Transient elevated serum prolactin in trans women is caused by cyproterone acetate treatment

Purpose: Hormone treatment in trans women in Europe usually consists of the administration of estrogens and antiandrogens, for example, cyproterone acetate (CPA). Mild serum prolactin elevations during follow-up are attributed to estrogen therapy. This analysis evaluates whether CPA contributes to the elevation of prolactin in trans women receiving gender affirming hormones. Methods: This study is part of the endocrine part of the European Network for the Investigation of Gender Incongruence (ENIGI). Belgian data were selected for this substudy. Trans women who initiated gender affirming hormone treatment and underwent orchiectomy were prospectively evaluated. Trans women were treated with oral CPA 50 mg in combination with estrogen substitution. Postsurgery, estrogen was reinitiated in an unchanged dose. Sex steroids, gonadotropins, and prolactin were compared at baseline, pre- and postsurgery in patients receiving orchiectomy, and at baseline, 12, and 18 months in patients who did not undergo orchiectomy. Results: One hundred and seven trans women participated in this analysis, with a mean age of 31.5 years. An increase in serum prolactin levels was seen in the group undergoing orchiectomy (23.72 mu g/L) and not undergoing orchiectomy (23.05 mu g/L) at the preoperative and 12-month visit, compared with baseline (9.42 mu g/L, P = 0.002 and 9.94 mu g/L, P < 0.001, respectively). After orchiectomy, a decline in prolactin levels (10.17 mu g/L, P < 0.001) occurred. Conclusions: CPA is likely to cause a temporary increase in serum prolactin, with prolactin levels returning to normal after orchiectomy and CPA discontinuation

Breast development in transwomen after 1 year of cross-sex hormone therapy : results of a prospective multicenter study

Context: Breast development is a key feature of feminization and therefore important to transwomen (male-to-female transgender persons). It is not exactly known when breast development starts after initiating cross-sex hormone therapy (CHT) and how much growth may be expected. Objective: To investigate breast development in transwomen during their first year of CHT and whether clinical or laboratory parameters predict breast development. Design: This study was performed as part of the European Network for the Investigation of Gender Incongruence, which is a prospective multicenter cohort study. Setting: Gender clinics in Amsterdam, Ghent, and Florence. Participants: Transwomen who completed the first year of CHT (n = 229). Intervention: CHT. Main Outcome Measures: Breast development in centimeter and cup size. Results: The median age of the included transwomen was 28 years (range, 18 to 69). Mean breast-chest difference increased to 7.9 +/- 3.1 cm after 1 year of CHT, mainly resulting in less than an AAA cup size (48.7%). Main breast development occurred in the first 6 months of therapy. Serum estradiol levels did not predict breast development after 1 year of CHT (first quartile, 3.6 cm [95% confidence interval (CI), 2.7 to 4.5], second quartile, 3.2 cm [95% CI, 2.3 to 4.2], third quartile, 4.4 cm [95% CI, 3.5 to 5.3], and fourth quartile, 3.6 cm [95% CI, 2.7 to 4.5]). Conclusion: This study shows that, after 1 year of CHT, breast development is modest and occurs primarily in the first 6 months. No clinical or laboratory parameters were found that predict breast development

Bone mineral density increases in trans persons after 1 year of hormonal treatment : a multicenter prospective observational study

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol

Variation in sensitivity and rate of change in body composition : steps toward individualizing transgender care

Objective: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. Design and methods: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. Results: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). Conclusions: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy

Incident Diabetes Risk Is Not Increased in Transgender Individuals Using Hormone Therapy

CONTEXT: In trans women receiving hormone therapy, body fat and insulin resistance increases, with opposite effects in trans men. These metabolic alterations may affect the risk of developing type 2 diabetes in trans women and trans men. CONTEXT: We aimed to compare the incidence of type 2 diabetes of adult trans women and trans men during hormone therapy with rates from their birth-assigned sex in the general population. METHODS: Retrospective data from the Amsterdam Cohort of Gender Dysphoria with transgender individuals on hormone therapy between 1972 and 2018 were linked to a nationwide health data registry. Because no central registry of diabetes is available, the occurrence of diabetes was inferred from the first dispense of a glucose-lowering agent. Standardized incidence ratios (SIR) were computed for trans women and trans men in comparison with the same birth sex from the general population. RESULTS: Compared with their birth-assigned sex in the general population, no difference in the incidence of type 2 diabetes mellitus was observed in trans women (N = 2585, 90 cases; SIR 0.94; 95% CI, 0.76-1.14) or trans men (N = 1514, 32 cases; SIR 1.40; 95% CI, 0.96-1.92). CONCLUSION: Despite studies reporting an increase in insulin resistance in feminizing hormone therapy and a decrease in insulin resistance in masculinizing hormone therapy, the incidence of diabetes in transgender individuals after initiation of hormone therapy was not different compared with the general population

The effect of transdermal gender-affirming hormone therapy on markers of inflammation and hemostasis

Background Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone therapy on markers of inflammation and hemostasis. Methods In this exploratory study, 48 trans women using estradiol patches plus cyproterone acetate (CPA) and 47 trans men using testosterone gel were included. They were between 18 and 50 years old and did not have a history of cardiovascular events. Measurements were performed before and after 3 and 12 months of hormone therapy. Results After 12 months, in trans women, systemic and endothelial inflammatory markers decreased (hs-CRP -66%, (95% CI -76; -53), VCAM-1-12%, (95% CI -16; -8)), while platelet activation markers increased (PF-4 +17%, (95% CI 4; 32), β-thromboglobulin +13%, (95% CI 2; 24)). The coagulation marker fibrinogen increased transiently, after 3 months (+15%, (95% CI 1; 32)). In trans men, hs-CRP increased (+71%, (95% CI 19; 145)); platelet activation and coagulation markers were not altered. In both trans women and trans men, leptin and adiponectin changed towards reference values of the experienced gender. Conclusions Platelet activation and coagulation marker concentrations increased in trans women using transdermal estradiol plus CPA, but not in trans men using testosterone. Also, concentrations of inflammatory markers decreased in trans women, while hs-CRP increased in trans men. Our results indicate that hormone therapy may affect hemostasis in transgender persons, which could be an underlying mechanism explaining the increased cardiovascular risk in this population

Bone geometry and trabecular bone score in transgender people before and after short- and long-term hormonal treatment

Background: Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT. Purpose: To investigate the bone geometry and TBS in adult transgender people at different time points, up to 25 years, of HT. Methods: A total of 535 trans women and 473 trans men were included, who were divided into three groups at time of their DXA: 20–29 years, 30–39 years, and 40–59 years. Subsequently, each group was divided into different HT durations: baseline, or after 5, 15, or 25 years of HT. Hip structure analysis was performed to measure subperiosteal width, endocortical diameter, average cortical thickness, and section modulus. TBS was calculated based on lumbar spine DXA images. Results: In trans women in all age groups and in young trans men, no differences were observed in periosteal width, endocortical diameter, average cortical thickness, and section modulus for different durations of HT. In trans men aged 40–59 years, subperiosteal width, endocortical diameter, and section modulus were slightly higher in the groups who were using HT compared to the (peri- or postmenopausal) baseline group. In younger trans women, TBS tended to be higher in those using HT compared to the baseline groups, and in older trans women TBS was higher in those using HT for 25 years versus baseline (+0.04, 95%CI +0.00; +0.08). In younger trans men, TBS tended to be lower in those who used HT compared to the baseline groups, and in older trans men TBS was lower in those using 5 years HT versus baseline (−0.05, 95%CI −0.08; −0.01). Conclusion: No differences in cortical bone geometry parameters were found during different HT-durations. TBS increased in trans women and decreased in trans men, indicating that estrogens have positive effects on TBS. These data may be helpful in determining what sex reference values for calculating T-scores and Z-scores in adult transgender people should be used

Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results from a Large Cohort Study

In hypogonadal/postmenopausal individuals, hormone therapy has been associated with an increased risk for cardiovascular events (CVEs). A steeply growing population that often receives exogenous hormones is transgender individuals. Although transgender individuals hypothetically have an increased risk of CVEs, there is little known about the occurrence of CVEs in this population.1 Therefore, we determined the incidences of acute/spontaneous strokes (ischemic/hemorrhagic, transient ischemic attack, or subarachnoid hemorrhage), myocardial infarctions (MIs), and venous thromboembolic events (VTEs) in transwomen and transmen receiving transgender hormone therapy (THT). Subsequently, we compared these incidences with those reported in women and men from the general population

The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment

© The Author(s) (2018). Benign brain tumours may be hormone sensitive. To induce physical characteristics of the desired gender, transgender individuals often receive cross-sex hormone treatment, sometimes in higher doses than hypogonadal individuals. To date, long-term (side) effects of cross-sex hormone treatment are largely unknown. In the present retrospective chart study we aimed to compare the incidence of common benign brain tumours: meningiomas, pituitary adenomas (non-secretive and secretive), and vestibular schwannomas in transgender individuals receiving cross-sex hormone treatment, with those reported in general Dutch or European populations. This study was performed at the VU University Medical Centre in the Netherlands and consisted of 2555 transwomen (median age at start of cross-sex hormone treatment: 31 years, interquartile range 23-41) and 1373 transmen (median age 23 years, interquartile range 18-31) who were followed for 23 935 and 11 212 person-years, respectively. For each separate brain tumour, standardized incidence ratios with 95% confidence intervals were calculated. In transwomen (male sex assigned at birth, female gender identity), eight meningiomas, one non-secretive pituitary adenoma, nine prolactinomas, and two vestibular schwannomas occurred. The incidence of meningiomas was higher in transwomen than in a general European female population (standardized incidence ratio 4.1, 95% confidence interval 1.9-7.7) and male population (11.9, 5.5-22.7). Similar to meningiomas, prolactinomas occurred more often in transwomen compared to general Dutch females (4.3, 2.1-7.9) and males (26.5, 12.9-48.6). Noteworthy, most transwomen had received orchiectomy but still used the progestogenic anti-androgen cyproterone acetate at time of diagnosis. In transmen (female sex assigned at birth, male gender identity), two cases of somatotrophinomas were observed, which was higher than expected based on the reported incidence rate in a general European population (incidence rate females = incidence rate males; standardized incidence ratio 22.2, 3.7-73.4). Based on our results we conclude that cross-sex hormone treatment is associated with a higher risk of meningiomas and prolactinomas in transwomen, which may be linked to cyproterone acetate usage, and somatotrophinomas in transmen. Because these conditions are quite rare, performing regular screenings for such tumours (e.g. regular prolactin measurements for identifying prolactinomas) seems not necessary