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Endocrine Care of Transgender Adults: A Multidisciplinary Approach
Abstract
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.
Purpose of Review
Many transgender and gender non-conforming (TGNC) people seek gender-affirming hormone therapy (GAHT). While GAHT is generally safe and increases well-being, it is essential to accurately understand potential unintended effects and risk factors to better inform and manage treatment. This narrative review covers recent literature documenting changes in sexual function following the initiation of GAHT and explores inflammation as a potential mediator of these changes.
Recent Findings
Generally, the initiation of GAHT is correlated with increased sexual desire in transgender men and decreased sexual desire in transgender women, with time-limited effects that return to levels approaching baseline after about a year; there are also changes in inflammation markers that parallel this timeline. Findings on other aspects of sexual function (e.g., orgasm, pain, and sexual quality of life) are more limited. As there is evidence from cisgender populations that inflammation acts as a mechanism by which hormones influence sexual function, we propose applying this model to TGNC people taking GAHT.
Summary
Sexual function may change in TGNC patients receiving GAHT, and those changes may be influenced by inflammation. However, these changes often return to baseline as TGNC patients’ bodies adjust to a new hormonal equilibrium.
Gender‐affirming hormone therapy (GAHT) can help transgender and/or gender diverse (TGD) individuals achieve emobidment goals that align with their transition needs. Clinical evidence from estradiol (E)‐GAHT patients indicate widespread changes in tissues sensitive to E and testosterone (T), particularly in the reproductive system. Notably, E‐GAHTs effects on hormones and reproduction vary greatly between patients. With the goal of informing clinical research and practice for TGD individuals taking E, this study examines intact male mice implanted with capsules containing one of three different E doses (low 1.25 mg; mid 2.5 mg; high 5 mg), or a blank control capsule. All E‐GAHT doses suppress T and follicle stimulating hormone levels while elevating E levels. Only the high E‐GAHT dose significantly supresses luteinizing hormone levels. All E‐GAHT doses affect epididymis tubule size similarly while seminiferous tubule morphology and bladder weight changes are dose‐dependent. E‐GAHT does not alter the presence of mature sperm, though E‐exposed sperm have altered motility. These data represent the first evidence that mouse models offer an effective tool to understand E‐GAHTs impact on reproductive health and the dose‐dependent effects of this model permit examinations of diverse patient outcomes.
The treatment of persistent uterine bleeding in those patients who identify as transmasculine or nonbinary is often straightforward, but can be difficult in a subset of patients. This article reviews the physiology of the normal menstrual cycle and the hormonal influences on the endometrium, and then explores options for the treatment of persistent bleeding for people both already on testosterone and for those who are either not ready for or who do not desire testosterone.
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.
Cross-sex hormonal treatment represents a main aspect of gender dysphoria health care pathway. However, it is still debated whether this intervention translates into a better mental well-being for the individual and which mechanisms may underlie this association. Although sex reassignment surgery has been the subject of extensive investigation, few studies have specifically focused on hormonal treatment in recent years. Here, we systematically review all studies examining the effect of cross-sex hormonal treatment on mental health and well-being in gender dysphoria. Research tends to support the evidence that hormone therapy reduces symptoms of anxiety and dissociation, lowering perceived and social distress and improving quality of life and self-esteem in both male-to-female and female-to-male individuals. Instead, compared to female-to-male individuals, hormone-treated male-to-female individuals seem to benefit more in terms of a reduction in their body uneasiness and personality-related psychopathology and an amelioration of their emotional functioning. Less consistent findings support an association between hormonal treatment and other mental health-related dimensions. In particular, depression, global psychopathology, and psychosocial functioning difficulties appear to reduce only in some studies, while others do not suggest any improvement in these domains. Results from longitudinal studies support more consistently the association between hormonal treatment and improved mental health. On the contrary, a number of cross-sectional studies do not support this evidence. This review provides possible biological explanation vs psychological explanation (direct effect vs indirect effect) for the hormonal treatment-induced better mental well-being. In conclusion, this review indicates that gender dysphoria-related mental distress may benefit from hormonal treatment intervention, suggesting a transient reaction to the nonsatisfaction connected to the incongruent body image rather than a stable psychiatric comorbidity. In this perspective, timely hormonal treatment intervention represents a crucial issue in gender dysphoria individuals’ mental health-related outcome.
Background:
Prior to the start of cross-sex hormone therapy (CSH), androgenic progestins are often used to induce amenorrhea in female to male (FtM) pubertal adolescents with gender dysphoria (GD). The aim of this single-center study is to report changes in anthropometry, side effects, safety parameters, and hormone levels in a relatively large cohort of FtM adolescents with a diagnosis of GD at Tanner stage B4 or further, who were treated with lynestrenol (Orgametril®) monotherapy and in combination with testosterone esters (Sustanon®).
Methods:
A retrospective analysis of clinical and biochemical data obtained during at least 6 months of hormonal treatment in FtM adolescents followed at our adolescent gender clinic since 2010 (n = 45) was conducted. McNemar's test to analyze reported side effects over time was performed. A paired Student's t test or a Wilcoxon signed-ranks test was performed, as appropriate, on anthropometric and biochemical data. For biochemical analyses, all statistical tests were done in comparison with baseline parameters. Patients who were using oral contraceptives (OC) at intake were excluded if a Mann-Whitney U test indicated influence of OC.
Results:
Metrorrhagia and acne were most pronounced during the first months of monotherapy and combination therapy respectively and decreased thereafter. Headaches, hot flushes, and fatigue were the most reported side effects. Over the course of treatment, an increase in musculature, hemoglobin, hematocrit, creatinine, and liver enzymes was seen, progressively sliding into male reference ranges. Lipid metabolism shifted to an unfavorable high-density lipoprotein (HDL)/low-density lipoprotein (LDL) ratio; glucose metabolism was not affected. Sex hormone-binding globulin (SHBG), total testosterone, and estradiol levels decreased, and free testosterone slightly increased during monotherapy; total and free testosterone increased significantly during combination therapy. Gonadotropins were only fully suppressed during combination therapy. Anti-Müllerian hormone (AMH) remained stable throughout the treatment. Changes occurred in the first 6 months of treatment and remained mostly stable thereafter.
Conclusions:
Treatment of FtM gender dysphoric adolescents with lynestrenol monotherapy and in combination with testosterone esters is effective, safe, and inexpensive; however, suppression of gonadotropins is incomplete. Regular blood controls allow screening for unphysiological changes in safety parameters or hormonal levels and for medication abuse.
Purpose of review:
Transgender individuals experience unique health disparities but are the subject of little focused health research. This manuscript reviews current literature on transgender medical and mental health outcomes and proposes research priorities to address knowledge gaps.
Recent findings:
Published research in transgender healthcare consists primarily of case reports, retrospective and cross-sectional studies, involving largely European settings. Challenges to US-based transgender health research include a diverse population where no single center has sufficient patient base to conduct clinical research with statistical rigor. Treatment regimens are heterogeneous and warrant study for best practices. Current research suggests increased mortality and depression in transgender individuals not receiving optimal care, and possibly a modest increase in cardiovascular risk related to hormone therapy. Current evidence does not support concerns for hormone-related malignancy risk.
Summary:
The priorities for transgender medical outcomes research should be to determine health disparities and comorbid health conditions over the life span, along with the effects of mental health, medical, and surgical interventions on morbidity and mortality. Specific outcomes of interest based on frequency in the literature, potential severity of outcome, and patient-centered interest, include affective disorders, cardiovascular disease, malignancies, fertility, and time dose-related responses of specific interventions.
Transsexual subjects are individuals who have a desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex, and a wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex. They seek to develop the physical characteristics of the desired gender, and should undergo an effective and safe treatment regimen. The goal of treatment is to rehabilitate the individual as a member of society in the gender he or she identifies with. Sex reassignment procedures necessary for the treatment of transsexual patients are allowed in our country, at Medical Services that have a multidisciplinary team composed of a psychologist, a social worker, a psychiatrist, an endocrinologist and surgeons (gynecologists, plastic surgeons, and urologists). Patients must be between 21 to 75 years old and in psychological and hormonal treatment for at least 2 years. Testosterone is the principal agent used to induce male characteristics in female transsexual patients, and the estrogen is the chosen hormone used to induce the female sexual characteristics in male transsexual patients. Based on our 15 years of experience, we can conclude that testosterone and estradiol treatment in physiological doses are effective and safe in female and male transsexual patients, respectively.
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.
The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts of the world are necessary. The SOC articulate standards of care while acknowledging the role of making informed choices and the value of harm reduction approaches. In addition, this version of the SOC recognizes that treatment for gender dysphoria i.e., discomfort or distress that is caused by a discrepancy between persons gender identity and that persons sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics) has become more individualized. Some individuals who present for care will have made significant self-directed progress towards gender role changes or other resolutions regarding their gender identity or gender dysphoria. Other individuals will require more intensive services. Health professionals can use the SOC to help patients consider the full range of health services open to them, in accordance with their clinical needs and goals for gender expression.
This study evaluates the short- and long-term cardiovascular- and cancer-related morbidities during cross-sex hormone therapy in a large sample of trans persons.
A specialist centre cross-sectional study compared 214 trans women (male-to-female transsexual persons) and 138 trans men (female-to-male trans persons) to an age- and gender-matched control population (1 to 3 matching). Participants were on cross-sex hormone therapy for an average of 7.4 years. We assessed physical health and possible treatment-related adverse events using questionnaires.
Five percent of trans women experienced venous thrombosis and/or pulmonary embolism during hormonal therapy. Five of these adverse events occurred during the first treatment year, while another 3 occurred during sex reassignment surgery. TRANS WOMEN EXPERIENCED MORE MYOCARDIAL INFARCTIONS COMPARED TO CONTROL WOMEN (P=0.001) BUT A SIMILAR PROPORTION COMPARED TO CONTROL MEN. CEREBROVASCULAR DISEASE PREVALENCE WAS HIGHER IN TRANS WOMEN COMPARED TO CONTROL MEN (P=0.03). TRANS MEN HAD SIMILAR RATES OF MYOCARDIAL INFARCTION AND CEREBROVASCULAR DISEASE COMPARED TO CONTROL MALE AND FEMALE SUBJECTS. TYPE 2 DIABETES PREVALENCE WAS HIGHER IN BOTH TRANS MEN AND WOMEN COMPARED TO THEIR RESPECTIVE CONTROLS, WHEREAS CANCER RATES WERE SIMILAR TO CONTROL MEN AND WOMEN.CONCLUSION: Morbidity rate during cross-sex hormone therapy was relatively low, especially in trans men. We observed a higher prevalence of venous thrombosis, myocardial infarction, cerebrovascular disease and type 2 diabetes in trans women compared to control population. Trans men had similar morbidity rates compared to controls aside from increased type 2 diabetes prevalence.
The formation of gender identity is a singularly complex part of an individual's development. When this process is further complicated by conflict between experienced gender and assigned gender or by medical conditions affecting sex development,lifetime consequenses can result.
Gender Dysphoria and Disorders of Sex Development offers up-to-date understanding and interventions in one comprehensive volume featuring expert coverage of developmental trajectories, comorbid conditions, current medical and psychological treatments, and an instructive history of professional conceptualizations of gender dysphoria (GD) and disorders of sex development (DSD).
Introductory chapters analyze the roles of sex hormones and genetics in brain organization and introduce an integrative biopsychosocial model of gender development. A framework for age-appropriate treatment for children (including guidelines for working with infants), adolescents, and adults is the book's core. And as sex reassignment continues to prove a viable option for some individuals, the latest endocrine-based and surgical interventions for adults are discussed as well. Throughout, this groundbreaking reference work emphasizes empirical knowledge, compassion, a strong ethical base, and coordinated interdisciplinary care. Among the topics covered:
• Genetic aspects of gender identity development and gender dysphoria
• Psychosexual development in individuals with disorders of sex development
• Gender identity diagnoses: history and controversies
• Early medical intervention in adolescents with gender dysphoria
• Psychiatric comorbidity in adults with gender identity problems
• The impact of stigma on transgender identity development and mental health
For researchers and clinicians, including psychologists, psychiatrists, endocrinologists, and surgeons working in the field of GD and DSD, Gender Dysphoria and Disorders of Sex Development provides a unique view of the state of the field and recommendations for future research and care.
Background
Hirsutism is frequently expressed in women affected by polycystic ovary syndrome (PCOS). The efficacy of oral contraceptive pill (OC) plus anti-androgens in the treatment of its severe expression is controversial due to the lack of randomized double-blind long-term studies.
Aim
The primary outcome was the reduction of hirsutism in PCOS women objectively measured by videodermoscopy (VD) on the androgen-sensitive skin areas assessed by the modified Ferriman&Gallwey (mF&G) total score, after 12 months of therapy with OC+Bicalutamide (BC) versus OC plus placebo (P). The secondary outcomes were to evaluate tolerability of bicalutamide and body composition as well as the occurrence of adverse events.
Design
This was an experimental, phase III, prospective, multicenter, randomized, double-blind, placebo-controlled trial. Patients were evaluated at the baseline visit, at the sixth and twelfth month during treatment and six months after its end.
Population study
70 women with classic PCOS (severe hirsutism, oligo-anovulation and ovarian PCO morphology) were evaluated.
Treatment protocols
Patients received a therapy with OCP+BC (50mg/die) or OCP+P for 12 months.
Results
The RM-ANOVA showed that both treatments were effective in reducing hirsutism: the OCP+BC group had a higher reduction compared to the OCP+P group. No adverse effects were described during treatment except an increase in total cholesterol and LDL in the OCP+BC group.
Conclusions
The association of OCP+BC is well tolerated and significantly more effective than OCP alone in treating severe hirsutism. Furthermore, we suggest a combined use of VDI and mF&G to evaluate correctly the effects of androgen deprivation therapy for hirsutism.
Context
Breast development is a key feature of feminization and therefore important to transwomen (male-to-female transgender persons). However, it is not exactly known when breast development starts after initiating cross-sex hormone therapy (CHT) and how much growth may be expected of CHT alone.
Objective
To investigate breast development in centimeters and bra cup-sizes in transwomen during their first year of CHT, and whether clinical or laboratory parameters predict the breast development.
Design
This study was performed as part of the European Network for the Investigation of Gender Incongruence (ENIGI), which is a prospective multicenter cohort study.
Setting
Specialized gender clinics in Amsterdam, Ghent, and Florence.
Participants
All transwomen who completed the first year of CHT (n=229) were eligible for analyses.
Intervention
Cross-sex hormone therapy.
Main outcome measures
Breast development in centimeter and cup-size.
Results
The median age of the included transwomen was 28 years (range 18;69 years). Mean breast – chest difference increased from 4.1±2.9cm at baseline to 7.9±3.1cm after one year of CHT, mainly resulting in less than an AAA cup-size (48.7%). Main breast development occurred in the first six months of therapy. Serum estradiol levels did not predict breast development after one year CHT (first quartile: +3.6cm(95% CI +2.7;+4.5cm), second quartile: +3.2cm(95% CI +2.3;+4.2cm), third quartile: +4.4(95% CI +3.5;+5.3cm), fourth quartile: +3.6cm(95% CI +2.7;+4.5cm)).
Conclusion
This study shows that after one year of CHT breast development is modest and occurs primarily in the first six months. No clinical or laboratory parameters were found that predict breast development.
Objectives
Gender identity disorder is defined as a strong and persistent cross-gender identification that is associated with a remarkable uneasiness of living in an incongruent gender (gender dysphoria). We performed a retrospective study on the hormonal and metabolic effects of cross-sex hormone therapy (CSHT) in a small cohort of transgender patients.
Study design
Retrospective study.
Mean outcome measures
Hormonal and biochemical parameters at baseline (i.e. before commencement of CSHT) and while on CSHT in 32 patients (21 male to female [MtF], 11 female to male [FtM]) referred to our Endocrinology Unit for gender dysphoria between January 2012 and February 2017.
Results
Compared with baseline, in MtF patients systolic blood pressure, red cell count, hemoglobin, hematocrit and total testosterone decreased significantly, while 17-β estradiol and SHBG increased significantly and trendwise significantly, respectively. In FtM patients, total testosterone, red cell count, hemoglobin, hematocrit, creatinine, ɣ-glutamyl transferase and alkaline phosphatase increased significantly, while fasting plasma glucose decreased trendwise significantly. In MtF patients 17-β estradiol correlated positively with SHBG and alkaline phosphatase and negatively with total cholesterol and HDL-c, whereas total testosterone correlated positively with systolic blood pressure, red cell count and hematocrit, and negatively with SHBG. In FtM patients total testosterone correlated positively with creatinine and alkaline phosphatase, while 17-β estradiol correlated positively with HDL-c.
Conclusions
Our data are partly in line with other studies concerning the impact of CSHT on hormonal and metabolic parameters in transgender people. Metabolic changes appear, overall, to be modest, confirming the safety of CSHT.
Background
The impact of sex steroids on bone health in transgender individuals is unclear.
Methods
A comprehensive search of several databases to April 7th 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CI).
Results
Thirteen studies evaluating 639 transgender individuals were identified (392 male to female [MTF], 247 female to male [FTM]). In FTM individuals and compared to baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck or total hip BMD when assessed at 12 and 24 months. In MTF individuals and compared to baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm²; 95% CI, 0.03, 0.06 g/cm²) and 24 months (0.06 g/cm²; 95% CI, 0.04, 0.08 g/cm²). Fracture rates were evaluated in a single cohort of 53 MTF/53FTM individuals with no events at 12 months. The body of evidence is mostly derived from observational studies at moderate risk of bias.
Conclusion
In FTM individuals, masculinizing hormone therapy does not seem to be associated with significant changes in BMD whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient important outcomes such as fracture risk is uncertain.
Background:
Whether patients on testosterone replacement therapy undergoing noncardiac surgery have an increased risk of postoperative in-hospital mortality and cardiovascular events remains unknown. We therefore sought to identify the impact of testosterone replacement on the incidence of a composite of postoperative in-hospital mortality and cardiovascular events in men undergoing noncardiac surgery.
Methods:
Data from male American Society of Anesthesiologists I through IV patients 40 yr or older who underwent noncardiac surgery between May 2005 and December 2015 at the Cleveland Clinic (Cleveland, Ohio) main campus were included. The primary exposure was preoperative testosterone use. The primary outcome was a composite of postoperative in-hospital mortality and cardiovascular events. We compared patients who received testosterone and those who did not using propensity score matching within surgical procedure matches.
Results:
Among 49,273 patients who met inclusion and exclusion criteria, 947 patients on testosterone were matched to 4,598 nontestosterone patients. The incidence of in-hospital mortality was 1.3% in the testosterone group and 1.1% in the nontestosterone group, giving an odds ratio of 1.17 (99% CI, 0.51 to 2.68; P = 0.63). The incidence of myocardial infarction was 0.2% in the testosterone group and 0.6% in the nontestosterone group (odds ratio = 0.34; 99% CI, 0.05 to 2.28; P = 0.15). Similarly, no significant difference was found in stroke (testosterone vs. nontestosterone: 2.0% vs. 2.1%), pulmonary embolism (0.5% vs. 0.7%), or deep venous thrombosis (2.0% vs. 1.7%).
Conclusions:
Preoperative testosterone is not associated with an increased incidence of a composite of postoperative in-hospital mortality and cardiovascular events.
Transgender medicine is a relatively new field in health care, with only a small amount of evidence-based literature available for reference. This is especially true for the older adult population, for whom most information must be extrapolated from younger adults. Be it a newly transitioned older adult or a transgendered individual who has been undergoing hormonal therapy for many years, it is important that healthcare professionals be aware of the significant effects that transgender pharmacotherapy can have on older adults. Healthcare providers must also recommend appropriate preventative screenings to transgendered persons.
Transgender women experience lifelong gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. They often seek hormone therapy, with or without surgery, to improve their gender dysphoria and to better align their physical and psychological features with a more feminine gender role. Some of the desired physical changes from oestrogen and anti-androgen therapy include decreased body and facial hair, decreased muscle mass, breast growth, and redistribution of fat. Overall the risks of treatment are low, but include thromboembolism, the risk of which depends on the dose and route of oestrogen administration. Other associated conditions commonly seen in transgender women include increased risks of depression and osteoporosis. The risk of hormone-sensitive cancer seems to be low in transgender women, with no increased risk of breast cancer compared with women and no increase in prostate cancer when compared with men. The evidence base for the care of transgender women is limited by the paucity of high-quality research, and long-term longitudinal studies are needed to inform future guidelines.
The World Professional Association for Transgender Health (WPATH) standards of care for transsexual, transgender, and gender non-conforming people (version 7) represent international normative standards for clinical care for these populations. Standards for optimal individual clinical care are consistent around the world, although the implementation of services for transgender populations will depend on health system infrastructure and sociocultural contexts. Some clinical services for transgender people, including gender-affirming surgery, are best delivered in the context of more specialised facilities; however, the majority of health-care needs can be delivered by a primary care practitioner. Across high-income and low-income settings alike, there often remains a dearth of educational programming for health-care professionals in transgender health, although the best evidence supports introducing modules on transgender health early during clinical education of clinicians and allied health professionals. While these challenges remain, we review the increasing evidence and examples of the defined roles of the mental health professional in transgender health-care decisions, effective models of health service provision, and available surgical interventions for transgender people.
Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function.
To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents.
Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis.
Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry.
GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased.
Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment.
Testosterone therapy is a cornerstone of medical treatment for transgender men who choose to undergo it. The goal of testosterone therapy is usually to achieve serum testosterone concentrations in the male reference range. Testosterone has several desired effects as well as undesired and unknown effects. The desired effects include increased facial and body hair, increased lean mass and strength, decreased fat mass, deepening of the voice, increased sexual desire, cessation of menstruation, clitoral enlargement, and reductions in gender dysphoria, perceived stress, anxiety, and depression. Achievement of these goals comes with potential undesired effects and risks including acne, alopecia, reduced HDL cholesterol, increased triglycerides, and a possible increase in systolic blood pressure. An additional benefit of testosterone therapy (with or without mastectomy) is a reduced risk of breast cancer. Most of the effects of testosterone start to develop within several months of starting therapy, although facial hair and alopecia continue to develop after 1 year. A major limitation in the study of testosterone therapy for transgender men is a paucity of high-quality data due to a shortage of randomised controlled trials (partly because of ethical issues), few prospective and long-term studies, the use of suboptimum control groups, loss to follow-up, and difficulties in recruitment of representative samples of transgender populations.
Objective:
To retrospectively compare the effectiveness and safety of 1-year administration of transdermal oestradiol (TE) with cyproterone acetate (CPA) or leuprolide acetate (Leu) in transwomen.
Design, patients and measurements:
Forty transwomen received 50 mg of CPA daily orally (n = 20; CPA+E group) or Leu at a dose of 3·75 mg i.m. monthly (n = 20; Leu+E group) in combination with TE at a dose of 1 or 2 mg daily for 1 year. Reproductive hormones, biochemical parameters, body composition and bone mineral density were assessed.
Results:
LH, FSH and total testosterone levels were significantly decreased by month three of hormone administration in both groups and continued to decrease until month 12; the decrease in LH levels in the first 12 months was significantly faster in the Leu+E group. Prolactin was significantly increased at month 12 in the CPA+E group only. Bone metabolism parameters and bone mineral density as detected at DEXA did not significantly change in either group, apart from a statistically significant increase in parathyroid hormone after 52 weeks of Leu administration. Total cholesterol and HDL-cholesterol were significantly increased in the Leu+E group and reduced in the CPA+E group. No major adverse effects were registered in either group. Psychological well-being parameters did not differ between the two groups.
Conclusions:
Preliminary results from this retrospective observational pilot study suggest that CPA and Leu in combination with TE are equally effective in the suppression of gonadotrophins and testosterone levels over 1 year. Whether the different effects on HDL-cholesterol may lead to long-term different cardiovascular safety profiles remains to be defined.
Sex hormones have been proposed as a possible risk factor for the development and growth of meningiomas. Hormonal therapy plays a fundamental role in the treatment of male-to-female transgenders and needs to be continued after sex reassignment surgery. Usually, this treatment leads to no adverse events; however, its impact on hormone-related tumours such as meningiomas has not yet been investigated thoroughly. We searched our cohort of 2810 male-to-female transgender persons, who have been treated between 1975 and 2010, for patients with meningiomas. Additionally, we conducted a literature search in PubMed and EMBASE. We found three patients who developed a meningioma in male-to-female transgenders in addition to five other who have been described in the literature. These findings support the role of female sex hormones in the development and growth of meningiomas. This might be an underrepresentation, because there is no standard protocol for screening for meningiomas in this population and meningiomas can remain asymptomatic for several years. We observed regression of multiple meningiomas in one of these three cases after discontinuation of hormonal treatment. The decision to stop or continue cross-sex hormone therapy in these particular patients should be carefully reconsidered individually.
Objective:
Transgender patients may seek hormone therapy to induce physical changes to simulate their expressed or experienced gender. However, many providers are uncomfortable prescribing transgender hormones due to fears over safety. The goal of this study was to determine if transgender hormone therapy with estrogen and spironolactone for male-to-female (MtF) patients or with testosterone for female-to-male (FtM) patients had adverse anthropomorphic or metabolic effects.
Methods:
This retrospective chart review study analyzed changes over time for 33 MtF and 19 FtM endocrine clinic patients at an academic endocrine practice with follow up for up to 18 months after hormone initiation.
Results:
Compared to baseline labs obtained prior to initiation of hormone therapy statistically significant changes for the MtF cohort included an increase in HDL and decrease in creatinine; however, triglycerides did not show a statistically significant change. In the FtM cohort, there was a statistically significant increase in body mass index, creatinine, hemoglobin, and hematocrit. These changes were minimal for both cohorts.
Conclusion:
In our practice, hormone therapy was found to be safe in this retrospective study.
To examine the clinical and basic studies regarding persistent adverse effects associated with 5α reductase inhibitor treatment for androgenetic alopecia.
Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation. Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase. Finally, 5α reductase inhibitors have also been found to alter semen parameters in healthy men.
Multiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5α reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.
The treatment of transwomen relies on the combined administration of antiandrogens or GnRH analogues to suppress androgen production and thereby reduce male phenotypic characteristics together with estrogens to develop female characteristics. In transwomen synthetic estrogens such as ethinylestradiol, as well as conjugated equine estrogens (CEE), should be avoided in order to minimize thromboembolic risks especially in older transwomen and in those with risk factors. Currently available short and long-term safety studies suggest that cross-sex hormonal therapy (CHT) can be considered safe in transwomen improving the well-being and quality of life of these individuals. Long-term monitoring should aim to decrease cardiovascular risks and should include prostate and breast cancer screenings. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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.
To describe weight, body mass index (BMI), blood pressure (BP), lipids, and hormone levels in transgender women and men presenting for initiation of cross-sex hormone therapy at a community clinic in the United States.
Twenty-three transgender women (persons assigned male at birth who identify as female and want to use estrogen to develop female secondary sex characteristics) and 34 transgender men (persons assigned female at birth who identify as male and want to use testosterone to develop male secondary sex characteristics) presenting for initiation of hormone therapy at a community health center were enrolled. Body mass index, BP, lipids, and sex hormone levels were measured at baseline and 6 months. Persistence of menses at 6 months in transgender men was recorded.
Sixteen transgender women and 31 transgender men completed the study. Baseline and 6-month median BPs and lipid values were within a normal clinical range. Median systolic BP in transgender women dropped from baseline 130.5 mmHg (interquartile range 11.5) to 120.5 mmHg (interquartile range 15.5) at 6 months (P=.006). Testosterone levels remained elevated in 33% and estradiol (E2) levels were supratherapeutic in 19% of transgender women at 6 months. Median BMI for transgender men was 29.1 kg/m (interquartile range 11.2) at baseline and 30.0 kg/m (interquartile range 11.4) at 6 months (P=.024). Six-month total testosterone levels were subtherapeutic in 32% and E2 levels remained elevated in 71% of transgender men.
In transgender women, estrogen therapy, with or without antiandrogen therapy, was associated with lower BP. In transgender men, testosterone therapy was associated with increased BMI. The study had insufficient power to detect other associations. Monitoring of hormone levels to guide therapy appears to be useful. LEVEL OF EVIDENCE:: III.
Cross-sex hormone treatment of transsexual people may be associated with the induction and growth stimulation of hormone-related malignancies. We report here five cases of breast cancer, three in female-to-male (FtoM) transsexual subjects and two in male-to-female (MtoF) transsexual subjects. In the general population the incidence of breast cancer increases with age and with duration of exposure to sex hormones. This pattern was not recognised in these five transsexual subjects. Tumours occurred at a relatively young age (respectively, 48, 41, 41, 52 and 46 years old) and mostly after a relatively short span of time of cross-sex hormone treatment (9, 9-10 but in one after 30 years). Occurrence of breast cancer was rare. As has been reported earlier, breast tumours may occur in residual mammary tissue after breast ablation in FtoM transsexual people. For adequate treatment and decisions on further cross-sex hormone treatment it is important to have information on the staging and histology of the breast tumour (type, grade and receptor status), with an upcoming role for the androgen receptor status, especially in FtoM transsexual subjects with breast cancer who receive testosterone administration. This information should be taken into account when considering further cross-sex hormone treatment.
© 2015 Blackwell Verlag GmbH.
Transgenderism and gender dysphoria are becoming more prevalent diagnoses and the patient population is increasing. Primary care practitioners, endocrinologists, and mental health professionals are all part of the medical care team that treats these patients, but family and internal medicine physicians continue to deliver the care in the long term. Transgender medicine is not a strong part of the medical curriculum, and recent studies have shown there is anxiety in new physicians in taking care of these patients. There are many aspects to transgender care that involve different specialities, including, but not limited to, mental health, primary care, endocrinology, surgery, and obstetrics and gynecology. This article gives an overview of the current guidelines for standards of care of transgender patients as delineated by the World Professional Association for Transgender Health and the Endocrine Society.
Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton.
The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy.
In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-beta estradiol 100 mu g/24 h for patients > 45 years old), both combined with oral cyproterone acetate 50 mg daily.
Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05).
Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.
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 **;**:**–**.
Introduction
There is a scarcity of research into the use of non-physician-sourced cross-sex hormones in the transgender population. However, when medication is not prescribed by health professionals, users' knowledge of such medication may be adversely affected.
Aims
This study aims to define the prevalence of Internet-sourced sex hormone use in a population attending for initial assessment at a gender identity clinic, to compare the prevalence between gender-dysphoric men and women, and to compare knowledge of cross-sex hormone side effects between users who source cross-sex hormones from medical doctors and those who source them elsewhere.
Methods
In the first part of the study, a cross-sectional design is used to measure the overall prevalence of sex hormone use among individuals referred to a gender clinic. The second part is a questionnaire survey aiming at measuring sex hormone knowledge among individuals referred to this clinic.
Main Outcome Measures
Main outcome measures were (i) categorical data on the prevalence and source of cross-sex hormone use and (ii) knowledge of sex hormone side effects in a population referred to a gender clinic.
Results
Cross-sex hormone use was present in 23% of gender clinic referrals, of whom 70% sourced the hormones via the Internet. Trans men using testosterone had a sex hormone usage prevalence of 6%; one-third of users sourced it from the Internet. Trans women had a sex hormone usage prevalence of 32%; approximately 70% of users sourced hormones from the Internet. Cross-sex hormone users who sourced their hormones from physicians were more aware of side effects than those who used other sources to access hormones.
Conclusion
One in four trans women self-prescribe cross-sex hormones before attending gender clinics, most commonly via the Internet. This practice is currently rare among trans men. Self-prescribing without medical advice leaves individuals without the knowledge required to minimize health risks.
Individuals with gender dysphoria experience distress associated with incongruence between their biologic sex and their identified gender. Gender dysphoric natal males receive treatment with antiandrogens and estrogens to become feminized (transsexual females), whereas natal females with gender dysphoria receive treatment with androgens to become masculinized (transsexual males). Because of the permanence associated with cross-sex hormone therapy (CSHT), adolescents diagnosed with gender dysphoria receive gonadotropin-releasing hormone analogs to suppress puberty. High rates of depression and suicide are linked to social marginalization and barriers to care. Behavior, emotional problems, depressive symptoms, and global functioning improve in adolescents receiving puberty suppression therapy. Gender dysphoria, psychological symptoms, quality of life, and sexual function improve in adults who receive CSHT. Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in both transsexual males and females, but preliminary data suggest that CSHT does not increase the risk. Cancer screenings for individuals of both natal and transitioned sexes should occur as recommended. More long-term studies are needed to ensure that CSHT regimens with the best outcomes can continue to be prescribed for the transsexual population.
Compelling studies have demonstrated that "gender identity"-a person's inner sense of self as male, female, or occasionally a category other than male or female-is not simply a psychosocial construct, but likely reflects a complex interplay of biologic, environmental, and cultural factors. An increasing number of pre-adolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"-i.e. the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender-dysphoric in early or middle childhood and still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"-clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender". Studies have shown that such distress may be ameliorated by a "gender-affirming" model of care. While endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development (DSD), many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a DSD. The goals of this article are to review studies that shed light on the biologic underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth.
Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-adminstration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.
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
Hormonal treatment of transgender people is becoming a normal part of medicine, though numbers of subjects remain small because of low prevalence. Information on treatment is scattered and this review brings together the latest information on treatment goals and potential side-effects of androgen treatment of female-to-male transsexual subjects.
Androgen treatment of female-to-male transsexuals is usually uneventful, with a good patient compliance. Goals of hormonal treatment are elimination of secondary sex characteristics of the female sex and induction of those of the male sex. Completion takes approximately 2 years. Hormonal treatment is eventually followed by surgical ablation of breasts and removal of uterus and ovaries. Phalloplasty may be considered. Concerns are the sequelae of hypogonadism following surgery, such as loss of bone mass. Contrary to earlier expectations, there is no increase in cardiovascular disease. (Hormone-related) cancers are rare, but vaginal, cervical, endometrial carcinomas have been reported. Cancers of the breasts are of greater concern and have been found in residual mammary tissue after breast ablation. So far, androgen treatment has not raised major safety concerns. Regrets about changing sex have not been reported.
Testosterone treatment of female-to-male transsexuals is effective and well tolerated.
In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women.
The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development.
A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014.
Effects of cross-sex hormone therapy and progestogens on breast development in trans women.
Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size.
Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. Wierckx K, Gooren L, and T'Sjoen G. Clinical review: Breast development in trans women receiving cross-sex hormones. J Sex Med **;**:**-**.
This review examines recent developments regarding the care of the elderly transgender patient. There is scant clinical or other relevant information related to this topic, as the phenomenon of gender incongruity has been largely misunderstood and underreported. It is important that guidelines for appropriate and sensitive care be established, as this population is proliferating due to media attention and greater access to care.
A preponderance of evidence exists establishing that gender nonconforming elders are subject to discriminatory healthcare treatment. Agencies that serve the elderly are rife with policies and practices that resist acknowledging the needs of this population. Most heathcare and service providers have little experience with this group and limited understanding of non-normative gender identification. Barriers to treatment amplify the challenges of ageing for the transgender person and can lead to nondisclosure of clinically relevant personal information.
Increasing numbers of ageing transgender individuals will be interfacing with health and care providers. Many of these individuals will require medical and surgical interventions for gender dysphoria. Therefore, a concise enunciation of guidelines and standards of care applicable to these elderly, and training of primary care and specialists to provide such care are necessary. Education for nurses, social workers, administrators and others who comprise the comprehensive care system must be mandatory. Finally, institutions and agencies must adapt and become inclusive of the spectrum of diverse individuals found across the changing social landscape.
Discussion of short and long-term issues of cross-hormone treatment of transgender individuals in the light of recent literature.
Gender nonconformity has been depathologized and replaced by gender dysphoria in the Diagnostic and Statistical Manual of Mental Disorders version V.Safety of cross-sex hormone treatment is still a matter of debate, but the latest findings in literature are quite reassuring about short-term and long-term effects. No dramatic changes in recommendations for treatment have emerged in the past years, and for the most part, clinical work is based on Endocrine Society Clinical Guidelines published in 2009.
Most recent findings agreed on the importance of maintaining cross-sex hormone serum concentration within the physiological range, avoiding or limiting maximum peaks and troughs.Treatment must be highly individualized and transitioning patients need to be engaged in a 'clinical contract' with the physician in order to ensure compliance with prescribed treatments.Although overall mortality appears to be higher among transgender individuals, this in not attributed to hormonal treatment but to other causes mostly related to lifestyle habits.
Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons.
This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons.
A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons).
Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction.
In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02).
HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons. Wierckx K, Elaut E, Van Hoorde B, Heylens G, De Cuypere G, Monstrey S, Weyers S, Hoebeke P, and T'Sjoen G. Sexual desire in trans persons: Associations with sex reassignment treatment. J Sex Med **;**:**-**.
Administration of cross-sex hormones to male-to-female transsexual subjects, usually oestrogens + often anti-androgens, such as cyproterone acetate, carries a risk of venous thromboembolism (VTE). VTE usually occurs in the first year of oestrogen administration. Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer, but people who take hormones without medical supervision use often oral contraceptives containing ethinyl oestradiol, many times in overdose. Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE. Other oral oestrogens should not be overdosed, and transdermal oestrogen is to be preferred. Thrombosis prophylaxis for surgery is mandatory. It seems advisable to stop hormone use at least 2 weeks before major surgery, to be resumed only after 3 weeks following full mobilisation.
Gender dysphoria is a sense of incongruity between an individual's self-identified gender and their birth gender. Diagnosis is made in accordance with the Diagnostic and Statistical Manual of Mental Disorders and treatment first involves psychiatric therapy which can help determine a patient's true goals in regards to achieving their gender identity. Patients who wish to transition to the opposite sex must undergo a supervised "real life" test and often are treated with hormonal therapy to develop physical characteristics consistent with their gender identity. Sex reassignment surgery is an option for patients who wish to transition completely. Transpatients face many barriers when it comes to basic health needs including education, housing and health care. This is a result of long-standing marginalization and discrimination against this community. Because of these barriers, many patients do not receive the proper health care that they need. Additionally, because of certain high-risk behaviors as well as long-term hormonal therapy, transpatients have different routine health care needs that should be addressed in the primary care setting. Gynecologists play an important role in caring for transgender patients and should be knowledgeable about the general principles of transgender health.
Sexual differentiation in mammals is largely driven by the presence of androgen in males and their absence in females. The presence of androgens induces a number of irreversible changes in males: prenatally, the genital differentiation; during puberty, the development of secondary sex characteristics - the larger facial bones, hand, feet and height in males. A large number of metabolic variables are influenced by sex hormones and consequently show difference between men and women, and this helps to explain differences in pathologies, such as cardiovascular disease, bone fractures and auto immune disease. There is some recent evidence that some sex differences in brain functions are not mediated by sex hormones, but by-products of genes located on the X and Y chromosomes. This communication reviews the results of administration of cross-sex hormone treatment to transsexual persons transitioning to the other sex. Natal males are treated with anti-androgens+oestrogens and natal females with testosterone. This provides a unique opportunity to study which metabolic functions are not irreversibly sex-differentiated but are determined by the prevailing milieu of sex steroids. The insights gained with these studies should lead to a better appreciation of the role of sex steroids in cardiovascular disease and diabetes mellitus which presently do not receive due attention.