Hormonal agents are administered to transgender persons to reduce psychological distress and to induce and maintain desired physical changes. There is little known, however, about the risk of these hormones on breast development or on the risk of developing BC among transgender women.

A recent review examined the impact of hormone regimens on breast development, the impact of these drugs on breast tissue, and BC risk for male-to-female transgender patients. The paper’s focus is on breast development in cisgender and transgender patients to compare them in terms of hormonal influences and to summarize hormonal regimens currently in use in this population.

In the United States, transgender women (i.e., women who received endocrine therapy and/or underwent transgender surgery) number about 3.29 women per 10,000 people.

For those transgender women on hormonal agents, breast development occurs mainly during the first 6 months of gender-affirming hormone therapy (GAHT). Little is known about the natural history and effects of different cross-sex hormones on breast development in transwomen.

Estrogen therapy produces numerous effects, including mood changes, decreased effects on libido and erections, and reductions in testosterone levels in addition to their outward physical effects on sexual features, including breast development, skin softening, and fat redistribution to the hips. Testosterone concentrations are reduced from the 200-300 ng/dL range found in cis-males but are higher than levels found in cis-females, which is around 75 ng/dL.

GAHT in transgender women consists of androgen-lowering drugs, peripheral androgen receptor blockers, gonadotropin-releasing hormone (GnRH) analogs, and estrogen therapy. Among the androgen-lowering drugs employed are cyproterone acetate in dosages of 50 mg to 100 mg/day or spironolactone in dosages of 100 mg to 200 mg/day (to a maximum of 400 mg/day). Spironolactone is preferred over cyproterone acetate, which has fallen out of favor due to the increased risk of developing a meningioma, increased risk of severe depression, and liver injury.

Flutamide may also be administered in a dosage of 50 mg to 75 mg/day as an antiandrogen. The peripheral androgen receptor blocker, finasteride, is administered in a dosage of 1.5 mg orally daily. While high-dose oral conjugated estrogen (2.5 mg-7.5 mg orally daily) has been used in the past, due to its increased risk of thromboembolism, current recommendations are for the use of estradiol valerate, which is given orally, IM every 2 weeks, one patch transdermal every 3 days, or the gel spray in a dosage of 0.8 mg to 3 mg daily in two divided doses. Higher estrogen doses are used in transgender women than are used in cisgender women for hormone replacement therapy. GnRH agonists are used in young patients to block pubertal development.

Data are limited on the effects of estrogen in transgender males. This has resulted in difficulty establishing risk factors and a timeframe to adverse events. Yet, different types of benign breast lesions, including fibrocystic, cystic ducts, and hyperplastic ducts, have been observed following treatment with estrogen and antiandrogens for at least 2 years.

There are no randomized studies examining the effects of GAHT on BC development in transgender women. Standardized incidence ratio data from a cohort from the Netherlands pointed to a 46-fold increased risk of BC in transgender women compared with cisgender men, but the risk of disease is lower than that found among cisgender women following a median duration of hormone therapy of 18 years. The data also indicated that BC develops at a younger age in transgender women versus ciswomen (median 50 years vs. 61 years, respectively).

There are no internationally recommended health screening guidelines for transgender patients. It remains unclear at what age screening for BC should be initiated. Some have even advocated for not screening transwomen for BC. Others have suggested that mammography should be performed every 2 years between the ages of 50 to 69 years. Yet, other authors have suggested starting to screen for BC after 5 years of hormonal treatment. This lack of consensus not only adds to confusion in the management of the transgender patient but also can adversely affect insurance coverage.

As societal efforts to enhance diversity, equity, and inclusion increase, this paper offers pharmacists a timely review of the limited information available that they can utilize to help transgender women navigate the complex realm of GAHT and its inherent risks.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to Breast Cancer Update.