Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology

Ikeda, Keiko; Baba, Tsuyoshi; Noguchi, Hiroko; Nagasawa, Kunihiko; Endo, Toshiaki; Kiya, Tamotsu; Saito, Tsuyoshi

doi:10.1093/humrep/des385

Cited by 143 publications

(65 citation statements)

References 22 publications

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“…Pathological conditions in humans that cause hyperandrogenism, for example, congenital adrenal hyperplasia (38) and studies in transsexual women treated with high doses of testosterone (39,40,41,42) show conflicting outcomes.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Design: Prospective case-control study. Methods: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E 1 ), estradiol (E 2 ), estriol (E 3 )) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Results: At 20 weeks of gestation: T (PZ0.019) and ADION (PZ0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E 1 , E 2 , and E 3 were not different. Maternal concentration at birth: T (PZ0.004) and ADION (PZ0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E 1 , E 2 and E 3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E 2 , E 3 , and AMH between the PCOS mothers and the controls respectively. E 1 was lower in girls from PCOS mothers (PZ0.007). Conclusions: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

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Section: Discussionmentioning

confidence: 99%

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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“…In human studies, increases in the numbers of atretic follicles were observed in the ovaries of androgen-administrated FTM persons [3,8,9]. The treatment periods were fairly long, averaging 38 months [3], 21 months [8] and 35 months [9], respectively. Consistent with those reports, we observed increases in the numbers of atretic follicles with long-term DHEA treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperandrogenism is the primary manifestation of PCOS, and it is the excess androgen exposure that appears to be the cause of the PCO morphology. However, we have shown that long-term administration of androgens for female-to-male transsexual (FTM) persons leads to an increase in the number of atretic follicles, not to the PCO morphology [3]. …”

Section: Introductionmentioning

confidence: 99%

“…In another study, reproductive-age rhesus monkeys receiving high doses of androgen in the short-term were equally as likely to exhibit an increase in small follicles as monkeys receiving low doses over a longer term [5]. In addition, examination of the histology of ovaries in androgen-administered FTM patients revealed increased follicular atresia, though the morphogenesis of polycystic ovaries is controversial [3,8,9]. Judging from these findings, it appears that androgen administration may impact folliculogenesis and subsequent ovarian morphology, leading to the development of the PCO morphology, but the effects of exogenous androgens on ovarian morphology may vary depending on the period and duration of the androgen administration and the amount of hormone administered.…”

Section: Introductionmentioning

confidence: 99%

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Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

et al. 2014

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BackgroundHyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression.MethodsWe divided 30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control groups were injected with 0.2 ml of sesame oil for the corresponding lengths of time. Resected ovaries were sectioned and examined to determine follicle numbers at each developmental stage, and immunostained to assess AMH expression.ResultsOn day 7, follicle numbers and AMH expression levels at each developmental stage of follicle growth were similar in the respective control and DHEA groups. On day 15, the total follicle number (P = 0.041), the percentage of primordial follicles (P = 0.039) and AMH expression were significantly greater in the DHEA than the control group. On day 30, the percentages of primordial (P = 0.005), primary (P = 0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA group, whereas the percentage of intermediary follicles (early pre-antral, late preantral, and early antral follicles) was significantly lower in the DHEA group (P = <0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively in the primordial (P = 0.0413) and late antral follicles (p = 0.028).ConclusionsAndrogen administration increases AMH production in a process that regulates the growth of primordial follicles. That is, androgen-induced AMH expression provides local negative feedback to folliculogenesis augmented by androgen.

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“…5,7 Ovarian cancer risk appears to be very low; there have been only three cases reported following testosterone therapy for a prolonged period. 58 Exogenous testosterone treatment is also associated with the development of a polycystic morphology, [63][64][65] the implications of this in the longer term are unknown and so oophorectomy is usually performed at the time of hysterectomy.…”

Section: Cancer Riskmentioning

confidence: 99%

A review of the physical and metabolic effects of cross-sex hormonal therapy in the treatment of gender dysphoria

Seal

2015

Ann Clin Biochem

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This review focuses on the effect that cross-gender sex steroid therapy has on metabolic and hormonal parameters. There is an emphasis on those changes that result in significant clinical effects such as the positive effects of the development of secondary sexual characteristics and negative effects such as haemostatic effects and thromboembolism in transwomen or dyslipidaemia in transmen. There is also a description of the current hormonal regimens used at the largest UK gender identity clinic. The overall safety of these treatments in the context of long-term outcome data is reviewed.

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Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology

Abstract: Our results are at variance with those of earlier studies and suggest that excessive androgen exposure in women of reproductive age may not be a factor in the pathogenesis of PCOS.

Cited by 143 publications

References 22 publications

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

A review of the physical and metabolic effects of cross-sex hormonal therapy in the treatment of gender dysphoria

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