Ovarian and endometrial cancer considerations in transgender men

Endometrial cancer

The administration of exogenous testosterone, which then undergoes aromatization to estrogen, as well as the possible anovulatory state induced by testosterone, may create a hormonal milieu of "unopposed" estrogen. This creates a theoretical risk of endometrial hyperplasia or cancer. Despite this theoretical risk, only one case report of an endometrioid adenocarcinoma exists in the literature.[1] Two studies suggest that the risk of endometrial hyperplasia is low, and that transgender men may commonly have endometrial atrophy when on testosterone: One observational study found endometrial atrophy on histological report in almost half (45%) of trans men on testosterone when histology was performed post routine hysterectomy.[2] Another case control study performed histopathology on samples comparing trans men on androgens for at least one year to pre and post-menopausal women undergoing hysterectomy or histopathology, and found trans men had endometrial atrophy similar to that found in post-menopausal women.[3]

A number of sources have recommended endometrial surveillance with annual pelvic ultrasounds in transgender men who are amenorrheic, however this recommendation is not evidence based. This recommendation may also be unrealistic since transgender men report avoiding gynecologic care due to lack of cultural competency among providers.[4]

As such, routine screening for endometrial cancer in transgender men using testosterone is not recommended. Unexplained vaginal bleeding (in the absence of missed or changed dosing of testosterone) in a patient previously with testosterone-induced amenorrhea should be explored. (Grading: X C M). Transgender men should be educated on the need to inform their provider in the event of unexplained vaginal bleeding.

Hysterectomy for primary prevention of endometrial cancer is not currently recommended (Grading: X C M); consideration of hysterectomy for the purpose of eliminating the need for cervical cancer screening may be discussed on a case-by-case basis, in recognition of the role of hysterectomy in reducing gender dysphoria, and in consideration of surgical risks and irreversible infertility.

Ovarian cancer

While there have been several case reports of ovarian cancer among transgender men,[5,6] there is no evidence to suggest that trans men on testosterone are at increased risk.

Testosterone causes the ovaries to develop cortical and thecal thickening similar to that seen in the polycystic ovarian syndrome (PCOS), however histologically there are differences in antral follicle counts.[2,7] Several studies have suggested an increased prevalence of PCOS in transgender men prior to testosterone therapy.[8-10] While historically concerns have existed about increased risk of ovarian cancer in transgender men using testosterone, these concerns were based mostly on the inaccurate premise that testosterone causes a PCOS-like ovary. Furthermore, recent data refutes the increased risk of ovarian cancer in non-transgender women with PCOS.[11]

From a primary care perspective, no effective screening algorithm is available for ovarian cancer screening in any individuals without a greater than average risk (i.e., known genetic or personal/family risk factors). Transgender men should receive the same recommended counseling and screenings for anyone with ovaries based on history and presentation. While a unilateral or bilateral oophorectomy may be performed in transgender men as part of the management of gender dysphoria or for a pathologic process, routine oophorectomy in for primary prevention of ovarian cancer is not recommended. Transgender men who undergo vaginectomy but retain one or both ovaries/gonads, and who require pelvic imaging, may be evaluated by transrectal or transabdominal sonogram.

References

1. Urban RR, Teng NNH, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011 May;204(5):e9-12.
2. Grynberg M, Fanchin R, Dubost G, Colau J-C, Brémont-Weil C, Frydman R, et al. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod Biomed Online. 2010 Apr;20(4):553-8.
3. Perrone AM, Cerpolini S, Maria Salfi NC, Ceccarelli C, De Giorgi LB, Formelli G, et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med. 2009 Nov;6(11):3193-200.
4. Reisner SL, Perkovich B, Mimiaga MJ. A mixed methods study of the sexual health needs of New England transmen who have sex with nontransgender men. AIDS Patient Care STDs. 2010 Aug;24(8):501-13.
5. Dizon DS, Tejada-Berges T, Koelliker S, Steinhoff M, Granai CO. Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient. Gynecol Obstet Invest. 2006;62(4):226-8.
6. Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E. Ovarian cancer in female-to-male transsexuals: report of two cases. Gynecol Oncol. 2000 Mar;76(3):413-5.
7. Gooren LJG, Giltay EJ. Review of studies of androgen treatment of female-to-male transsexuals: effects and risks of administration of androgens to females. J Sex Med. 2008 Apr;5(4):765-76.
8. Balen AH, Schachter ME, Montgomery D, Reid RW, Jacobs HS. Polycystic ovaries are a common finding in untreated female to male transsexuals. Clin Endocrinol (Oxf). 1993 Mar;38(3):325-9.
9. Mueller A, Gooren LJ, Naton-Schötz S, Cupisti S, Beckmann MW, Dittrich R. Prevalence of polycystic ovary syndrome and hyperandrogenemia in female-to-male transsexuals. J Clin Endocrinol Metab. 2008 Apr;93(4):1408-11.
10. Baba T, Endo T, Honnma H, Kitajima Y, Hayashi T, Ikeda H, et al. Association between polycystic ovary syndrome and female-to-male transsexuality. Hum Reprod Oxf Engl. 2007 Apr;22(4):1011-6.
11. Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2014 Oct;20(5):748-58. June 17, 2016 117.