The effect of testosterone on ovulatory function in transmasculine individuals

Taub, Rebecca L.; Ellis, Simon; Neal‐Perry, Genevieve; Magaret, Amalia; Prager, Sarah; Micks, Elizabeth

doi:10.1016/j.ajog.2020.01.059

Cited by 78 publications

(42 citation statements)

References 22 publications

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“…In the present study, 25% (10 of 40) of patients showed cycling activity with proliferative and secretory endometrium and presence of corpora lutea. These findings are concordant with the reports in the literature indicating long-term testosterone users can still experience ovulatory events 18 and unplanned pregnancies can occur in transmasculine individuals receiving testosterone; therefore, testosterone should not be used as a contraceptive method. 19 Androgens have been shown to be important regulators of folliculogenesis and also play a role in polycystic ovary syndrome.…”

Section: Discussionsupporting

confidence: 90%

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery

Lin

Hernández

Marcus

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs. Objective.— To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens. Design.— This is an institutional review board–approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists. Results.— Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18–56) and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy. Conclusions.— A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population.

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Section: Discussionsupporting

confidence: 90%

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery

Lin

Hernández

Marcus

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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“…Although TRT is the mainstay of gender-affirming medical care in TGM [ 77 , 78 ] and secondary amenorrhea is common in testosterone-treated individuals [ 79 – 81 ], the exact mechanism of menstrual suppression is unknown. Although one recent study observed high rates of anovulation in TGM undergoing TRT [ 82 ], few studies have assessed the effects of testosterone on ovarian follicle structure and function. Given this limited knowledge, the current standard of care is to counsel patients interested in gender-affirming testosterone therapy after female sex assignment at birth regarding the potential for decreased fertility [ 77 , 78 , 83 – 86 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse

et al. 2021

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Background In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown. Methods In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system. Results Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis). Conclusions Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.

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“…regard to onset of anovulatory state, and breakthrough ovulation may also influence bleeding patterns. 12 The contribution of endogenous hormonal production to breakthrough bleeding is also supported by the successful use of GnRHa to suppress breakthrough bleeding in 2 patients; however, it is unclear why other centrally suppressing agents (eg, combined oral contraceptive pills) were not as efficacious. Some of this may be due to the small numbers, as amenorrhea is not universal among individuals treated with menstrual suppression (other than GnRHa), even in those patients not on T-GAHT.…”

Section: Jid: Pedadomentioning

confidence: 99%

“…4 , 12 In addition to the hysterectomy data, another recent study of ovulation patterns in TGD patients on T-GAHT found that 26% of those who were on testosterone for a median duration of 11 months (range 1-60 months) had breakthrough bleeding. 12 There remain insufficient data on the frequency of breakthrough bleeding in patients on long-term T-GAHT, including in patients who had initially experienced successful induction of amenorrhea. Additionally, there is a lack of data on breakthrough bleeding patterns in TGD AYA who have used puberty blockers or other menstrual suppression agents early in adolescence prior to initiating testosterone.…”

Section: Introductionmentioning

confidence: 99%

Breakthrough Bleeding in Transgender and Gender Diverse Adolescents and Young Adults on Long-Term Testosterone

Grimstad

Kremen

Shim

et al. 2021

Journal of Pediatric and Adolescent Gynecology

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The effect of testosterone on ovulatory function in transmasculine individuals

Cited by 78 publications

References 22 publications

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery

Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse

Breakthrough Bleeding in Transgender and Gender Diverse Adolescents and Young Adults on Long-Term Testosterone

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