Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

doi:10.1016/0046-8177(94)90037-X

Human Pathology

Volume 25, Issue 11, November 1994, Pages 1198-1204

https://doi.org/10.1016/0046-8177(94)90037-X Get rights and content

Abstract

Androgen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycystic ovarian disease (PCOD). In the normal ovaries germinal epithelium, granulosa cells of antral follicles, corpus luteum, and thecal and stromal cells exhibited moderate AR expression. The more intense and uniform staining of ovarian stroma of female transsexual patients and those of patients with PCOD compared with ovarian stroma of normal controls was most remarkable. This similarity in histology and distribution of ARs supports the hypothesis that PCOD is an androgen-mediated disorder. Immunostaining for ARs was only occasionally detectable in the uteri of premenopausal and postmenopausal women. In contrast, myometrial and endometrial stroma of the uteri of female transsexual patients displayed an intense and diffuse nuclear immunostaining, but glandular epithelia remained unstained. Western blot analysis of the ovaries and uterine myometrial tissue samples from transsexual female patients confirmed the presence of the 110-kd AR molecule. Because the androgen treatment of some transsexual female patients was discontinued 6 weeks before they underwent hysterosalpingo-oophorectomy, our data indicate a stable and persistent androgen-induced up-regulation of AR expression in ovaries.

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Citation Excerpt :
In our clinic, a similar approach is often used with transgender men in an attempt to reduce the burden and potential gender dysphoria associated with multiple rounds of COS. Interestingly, studies evaluating ovarian histological changes after testosterone exposure in birth-assigned females have reported an ovarian phenotype similar to polycystic ovary syndrome—polycystic follicles with increased AFC with increased collagenization of the tunica albuginea, stromal hyperplasia, and luteinization of stromal cells (9–11). Patients with this ovarian morphology, particularly with a high AFC, as seen in patient 1 of our series, are known to be at higher risk for ovarian hyperstimulation syndrome (12).
To report two cases of fertility preservation in two transgender men without an extended period of higher dose testosterone cessation.
Chart abstraction was completed for two cases of oocyte preservation in transgender men without stopping testosterone gender-affirming therapy before controlled ovarian stimulation (COS).
A university-affiliated fertility clinic in San Francisco, California.
Two 27-year-old transgender men on higher dose testosterone undergoing oocyte cryopreservation.
Not applicable.
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This is emphasized in our work by the highest nuclear AR immunostaining in endometrial stromal cells and myometrium smooth muscle cells observed in androgenized rats after the treatment period; a similar condition was described to the uterine tissue in a rat model of PCOS using dehydroepiandrosterone [52]. Female-to-male transsexual’s after a long term androgen administration also induces up-regulation of AR in the uterine stroma and myometrium compared to non-treated individuals, suggesting a feed-forward mechanism of androgen action in the endometrium [53,54]. Similarly, postmenopausal women administered with either E2 or a combination of E2 with T displayed a significant increase in AR immunoreactivity in the stroma [55].
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Original contributionAndrogen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

Abstract

Hum Pathol

J Steroid Biochem Mol Biol

Biochem Biophys Acta

Biochem Biophys Res Commun

Mol Cell Endocrinol

J Biol Chem

Prostaglandins

Fertil Steril

Histological changes in the genital tract in transsexual women following androgen therapy

Histopathology

Histopathological effects of exogenously administered testosterone in 19 female to male transsexuals

J Clin Endocrinol Metab

Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome?

Histopathology

Androgen receptor expression in human tissues. An immunohistochemical study

J Histochem Cytochem

Original contribution
Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women