Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence.

In trans persons on gender-affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone-naïve trans persons. Gender-affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82-5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94-3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50-4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender-affirming hormonal treatment.

A European Network for the Investigation of Gender Incongruence: Endocrine Part.

INTRODUCTION: Cross-sex hormone therapy is an essential part of gender affirming treatment of transgender individuals. Studies systematically describing the physical and psychological effects of hormonal treatment of transgender persons are scarce. AIM: The aim of the current protocol is to evaluate clinical and side-effects of cross-sex hormonal treatment in trans persons. METHODS: The European Network for the Investigation of Gender Incongruence (ENIGI) is a multicenter prospective study. Because of the relatively low prevalence of the condition and small number of specialized centers, international collaboration is warranted. Four European treatment centers, Ghent, Oslo, Florence, and Amsterdam, developed a common study and treatment protocol. MAIN OUTCOME MEASURES: Outcome measures include hormonal and metabolic parameters, bone density, secondary sex and anthropometric characteristics, and physical and psychological well-being. RESULTS: Thus far, 333 trans women and 343 trans men have been included in the ENIGI Endocrine protocol. The study is still ongoing. CONCLUSION: In recent years, the number of trans persons seeking gender affirming treatment has increased. However, well-designed prospective studies evaluating safety and effectiveness of current hormonal treatment protocols are lacking. Therefore we started the ENIGI collaboration. In this article we give a detailed description of the study protocol, objectives, and design of the ENIGI Endocrine protocol.

Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI).

PURPOSE: To assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy. METHODS: In a prospective controlled study, we included 23 trans men (female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks). RESULTS: Before hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (-9.7%) (all P<0.001) and increased the levels of P1NP and CTX (both P<0.01). Areal and volumetric bone parameters remained largely unchanged apart from a small increase in trabecular vBMD at the distal radius and in BMD at the total hip in trans men (P=0.036 and P=0.001 respectively). None of these changes were observed in the control group. CONCLUSIONS: Short-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss.

Semen characteristics of transwomen referred for sperm banking before sex transition: a case series.

Transwomen (TW) can now turn to cryopreserve spermatozoa before gender reassignment (GR). The objective is to assess semen quality of TW and evaluate adequacy for assisted reproduction technology (ART). Pre-freezing (PF) and post-thaw (PT) semen parameters of 2 and PF data of 27 TW who were referred for sperm banking in Cleveland Clinic/USA and Ghent Center/Belgium, before GR, were retrospectively analysed. The study period was between February, 2003 and October, 2011. We also evaluated adequacy of 24-h PT data for ART. PF data of 29 TW, mean age of 28.9 years, showed high incidence of oligozoospermia (27.58%), asthenozoospermia (31%) and teratozoospermia (31%). Mean sperm concentration was 46.9 × 10(6) /ml, mean per cent motility was 42.9 and mean per cent sperm morphology (Kruger's) was 7.98. The 24-h PT data, for 2 TW, showed mean motility 22.4%, mean total motile sperm count 13.7 × 10(6) and total motile sperm concentration 8.7 × 106/ml. Single patient had used the frozen spermatozoon for intrauterine insemination (IUI) of a surrogate mother resulting in birth of healthy newborn. It is concluded that poor PF and 24-h PT semen quality is frequently seen among TW. As such, considerable proportion of TW should use more expensive method of ART, for example IVF/ICSI rather than inexpensive IUI.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

UNLABELLED: 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. PURPOSE: 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. METHODS: 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-ß estradiol 100 µg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. RESULTS: 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). CONCLUSIONS: 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.

Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study.

OBJECTIVE: This study evaluated the short- and long-term cardiovascular- and cancer-related morbidities during cross-sex hormone therapy in a large sample of trans persons. SUBJECTS AND METHODS: A specialist center cross-sectional study compared 214 trans women (male-to-female transsexual persons) and 138 trans men (female-to-male trans persons) with an age- and gender-matched control population (1-3 matching). The 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. RESULTS: Five percent of trans women experienced venous thrombosis and/or pulmonary embolism during hormone therapy. Five of these adverse events occurred during the first year of treatment, while another three occurred during sex reassignment surgery. Trans women experienced more myocardial infarctions than the control women (P=0.001), but a similar proportion compared with control men. The prevalence of cerebrovascular disease (CVD) was higher in trans women than in the control men (P=0.03). The rates of myocardial infarction and CVD in trans men were similar to the control male and female subjects. The prevalence of type 2 diabetes was higher in both trans men and women than in their respective controls, whereas the rates of cancer were similar compared with the 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, CVD, and type 2 diabetes in trans women than in the control population. Morbidity rates in trans men and controls were similar, with the exception of the increased prevalence of type 2 diabetes.

Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy.

OBJECTIVE: Cross-sex hormonal therapy and sex reassignment surgery (including gonadectomy) in transsexual persons has an impact on body composition and bone mass and size. However, it is not clear whether baseline differences in bone and body composition between transsexual persons and controls before cross-sex hormonal therapy play a role. DESIGN: A cross-sectional study with 25 male-to-female transsexual persons (transsexual women) before cross-gender sex steroid exposure (median age 30 years) in comparison with 25 age-matched control men and a male reference population of 941 men. MAIN OUTCOME MEASURES: Areal and volumetric bone parameters using respectively dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), body composition (DXA), grip strength (hand dynamometer), Baecke physical activity questionnaire, serum testosterone and 25-OH vitamin D. RESULTS: Transsexual women before cross-sex hormonal therapy presented with less muscle mass (p≤0.001) and strength (p≤0.05) and a higher prevalence of osteoporosis (16%) with a lower aBMD at the hip, femoral neck, total body (all p<0.001) and lumbar spine (p=0.064) compared with control men. A thinner radial cortex (p≤0.01) and lower cortical area at the radius and tibia (both p<0.05) was found in transsexual women vs. control men. Serum testosterone was comparable in all 3 groups, but 25-OH vitamin D was lower in transsexual women (p≤0.001). CONCLUSIONS: Transsexual women before the start of hormonal therapy appear to have lower muscle mass and strength and lower bone mass compared with control men. These baseline differences in bone mass might be related to a less active lifestyle.

Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy.

CONTEXT: Female-to-male transsexual persons (transsexual men) undergo extreme hormonal changes due to ovariectomy and testosterone substitution, allowing studies on sex steroid effects on bone geometry and physiology in the adult. OBJECTIVE: The objective of the study was to examine the effects of cross-gender sex steroid exposure on volumetric bone parameters in transsexual men. DESIGN: This was a cross-sectional study. SETTING: Participants were recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital (Ghent, Belgium). PARTICIPANTS: Fifty transsexual men after sex reassignment surgery with 50 age-matched control women and an additional 16 transsexual men before testosterone substitution and sex reassignment surgery with 16 control women participated in the study. MAIN OUTCOME MEASURES: The main outcome measures were areal and volumetric bone parameters using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, body composition (dual-energy X-ray absorptiometry), sex steroids, markers of bone turnover and grip strength. RESULTS: Before hormonal treatment, transsexual men had similar body composition and bone geometry as female controls. The transsexual men on long-term testosterone therapy, however, demonstrated a higher lean body mass and muscle mass and a greater grip strength as well as a lower body and subcutaneous fat mass and a larger waist and smaller hip circumference compared with female controls (all P < 0.001). We observed a larger radial cortical bone size (P < 0.001) and lower cortical volumetric bone mineral density at the radius and tibia (P < 0.05) in transsexual men on testosterone therapy. CONCLUSIONS: Transsexual men on testosterone substitution therapy present with a different body composition with more muscle mass and strength and less fat mass as well as an altered bone geometry with larger bones compared with female controls.