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DHEA: What the Randomized Trials and Reviews Report in Adults

Por Benn Bluestein-Veyra, M.Sc. en Química Orgánica · Actualizado el 8 de noviembre de 2026

Systematic reviews of the randomized trials report few measurable effects of systemic DHEA in adults. The 2015 Cochrane review of 28 trials in 1,273 peri- and postmenopausal women concluded that "There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects", adding that "DHEA may slightly improve sexual function compared with placebo."^[1] Meta-analyses in postmenopausal women and in older men reported no effect on lipids, glucose, bone or sexual function, and the Endocrine Society's 2014 guideline recommends "against the routine use of dehydroepiandrosterone due to limited data concerning its effectiveness and safety in normal women or those with adrenal insufficiency."^[2][3][4]

This page reports what the trials, the reviews and two Endocrine Society guidelines state about DHEA, how federal law classifies the oral supplement and the one FDA-approved product, and the safety findings the sources record. The compounded hormone question is covered on the sibling page on the NASEM 2020 review.^[5][6]

The Endocrine Society describes DHEA as an adrenal precursor whose sulfate declines after early adulthood

Dehydroepiandrosterone is a C19 steroid, identified chemically as 3β-hydroxyandrost-5-en-17-one, secreted mainly by the adrenal cortex and circulating largely as its sulfate, DHEA-S.^[6] The Endocrine Society's adrenal insufficiency guideline describes it as an "adrenal androgen precursor" that "is activated to sex steroids in a wide variety of peripheral tissues and in the gonads", and states that "Serum DHEAS concentrations physiologically peak between ages 20 and 30 years, followed by a gradual decline that is independent of menopause."^[7] The FDA-approved prasterone label states the same mechanism in regulatory language: "Prasterone is an inactive endogenous steroid and is converted into active androgens and/or estrogens."^[6]

Labrie, whose company developed the intravaginal product, described this conversion inside target cells as intracrinology and wrote that adrenal DHEA secretion "has already decreased by an average of 60% at the time of menopause and it continues to decrease thereafter."^[8] That age-related decline is the premise most supplementation trials set out to test: whether restoring circulating DHEA-S toward young-adult values changes measurable outcomes.^[2][9]

Federal law classifies oral DHEA as a dietary supplement and intravaginal prasterone as an approved drug

The Controlled Substances Act defines an anabolic steroid as "any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone)".^[5] That parenthetical exclusion entered the statute with the Anabolic Steroid Control Act of 2004 (Pub. L. 108-358), which rewrote paragraph (41), and it is why DHEA is sold over the counter while testosterone is a Schedule III substance.^[5] As a dietary supplement it falls under the framework FDA describes: "Under DSHEA, FDA does not have the authority to approve dietary supplements before they are marketed", and firms "are responsible for evaluating the safety and labeling of their products before marketing".^[10][11]

FDA approved prasterone as Intrarosa, a vaginal insert, on 16 November 2016 under NDA 208470, classified as a new active ingredient.^[12] As of 8 November 2026 the DailyMed label (revised January 2026, Millicent US) states that "INTRAROSA is a steroid indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause", lists "DEA Schedule: None", and carries no boxed warning.^[6] Its one warning reads: "Estrogen is a metabolite of prasterone. Use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer. INTRAROSA has not been studied in women with a history of breast cancer."^[6]

Section 503A permits a pharmacy to compound with bulk substances that meet an applicable USP or NF monograph or, "if such a monograph does not exist, are drug substances that are components of drugs approved by the Secretary".^[13] FDA asked the NASEM committee to give DHEA priority in its 2020 review of compounded hormone preparations, and the committee found the evidence base for those preparations insufficient to support claims of superior safety or efficacy.^[14]

The Endocrine Society recommends against routine DHEA use and suggests a limited trial in adrenal insufficiency

The 2014 guideline on androgen therapy in women, written with ACOG, ASRM, the European Society of Endocrinology and the International Menopause Society, recommends "against the routine prescription of T or dehydroepiandrosterone for the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, surgical menopause, pharmacological glucocorticoid administration, or other conditions associated with low androgen levels because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk."^[4]

The 2016 primary adrenal insufficiency guideline is the one Society document that makes room for DHEA. Recommendation 3.11 reads: "We suggest a trial of DHEA replacement in women with PAI and low libido, depressive symptoms, and/or low energy levels despite otherwise optimized glucocorticoid and mineralocorticoid replacement."^[7] Recommendation 3.12 asks that DHEA be discontinued after an initial period "If the patient does not report a sustained, beneficial effect of replacement", and 3.13 suggests "monitoring DHEA replacement by measuring morning serum DHEA sulfate (DHEAS) levels (aiming at the midnormal range)".^[7] All three are graded weak with low-quality evidence, and the evidence text notes that meta-analyses "have not shown any substantial clinical benefit" and that long-term outcome studies "are lacking and are unlikely to be available soon due to a lack of commercial interest and the ready availability of DHEA over the counter or through internet orders."^[7]

Nair 2006 reported no physiologically relevant benefit in older adults over two years

The landmark trial ran at the Mayo Clinic with National Institute on Aging support and is registered as NCT00254371.^[15] It randomized 87 older men with low DHEA-S and bioavailable testosterone to DHEA, testosterone or placebo, and 57 older women with low DHEA-S to DHEA or placebo, for two years, double-blind.^[9] DHEA raised DHEA-S as intended, yet the authors reported "no significant effect of DHEA on body-composition measurements", no change in peak oxygen uptake, muscle strength or insulin sensitivity, and no improvement in quality of life.^[9]

Two bone findings stood apart: men in both active groups had an increase in femoral neck bone mineral density, and women on DHEA had an increase at the ultradistal radius.^[9] The authors concluded that "Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life", and reported no major adverse effects.^[9]

The Cochrane review and two meta-analyses found little effect on sexual function, metabolism or bone

Scheffers and colleagues pooled data from 16 of the 28 included trials. Against placebo, DHEA did not improve quality of life (eight studies, 287 women, moderate-quality evidence), was associated with androgenic side effects, mainly acne (odds ratio 3.77, five studies, 376 women), and improved sexual function by a small standardized margin (SMD 0.31, five studies, 261 women).^[1] Whether DHEA changed menopausal symptoms was unclear because the trials measured them in ways that could not be pooled.^[1]

Elraiyah and colleagues, in a review commissioned for the 2014 Endocrine Society guideline, analyzed 23 randomized trials enrolling 1,188 postmenopausal women with normal adrenal function and found that DHEA "was not associated with significant improvement in libido or sexual function", with "no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density".^[2] They rated confidence in these results as low because of imprecision, risk of bias and inconsistency.^[2]

Corona and colleagues pooled 25 double-blind placebo-controlled trials enrolling 1,353 older men with a mean follow-up of 36 weeks.^[3] DHEA was associated with a small reduction in fat mass, but "the association with fat mass disappeared in a multivariate regression model after adjusting for DHEA-related metabolite increases such as total testosterone and estradiol", and no effect was seen on "lipid and glycemic metabolism, bone health, sexual function, and quality of life."^[3]

Later meta-analyses on body composition and bone reported small changes the authors framed cautiously

Wang and colleagues reported in 2020 that DHEA did not change body weight or body mass index, increased lean body mass by a weighted mean of 0.45 kg, decreased fat mass by 0.85 percentage points and had a neutral effect on blood pressure, and added that "debate persists when translating the results into clinical benefit."^[16] Lin and colleagues, pooling placebo-controlled trials in healthy older adults, reported a significant increase in hip bone mineral density in women and no comparable result in men, and concluded that "More trials may be necessary to allow for a positive and clinically significant effect of DHEA on BMD."^[17]

Phase 3 trials of intravaginal prasterone reported local effects in postmenopausal women

The intravaginal route was studied separately from the oral supplement. In the phase 3 trial Labrie and colleagues published in 2016, the intent-to-treat population was 157 women on placebo and 325 on prasterone, all postmenopausal with moderate to severe dyspareunia as their most bothersome symptom; at 12 weeks the four coprimary measures FDA had suggested (parabasal cells, superficial cells, vaginal pH and pain at sexual activity) each differed from placebo, with pain scores 0.36 severity units lower than placebo.^[18] The authors reported serum steroid levels "well within the normal postmenopausal values" and vaginal discharge from the melting vehicle in about 6 percent of participants.^[18] The lead author founded EndoCeutics, the developer of the product.^[8][18]

A 2026 meta-analysis of five unique randomized trials (1,611 postmenopausal women) reported mean differences against placebo for vaginal dryness and dyspareunia and stated that "No major safety concerns were reported, and adverse effects were mild and infrequent."^[19] The approved label reports vaginal discharge in 5.71 percent of 665 women on prasterone and 3.66 percent of 464 on placebo across four 12-week trials, and vaginal discharge and abnormal Pap smear as the most frequent reactions in a 52-week open-label trial.^[6] Its pharmacokinetic section states that testosterone and estradiol exposure "were also slightly higher" than with placebo.^[6]

The reported safety signals center on androgenic effects and HDL cholesterol

Androgenic effects, chiefly acne, are the one adverse finding the Cochrane review pooled with moderate-quality evidence, and it found no association with other adverse effects.^[1] Qin and colleagues, pooling 23 trials on lipids, reported no change in total cholesterol, LDL cholesterol or triglycerides and a reduction in HDL cholesterol that reached significance in studies of women and not in studies of men; they wrote that "Further long-term RCTs are required to investigate the effects of DHEA particularly on major adverse cardiac events."^[20]

The guidelines frame the gap the same way: the 2014 guideline cites "no long-term studies of risk", and the 2016 guideline expects none soon.^[4][7] Because estrogen is a metabolite of prasterone, the approved label carries its breast cancer warning, and the guideline's suggestion to check morning DHEA-S applies to replacement in adrenal insufficiency, the one population in which a Society guideline suggests a trial.^[6][7]

What the sources leave a prescribing practice to document

The guidelines and label set the reference points a practice would record when DHEA or prasterone appears on a prescription.^[4][6][7]

• The population and guideline the prescription is documented against: the 2016 adrenal insufficiency guideline for women with primary adrenal insufficiency, or the approved prasterone label for its stated indication.
• Baseline and follow-up morning DHEA-S where the 2016 guideline's monitoring suggestion applies, with the stopping point it describes.
• Which form is in use: an over-the-counter supplement without FDA premarket review, the FDA-approved insert, or a 503A compounded preparation.
• Counseling on the androgenic effects the Cochrane review reported and, for prasterone, the label's breast cancer warning.

ExaVeyra's compounded hormone preparations, DHEA among them, reach a practice through a licensed 503A pharmacy partner on a patient-specific prescription. The partner dispenses testosterone and any other controlled substance under its own DEA registration and supplies a certificate of analysis for each lot on request. Diagnosis, the choice of product and the monitoring plan are decisions for the prescribing practitioner.^[13]

This article summarizes published clinical practice guidelines, trial reports and federal regulation for licensed practitioner education. It is not legal advice, medical advice, or regulatory guidance, and it does not establish that any particular product or practice is compliant. Confirm current federal and state obligations with qualified counsel.