Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome

Context: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. Objective: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. Design and Setting: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. Participants and interventions: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. Results: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) μg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 μg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value. Conclusions: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice

Ovarian tissue cryopreservation in female-to-male transgender people: insights into ovarian histology and physiology after prolonged androgen treatment

Female-to-male transgender people (trans men) are faced with the risk of losing their reproductive potential owing to gender-affirming hormone treatment and genital reconstructive surgery. This observational, prospective cohort study investigates the effect of prolonged androgen therapy on their ovarian histology and fertility preservation perspectives. Hormone serum levels, ovarian histology and cumulus-oocyte complexes (COC) of 40 trans men were analysed at the moment of hysterectomy with bilateral oophorectomy in the context of genital reconstructive surgery after testosterone treatment (58.18 ± 26.57 weeks). In the cortex, most follicles were primordial (68.52% total follicle count) compared with 20.26% intermediate and 10.74%primary follicles. Few secondary follicles (0.46%) and a single antral follicle were found in the sections analysed. In total, 1313 COC were retrieved from the medulla of 35 patients (37.51 ± 33.58 COC per patient). Anti-Müllerian hormone serum levels were significantly correlated with number of COC (Rs 0.787, P < 0.001). After 48 h in-vitro maturation, 34.30% metaphase II oocytes were obtained, with 87.10% having a normal spindle structure. In conclusion, the cortical follicle distribution in trans men, after more than a year of testosterone treatment, seems to be surprisingly normal. This work confirms the presence and in-vitro maturation potential of cumulus-oocyte complexes

Antimüllerian hormone levels decrease in female-to-male transsexuals using testosterone as cross-sex therapy

Objective: To investigate the effect of hormonal androgenic treatment on antimullerian hormone (AMH) serum levels in female-to-male (FtM) transsexuals. Polycystic ovary syndrome (PCOS) is associated with elevated AMH levels. Some hypothesize that the high AMH level is a consequence of androgen-induced excessive development of small antral follicles. However, this role of androgens is not yet clear. Design: Observational, prospective, cohort study. Setting: Tertiary academic medical center. Patient(s): Twenty-two FtM transsexuals, healthy native females receiving cross-sex hormone therapy/androgenic treatment. Intervention(s): Androgenic treatment with testosterone (T) and an aromatase inhibitor while endogenous hormone secretion was suppressed with the use of a GnRH agonist. Main Outcome Measure(s): Hormone concentrations were measured before and after androgenic treatment (administration of T and aromatase inhibitor). Measured hormones: AMH, inhibin B, T, androstenedione, DHEAS, E-2, SHBG, LH, and FSH. Result(s): AMH concentrations were significantly lower after androgenic treatment (4.4 +/- 4.4 mg/L vs. 1.4 +/- 2.1 mg/L). Androgenic treatment resulted in a strong suppression of AMH secretion over a relative short period of 16 weeks. Conclusion(s): Our data underscore the likely important role of androgens in the dynamics of folliculogenesis. It challenges the idea that androgens induce high AMH levels, which is gaining more interest nowadays as an important particular PCOS feature. This strong decline furthermore indicates that AMH must be interpreted in the context of other reproductive endocrine conditions. Clinical Trial Registration Number: NTR2493. (C) 2015 by American Society for Reproductive Medicine

Anti-Müllerian hormone levels in adolescence in relation to long-term follow-up for presence of polycystic ovary syndrome

Context: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. Objective: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. Design and Setting: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. Participants and interventions: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. Results: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) μg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 μg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value. Conclusions: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice

Endometrial thickness assessed by transvaginal ultrasound in transmasculine people taking testosterone compared with cisgender women

Research question: What is the endometrial thickness of endometrium exposed to testosterone in transmasculine people compared with unexposed endometrium in cisgender women as determined by transvaginal ultrasound (TVU)? Design: Single centre, cross-sectional cohort study conducted the Centre of Expertise on Gender Dysphoria in Amsterdam. Between 2013 and 2015, transmasculine people scheduled for gender affirming surgery (GAS) were included in this study after they provided informed consent. They were undergoing gender affirming hormone therapy (testosterone) for at least 1 year. Endometrial thickness (mm) was measured by TVU in transmasculine people, immediately before their GAS while under general anaesthesia. Cisgender control women from the general population underwent the exact same TVU measurements in an outpatient clinical setting on cycle days 2–5. Result: Fifty-one transmasculine people and 77 controls were included. The mean duration of testosterone use was 30.2 months (SD 8.8). Endometrial thickness was significantly lower in transmasculine people compared with cisgender women: median 3.9 mm (interquartile range [IQR] 2.8–5.1) and 4.9 mm (IQR 4.0–6.3), respectively (P < 0.001), after correcting for confounding factor (current gonadotrophin releasing hormone agonist use). Conclusions: Endometrial thickness in transmasculine people exposed to testosterone is significantly lower compared with cisgender women without testosterone exposure. These results suggest an absence of endometrial proliferation by exogenous testosterone

Effects of long-term exogenous testosterone administration on ovarian morphology, determined by transvaginal (3D) ultrasound in female-to-male transsexuals

STUDY QUESTION Does long-term exogenous testosterone administration result in polycystic ovarian morphology (PCOM), determined by (3D) transvaginal ultrasound (TVU) in female-to-male transsexuals (FtMs). SUMMARY ANSWER Long-term exogenous testosterone administration in FtMs does not result in PCOM determined by (3D) TVU. WHAT IS KNOWN ALREADY The role of androgens in the pathophysiology of polycystic ovary syndrome (PCOS) is still unclear. From animal studies, intra-ovarian androgens have been suggested to disturb folliculogenesis, through a pro-atretic effect on growing follicles. It remains debatable whether exogenous androgens induce PCOM in humans. In the past histomorphologic studies indicated that androgen administration in FtMs could cause PCO-like changes. However, ultrasound morphology is an established criterion for PCOS, TVU data of ovaries after prolonged androgen exposure are lacking. STUDY DESIGN, SIZE, DURATION Prospective, observational, case-control study, in an academic setting, performed in 2014-2015, including 56 FtMs and 80 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS The study population consisted of adult FtMs treated with long-term testosterone, as part of their cross-sex hormone treatment, and scheduled for sex-reassignment surgery (bilateral salpingo-oophorectomy). Prior to the operation, under anaesthetics TVU measurements (3D transvaginal probe 3-9 MHz; HD11, Philips Ultrasound, Inc.) of the ovaries were performed. The control group consisted of females from a general population who underwent the same TVU and analysis. Antral follicle count (AFC) (3D) and ovarian volume (3D) were calculated using specialized software. PCOM was defined as AFC of 12 or more follicles (2-10 mm) in at least one ovary. MAIN RESULTS AND THE ROLE OF CHANCE Prevalence rates of PCOM were not significantly different in the FtMs compared to controls, determined by (3D) TVU: 32.1% (17/53) versus 30.7% (23/75), P = 0.87. LIMITATIONS, REASONS FOR CAUTION Testosterone levels in FtMs are supraphysiological, and may not be comparable to the testosterone levels in women with PCOS. However, we applied a unique and ethically acceptable opportunity of exploring the effects of androgens on human ovaries. WIDER IMPLICATIONS OF THE FINDINGS This first explorative study shows that long-term exogenous testosterone administration in adult women does not seem to induce PCOM determined by TVU. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER The trial was registered at the Dutch Trial Register (www.trialregister.nl), registration number NTR4784