Endocrine Abstracts

Introduction: We have recently reported that the use of cyproterone acetate (CPA) is associated with a highly significant increase of the risk of hypertension development after 5 years (adjusted hazard ratio 0.227, P< 0.001) in young transgender women. Due to the risks associated with the prolonged use of CPA (including the development of meningioma), the EMA presently recommends avoiding the use of doses > 10 mg CPA daily if possible. In fact, acceptable efficacy for androgen blockade in female transgender people has been reported with doses as low as 10 mg daily, but in our country the only available presentation is a 50 mg pill and dosages < 25 mg daily are impractical, while the standard protocols recommend doses up to 100 mg daily, depending on the clinical and analytical results.

Methods: Retrospective review of the clinical records of the transgender women < 30 years old, treated with CPA plus estradiol and followed for 5 years, stratified according to their cumulative dosage of CPA:

- A: up to 6500 mg (mean up to 25 mg/day)

- B: 6501 to 13000 mg (mean >25 -50 mg/day)

- C: 13001 to 18500 mg (mean >50-75 mg/day)

- D: 18501 to 26000 mg (mean >75-100 mg/day)

Hypertension was diagnosed when a repeated clinical sitting BP ≥ 140/90 mmHg or ambulatory (ABPM or systematic HBPM) ≥ 135/85 mmHg was present in a previously normotensive patient. All patients gave their informed consent.

Results: Data from 56 transgender women continuously treated with CPA + estradiol for at least 5 years were obtained. The adjusted yearly hypertension incidence was 4.96% vs. 0.98% in women treated with estradiol without androgen blockade. There were 6/25/18/7 patients in the strata A/B/C/D and their adjusted yearly hypertension incidence was 2.3%/4.2%/5.9%/7.6% (P< 0.001 for the difference).

Conclusions: There is a clear-cut dose dependence in the development of hypertension associated with CPA + estrogen treatment in young transgender women. However, even relatively low (up to 25 mg/day) dosages of CPA are apparently associated with significantly increased risk of hypertension development. Considering also other risks associated to the CPA plus estradiol combination (meningioma, obesity, depression, low libido, liver toxicity, thrombophilia, hyperprolactinemia\..), we conclude that the use for this indication should be reconsidered. We cannot however exclude that very low dosages, in the order of 10 mg/day, may be safe for hypertension development.