DHEA (Dehydroepiandrosterone) — Reproduction
Adrenal hormone precursor available OTC as a supplement. Weak evidence for fertility, anti-aging, and adrenal support applications.
Overview
Dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-S are the most abundant circulating steroid hormones in humans, produced primarily by the adrenal cortex zona reticularis. DHEA serves as a precursor hormone that is converted peripherally to androgens (testosterone, DHT) and estrogens (estradiol, estrone) by tissue-specific enzymes. DHEA levels peak in the mid-20s and decline progressively with age, falling 80-90% by age 70-80. This decline has led to the 'DHEA replacement' hypothesis — that supplementing DHEA could reverse age-related hormonal decline and its consequences. However, large-scale clinical trials (including the DHEAge study) have shown modest and inconsistent benefits of DHEA supplementation for anti-aging purposes in healthy elderly adults. In fertility medicine, DHEA supplementation (75 mg daily for 6-16 weeks) has been studied for 'poor ovarian responders' undergoing IVF, with some studies suggesting improved ovarian reserve markers (AMH, antral follicle count) and pregnancy rates. An FDA-approved vaginal DHEA formulation (Intrarosa/prasterone) is available for the treatment of dyspareunia in postmenopausal women, where local conversion to estrogens and androgens improves vaginal atrophy. DHEA is available OTC as a dietary supplement in the US (unique regulatory status — it is a hormone sold as a supplement).
Indications
- FDA-approved (vaginal): Dyspareunia in postmenopausal women (Intrarosa/prasterone)
- Dietary supplement: Adrenal support and hormonal precursor
- Off-label: Poor ovarian response in IVF (fertility enhancement)
- Off-label: Adrenal insufficiency (physiologic replacement)
- Off-label: Anti-aging (controversial, weak evidence in healthy adults)
Mechanism of Action
DHEA is converted peripherally to testosterone and estradiol by tissue-specific steroidogenic enzymes (3β-HSD, 17β-HSD, aromatase)
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| DHEA | 25-50 mg | Once daily (morning) | Standard supplemental dose for anti-aging |
| DHEA | 75 mg | Once daily | Fertility dose for poor ovarian responders (6-16 weeks pre-IVF) |
| Prasterone (Intrarosa) | 6.5 mg | Once daily at bedtime | FDA-approved for postmenopausal dyspareunia |
Evidence Grade
GRADE B
Safety & Contraindications
- Androgenic side effects in women: acne, hirsutism, deepening voice at higher doses
- May increase estrogen levels — caution in hormone-sensitive cancers
- Oily skin and body odor
- Insomnia and irritability at higher doses
- WADA prohibited substance
- Drug interactions with anticoagulants, insulin, and estrogen therapy
- OTC supplement — quality varies; some products contain more or less than labeled