DHEA

Dehydroepiandrosterone (DHEA; drug name prasterone) is an endogenous C19 steroid secreted mainly by the adrenal cortex and circulating largely as DHEA sulfate (DHEA-S). It is a precursor of androgens and estrogens. The only FDA-approved prasterone product is Intrarosa, a 6.5 mg vaginal insert. No oral prasterone product is FDA approved; compounded oral preparations are made pursuant to patient-specific prescriptions. DHEA is excluded from the federal definition of anabolic steroids and is not a controlled substance.

FDA-labeled indication (Intrarosa, vaginal): moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

Prescribers use oral DHEA for individualized hormone therapy, including low DHEA-S levels with age, women with adrenal insufficiency who have low libido or reduced well-being despite glucocorticoid and mineralocorticoid replacement (a use addressed in Endocrine Society guidance), and as an adjunct in some fertility care. Lake Hills also prepares DHEA with anastrozole or clomiphene on prescription.

DHEA is converted within peripheral tissues by 3-beta-hydroxysteroid dehydrogenase, 17-beta-hydroxysteroid dehydrogenase, 5-alpha-reductase and aromatase to androstenedione, testosterone, dihydrotestosterone and estradiol, which act on androgen and estrogen receptors locally. DHEA and DHEA-S also act as neurosteroids, modulating GABA-A, NMDA and sigma-1 receptors.

Oral DHEA is absorbed and undergoes extensive first-pass sulfation to DHEA-S. DHEA itself has a short half-life (under an hour), while DHEA-S circulates far longer (roughly 10 to 20 hours) and serves as a reservoir. Endogenous levels peak in early adulthood and decline with age. After oral dosing, women generally show larger rises in testosterone than men, whose conversion favors estrogens. Sustained-release bases are used to moderate peak levels.

• Undiagnosed abnormal genital bleeding (prasterone label).
• Known or suspected hormone-sensitive malignancy, such as breast, endometrial, ovarian or prostate cancer.
• Pregnancy and breastfeeding.
• Hypersensitivity to DHEA or any component.

• Hormone-sensitive tissues: estrogen is a metabolite of prasterone. Use in women with a current or past history of breast cancer has not been studied. In men, evaluate the prostate and PSA before and during therapy.
• Androgenic effects in women, including hirsutism, acne, scalp hair loss and voice deepening, can be irreversible; use caution in polycystic ovary syndrome and other hyperandrogenic states.
• DHEA can lower HDL cholesterol.
• Psychiatric effects: irritability, insomnia and, rarely, mania have been reported, particularly in patients with bipolar disorder or other mood disorders.
• Palpitations and arrhythmia have been reported rarely.
• DHEA is prohibited in competitive sport by the World Anti-Doping Agency.

• Estrogens, progestins, testosterone and other androgens: additive hormonal effects; adjust and monitor.
• Aromatase inhibitors such as anastrozole reduce conversion of DHEA to estrogens. They are combined intentionally in some prescriptions, with monitoring of estradiol and testosterone.
• Hormonal cancer therapies (for example tamoxifen or aromatase inhibitors for breast cancer, androgen deprivation for prostate cancer): DHEA may counteract them and is avoided.
• 5-alpha-reductase inhibitors reduce conversion of DHEA-derived testosterone to DHT.

Acne, oily skin, hirsutism, scalp hair thinning, voice deepening, menstrual irregularity, breast tenderness, gynecomastia in men, decreased HDL cholesterol, insomnia, irritability, mood elevation, headache, fatigue and palpitations. With the vaginal insert, vaginal discharge and abnormal Pap smear findings were reported.

DHEA is not used in pregnancy, because androgenic and estrogenic metabolites could affect fetal development. No lactation data exist, and it is not used during breastfeeding. Intrarosa is indicated only for postmenopausal women.

Baseline and periodic DHEA-S, with testosterone and estradiol as relevant; lipids; PSA and prostate assessment in men; signs of androgen excess in women; mood and sleep; and routine breast and endometrial evaluation in women per standard care.

• Intrarosa (prasterone) vaginal inserts Prescribing Information.
• Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.
• AHFS Drug Information. American Society of Health-System Pharmacists.