Will DHEA supplementation worsen hirsutism in a reproductive‑age woman, and if so, what dose and monitoring are recommended?

DHEA and Hirsutism in Reproductive-Age Women

DHEA supplementation can worsen hirsutism in reproductive-age women because DHEA is converted to androgens (testosterone and DHT) in peripheral tissues, and these androgens directly stimulate hair follicles to produce terminal hair growth in androgen-sensitive areas. 1, 2

Mechanism of Androgenic Side Effects

DHEA acts as a precursor hormone that undergoes peripheral conversion to active androgens through intracrine mechanisms:

• DHEA is metabolized to testosterone and dihydrotestosterone (DHT) in target tissues, including skin and hair follicles, where it exerts androgenic effects 3
• In women receiving DHEA supplementation, serum testosterone increases by approximately 50% (about 0.8 nM), though this increase is less detectable in men who have higher baseline levels 3
• The conjugated metabolites of DHT (androsterone glucuronide, androstane-3α,17β-diol-G) increase by 125-150% in women taking DHEA, reflecting substantial intracrine androgen formation in peripheral tissues 3
• Importantly, these androgenic effects occur even when serum levels of active androgens appear unchanged, because DHEA's conversion happens locally in tissues rather than systemically 3

Clinical Evidence of Hirsutism Risk

Hirsutism is a well-documented androgenic side effect of DHEA and related androgen therapies:

• Attenuated androgens (danazol, stanozolol, oxandrolone) used for other conditions cause hirsutism as a specific side effect in women, along with virilization, voice deepening, and menstrual irregularities 4
• DHEA supplementation is associated with androgenic side effects, primarily acne (OR 3.77,95% CI 1.36-10.4), which shares the same pathophysiology as hirsutism—both result from androgen stimulation of pilosebaceous units 5
• The Polish Menopause and Andropause Society notes that despite DHEA's benefits in certain populations, no serious adverse effects have been reported, but this statement does not exclude common androgenic effects like hirsutism 6

Dose Considerations and Monitoring

If DHEA is clinically indicated despite hirsutism risk, use the lowest effective dose with careful monitoring:

Starting Dose

• Begin with 25 mg orally once daily in the morning for most indications (vaginal atrophy, sexual dysfunction, adrenal insufficiency) 2
• For intravaginal DHEA (prasterone) specifically for vaginal atrophy, the FDA-approved dose is 6.5 mg nightly, which has lower systemic absorption 1, 2
• Dose range can be adjusted between 10-50 mg daily based on clinical response, but lower doses minimize androgenic effects 2

Monitoring Protocol

• Assess for signs of virilization at baseline and every 3 months: hirsutism (using Ferriman-Gallwey score if possible), acne, voice changes, clitoromegaly, male-pattern hair loss 4, 2
• Measure baseline hormone levels before starting: total and free testosterone, DHEA-S, androstenedione 4, 7
• Recheck hormone levels at 4-6 weeks after starting DHEA: estradiol, testosterone (total and free), DHEA-S 7
• Monitor menstrual regularity, as DHEA can cause cycle disturbances through androgenic effects 4
• Implement a 6-month trial period before determining long-term use, evaluating treatment effect after 3-6 months 2

Management of Hirsutism if It Develops

If hirsutism worsens during DHEA therapy:

• Reduce DHEA dose by 50% (e.g., from 25 mg to 10-12.5 mg daily) or switch to intravaginal formulation if treating vaginal atrophy 2
• Consider adding spironolactone 100-200 mg daily, an androgen receptor antagonist effective for hirsutism, though this may theoretically reduce DHEA's efficacy 4
• Discontinue DHEA if hirsutism is severe or progressive despite dose reduction 2
• Counsel that cosmetic treatments (laser hair removal, electrolysis) may be needed for established terminal hair growth, as hair follicles that have converted to terminal hairs will not revert even after stopping DHEA 4

Special Populations at Higher Risk

Certain women are at increased risk of androgenic side effects from DHEA:

• Women with polycystic ovary syndrome (PCOS) already have elevated androgens and should generally avoid DHEA supplementation 4
• Women with elevated baseline DHEA-S levels (>3800 ng/mL age 20-29, >2700 ng/mL age 30-39) should not receive additional DHEA 4
• Women on aromatase inhibitors for breast cancer may experience more pronounced androgenic effects because estrogen conversion is blocked, leaving androgens unopposed 1, 2
• Women with genetic or ethnic predisposition to hirsutism (Mediterranean, Middle Eastern, South Asian ancestry) are more sensitive to androgen-induced hair growth 4

Contraindications Related to Androgen Excess

DHEA should be avoided in women with:

• Current hirsutism or clinical hyperandrogenism 4
• History of hormone-dependent cancers (breast, endometrial), as DHEA can be converted to estrogens as well as androgens 1, 2
• Undiagnosed menstrual irregularities or anovulation, which may indicate underlying PCOS 4
• Elevated baseline androgens (testosterone >2.5 nmol/L, androstenedione >10.0 nmol/L) 4

Alternative Options to Minimize Hirsutism Risk

For women requiring treatment of vaginal atrophy or sexual dysfunction who are concerned about hirsutism:

• Intravaginal DHEA (prasterone 6.5 mg) has lower systemic absorption than oral DHEA and may cause fewer androgenic side effects 1, 2, 5
• Low-dose vaginal estrogen (estradiol tablets, cream, or ring) is highly effective for vaginal atrophy without androgenic effects 1, 2
• Ospemifene (oral SERM) treats vaginal atrophy and dyspareunia without androgenic effects, though contraindicated in breast cancer 1, 2
• Non-hormonal options (vaginal moisturizers 3-5 times weekly, water-based lubricants, pelvic floor physical therapy) should always be tried first 1, 2

Common Pitfalls

• Failing to obtain baseline androgen levels and Ferriman-Gallwey score before starting DHEA makes it impossible to objectively assess worsening hirsutism 4, 2
• Not counseling patients about irreversibility of terminal hair growth—once vellus hairs convert to terminal hairs under androgen stimulation, they persist even after stopping DHEA 4
• Assuming serum testosterone levels reflect total androgenic activity—DHEA's intracrine conversion means tissue androgen levels (reflected by DHT metabolites) are far higher than serum levels suggest 3
• Prescribing DHEA to women with undiagnosed menstrual irregularities without first ruling out PCOS, which would be exacerbated by additional androgens 4
• Using DHEA in women on aromatase inhibitors without recognizing that circulating androgens can be converted to estrogens, potentially reducing cancer treatment efficacy 1, 7, 2