Update on case reports: Cyproterone acetate and meningioma in trans women

Disclaimer: I am not a doctor, and this is not medical advice. Do not take any medication without appropriate medical supervision.

Summary

Cyproterone acetate (CPA) is commonly used as an antiandrogen in HRT for trans women outside of the United States. CPA has been associated with an increased risk of meningioma, a usually-benign brain tumor, in both cis and trans populations, and trans women may face a greater risk due to the high dosage of CPA typically prescribed.

Earlier this year, I reviewed the occurrence of meningioma, a typically benign brain tumor, among trans women using the antiandrogen cyproterone acetate (CPA). Meningiomas, the most common type of brain tumor (Saraf, McCarthy & Villano, 2011), develop in the membranes surrounding the brain and can produce symptoms such as headaches, seizures, muscle weakness, vision loss, and memory loss, while others are asymptomatic and may only be found incidentally in medical imaging (Spasic et al., 2016). About 70-88% of meningiomas express progesterone receptors (Blitshteyn, Crook, & Jaeckle, 2008; Korhonen et al., 2006), suggesting that the progestogenic action of CPA may encourage growth of these tumors. Use of CPA in high doses – 50 mg/day or more – has been found to be associated with an increased incidence of meningioma in cis women and cis men (Gil et al., 2011).

New findings on prevalence of meningioma in trans women using CPA

Several case reports of meningioma in trans women using CPA have previously been published (Gazzeri, Galarza, & Gazzeri, 2007; Cebula et al., 2010; Bergoglio et al., 2013; Knight & McDonald, 2013; Borghei-Razavi et al., 2014; Mancini et al., 2017; Boer et al., 2018), and in a study of 2,810 trans women, three were found to have meningiomas (Ter Wengel et al., 2016). All three were using CPA, and meningioma was estimated to occur in 126 in 100,000 trans women, compared to a prevalence of 97.5 in 100,000 in the general population.

However, Nota et al. (2018) more recently found that among a cohort of 2,555 trans women, meningioma occurred about four times more frequently than in cis women. Once again, all of these identified cases occurred in trans women using CPA. Additionally, Raj et al. (2018) have reported two new cases of multiple meningiomas with vision loss in trans women after several years of treatment with high doses of CPA (50 mg/day). While both underwent surgical resection of these tumors, one experienced permanent blindness.

Potential implications for treatment with HRT

Nota et al. (2018) have noted that in European countries, CPA is typically prescribed to trans women at a dosage of 50 mg/day or more (Dekker et al., 2016), a high dosage known to be associated with a greater likelihood of meningioma occurrence. Because of this risk, the authors suggest that trans women using CPA long-term, such as those not planning to receive orchiectomy or vaginoplasty, should take a lower dose or switch to another antiandrogen:

Although CPA is usually discontinued after orchiectomy, as described previously, in case of hirsutism CPA is sometimes continued. Furthermore, since legal gender change in the Netherlands does not require orchiectomy any longer, there is an increasing number of transwomen who desire long-term anti-androgen treatment. While the actual risk of meningiomas in transwomen still seems low, the potential (dose-dependent) risk of meningioma development might make it recommendable to use as low a dose of CPA as possible in transwomen with hirsutism and to consider other types of anti-androgens in transwomen without a wish for orchiectomy.

Again, although the development of meningioma remains uncommon overall in this population, trans women taking CPA should be aware of the possibility of experiencing tumor growth and pay attention to any potential symptoms that could indicate meningioma. ■