Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series

Grimstad, Frances; Fowler, Kylie; New, Erika P.; Ferrando, Cecile A.; Pollard, R.R.; Chapman, Graham; Gómez-Lobo, Veronica; Gray, M. L.

doi:10.1016/j.ajog.2018.12.021

Cited by 85 publications

(55 citation statements)

References 26 publications

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“…There are currently no contraindications to using estrogen-containing contraception in transmasculine individuals on testosterone hormone therapy, as previous studies show these individuals maintain blood estradiol levels within the expected range of transmasculine individuals using testosterone. 25,26 Yet the literature recommends that transmasculine individuals using testosterone avoid estrogen-containing contraceptives as to not counteract the masculinizing effects of testosterone. 27 The inconsistencies in the literature complicate provider counseling, underscoring the necessity for further research on the effects of combining estrogen contraceptives and testosterone therapy in transmasculine individuals.…”

Section: Discussionmentioning

confidence: 99%

Do Transgender and Gender Diverse Individuals Receive Adequate Gynecologic Care? An Analysis of a Rural Academic Center

2020

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The transgender population faces disparities accessing gynecologic health care services, especially in rural settings. There is limited knowledge among medical providers regarding transgender-specific gynecologic care. Methods: A retrospective chart review of 255 transgender and gender diverse patients at a rural, academic center and associated ambulatory clinics was performed. Demographics, insurance status, and utilization rates of screening services, including cervical cancer, breast cancer, human papillomavirus (HPV) vaccination status, and contraceptive status, were analyzed using descriptive statistics. These rates were compared with national rates of cisgender individuals. Chi-square tests were performed to assess the association of insurance status with receipt of services. Results: Prevalence of HPV vaccination was lowest among transgender men (20%) compared with transgender women (60%) and gender nonbinary/nonconfirming and gender diverse individuals (60%), p < 0.001. Our cohort was significantly less likely to receive Papanicolaou smears (51% vs. 81%, p < 0.05) and contraception (48% vs. 65%, p < 0.05) than cisgender individuals. Around 18% of transgender women had a documented pelvic examination in the past year. There was no significant difference in utilization rates based on insurance status. Conclusion: In our rural setting, there is lower utilization of gynecologic services among transgender and gender diverse individuals. Although participants in our study had high rates of access to insurance and health care providers, they still had lower rates of gynecologic screening and prevention services. To address these disparities, we advocate for developing transgender-specific gynecologic health maintenance guidelines, robust provider education, and an inclusive electronic medical record to ensure appropriate gynecologic health screening.

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Section: Discussionmentioning

confidence: 99%

Do Transgender and Gender Diverse Individuals Receive Adequate Gynecologic Care? An Analysis of a Rural Academic Center

2020

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“…(3) Importantly, the majority of studies have reported long-term androgen administration at high doses to women and transmen can induce endometrial atrophy (Chadha et al 1994, Perrone et al 2009) without stimulating endometrial proliferation (Zang et al 2007, Wood et al 2009, Simitsidellis et al 2018). However, a recent report on 94 transmasculine persons given testosterone demonstrated that there was persistence of endometrial activity in 67% of the subjects, highlighting the potential for variation in the response of individuals to high doses of androgens (Grimstad et al 2019). In the current study as in others, administering androgens to ovariectomised rodents, treatment with DHT, GTx-024 or Danazol increased the percentage of Ki67-positive cells in the stroma and had a variable impact on epithelial cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus

Simitsidellis

Esnal-Zuffiaure

Kelepouri

et al. 2019

Journal of Endocrinology

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Selective androgen receptor modulators (SARMs) have been proposed as therapeutics for women suffering from breast cancer, muscle wasting or urinary incontinence. The androgen receptor (AR) is expressed in the uterus but the impact of SARMs on the function of this organ is unknown. We used a mouse model to compare the impact of SARMs (GTx-007/Andarine®, GTx-024/Enobosarm®), Danazol (a synthetic androstane steroid) and dihydrotestosterone (DHT) on tissue architecture, cell proliferation and gene expression. Ovariectomised mice were treated daily for 7 days with compound or vehicle control (VC). Uterine morphometric characteristics were quantified using high-throughput image analysis (StrataQuest; TissueGnostics), protein and gene expression were evaluated by immunohistochemistry and RT-qPCR, respectively. Treatment with GTx-024, Danazol or DHT induced significant increases in body weight, uterine weight and the surface area of the endometrial stromal and epithelial compartments compared to VC. Treatment with GTx-007 had no impact on these parameters. GTx-024, Danazol and DHT all significantly increased the percentage of Ki67-positive cells in the stroma, but only GTx-024 had an impact on epithelial cell proliferation. GTx-007 significantly increased uterine expression of Wnt4 and Wnt7a, whereas GTx-024 and Danazol decreased their expression. In summary, the impact of GTx-024 and Danazol on uterine cells mirrored that of DHT, whereas GTx-007 had minimal impact on the tested parameters. This study has identified endpoints that have revealed differences in the effects of SARMs on uterine tissue and provides a template for preclinical studies comparing the impact of compounds targeting the AR on endometrial function.

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“…The development of SARMs has prompted renewed interest in targeting of AR in reproductive disorders while also raising concerns related to side effects including hirsutism that are a hallmark of excess androgens in PCOS. Transgender individuals may be one group who might benefit from SARMs, as administration of high concentrations of testosterone can result in abnormal uterine bleeding and metabolism to oestrogen may explain increased rates of endometrial cancer (Grimstad et al 2019), but there are no registered clinical trials.…”

Section: Targeting Androgen Receptors In Endometrial Disordersmentioning

confidence: 99%

Androgens, oestrogens and endometrium: a fine balance between perfection and pathology

Gibson

Simitsidellis

Collins

et al. 2020

Journal of Endocrinology

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The endometrium is a complex multicellular tissue that is exquisitely sensitive to the actions of sex steroids synthesised in the ovary (endocrine system). Recent studies have highlighted a previously under-appreciated role for local (intracrine) metabolism in fine-tuning tissue function in both health and disease. In this review we have focused on the impact of oestrogens and androgens on endometrial function summarising data from studies on normal endometrial physiology and disorders including infertility, endometriosis and cancer. We consider the evidence that expression of enzymes including aromatase, sulphatase and AKR1C3 by endometrial cells plays an important role in tissue function, and malfunction, and discus results from studies using drugs targeting intracrine pathways to treat endometrial disorders. We summarise studies exploring the spatial and temporal expression of oestrogen receptors (ERalpha, ERbeta and GPER) and their role in mediating the impact of endogenous and synthetic ligands on cross-talk between vascular, immune, epithelial and stromal cells. There is a single androgen receptor and androgens play a key role in stromal-epithelial cross talk, scar-free healing of endometrium during menstruation and regulation of cell proliferation. The development of new receptor-selective drugs (SERMs, SARMs, SARDs) has reinvigorated interest in targeting receptor subtypes in treatment of disorders including endometriosis and endometrial cancer and some show promise as novel therapies. In summary, understanding the mechanisms regulated by sex steroids provides the platform for improved personalised treatment of endometrial disorders as well as novel insights into the impact of steroids on processes such as tissue repair and regeneration.

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Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series

Cited by 85 publications

References 26 publications

Do Transgender and Gender Diverse Individuals Receive Adequate Gynecologic Care? An Analysis of a Rural Academic Center

Do Transgender and Gender Diverse Individuals Receive Adequate Gynecologic Care? An Analysis of a Rural Academic Center

Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus

Androgens, oestrogens and endometrium: a fine balance between perfection and pathology

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