinary treatment 1 and the goal of medical and surgical treatment is to improve the well-being and quality of life of transgender in general. 2,3 In Germany, one common method to reduce testosterone, and allow feminization in transwomen is the use of cyproterone acetate (CPA) followed by the combination of estrogens with anti-androgens. 4 As an anti−androgen CPA acts as a testosterone antagonist. ...
Article
Background Little information is available on steroid hormone profiles in transwomen on the day of gender affirming surgery (GAS) after gender affirming hormone therapy (GAHT). Aim We compared extended serum steroid hormone profiles of 77 transwomen with 3 different treatment regimens in order to get more insight on how GAHT changes the hormone system. Methods Samples were obtained from 3 independent clinics. Individuals in clinic A (n = 13) and B (n = 51) discontinued GAHT 4–6 weeks and 2 weeks before GAS, individuals in clinic C (n = 13) continued treatment. Testicular tissue, blood samples and questionnaires on age, weight, height, and medication use were received from each patient. Steroid hormones were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), 6 sex hormones were determined by immunofluorometric assays, and ELISA. Spermatogenesis was scored using the Bergman/Kliesch score. Outcomes Participants were not different with regard to age, BMI, treatment duration, and dosage. Feminized blood serum levels with low LH, low FSH and low testosterone, however, were achieved in persons taking GAHT until GAS. Significantly reduced cortisone levels were seen after stopping GAHT before GAS. Results GAHT had marked effects on the sex-steroid profile in each person. Factor analysis provided a model explaining 78% of the variance and interdependency of sex steroid levels. Stopping treatment was inversely associated with intactness of the corticosteroid-axis with adrenal steroidogenesis as well as it was inversely associated with pituitary-gonadal hormone production. Clinical Implications Transwomen generally did not have elevated cortisone levels but differed significantly depending on and when GAHT was stopped. Strengths & Limitations This is the first study examining the steroid hormone profiles of transgender persons on the day of GAS in a multi-center setting. Additional studies (including follow ups before and after GAS and stress questionnaires) will be necessary to assess these conflicting results about the possible psychological impact on persons undergoing GAS to improve care. Conclusion Concerning feminized blood serum levels, continued GAHT seems the better alternative, however stopping treatment 4–6 weeks prior to surgery was associated with reduced cortisone levels. Schneider F, Wistuba J, Holterhus P-M, et al. New Insights Into Extended Steroid Hormone Profiles in Transwomen in a Multi-Center Setting in Germany. J Sex Med 2021;18:1807–1817.
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Standards of care for the health of transgender people recommend that all transgender individuals of young age should receive appropriate counselling on the potential negative impact of gender-affirming hormone treatment and sex reassignment surgery on future fertility, as well as counselling on fertility preservation options. This chapter describes the current clinical options for transgender patients interested in fertility preservation.
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Gender identity does not always develop in line with biological sex. Gender dysphoria at young age implies a strong incongruence between gender identity and the assigned sex; the rejection of one\'s sexual attributes and the desire to belong to the opposite sex; and a significant clinical suffering or impaired individual functioning in life spheres. The purpose of this chapter is a narrative review of the literature available on puberty suppression therapy through GnRH analogues. Biological puberty provides intense suffering to the adolescent with gender dysphoria who does not recognize himself in his own body. These drugs suppress the production of endogenous gametes and sex hormones. Although the effects of therapy are reversible, and biological development resumes spontaneously once the medication is stopped, the administration of GnRH analogues at a young age has fueled a scientific debate on the matter of the ethics of pharmacological intervention with minors. In conclusion, the studies considered show that GnRH analogues do not have long-term harmful effects on the body; prevent the negative psychosocial consequences associated with gender dysphoria in adolescence (suicidal ideation and attempts, self-medication, prostitution, self-harm); improve the psychological functioning of young transsexuals; and are diagnostic tools that allow adolescents to buy time to explore their gender identities.
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Transsexualismus bezeichnet eine Form der Geschlechtsidentität. Sie stellt primär kein Problem der Sexualität dar, sondern eine Abweichung des Identitätserlebens („Transidentität“, „Geschlechtsinkongruenz“). Betroffene haben das sichere Gefühl „in einem falschen Körper gefangen“ zu sein. Die dauerhafte Gewissheit, sich dem biologisch anderen Geschlecht zugehörig zu fühlen, die Ablehnung der mit dem biologischen Geschlecht verbundenen Rollenerwartungen und der drängende Wunsch, sozial und juristisch anerkannt im gewünschten Geschlecht zu leben, kennzeichnen den Transsexualismus und erklären den enormen Leidensdruck („Geschlechtsdysphorie“). Aus einer in unterschiedlichem Maße auftretenden Ablehnung der Merkmale des angeborenen Geschlechtes resultiert u. a. das Bedürfnis, durch hormonelle und chirurgische Maßnahmen soweit als möglich die körperliche Erscheinungsform dem Identitätsgeschlecht anzugleichen.
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Primary care clinicians have an important role in the health and wellness of transgender and gender-diverse (TGD) adults and need to know best practices of health maintenance and disease prevention interventions. This article focuses on how exogenous use of sex steroids provided as hormone therapy and gender-affirming procedures affect screening and prevention. Hormone therapy can affect the heart, liver, lipids, bones, brain, skin, and reproductive organs; likewise, behaviors and gender-affirming procedures may alter the risks, prevalence, and screening techniques of sexually transmitted infections. Where applicable, modifications accounting for those differences should be incorporated into the primary care of TGD adults.
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This chapter will try to answer common questions: About Puberty What is Puberty? What happens in puberty? What are hormones? What happens to a girl and a boy in puberty? How long does it take to go through puberty? How do you know where you are in the puberty process? About Blockers What is the ‘blocker’? How does it work? If I come off it, will it have harmed me? Do blockers weaken my bones? Do blockers stop me growing? What happens when I stop going through puberty? About Sex Hormones What are sex hormones? Do they make natural changes of puberty happen? Do they have any side effects? If I am non-binary, do I have other choices?
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Objective To retrospectively evaluate and compare safety and efficacy of short and long‐acting testosterone (T) parenteral formulations over five years in transmen. Design and methods Fifty transmen between 21‐42 years of age were enrolled. Twenty‐five received T undecanoate 1000 mg IM (weeks 0 and 6 then every 12‐16 weeks) and 25 received T enanthate 250 mg IM (every 3‐4 weeks). Hormonal and biochemical parameters, anthropometric characteristics and blood pressure were assessed at baseline and then every 12 months. Body composition was evaluated at baseline and then after one, three and five years of T treatment. Global satisfaction was assessed at baseline and after one and five years. Results Both T formulations led to amenorrhea in all subjects within one year of T administration. Both T treatments led to a similar increase in haemoglobin and haematocrit which always remained within the physiological range. T administration was associated with an increase in total cholesterol, low‐density lipoprotein cholesterol and triglycerides and a slight reduction of high‐density lipoprotein cholesterol. Coagulative and glucidic profiles and blood pressure did not change significantly in either group. Body weight and BMI showed a slight but not significant increase in both groups, while lean mass rose significantly in both groups. Global satisfaction was increased at years one and five in both groups. Conclusions Preliminary results from this pilot study suggest that administration of either TU or TE for five years in young transmen is both effective and safe. Our study presents the longest follow‐up published so far reporting no adverse events and this data is consistent with previous reports with a shorter follow‐up. This article is protected by copyright. All rights reserved.
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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.
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What is it about sexuality that makes it such a burning matter since the dawn of mankind? Much was lost of humankind heritage because of society’s attitude toward sex and gender, but we’ve made progress. Medical knowledge progressed incredibly and so did social and cultural norms. In these days, on most places on the planet, there is acceptance. Still, gender issues take a center stage, often inflaming the social and political milieu everywhere. So how informed and prepared is the medical community to deal with these issues? Aside from medical treatments, gender dysphoric patients need mental health and social support throughout life. Do we have enough guidelines for treatments that have life-long effects? Do we actually know all of those effects? There are many issues to consider, like fertility preservation, puberty suppression with its adverse effects, and not in the least, the effects of the hormonal therapy on the target tissues.
Transsexuality, or being transgender according to the current nomenclature, describes people who persistently seek to be accepted as members of the opposite sex, wish to change their primary and / or secondary sexual characteristics through both hormonal and surgical medical interventions to feminize or masculinize themselves. (Table 1) This discordance between their "biological" and "psychological" sex, generates clinically significant stress with profound rejection of the body of the anatomical sex, the gender assigned at birth and, therefore, persistent alteration in daily functioning (more than 6 months), is called gender dysphoria feel that they were born in the “wrong Body”. The goal of medical intervention is to improve gender dysphoria and, consequently, improve the well-being and quality of life of transgender people. In the Journal of the Chilean Society of Obstetrics and Child and Adolescent Gynecology, we have recently published two review articles on the introduction of Hormonotherapy in transgender people, goals of therapy, transition in adolescence, and the male-to-female transition, so this paper will focus only on Hormonal Therapy of the female to male transition (FTM), are people who transit from woman to man, or male trans, male transgender. (1,2)
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There are an estimated 1.4 million transgender adults in the United States, and lack of providers knowledgeable in transgender care is a barrier to health care. Obstetricians and Gynecologists can help increase access in part by becoming competent in gender-affirming hormone therapy. For transgender men, testosterone protocols can be extrapolated from those used for hypogonadal cisgender men. Unfortunately, there are not any high-quality, long-term prospective studies on the effectiveness and safety of different testosterone regimens specifically in transgender men, but the available data suggest that gender-affirming testosterone therapy is safe and effective with proper screening and monitoring.
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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.
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Although the acronym LGBTQ is often used as a catchall label for sexual and gender minorities, transgender people have unique and individual health needs and unfortunately experience significant health disparities. This article reviews essential terminology and concepts relevant to discussions of gender and gender identity, practical tips for changes that can be made on the clinical and institutional levels in order to create a welcoming and safe environment for transgender patients, as well as current recommendations for the provision of gender-affirming medical therapy.
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Objectives To identify the most eagerly anticipated change resulting from hormone therapy using gender‐affirming hormones for patients with gender incongruence undergoing a clinical trial. Methods Patients diagnosed with gender identity disorders based on the International Classification of Diseases 10th revision classification at three institutions in Japan for whom hormone therapy using gender‐affirming hormones was initiated were analyzed. They were asked what the most anticipated change was due to gender‐affirming hormone that they had thought of between giving informed consent and the first administration of the drug. Results The responders were 336 transgender men who were administered androgens and 48 transgender women who received estrogens. The median age at commencement of hormone therapy was 24 years for transgender men and 28 years for transgender women. For transgender men, the most frequent answer was cessation of menses (52.7%) followed by a deepened voice (32.4%). For transgender women, breast development (35.4%) was the most anticipated change, followed by gynoid fat deposition (29.2%). Conclusions Cessation of menses in transgender men and breast development/gynoid fat deposition in transgender women might represent primary end‐points in clinical trials evaluating the efficacy of hormonal treatment in these patients.
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The medical care of transgender patients relies on the use of sex hormones to develop and maintain the physical characteristics consistent with gender identity as the first step in transitioning. Hormonal therapy is usually continued indefinitely, even following gender-affirming surgeries. The use of hormonal treatments is associated with a multitude of positive effects as well as complications and side effects. The risk of venous thromboembolism (VTE) is a major concern. Transgender patients are often referred to coagulation specialists for advice regarding an individual patient's risk for VTE, especially if there is a personal or family history of VTE. Coagulation specialists need to be familiar with endocrine therapy including the goals of treatment and the VTE risks associated with currently used hormone regimens. We will review common referral questions and the available data and its limitations for the use of hormonal therapy in transgender patients focusing on the risk of VTE.
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Background: Many transgender individuals choose to undergo gender-affirming hormone treatment (GAHT) and/or sex reassignment surgery (SRS) to alleviate the distress that is associated with gender dysphoria. Although these treatment options often succeed in alleviating such symptoms, they can also negatively impact future reproductive potential. Objective and rationale: The purpose of this systematic review was to synthesize the available psychosocial and medical literature on fertility preservation (FP) for transgender adolescents and young adults (TAYAs), to identify gaps in the current research and provide suggestions for future research directions. Search methods: A systematic review of English peer-reviewed papers published from 2001 onwards, using the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines, was conducted. Four journal databases (Ovid MEDLINE, PubMed Medline, Ovid Embase and Ovid PsychINFO) were used to identify all relevant studies exploring psychosocial or medical aspects of FP in TAYAs. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Bibliographies of the selected articles were also hand searched and cross-checked to ensure comprehensive coverage. All selected papers were independently reviewed by the co-authors. Characteristics of the studies, objectives and key findings were extracted, and a systematic review was conducted. Outcomes: Included in the study were 19 psychosocial-based research papers and 21 medical-based research papers that explore fertility-related aspects specific for this population. Key psychosocial themes included the desire to have children for TAYAs; FP discussions, counselling and referrals provided by healthcare providers (HCPs); FP utilization; the attitudes, knowledge and beliefs of TAYAs, HCPs and the parents/guardians of TAYAs; and barriers to accessing FP. Key medical themes included fertility-related effects of GAHT, FP options and outcomes. From a synthesis of the literature, we conclude that there are many barriers preventing TAYAs from pursuing FP, including a lack of awareness of FP options, high costs, invasiveness of the available procedures and the potential psychological impact of the FP process. The available medical data on the reproductive effects of GAHT are diverse, and while detrimental effects are anticipated, the extent to which these effects are reversible is unknown. Wider implications: FP counselling should begin as early as possible as a standard of care before GAHT to allow time for informed decisions. The current lack of high-quality medical data specific to FP counselling practice for this population means there is a reliance on expert opinion and extrapolation from studies in the cisgender population. Future research should include large-scale cohort studies (preferably multi-centered), longitudinal studies of TAYAs across the FP process, qualitative studies of the parents/guardians of TAYAs and studies evaluating the effectiveness of different strategies to improve the attitudes, knowledge and beliefs of HCPs.
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OBJECTIVE: To conduct a cross-sectional study of transgender men who had been pregnant and delivered after transitioning from female-to-male gender to help guide practice and further investigation. MATERIALS AND METHODS: We administered a web-based survey from March to December 2013 to inquire about demographics, hormone use, fertility, pregnancy experience, and birth outcomes. Participants were not required to have been on hormone therapy to be eligible. We used a mixed-methods approach to evaluate the quantitative and qualitative data. RESULTS: Forty-one self-described transgender men completed the survey. Before pregnancy, 61% (n=25) had used testosterone. Mean age at conception was 28 years with a standard deviation of 6.8 years. Eighty-eight percent of oocytes (n=36) came from participants' own ovaries. Half of the participants received prenatal care from a physician and 78% delivered in a hospital. Qualitative themes included low levels of health care provider awareness and knowledge about the unique needs of pregnant transgender men as well as a desire for resources to support transgender men through their pregnancy. CONCLUSION: Transgender men are achieving pregnancy after having socially, medically, or both transitioned. Themes from this study can be used to develop transgender-appropriate services and interventions that may improve the health and health care experiences of transgender men.
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Introduction: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events. Areas covered: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease.
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Received November 21 st , 2013; revised December 22 nd , 2013; accepted January 17 th , 2014 Copyright © 2014 Alicia Garcia-Falgueras. This is an open access article distributed under the Creative Com-mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, pro-vided the original work is properly cited. In accordance of the Creative Commons Attribution License all Copy-rights © 2014 are reserved for SCIRP and the owner of the intellectual property Alicia Garcia-Falgueras. All Copyright © 2014 are guarded by law and by SCIRP as a guardian. Gender Dysphoria and Body Integrity Identity Disorder are sometimes together in the 19% of the cases. Other discomfort diseases related to identity, body scheme and/or integrity are discussed in relation to Gender Dysphoria. Because persons experiencing Gender Dysphoria need a precise diagnostic that pro-tects their access to care and will not be used against them in social, occupational or legal areas a distinc-tion diseases is provided in this text, because a meticulous description with clear exclusion criteria is re-quired.
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BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women.METHODS We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated.RESULTSFrom 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P < 0.008), but the risk of ovarian and breast cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P < 0.11 and OR, 0.95; 95% CI, 0.64-1.39, P < 0.78, respectively). However when studies which included women aged over 54 years were excluded from the analysis, the risk for women with PCOS increased further for endometrial cancer (OR, 4.05; 95% CI, 2.42-6.76, P < 0.00001), became significantly increased for ovarian cancer (OR, 2.52; 95% CI, 1.08-5.89, P < 0.03), but remained non-significant for breast cancer (OR, 0.78; 95% CI, 0.46-1.32, P < 0.35).CONCLUSIONS This is the first meta-analysis to examine gynaecological cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias in the studies may have resulted in an exaggeration of the increased risk. Furthermore, women who have PCOS should also be made aware that any increased risk for endometrial cancer must be judged in the context of its relatively low incidence in the general population. A large well-controlled prospective study is required in order to gain a more accurate estimate of the risk of gynaecological cancers in women with PCOS.PROSPERO CRD REGISTRATION NUMBERCRD42012003500.
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An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly. We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation. In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥75 years (ptrend = 0.03), while no trend was seen for PDE5I (ptrend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11). In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
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Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety. To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease. A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke. Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, -1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
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Introduction: Transsexual people receive cross-sex hormones as part of their treatment, potentially inducing hormone-sensitive malignancies. Aim: To examine the occurrence of breast cancer in a large cohort of Dutch male and female transsexual persons, also evaluating whether the epidemiology accords with the natal sex or the new sex. Main outcome measure: Number of people with breast cancer between 1975 and 2011. Methods: We researched the occurrence of breast cancer among transsexual persons 18-80 years with an exposure to cross-sex hormones between 5 to >30 years. Our study included 2,307 male-to-female (MtF) transsexual persons undergoing androgen deprivation and estrogen administration (52,370 person-years of exposure), and 795 female-to-male (FtM) subjects receiving testosterone (15,974 total years of exposure). Results: Among MtF individuals one case was encountered, as well as a probable but not proven second case. The estimated rate of 4.1 per 100,000 person-years (95% confidence interval [CI]: 0.8-13.0) was lower than expected if these two cases are regarded as female breast cancer, but within expectations if viewed as male breast cancer. In FtM subjects, who were younger and had shorter exposure to cross-sex hormones compared with the MtF group, one breast cancer case occurred. This translated into a rate of 5.9 per 100,000 person-years (95% CI: 0.5-27.4), again lower than expected for female breast cancer but within expected norms for male breast cancer. Conclusions: The number of people studied and duration of hormone exposure are limited but it would appear that cross-sex hormone administration does not increase the risk of breast cancer development, in either MtF or FtM transsexual individuals. Breast carcinoma incidences in both groups are comparable to male breast cancers. Cross-sex hormone treatment of transsexual subjects does not seem to be associated with an increased risk of malignant breast development.
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To date, the effects of long-term testosterone (T) administration on the human vagina are not completely understood. Thus, the aim of this study was to investigate the effects of long-term T treatment on vaginal tissue histology, estrogen receptor alpha (ERα) and beta (ERβ) expression and proliferation in female to male transsexual subjects (FtM). We compared vaginal samples from FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M) not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples from 16 FtM subjects treated with T (intramuscular injections of 100 mg Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for prolapse, were collected. For each sample, morphology, glycogen content, proliferation (ki-67), ERα and ERβ expression were evaluated. Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted. T administration resulted in a strong proliferation reduction when compared with both M and PrM subjects. Stromal and epithelial ERα as well as ERβ were significantly decreased in FtM when compared with PrM subjects. In conclusion, our data suggests that systemic T administration at supraphysiological dosage, determines profound changes in histomorphology and reduces ERs expression and proliferation of vaginal epithelium.International Journal of Impotence Research advance online publication, 4 April 2013; doi:10.1038/ijir.2013.9.
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Aim. Testosterone treatment is essential for the induction and maintenance of virilization of female-to-male transsexuals. This study tested the suitability of a novel testosterone preparation for this purpose. Methods. Parenteral long-acting testosterone undecanoate (TU) was administered to 12 female-to-male transsexuals. Observations were made while subjects received treatment. Main Outcome Measures. Virilization of female-to-male transsexuals and side effects of testosterone administration. Results. The testosterone levels were largely identical to those in hypogonadal men receiving testosterone treatment with TU. There were no side effects. There was a small but significant decrease in plasma cholesterol and low-density lipoprotein, but plasma high-density lipoprotein did not change significantly. Both levels of hemoglobin and hematocrit rose upon administration but remained within the physiological range. Conclusions. TU is suited for induction of virilization in female-to-male transsexuals without significant side effects. Jacobeit JW, Gooren LJ, and Schulte HM. Long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals. J Sex Med 2007;4:1479–1484.
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The optimal approach to treating minors with gender dysphoria/gender variance (GD/GV) is much more controversial than treating these phenomena in adults. This is because children have limited capacity to participate in decision making regarding their own treatment, and even adolescents have no legal ability to provide informed consent. Minors must, therefore, depend on parents or other caregivers to make treatment decisions on their behalf, including those that will influence the course of their lives in the long term. Presently, the highest level of evidence available for selecting among the various approaches to treatment is best characterized as "expert opinion." Yet, opinions vary widely among experts and are influenced by theoretical orientation and assumptions and beliefs regarding the origins of gender identity, as well as its perceived malleability at particular stages of development. This article outlines some of the more salient points raised by the clinicians who treat GD/GV and their discussants. This article summarizes what the editors believe is known and what has yet to be learned about minors with GD/GV, their families, their treatment, and their surrounding cultures.
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The Dutch approach on clinical management of both prepubertal children under the age of 12 and adolescents starting at age 12 with gender dysphoria, starts with a thorough assessment of any vulnerable aspects of the youth's functioning or circumstances and, when necessary, appropriate intervention. In children with gender dysphoria only, the general recommendation is watchful waiting and carefully observing how gender dysphoria develops in the first stages of puberty. Gender dysphoric adolescents can be considered eligible for puberty suppression and subsequent cross-sex hormones when they reach the age of 16 years. Currently, withholding physical medical interventions in these cases seems more harmful to wellbeing in both adolescence and adulthood when compared to cases where physical medical interventions were provided.
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Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study. The majority (64%) of transsexual men were currently involved in a relationship. Eleven participants (22.0%) reported having children. For eight participants, their female partner was inseminated with donor sperm, whereas three participants gave birth before hormonal therapy and SRS. At the time of interview, more than half of the participants desired to have children (54%). There were 18 participants (37.5%) who reported that they had considered freezing their germ cells, if this technique would have been available previously. Participants without children at the time of investigation expressed this desire more often than participants with children (χ²; test: P= 0.006). Our data reveal that the majority of transsexual men desire to have children. Therefore, more attention should be paid to this topic during the diagnostic phase of transition and to the consequences for genetic parenthood after starting sex reassignment therapy.
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Testosterone is important for the development of secondary sexual characteristics in female-to-male (FtM) transsexuals, but it may increase breast cancer risk. To date, only one breast cancer case has been reported in the literature in a FtM transsexual after 10 years of testosterone therapy. We describe 2 cases of breast cancers diagnosed in FtM transsexuals who have been treated with supraphysiological doses of testosterone. Our 2 cases demonstrate the unique issues that concern the management of FtM transsexuals with breast cancer and examine possible roles of testosterone in the development of breast cancer.
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The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment steps, and to obtain improved results in the physical appearance of those who opt to continue with sex reassignment. The effects of GnRHa are reversible. However, concerns have been raised about the risk of making the wrong treatment decisions, as gender identity could fluctuate during adolescence, adolescents in general might have poor decision-making abilities, and there are potential adverse effects on health and on psychological and psychosexual functioning. Proponents of puberty suppression emphasize the beneficial effects of GnRHa on the adolescents' mental health, quality of life and of having a physical appearance that makes it possible for the patients to live unobtrusively in their desired gender role. In this Review, we discuss the evidence pertaining to the debate on the effects of GnRHa treatment. From the studies that have been published thus far, it seems that the benefits outweigh the risks. However, more systematic research in this area is needed to determine the safety of this approach.
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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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Structural gender differences in bone mass - characterized by wider but not thicker bones - are generally attributed to opposing sex steroid actions in men and women. Recent findings have redefined the traditional concept of sex hormones as the main regulators of skeletal sexual dimorphism. GH-IGF1 action is likely to be the most important determinant of sex differences in bone mass. Estrogens limit periosteal bone expansion but stimulate endosteal bone apposition in females, whereas androgens stimulate radial bone expansion in males. Androgens not only act directly on bone through the androgen receptor (AR) but also activate estrogen receptor-α or -β (ERα or ERβ) following aromatization into estrogens. Both the AR and ERα pathways are needed to optimize radial cortical bone expansion, whereas AR signaling alone is the dominant pathway for normal male trabecular bone development. Estrogen/ERα-mediated effects in males may - at least partly - depend on interaction with IGF1. In addition, sex hormones and their receptors have an impact on the mechanical sensitivity of the growing skeleton. AR and ERβ signaling may limit the osteogenic response to loading in males and females respectively, while ERα may stimulate the response of bone to mechanical stimulation in the female skeleton. Overall, current evidence suggests that skeletal sexual dimorphism is not just the end result of differences in sex steroid secretion between the sexes, but depends on gender differences in GH-IGF1 and mechanical sensitivity to loading as well.
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Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer such as African-Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score above 19, or uncontrolled or poorly controlled heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.
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To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement, and controls, during six months. We assessed, through ADAM, AMS, IIEF-5 and SF-36 questionnaires, and through clinical and laboratory examinations, 62 patients divided into three groups: 17 hypogonadal males (HR) used intramuscular testosterone every three weeks; 14 hypogonadal males (HV) and 31 non-hypogonadal males (CV) used oral vitamins daily. When compared to others, HR group obtained libido improvement assessed by ADAM 1 (p = 0.004), and borderline sexual potency improvement assessed by IIEF-5 (p = 0.053), besides a decrease in waist circumference after eight weeks (p = 0.018). The remaining parameters did not differ between the groups. PSA and hematocrit remained stable in those using testosterone. Six months of testosterone replacement improved sexuality and body composition, with prostatic and hematological safety.
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All forms of hypogonadism – primary, secondary and late-onset – require testosterone substitution. The indication is given when the patient presents with symptoms of androgen deficiency and the serum testosterone levels are below normal. Several testosterone preparations and modes of application are available of which those producing physiologic serum levels should be preferred e.g. preferentially transdermal gels and long-acting intramuscular testosterone undecanoate. Testosterone substitution must be monitored at regular intervals, best at 3, 6 and 12 months after initiation and then annually. Parameters for surveillance include well-being, libido and sexual activity, measurement of serum testosterone levels, haemoglobin and haematocrit, PSA and digital rectal examination, and, biannually, bone mineral density. Testosterone has positive effects on comorbidities such as obesity, metabolic syndrome, diabetes type II, cardiovascular diseases and osteoporosis.
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IntroductionGender dysphoria is characterized by a strong discomfort with the gender assigned at birth and the urge to live as a member of the opposite gender. The acquisition of phenotypic features of the desired gender requires the use of cross-sex hormones. Female-to-male (FtM) transsexual persons are treated with testosterone to induce virilization.AimThe aim of the study was to assess the effects of three different testosterone formulations on body weight and composition and metabolic and bone parameters.Methods Forty-five FtM transsexuals were randomly assigned to receive testoviron depot (i.m.: 100 mg/10 days; n = 15), testosterone gel (50 mg/die; n = 15), and testosterone undecanoate (i.m.: 1,000 mg every 6 weeks for the first 6 weeks and then every 12 weeks, n = 15). FtM individuals were studied before, at week 30, and at week 54 of testosterone treatment.Main Outcome MeasuresAnthropometric, metabolic, bone, hematological, and biochemical parameters were evaluated at baseline and after 12 months of treatment.ResultsLean body mass significantly increased and fat mass decreased in all groups. No modifications were reported in fasting insulin and insulin sensitivity index. High-density plasma lipoprotein levels declined significantly and low-density lipoprotein concentrations increased significantly in the three groups. The activated partial thromboplastin time and factor I did not change while prothrombin time significantly increased in all groups. At week 54, all subjects were amenorrheic and time to amenorrhea did not differ between the three groups. Current general life satisfaction was increased in all subjects after 1 year of treatment.Conclusions One-year testosterone administration in FtM transsexuals appears to be very safe with no differences among the testosterone formulations used. Our study is preliminary, and the detection of subtle or long-term differences in the effects of the three formulations may require further larger and longer term studies in this and other populations. Pelusi C, Costantino A, Martelli V, Lambertini M, Bazzocchi A, Ponti F, Battista G, Venturoli S, and Meriggiola MC. Effects of three different testosterone formulations in female-to-male transsexual persons. J Sex Med **;**:**–**.
Article
Purpose: Despite international guidelines being available, not all gender clinics are able to face gender dysphoric (GD) youth population needs specifically. This is particularly true in Italy. Centers offering specialized support are relatively few and a commonly accepted Italian approach to GD youth has still not been defined. The aim of the present Position Statement is to develop and adhere to Italian guidelines for treatment of GD adolescents, in line with the "Dutch Approach", the Endocrine Society (ES), and the World Professional Association for Transgender Health (WPATH) guidelines. Methods: An in-depth brainstorming on the application of International guidelines in the Italian context was performed by several dedicated professionals. Results: A staged approach, combining psychological support as well as medical intervention is suggested. In the first phase, individuals requesting medical help will undergo a psycho-diagnostic procedure to assess GD; for eligible adolescents, pubertal suppression should be made available (extended diagnostic phase). Finally, from the age of 16 years, cross-sex hormonal therapy can be added, and from the age of 18 years, surgical sex reassignment can eventually be performed. Conclusions: The current inadequacy of Italian services offering specialized support for GD youth may lead to negative consequences. Omitting or delaying treatment is not a neutral option. In fact, some GD adolescents may develop psychiatric problems, suicidality, and social marginalization. With access to specialized GD services, emotional problems, as well as self-harming behavior, may decrease and general functioning may significantly improve. In particular, puberty suppression seems to be beneficial for GD adolescents by relieving their acute suffering and distress and thus improving their quality of life.
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Trans people are those people whose sex assigned at birth does not align with their gender identity – a condition that can cause marked distress. Consequently, many trans people seek to change their gender, often permanently. Most usually that change is to male or female although sometimes the change is to a non-binary gender form. However, as the last of these is less usual this commentary will consider only trans people who identify as male or female. The options available to trans people vary according to cultural context and so this commentary considers such matters from a context in which hormonal and surgical assistance is comparatively readily available. Within such contexts, people who choose to transition often use hormones and surgery to create a body that is more congruent with their perception of themselves as men or women. Thus people assigned as female at birth who identify and live as men (trans men) may take testosterone in order to grow facial hair and thicker body hair, increase musculature, create a deeper voice and ensure the cessation of menses. If they have the genetic propensity they will go bald. They will commonly have surgery to remove their breasts and produce a male chest contour and, less commonly, to have a surgically constructed penis. They will also be likely to have a hysterectomy and oophorectomy. Those people assigned as male at birth who identify and live as women (trans women) may have androgen suppression as well as estrogens in order to develop breasts and a more female body contour. Body hair may lessen, but facial hair will need removing by electrolysis. Scalp hair loss will stop, but hair will not regrow and hairpieces may therefore be used. The masculine voice is not affected by estrogens and speech therapy and sometimes surgery can …
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Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. Aim. The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). Methods. This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 mu g/24 hours transdermal 17-beta estradiol. Main Outcome Measures. Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. Results. No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P
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There are similar time intervals between starting testosterone therapy (TT) and development of thrombotic (~ 4.5 months) or cardiovascular (CVD) events (~ 3 months) which may, speculatively, reflect a shared pathophysiology. We have described thrombotic events 5 months (median) after starting TT in 38 men and 4 women, including 27 with deep venous thrombosis-pulmonary embolism, 12 with osteonecrosis, 1 with central retinal vein thrombosis, 1 with amaurosis fugax, and 1 with spinal cord infarction. In 8 men whose TT was continued, second thrombotic events occurred despite adequate anticoagulation with Coumadin in 8 men, 3 of whom had a third thrombotic event. Of these 42 cases, 40 had measures of thrombophilia-hypofibrinolysis, and 39 were found to have previously undiagnosed thrombophilia-hypofibrinolysis. Before beginning TT, especially in men with previous history of thrombotic events, we suggest that, at a minimum, measurements be made for the Factor V Leiden and Prothrombin mutations, Factors VIII and XI, and homocysteine, to identify men who should not receive TT. We need prospective data focused on whether there should be pre-TT screening based on history of previous venous thromboembolism or for all subjects for major gene thrombophilias. To better resolve questions about TT and all cause and cardiovascular morbidity and mortality and thrombosis, a long term, prospective, randomized, blinded study following the example of the Women’s Health Initiative is needed. While we wait for prospective placebo-controlled TT outcome data, TT should be restricted to men with well-defined androgen deficiency syndromes.
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Guidelines for cross-sex hormone treatment of transsexual people are now in place. However, little attention has been paid to the issue of treatment suitability for older people. Does existing treatment need to be adapted as subjects age, and does it make a difference if treatment is only started when the subject is already older? To assess the necessity of adapting cross-sex hormone administration for elderly transsexual people. Risks/benefits of continued use of cross-sex hormones with regard to bone health, cardiovascular risks, and malignancies. Due to lack of data on the subject population, sex hormone treatment of other conditions in older non-transsexual people has been taken as the best available analogy to determine the extent to which these might be applicable to comparable transsexual persons. Findings in transsexual people receiving cross-sex hormone treatment sometimes modified the above approach of applying guidelines for the elderly to the aging transsexual population. Testosterone administration to female-to-male transsexual persons (FtoM) carries little risk with regard to cardiovascular disease and cancer. For those with high hematocrit or cardiac insufficiency the dose can be reduced. Administration of estrogens to male-to-female transsexual persons (MtoF), particularly when combined with progestins, does significantly increase the risk of developing cardiovascular disease (almost a twofold incidence compared with the general population). This may require dose adjustment or changing from oral to safer transdermal estrogens. Tumors of the breasts, prostate and pituitary may occur. In FtoM, breast cancer can occur even after breast ablation. Older subjects can commence cross-sex hormone treatment without disproportionate risks. Cross-sex hormones may be continued into old age but monitoring for cardiovascular disease and malignancies, both of the old and new sex, is recommended. MtoF will have more health complications in old age than FtoM requiring adaptations of treatment. Gooren L and Lips P. Conjectures concerning cross-sex hormone treatment of aging transsexual persons. J Sex Med **;**:**-**.
Article
Our knowledge concerning the effects of testosterone (T) therapy on the skin of trans men (female-to-male transsexuals) is scarce. The aim of this study was to evaluate the short- and long-term clinical effects of T treatment on the skin of trans men. We conducted a prospective intervention study in 20 hormone naive trans men and a cross-sectional study in 50 trans men with an average of 10 years on T therapy. Acne lesions were assessed using the Gradual Acne Grading Scale, hair patterns using the Ferriman and Gallwey classification (F&G), and androgenetic alopecia using the Norwood Hamilton Scale. T treatment increased facial and body hair growth. The F&G score increased progressively from a median value of 0.5 at baseline to a value of 12 after 12 months of T administration. After long-term T treatment, all but one trans man achieved an F&G score indicative of hirsutism in women, with a median value of 24. Only one trans man acquired mild frontotemporal hair loss during the first year of T treatment, whereas 32.7% of trans men had mild frontotemporal hair loss and 31% had moderate to severe androgenetic alopecia after long-term T therapy. The presence and severity of acne increased during the first year of T therapy, and peaked at 6 months. After long-term T treatment, most participants had no or mild acne lesions (93.9%). Dermatological outcome was not demonstrably related to individual serum T or dihydrotestosterone levels. T treatment increased facial and body hair in a time-dependent manner. The prevalence and severity of acne in the majority of trans men peaked 6 months after beginning T therapy. Severe skin problems were absent after short- and long-term T treatment. Wierckx K, Van de Peer F, Verhaeghe E, Dedecker D, Van Caenegem, E, Toye K, Kaufman JM, and T'Sjoen G. Short- and long-term clinical skin effects of testosterone treatment in trans men. J Sex Med **;**:**-**.
Article
Gender identity disorder (transgenderism) is poorly understood from both mechanistic and clinical standpoints. Awareness of the condition appears to be increasing, probably because of greater societal acceptance and available hormonal treatment. Therapeutic options include hormone and surgical treatments but may be limited by insurance coverage because costs are high. For patients seeking male-to-female (MTF) change, hormone treatment includes estrogens, finasteride, spironolactone, and gonadotropin-releasing hormone (GnRH) analogs. Surgical options include feminizing genital and facial surgery, breast augmentation, and various fat transplantations. For patients seeking a female-to-male (FTM) gender change, medical therapy includes testosterone and GnRH analogs and surgical therapy includes mammoplasty and phalloplasty. Medical therapy for both FTM and MTF can be started in early puberty, although long-term effects are not known. All patients considering treatment need counseling and medical monitoring.
Article
Introduction. Sexual function following genital sexual reassignment surgery (SRS) is an important outcome for many transsexuals, affecting the choice of surgical technique, satisfaction with surgery, and quality of life. However, compared to other outcome measures, little clinical and research attention has been given to sexual functioning following SRS. Aim. To discuss the potential impact of cross-sex hormone therapy and SRS on sexual function and to summarize the published empirical research on postsurgical sexual functioning in male-to-female (MtF) and female-to-male (FtM) transsexuals. Methods. Cross-sex hormone therapy and SRS techniques are outlined, the potential roles of cross-sex hormone therapy and SRS on sexual function are discussed, and peer-reviewed literature published in English on postoperative sexual functioning in MtF and FtM transsexuals is reviewed. Main Outcome Measures. Sexual desire, sexual arousal, and ability to achieve orgasm following SRS. Results. Contrary to early views, transsexualism does not appear to be associated with a hyposexual condition. In MtF transsexuals, rates of hypoactive sexual desire disorder (HSDD) are similar to those found in the general female population. In FtM transsexuals, sexual desire appears unequivocally to increase following SRS. Studies with MtF transsexuals have revealed not only vasocongestion, but also the secretion of fluid during sexual arousal. Research on sexual arousal in FtM transsexuals is sorely lacking, but at least one study indicates increased arousal following SRS. The most substantial literature on sexual functioning in postoperative transsexuals pertains to orgasm, with most reports indicating moderate to high rates of orgasmic functioning in both MtF and FtM transsexuals. Conclusions. Based on the available literature, transsexuals appear to have adequate sexual functioning and/or high rates of sexual satisfaction following SRS. Further research is required to understand fully the effects of varying types and dosages of cross-sex hormone therapies and particular SRS techniques on sexual functioning. Klein C, and Gorzalka BB. Sexual functioning in transsexuals following hormone therapy and genital surgery: A review. J Sex Med 2009;6:2922–2939.
Article
Recent data report an important role of testosterone (T) in modulating female sexual responses, but little is known about the expression and distribution of androgen receptor (AR) in the human vagina. Therefore, the aims of our study were to evaluate the expression of AR in the human vagina in premenopausal (PrM) and menopausal (M) women and in T-treated women. Vaginal biopsies were obtained from PrM and postmenopausal women and from women with gender identity disorder (female to male (FtM)) receiving exogenous T. AR gene and protein expression levels in vaginal tissues were determined by real-time PCR and western blot analysis, respectively, whereas the localization of AR in vaginal mucosa and stroma was performed by immunohistochemistry. ARs were detected by immunostaining both in the mucosa and stroma. In vaginal mucosa, AR density score decreases with age but does not change with T administration. In stromal tissue, AR density score does not change with age but significantly increases with T administration (P<0.01). AR protein expression was significantly increased in FtM subjects (P<0.001). The expression of AR messenger RNA (mRNA) evaluated by Real-time PCR showed a significantly higher mRNA expression in FtM versus M patients (P<0.01) and in PrM versus M subjects (P<0.05). In conclusion, we found AR protein and mRNA expression both in the epithelium and stroma of the human vagina in all groups of women. A negative correlation exists between age and AR expression in the vaginal mucosa. T administration increases AR expression in both the mucosa and stroma.International Journal of Impotence Research advance online publication, 28 June 2012; doi:10.1038/ijir.2012.25.
Article
It is unknown whether long term cross-sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28–63 months in 20 male-to-female transsexuals (M → F) treated with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F → M) treated with androgens. They underwent gonadectomy 13–35 months after the start of cross-sex hormone administration. Bone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28–63 months of cross-sex hormone administration. In oestrogen-treated M → F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28–63 months of cross-sex hormones. In F → M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28–63 months following ovariectomy. In both M → F and F → M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long-term LH levels were more elevated in testosterone-treated F → M than in oestrogen-treated M → F transsexuals. In M → F, oestrogen treatment prevented bone loss after testosterone deprivation. In F → M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non-compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.
Chapter
Multiple lines of evidence support a central role of hormones in the etiology of breast, endometrial and ovarian cancers. Evidence of an association between circulating hormones and these cancers varies by both hormone and cancer site, with the most consistent associations observed for sex steroid hormones and breast cancer risk among postmenopausal women. Recently, evidence has begun to accumulate suggesting an important role for endogenous hormones in premenopausal breast cancer, endometrial cancer and possibly ovarian cancer. In this chapter, prospective epidemiologic studies, where endogenous hormones are measured in study subjects prior to disease diagnosis, are summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two-to-three-fold higher risk of breast cancer. Evidence among premenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. Evidence to date of hormonal associations for endometrial cancer is limited, though a strong association with sex steroid hormones is suggested. Studies of ovarian cancer have been few and small with no consistent associations observed with endogenous hormones. Clearly more evaluation is needed to confirm the role of endogenous hormones in premenopausal breast cancer, endometrial cancer and ovarian cancer.
Article
Female-to-male transsexual persons (transsexual men) undergo extreme hormonal changes due to ovariectomy and testosterone substitution, allowing studies on sex steroid effects on bone geometry and physiology in the adult. The objective of the study was to examine the effects of cross-gender sex steroid exposure on volumetric bone parameters in transsexual men. This was a cross-sectional study. Participants were recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital (Ghent, Belgium). Fifty transsexual men after sex reassignment surgery with 50 age-matched control women and an additional 16 transsexual men before testosterone substitution and sex reassignment surgery with 16 control women participated in the study. The main outcome measures were areal and volumetric bone parameters using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, body composition (dual-energy X-ray absorptiometry), sex steroids, markers of bone turnover and grip strength. Before hormonal treatment, transsexual men had similar body composition and bone geometry as female controls. The transsexual men on long-term testosterone therapy, however, demonstrated a higher lean body mass and muscle mass and a greater grip strength as well as a lower body and subcutaneous fat mass and a larger waist and smaller hip circumference compared with female controls (all P < 0.001). We observed a larger radial cortical bone size (P < 0.001) and lower cortical volumetric bone mineral density at the radius and tibia (P < 0.05) in transsexual men on testosterone therapy. Transsexual men on testosterone substitution therapy present with a different body composition with more muscle mass and strength and less fat mass as well as an altered bone geometry with larger bones compared with female controls.
Article
Introduction Several retrospective and prospective studies have reported on the association between childhood gender variance and sexual orientation and gender discomfort in adulthood. In most of the retrospective studies, samples were drawn from the general population. The samples in the prospective studies consisted of clinically referred children. In understanding the extent to which the association applies for the general population, prospective studies using random samples are needed. Aim This prospective study examined the association between childhood gender variance, and sexual orientation and gender discomfort in adulthood in the general population. Methods In 1983, we measured childhood gender variance, in 406 boys and 473 girls. In 2007, sexual orientation and gender discomfort were assessed. Main Outcome Measures Childhood gender variance was measured with two items from the Child Behavior Checklist/4–18. Sexual orientation was measured for four parameters of sexual orientation (attraction, fantasy, behavior, and identity). Gender discomfort was assessed by four questions (unhappiness and/or uncertainty about one's gender, wish or desire to be of the other gender, and consideration of living in the role of the other gender). Results For both men and women, the presence of childhood gender variance was associated with homosexuality for all four parameters of sexual orientation, but not with bisexuality. The report of adulthood homosexuality was 8 to 15 times higher for participants with a history of gender variance (10.2% to 12.2%), compared to participants without a history of gender variance (1.2% to 1.7%). The presence of childhood gender variance was not significantly associated with gender discomfort in adulthood. Conclusions This study clearly showed a significant association between childhood gender variance and a homosexual sexual orientation in adulthood in the general population. In contrast to the findings in clinically referred gender‐variant children, the presence of a homosexual sexual orientation in adulthood was substantially lower. Steensma TD, van der Ende J, Verhulst FC, and Cohen‐Kettenis PT. Gender variance in childhood and sexual orientation in adulthood: A prospective study. J Sex Med 2013;10:2723–2733.
Article
Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. Total mortality in testosterone-treated compared with untreated men was measured. Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P<0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease. In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.
Article
In 2007, an interdisciplinary clinic for children and adolescents with disorders of sex development (DSD) or gender identity disorder (GID) opened in a major pediatric center. Psychometric evaluation and endocrine treatment via pubertal suppressive therapy and administration of cross-sex steroid hormones was offered to carefully selected patients according to effective protocols used in Holland. Hembree et al.'s (2009) Guidelines for Endocrine Treatment of Transsexual Persons published by the Endocrine Society endorsed these methods. A description of the clinic's protocol and general patient demographics are provided, along with treatment philosophy and goals.
Article
Gender identity disorder (GID), or transsexualism, is an increasingly recognized medical condition with an expanding body of medical literature to support the use of established therapeutic guidelines. Transsexualism can be effectively managed through exogenous cross-sex hormone administration used to induce development of desired sex characteristics, as well as use of other agents, such as aldosterone antagonists, aimed at decreasing physical characteristics of the undesired sex. Many complications can arise with the use of the available therapies, and these must be considered before determining the appropriate course of action. This review describes methods, including both pharmacotherapy and surgical interventions, for effective medical management of both male and female adults with GID. In addition, specific goals of therapy as well as safety aspects with long-term use of pharmacotherapeutic agents are discussed. This review also discusses some special considerations for treating patients with significant, yet common, comorbid diseases such as human immunodeficiency virus infection, acquired immunodeficiency syndrome, and viral hepatitis, as these conditions may complicate the clinical course and preclude some patients from using certain therapies. Pharmacist involvement in the management of transsexualism can be extremely beneficial to patients and other health care providers. Pharmacists can help determine the appropriate therapy, optimize dosages, monitor for adverse effects, and educate patients on what to expect during their therapy. Pharmacists should become knowledgeable about guidelines and current literature on transsexualism, understand the monitoring parameters for safe and effective therapy, and establish themselves as partners in the collaborative management of this disorder.
Article
To describe the patients with gender identity disorder referred to a pediatric medical center. We identify changes in patients after creation of the multidisciplinary Gender Management Service by expanding the Disorders of Sex Development clinic to include transgender patients. Data gathered on 97 consecutive patients <21 years, with initial visits between January 1998 and February 2010, who fulfilled the following criteria: long-standing cross-gender behaviors, provided letters from current mental health professional, and parental support. Main descriptive measures included gender, age, Tanner stage, history of gender identity development, and psychiatric comorbidity. Genotypic male:female ratio was 43:54 (0.8:1); there was a slight preponderance of female patients but not significant from 1:1. Age of presentation was 14.8 ± 3.4 years (mean ± SD) without sex difference (P = .11). Tanner stage at presentation was 4.1 ± 1.4 for genotypic female patients and 3.6 ± 1.5 for genotypic male patients (P = .02). Age at start of medical treatment was 15.6 ± 2.8 years. Forty-three patients (44.3%) presented with significant psychiatric history, including 20 reporting self-mutilation (20.6%) and suicide attempts (9.3%). After establishment of a multidisciplinary gender clinic, the gender identity disorder population increased fourfold. Complex clinical presentations required additional mental health support as the patient population grew. Mean age and Tanner Stage were too advanced for pubertal suppressive therapy to be an affordable option for most patients. Two-thirds of patients were started on cross-sex hormone therapy. Greater awareness of the benefit of early medical intervention is needed. Psychological and physical effects of pubertal suppression and/or cross-sex hormones in our patients require further investigation.
Article
Multiple lines of evidence support a central role of hormones in the etiology of breast, endometrial and ovarian cancers. Evidence of an association between circulating hormones and these cancers varies by both hormone and cancer site, with the most consistent associations observed for sex steroid hormones and breast cancer risk among postmenopausal women. Recently, evidence has begun to accumulate suggesting an important role for endogenous hormones in premenopausal breast cancer, endometrial cancer and possibly ovarian cancer. In this chapter, prospective epidemiologic studies, where endogenous hormones are measured in study subjects prior to disease diagnosis, are summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two-to-three-fold higher risk of breast cancer. Evidence amongpremenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. Evidence to date of hormonal associations for endometrial cancer is limited, though a strong association with sex steroid hormones is suggested. Studies of ovarian cancer have been few and small with no consistent associations observed with endogenous hormones. Clearly more evaluation is needed to confirm the role of endogenous hormones in premenopausal breast cancer, endometrial cancer and ovarian cancer.
Article
Although sexual health after genital surgery is an important outcome factor for many transsexual persons, little attention has been attributed to this subject. To provide data on quality of life and sexual health after sex reassignment surgery (SRS) in transsexual men. A single-center, cross-sectional study in 49 transsexual men (mean age 37 years) after long-term testosterone therapy and on average 8 years after SRS. Ninety-four percent of the participants had phalloplasty. Self-reported physical and mental health using the Dutch version of the Short Form-36 Health Survey; sexual functioning before and after SRS using a newly constructed specific questionnaire. Compared with a Dutch reference population of community-dwelling men, transsexual men scored well on self-perceived physical and mental health. The majority reported having been sexually active before hormone treatment, with more than a quarter having been vaginally penetrated frequently before starting hormone therapy. There was a tendency toward less vaginal involvement during hormone therapy and before SRS. Most participants reported an increase in frequency of masturbation, sexual arousal, and ability to achieve orgasm after testosterone treatment and SRS. Almost all participants were able to achieve orgasm during masturbation and sexual intercourse, and the majority reported a change in orgasmic feelings toward a more powerful and shorter orgasm. Surgical satisfaction was high, despite a relatively high complication rate. Results of the current study indicate transsexual men generally have a good quality of life and experience satisfactory sexual function after SRS.
Article
To describe sexual desire in female-to-male transsexual persons post sex reassignment surgery (SRS). The associations between serum androgen levels and sexual desire are examined. Single center cross-sectional study. Forty-five female-to-male transsexual persons post SRS completed a standardized questionnaire assessing sexual desire (Sexual Desire Inventory). In addition, participants were asked questions on sexual desire before starting hormone treatment and having SRS. Serum levels of testosterone, LH and sex hormone-binding globulin were measured on fasting morning serum samples. In retrospect, 73.9% of the participants reported an increase in sexual desire after hormone treatment and SRS. Solitary sexual desire scores were significantly correlated with frequency of masturbation (r=0.835; P<0.001), whereas frequency of sexual intercourse with a partner was not. No direct associations were found between testosterone and solitary or dyadic sexual desire. However, ANOVA showed an independent effect of LH on solitary sexual desire (P<0.001). Post hoc analysis revealed that female-to-male transsexual persons with elevated levels of LH, indicating suboptimal testosterone therapy, reported significantly lower solitary sexual desire levels (than those with low LH levels; P=0.007). Suppressed LH levels were also associated with having a higher need for sexual activities (P=0.009) and a higher frequency of excessive sexual desire (P=0.007). Most female-to-male transsexual persons report on a marked increase in sexual desire after testosterone treatment and SRS. No direct associations between levels of testosterone and solitary or dyadic sexual desire were found. However, measures of sexual desire were inversely associated with LH levels.
Article
The prevalence of transsexualism is thought to differ among socio-geographic backgrounds, and little is known about its prevalence in Japan. Polycystic ovary syndrome (PCOS), which is known to be associated with insulin resistance and metabolic syndrome, is often seen in female-to-male (FTM) transsexual patients. Consequently, detection of PCOS is an important part of health care for these individuals. The purpose of this study was to assess the prevalence of transsexuality in Japan, as well as the incidences of PCOS and insulin resistance among Japanese FTM transsexual patients. One hundred four male-to-female (MTF) and 238 FTM Japanese transsexual patients were studied. Medical histories, including histories of menstrual cycling and hormone treatment, were taken. To exclude other diseases, such as congenital adrenal hyperplasia and hormone-secreting tumors, thorough medical assessments, including transvaginal or transrectal ultrasonography and measurement of serum hormone levels and insulin resistance indexes, were performed. The diagnosis of PCOS was based on the Rotterdam 2003 criteria. Based on demographic statistics, the prevalences of MTF and FTM transsexuality are about 3.97 and 8.20 per 100,000 people, respectively, making the MTF-to-FTM ratio about 1:2. Of the FTM transsexual patients studied, 128 had not taken hormones before their initial assessment (untreated group); the remaining 50 self-administered androgen. Among the untreated group, 32.0% were diagnosed with PCOS, 30.1% were insulin-resistant, and 31.1% showed hypoadiponectinemia. The sex ratio among Japanese transsexuals is different than among Caucasians. PCOS and insulin resistance are common findings in FTM transsexual patients at initial presentation.
Article
We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.
Article
The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks. The aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals. Forty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months. Body composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded. There was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period. There was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy.
Article
To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). Prospective cohort study. Academic research institution. Five hormone-naïve FtM transsexuals before and after HT. Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. Differential regulation of specific genes and gene expression signatures. We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.