Spironolactone and Feminization in Cisgender Females
Spironolactone does not make cisgender females "more feminine" in the sense of enhancing female characteristics, but rather reduces masculine features caused by excess androgens (such as acne, excess body/facial hair, and androgenic alopecia) by blocking androgen receptors and reducing androgen production. 1, 2
Mechanism of Action in Females
Spironolactone works through two primary mechanisms that affect androgen-related conditions:
- Blocks androgen receptors on target tissues (sebocytes, hair follicles, skin), preventing testosterone and dihydrotestosterone from binding and exerting masculinizing effects 1, 2, 3
- Reduces adrenal androgen synthesis, decreasing overall androgen production in the body 1, 4
- May increase sex hormone-binding globulin (SHBG), though this effect is inconsistent across studies 5, 6
Clinical Effects in Cisgender Women
The drug's effects are subtractive rather than additive—it removes masculine features rather than creating new feminine ones:
- Reduces sebum production, improving acne in 84-86% of women with 40-66% achieving complete clearance 2
- Decreases body and facial hair growth (hirsutism), with improvement in 2 of 10 patients in one study, though effects vary 6, 7
- Arrests androgenic alopecia progression and may promote partial hair regrowth in women with female pattern hair loss 3, 4
- Does not create breast development, fat redistribution, or other feminizing changes seen in transgender hormone therapy—these effects require estrogen therapy 1
Critical Distinction: Transgender vs. Cisgender Context
In transgender women (assigned male at birth), spironolactone is used as part of feminizing hormone therapy alongside estrogen to achieve feminine physical characteristics:
- When combined with estrogen, the regimen produces breast development, increased fat mass, decreased muscle mass, softer skin, and feminized body composition 1
- Spironolactone alone in transgender women primarily suppresses testosterone but requires estrogen to produce feminizing effects 1
- In one study of 50 transgender women, spironolactone (200-600 mg/day) with physiologic female hormones produced "excellent clinical response including decreased male pattern hair, breast development, feminization" over 12 months 8
In cisgender females (assigned female at birth), spironolactone only reduces hyperandrogenic symptoms—it does not enhance femininity beyond what would be normal for that individual:
- Cisgender women already have physiologic estrogen levels, so spironolactone's anti-androgen effects simply normalize androgen-related symptoms 1, 2
- The drug treats pathologic masculinization (acne, hirsutism, hair loss), not enhancement of feminine features 7, 9
Practical Dosing and Timeline
- Start with 100 mg daily in the evening, which can be increased to 200 mg/day if needed after 3-5 months 2, 3
- Expect 3 months for initial response and 5 months for maximum effect on androgen-related conditions 2
- Lower doses (75-100 mg) are as effective as higher doses (150-300 mg) with fewer side effects 2
Important Safety Considerations
- Pregnancy category C with risk of feminization of male fetuses—absolute contraindication in pregnancy 1, 2, 3, 10
- Most common side effect is menstrual irregularities (15-30%), which is dose-dependent with relative risk of 4.12 at 200 mg/day 2, 3
- Concomitant oral contraceptives or hormonal IUDs minimize menstrual irregularities 1
- Other side effects include breast tenderness (3-5%), dizziness (3-4%), nausea (2-4%) 1, 2
- No routine potassium monitoring needed in young healthy women, but required in older patients or those with renal/cardiovascular disease 3, 10
Common Pitfall to Avoid
Do not confuse spironolactone's role in transgender feminization (where it is combined with estrogen) with its effects in cisgender women (where it only reduces androgen effects). The drug itself does not create feminine characteristics—it only blocks masculine ones. 1