Effects of adult male rat feminization treatments on brain morphology and metabolomic profile.

Body feminization, as part of gender affirmation process of transgender women, decreases the volume of their cortical and subcortical brain structures. In this work, we implement a rat model of adult male feminization which reproduces the results in the human brain and allows for the longitudinal investigation of the underlying structural and metabolic determinants in the brain of adult male rats undergoing feminization treatments. Structural MRI and Diffusion Tensor Imaging (DTI) were used to non-invasively monitor in vivo cortical brain volume and white matter microstructure over 30 days in adult male rats receiving estradiol (E2), estradiol plus cyproterone acetate (CA), an androgen receptor blocker and antigonadotropic agent (E2 + CA), or vehicle (control). Ex vivo cerebral metabolic profiles were assessed by 1H High Resolution Magic Angle Spinning NMR (1H HRMAS) at the end of the treatments in samples from brain regions dissected after focused microwave fixation (5 kW). We found that; a) Groups receiving E2 and E2 + CA showed a generalized bilateral decrease in cortical volume; b) the E2 + CA and, to a lesser extent, the E2 groups maintained fractional anisotropy values over the experiment while these values decreased in the control group; c) E2 treatment produced increases in the relative concentration of brain metabolites, including glutamate and glutamine and d) the glutamine relative concentration and fractional anisotropy were negatively correlated with total cortical volume. These results reveal, for the first time to our knowledge, that the volumetric decreases observed in trans women under cross-sex hormone treatment can be reproduced in a rat model. Estrogens are more potent drivers of brain changes in male rats than anti-androgen treatment.

Kidney Transplantation in Transgender Patients.

PURPOSE OF REVIEW: Kidney transplantation and gender affirmation treatments are becoming increasingly more prevalent due to advances in technology. However, there is a paucity of data regarding kidney transplantation in transgender patients. Interesting considerations must be made in this patient population, since there are many hormonal interactions with kidney function and the transplantation process. RECENT FINDINGS: The diagnosis of estimated glomerular filtration rate (eGFR), preoperative assessment/counseling, decreased testosterone levels in a transgender male to female patient, increased estrogen/progesterone in a female to male patient, and drug side effects all have important and unique implications for kidney transplant recipients. Kidney transplantation can be safely and effectively managed in transgender patients with special considerations in eGFR calculations, mental health/lifestyle counseling, and drug interactions.

Sex, Gender, and Transgender: Metabolic Impact of Cross Hormone Therapy.

Most preclinical and clinical, animal, and human research has been biased with respect to sex and even more so with respect to gender. In fact, little is known about the impact of sex and even less about the influence of gender on overall metabolic processes. The National Institutes of Health has recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes and to include gender as variables influencing physiological processes such as metabolism. It is therefore critical to understand and appreciate how to incorporate sex and gender in preclinical and clinical research in order to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. In this chapter, we define sex and gender and discuss when sex and gender are not aligned, such as that which occurs in transgender individuals, and how this impacts metabolic processes. We discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes rather than focusing on their relative contributions to metabolism in isolation. This knowledge will optimize therapies specific for individuals which need to encompass sex and gender.

METABOLIC EFFECTS OF HORMONE THERAPY IN TRANSGENDER PATIENTS.

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 the initiation of hormone therapy, significant changes for the MtF cohort included an increase in high-density lipoprotein (HDL) and decrease in creatinine; however, triglycerides did not show a statistically significant change. In the FtM cohort, there were significant increases in body mass index, creatinine, hemoglobin, and hematocrit. Although statistically significant, these changes were minimal for both cohorts. CONCLUSION: In our practice, hormone therapy was found to be safe in this retrospective study.

Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of Transsexuals do not Alter Serum Cholesterol Acceptor Capacity.

INTRODUCTION: Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available. AIM: The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages. METHODS: Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models. MAIN OUTCOME MEASURES: CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells). RESULTS: Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC. CONCLUSIONS: Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis.

Hormone and genetic study in male to female transsexual patients.

BACKGROUND: Data of the literature demonstrated controversial results of a correlation between transsexualism and genetic mutations. AIM: To evaluate the hormone and gene profile of male-female (M-F) transsexual. SUBJECTS AND METHODS: Thirty M-F transsexuals aged 24-39. Seventeen had already undergone sex reassignment surgery, 13 were awaiting. All subjects had been undergoing estrogen and antiandrogen therapy. We studied hormones of the hypothalamus- pituitary-testicular axis, thyroid and adrenal profile, GH basal and after GHRH stimulation, IGF-I. The gene study analyzed SRY, AR, DAX1, SOX9, AZF region of the Y chromosome. RESULTS: Pre-surgery subjects had elevated PRL, reduced testosterone and gonadotropins. Post-surgery subjects showed reduced androgens, a marked increase in LH and FSH and normal PRL. Cortisol and ACTH were similar to reference values in pre- and post-surgery patients. There was a marked increase in the baseline and post-stimulation GH values in 6 of the 13 pre-surgery patients, peaking at T15. IGF-I was similar to reference values in both groups except for one post-surgery patient, whose level was below the normal range. There were no polymorphisms in the amplified gene region for SOX9, and a single nucleotide synonimous polymorphism for DAX1. No statistically significant differences were seen in the mean of CAG repeats between controls and transsexual subjects. SRY gene was present in all subjects. Qualitative analysis of the AZFa, AZFb, and AZFc regions did not reveal any microdeletions in any subject. CONCLUSIONS: This gender disorder does not seem to be associated with any molecular mutations of some of the main genes involved in sexual differentiation.

A study of changes in bone metabolism in cases of gender identity disorder.

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

The effect of circulating estradiol concentrations on gonadotropin secretion in young and old castrated male-to-female transsexuals.

CONTEXT: In aging men, circulating testosterone (T) declines which is associated with an increase in the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) , albeit insufficient to maintain T at its original level. It has been speculated that a higher sensitivity of the hypothalamus and/or pituitary for the feedback effect of circulating sex hormones in older men is responsible. OBJECTIVE: To compare the effect of experimentally varied plasma levels of estradiol on the LH and FSH secretion in young and old castrated male-to-female transsexuals, in almost absence of T. DESIGN, SUBJECTS, AND INTERVENTIONS: In 10 healthy, young (mean age 37.6 ± 6.2 years) and 11 healthy, old (mean age 68.1 ± 7.0) male-to-female transsexuals after gonadectomy plasma estradiol levels were experimentally varied with estradiol patches (the first week 100 µg/day patches, the second week 50 µg/day, the third week 25 µg/day and the fourth week no patch was applied) and plasma levels of LH and FSH were monitored after every week. RESULTS: Mean plasma bioavailable estradiol (E2) levels in the two groups ranged between 13.6 and 104 pmol/l. LH and FSH were inversely related to peripheral estradiol levels, were lower in the old group at all time points reaching statistical significance in the last week of the study when no patch was applied and estradiol levels were extremely low. CONCLUSIONS: The results of this study do not support the hypothesis of an age related increasing sensitivity of the hypothalamo-pituitary compartment for the negative feedback of E2, but suggest a deficient feed-forward drive in older male-to-female transsexuals.

The role of androgens in clitorophallus development and possible applications to transgender patients.

BACKGROUND: The clitorophallus, or glans, is a critical structure in sexual development and plays an important role in how gender is conceptualized across the life span. This can be seen in both the evaluation and treatment of intersex individuals and the use of gender-affirming masculinizing therapies to help those born with a clitoris (small clitorophallus with separate urethra) enlarge or alter the function of that structure. OBJECTIVES: To review the role of testosterone in clitorophallus development from embryo to adulthood, including how exogenous testosterone is used to stimulate clitorophallus enlargement in masculinizing gender-affirming therapy. MATERIALS AND METHODS: Relevant English-language literature was identified and evaluated for data regarding clitorophallus development in endosex and intersex individuals and the utilization of hormonal and surgical masculinizing therapies on the clitorophallus. Studies included evaluated the spectrum of terms regarding the clitorophallus (genital tubercle, clitoris, micropenis, penis). RESULTS: Endogenous testosterone, and its more active metabolite dihydrotestosterone, plays an important role in the development of the genital tubercle into the clitorophallus, primarily during the prenatal and early postnatal periods and then again during puberty. Androgens contribute to not only growth but also the inclusion of a urethra on the ventral aspect. Exogenous testosterone can be used to enlarge the small clitorophallus (clitoris or micropenis) as part of both intersex and gender-affirming care (in transmasculine patients, up to 2 cm of additional growth). Where testosterone is insufficient to provide the degree of masculinization desired, surgical options including phalloplasty and metoidioplasty are available. DISCUSSION AND CONCLUSION: Endogenous testosterone plays an important role in clitorophallus development, and there are circumstances where exogenous testosterone may be useful for masculinization. Surgical options may also help some patients reach their personal goals. As masculinizing gender-affirming care advances, the options available for clitorophallus modifications will likely continue to expand and improve.

Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender-confirming surgery: An observational study.

BACKGROUND: Anti-Müllerian hormone and inhibin B are produced by Sertoli cells. Anti-Müllerian hormone secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility. Identification of markers reflecting the presence of germ cells is of particular relevance in trans persons undergoing gender-affirming hormone therapy in order to offer individualized fertility preservation methods. OBJECTIVES: Serum and intratesticular inhibin B and anti-Müllerian hormone values were assessed and related to clinical features, laboratory values, and germ cell numbers. MATERIALS AND METHODS: Twenty-two trans women from three clinics were included. As gender-affirming hormone therapy, 10-12.5 mg of cyproterone acetate plus estrogens were administered. Height, weight, age, medication, and treatment duration were inquired by questionnaires. Serum luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol were measured by immuno-assays. Serum and intratesticular inhibin B and anti-Müllerian hormone were measured by commercially available ELISAs. Spermatogonia were quantified as spermatogonia per cubic millimeter testicular tissue applying a morphometric analysis of two independent testicular cross-sections per individual after MAGEA4 immunostaining. RESULTS: Patients with high inhibin B levels presented with a higher number of spermatogonia (*p < 0.05). Furthermore, mean serum inhibin B was associated with low age (*p < 0.05), low follicle-stimulating hormone (*p < 0.05), and low testosterone (*p < 0.05). Serum anti-Müllerian hormone, however, was not related to spermatogonial numbers. It correlated with high testosterone (*p < 0.05) and high follicle-stimulating hormone (*p < 0.05) only. High intratesticular inhibin B was accompanied by high luteinizing hormone (*p < 0.05), high follicle-stimulating hormone (**p < 0.01), and high testosterone levels (**p < 0.01). Higher the intratesticular anti-Müllerian hormone levels, the longer gender-affirming hormone therapy was administered (*p < 0.05). DISCUSSION AND CONCLUSION: Serum inhibin B levels indicate the presence of spermatogonia, whereas anti-Müllerian hormone seems not to be a reliable marker concerning germ cell abundance.

Lipoprotein subtypes after testosterone therapy in transmasculine adolescents.

Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 µmol/L vs 2.7 ± 1.2 µmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men.

Estradiol-driven metabolism in transwomen associates with reduced circulating extracellular vesicle microRNA-224/452.

OBJECTIVE: Sex steroid hormones like estrogens have a key role in the regulation of energy homeostasis and metabolism. In transwomen, gender-affirming hormone therapy like estradiol (in combination with antiandrogenic compounds) could affect metabolism as well. Given that the underlying pathophysiological mechanisms are not fully understood, this study assessed circulating estradiol-driven microRNAs (miRs) in transwomen and their regulation of genes involved in metabolism in mice. METHODS: Following plasma miR-sequencing (seq) in a transwomen discovery (n = 20) and validation cohort (n = 30), we identified miR-224 and miR-452. Subsequent systemic silencing of these miRs in male C57Bl/6 J mice (n = 10) was followed by RNA-seq-based gene expression analysis of brown and white adipose tissue in conjunction with mechanistic studies in cultured adipocytes. RESULTS: Estradiol in transwomen lowered plasma miR-224 and -452 carried in extracellular vesicles (EVs) while their systemic silencing in mice and cultured adipocytes increased lipogenesis (white adipose) but reduced glucose uptake and mitochondrial respiration (brown adipose). In white and brown adipose tissue, differentially expressed (miR target) genes are associated with lipogenesis (white adipose) and mitochondrial respiration and glucose uptake (brown adipose). CONCLUSION: This study identified an estradiol-drive post-transcriptional network that could potentially offer a mechanistic understanding of metabolism following gender-affirming estradiol therapy.

Valuing the Vulnerable - The Important Role of Transgender Communities in Biomedical Research.

Every cell has a genetic sex that is determined at the time of fertilization. However, the natal sex of cells may not match the hormonal environment in which they reside in transgender individuals. This discordance provides a unique opportunity to study the short- and long-term effects across a range of cellular functions, health conditions, physiologic processes and psychosocial outcomes to the benefit of transgender and cisgender communities. While there is a growing body of knowledge as the literature on sex differences in virtually every organ system accumulates, there remains a paucity of data on the effect of cross hormonal therapy on cellular function in transgender individuals. Beyond cellular function, the effect of cross hormonal therapy on neuroanatomy, the interpretation of neuropsychological assessments or even the effect of daily stressors of stigma and discrimination on long-term neurocognitive function remain unclear. In 2011 the Institute of Medicine indicated that transgender adults were an understudied population and in critical need of more biomedical and population health research, yet the experience of stigma, discrimination, microaggressions, limited access to culturally competent care continue to make this an unfulfilled mandate. In addition to using a life course perspective, it is essential to identify research gaps and formulate a responsive research agenda while maintaining scientific rigor and respectful involvement of the population under study. None of this, however, will enhance the participation of transgender communities in biomedical research until the transgender and biomedical research communities can engage in open, respectful and bidirectional dialogue. From respectful, sensitive and appropriate health care to culturally competent research engagement from study inception to data dissemination, transgender communities can make an important and valuable contribution to biomedical research. Inclusion of their voices at all levels, including investigators from transgender communities, are essential to advance this much overdue scientific agenda. Transgender, cisgender and the biomedical research communities will all benefit from a more inclusive and expansive research agenda.

Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People.

OBJECTIVE: The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study. RESEARCH DESIGN AND METHODS: Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated. RESULTS: In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01) increased. Fasting insulin (-1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (-1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (-1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (-0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (-2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (-1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] × min; P < 0.01), but fasting glucose (-0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged. CONCLUSIONS: In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.

Testosterone effects on functional amygdala lateralization: A study in adolescent transgender boys and cisgender boys and girls.

The influence of testosterone on the development of human brain lateralization has been subject of debate for a long time, partly because studies investigating this are necessarily mostly correlational. In the present study we used a quasi-experimental approach by assessing functional brain lateralization in trans boys (female sex assigned at birth, diagnosed with Gender Dysphoria, n = 21) before and after testosterone treatment, and compared these results to the functional lateralization of age-matched control groups of cisgender boys (n = 20) and girls (n = 21) around 16 years of age. The lateralization index of the amygdala was determined with functional magnetic resonance imaging (fMRI) during an emotional face matching task with angry and fearful faces, as the literature indicates that boys show more activation in the right amygdala than girls during the perception of emotional faces. As expected, the lateralization index in trans boys shifted towards the right amygdala after testosterone treatment, and the cumulative dose of testosterone treatment correlated significantly with amygdala lateralization after treatment. However, we did not find any significant group differences in lateralization and endogenous testosterone concentrations predicted rightward amygdala lateralization only in the cis boys, but not in cis girls or trans boys. These inconsistencies may be due to sex differences in sensitivity to testosterone or its metabolites, which would be a worthwhile course for future studies.

Prevalence of low bone mass in relation to estrogen treatment and body composition in male-to-female transsexual persons.

Bone health is a parameter of interest in the daily follow-up of male-to-female (M --> F) transsexual persons both before and after sex reassignment surgery (SRS) due to an intensely changing hormonal milieu. We have studied body composition, areal, geometric, and volumetric bone parameters, using DXA and peripheral quantitative computed tomography at different sites in 50 M --> F transsexual persons, at least 3 yr after the start of the hormonal treatment and 1 yr after SRS. In this cross-sectional study, hormone levels and markers of bone metabolism were assessed using immunoassays. Prevalence of low bone mass as defined by a Z-score < or = -2.0 according to DXA criteria was 26% at lumbar spine and 2% at the total hip. We found no major differences in hormonal parameters between participants with a Z-score < or = or > -2.0. Markers of bone turnover were comparable between subjects with or without low bone mass, indicating a stable bone turnover at the time of investigation. No significant differences in bone size or density were observed between patients on transdermal vs. oral estrogens. Low bone mass is not uncommon in M --> F transsexual persons. Smaller bone size, and a strikingly lower muscle mass compared with men appear to underlie these findings.

Transmasculine Hormone Therapy.

Prescribing gender-affirming hormonal therapy in transgender men (TM) not only induces desirable physical effects but also benefits mental health. In TM, testosterone therapy is aimed at achieving cisgender male serum testosterone to induce virilization. Testosterone therapy is safe on the short term and middle term if adequate endocrinological follow-up is provided. Transgender medicine is not a strong part of the medical curriculum, although a large number of transgender persons will search for some kind of gender-affirming care. Because hormonal therapy has beneficial effects, all endocrinologists or hormone-prescribing physicians should be able to provide gender-affirming hormonal care.

Hormone Therapy in Children and Adolescents.

For children and adolescents with gender dysphoria, an interdisciplinary care team is essential for proper diagnosis and appropriate treatment. For children who present with gender dysphoria, once puberty begins, they can be treated with gonadotropin-releasing hormone analogs to stop pubertal progression. This allows for further gender exploration, relief of dysphoria, and better cosmetic outcomes by avoiding the physical changes associated with puberty of the gender assigned at birth. After pubertal suppression, the individual may opt to proceed with puberty or start treatment with gender-affirming hormones.

What has sex got to do with it? The role of hormones in the transgender brain.

Sex differences and hormonal effects in presumed cisgender individuals have been well-studied and support the concept of a mosaic of both male and female "characteristics" in any given brain. Gonadal steroid increases and fluctuations during peri-puberty and across the reproductive lifespan influence the brain structure and function programmed by testosterone and estradiol exposures in utero. While it is becoming increasingly common for transgender and gender non-binary individuals to block their transition to puberty and/or use gender-affirming hormone therapy (GAHT) to obtain their desired gender phenotype, little is known about the impact of these manipulations on brain structure and function. Using sex differences and the effects of reproductive hormones in cisgender individuals as the backdrop, we summarize here the existing nascent neuroimaging and behavioral literature focusing on potential brain and cognitive differences in transgender individuals at baseline and after GAHT. Research in this area has the potential to inform our understanding of the developmental origins of gender identity and sex difference in response to gonadal steroid manipulations, but care is needed in our research questions and methods to not further stigmatize sex and gender minorities.

Transfeminine Hormone Therapy.

Transgender women often seek hormone therapy to attain feminine physical features congruent with their gender identity. The aim of feminizing hormone therapy (FHT) is to provide suppression of endogenous testosterone and to maintain estradiol levels within the normal female range. Overall, FHT is safe if provided under supervision of an experienced health care provider and has been shown to improve quality of life. Data on care of transgender women are scarce and high-quality evidence-based recommendations are lacking. This article aims to review the published literature on FHT and provide guidance to clinicians caring for transgender women.