Medroxyprogesterone Acetate Dosing in Transgender Feminizing Hormone Therapy
In a transgender patient already taking estradiol 6 mg daily (2 mg three times daily) and cyproterone acetate 25 mg daily, adding medroxyprogesterone acetate (MPA) is not recommended, as the patient is already receiving adequate progestogenic endometrial protection from cyproterone acetate, which has potent progestogenic activity. 1
Why Additional MPA is Unnecessary
Cyproterone acetate already provides progestogenic endometrial protection at doses as low as 1 mg daily when combined with estradiol, making additional progestogen supplementation redundant 1
The patient's current regimen of cyproterone acetate 25 mg daily provides more than adequate progestogenic activity to prevent endometrial hyperplasia, as this dose far exceeds the 1 mg daily shown effective in sequential hormone replacement therapy 1
Adding MPA would create unnecessary polypharmacy without additional benefit, potentially increasing side effects and metabolic risks 2, 3
Current Regimen Assessment
The estradiol dose of 6 mg daily (2 mg three times daily) is higher than typical postmenopausal hormone replacement but may be appropriate for transgender feminizing therapy to achieve physiologic female estradiol levels 4, 5
Cyproterone acetate 25 mg daily provides both anti-androgenic effects and progestogenic endometrial protection simultaneously 1, 6
Recent evidence shows cyproterone acetate 12.5 mg daily effectively suppresses testosterone to female ranges (achieving testosterone <2 nmol/L in most patients), suggesting the current 25 mg dose provides robust testosterone suppression 6
If Progestogen Change is Desired
If there is a specific reason to discontinue cyproterone acetate and switch to MPA alone, the appropriate dosing would be:
For continuous combined regimen: MPA 2.5-5 mg daily continuously, with 5 mg providing better endometrial protection and higher rates of amenorrhea 7, 2
For sequential regimen: MPA 10 mg daily for 12-14 days per month 7
The continuous 5 mg daily dose showed superior endometrial protection with 100% amenorrhea rates by 24 months compared to 2.5 mg daily, which had persistent proliferative endometrium in some patients 2
Critical Clinical Considerations
Cyproterone acetate serves dual purposes in transgender care: testosterone suppression through anti-androgenic activity and endometrial protection through progestogenic activity 1, 8
If cyproterone acetate is discontinued, alternative testosterone suppression would be needed (such as GnRH agonist or spironolactone) in addition to progestogen for endometrial protection 8
The health risks of long-term cyproterone acetate use (including meningioma risk at higher doses and hepatotoxicity) are debated, but 25 mg daily is considered a moderate dose 8