DHEA: Benefits, Forms, Dosing, and Side Effects

Table of Contents

• Current evidence position
• Key safety points
• Brad's videos on this topic
• Overview
• Forms and Bioavailability
• Evidence for Health Benefits
• Recommended Dosing
• Safety and Side Effects
• Drug Interactions
• Dietary Sources
• References

Current evidence position

Brad has not made a video on this topic; this is a summary of the evidence, not his view. In a trial of 110 men and 115 women aged 55 to 85, 50 mg a day of oral DHEA for 1 year did no better than placebo for thinking, mood, quality of life or sexual function ^[14]; a 2-year trial in older men and women also found no benefit for body composition, physical performance, insulin sensitivity or quality of life ^[15]. The best-supported use is a prescription vaginal insert of 6.5 mg DHEA (prasterone), which eased pain during sex in a phase III trial in postmenopausal women ^[62] and is approved by the US Food and Drug Administration (FDA) for that use ^[61]. In women with adrenal insufficiency, 50 mg a day for four months improved well-being and sexuality in one trial ^[8], but a trial of 25 mg a day for 9 months found no benefit and frequent side effects ^[34]. DHEA can raise testosterone and estradiol, particularly in women ^[13], and a review advises caution in postmenopausal women because of a possible link with breast cancer ^[68].

Brad's videos on this topic

None yet.

1. Overview

Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA sulfate (DHEA-S), are the main hormones released by the adrenal glands ^[47] and the most abundant circulating steroid hormones in humans ^[2]. They form a large reservoir that tissues turn into androgens (such as testosterone) and estrogens ^[4], and DHEA also acts through several receptors of its own ^[3].

DHEA levels follow a distinctive age-related pattern. In a study of 981 men and 481 women, DHEA-S peaked at ages 20-24 in men and 15-19 in women, then declined steadily into old age ^[71]. This decline led to DHEA being marketed as a supplement to slow ageing ^[2], though long-term trials in older adults found little benefit ^{[14, 15]}.

In the United States, DHEA is available without a prescription ^[49]. A 6.5 mg vaginal insert of prasterone (the drug name for DHEA) is an FDA-approved treatment for moderate to severe pain during sex caused by menopause ^{[61, 62]}. The FDA did not approve an oral prasterone product for lupus ^[74]. WADA, the World Anti-Doping Agency, bans DHEA in sport ^[6].

Yam extracts are used to make commercial steroids, but a yam extract did not raise DHEA-S in older adults ^[73].

7-keto DHEA (3-acetyl-7-oxo-dehydroepiandrosterone) is a related compound studied for weight loss. In a crossover trial in 40 overweight adults on a diet, 7 days of 7-keto DHEA raised resting metabolic rate compared with placebo ^[7].

2. Forms and Bioavailability

Oral DHEA

Oral DHEA comes as capsules or tablets and is the form used in most trials. In women with adrenal insufficiency, 50 mg each morning raised low blood levels of DHEA, DHEA-S, androstenedione and testosterone into the normal range ^[8].

In healthy adults aged 60-79 years, 50 mg of DHEA a day restored DHEA-S to young-adult levels, with a small rise in testosterone and estradiol, mostly in women ^[13]. At 100 mg a day, DHEA raised androgens in women above the young-adult range, with no detectable change in men ^[48].

Micronized vs. Unmicronized DHEA

Some supplements contain micronized DHEA, ground into smaller particles. In a single-dose study, 7 premenopausal women took 300 mg of micronized or standard crystalline DHEA; both forms raised DHEA, DHEA-S and testosterone ^[10]. Micronized DHEA was converted less to testosterone ^[10].

Topical DHEA Cream

DHEA can be applied to the skin, which avoids its first pass through the liver; a DHEA solution applied for 2 weeks raised testosterone by about 50% in women ^[9]. In 14 women aged 60 to 70 who applied a 10% DHEA cream daily for 12 months, hip bone density rose from 0.744 to 0.759 g/cm2 and the vaginal lining matured, while the lining of the womb stayed thin ^[11]. That study had no placebo group.

Vaginal DHEA (Intrarosa/Prasterone)

The prescription vaginal insert contains 6.5 mg of prasterone (0.50%) and is an FDA-approved treatment for moderate to severe pain during sex due to menopause ^{[61, 62]}. It acts locally: in its phase III trial, blood steroid levels stayed within the normal postmenopausal range ^[62]. Its label says it should not be used with undiagnosed abnormal genital bleeding, and in a 52-week open-label trial 11 of 521 women (2.1 percent) had an abnormal Pap smear ^[76].

In that randomized, placebo-controlled trial (325 women on DHEA, 157 on placebo), 12 weeks of daily use lowered vaginal pH, improved vaginal cells and reduced pain during sex compared with placebo ^[62]. The only side effect judged related to treatment was vaginal discharge, in about 6% of women ^[62].

Bioavailability Enhancers

The DHEA trials on this page tested DHEA on its own.

Comparison of DHEA Forms

3. Evidence for Health Benefits

Anti-Aging and General Well-Being

The age-related decline in DHEA is the main reason it is sold to older adults ^[2]. Trials have not shown general benefits ^{[14, 15, 31]}.

Negative evidence from large trials: A meta-analysis of 23 randomized trials in 1188 postmenopausal women with normal adrenal function found no significant effect on libido, sexual function, lipids, glucose, weight or bone density, though confidence in the evidence was low ^[31]. A meta-analysis of 25 trials in 1353 older men found no effect on lipids, glucose, bone, sexual function or quality of life ^[44].

The DHEAge study gave 280 healthy men and women aged 60-79 years either 50 mg of DHEA or placebo daily for a year. DHEA-S returned to young-adult levels without harmful build-up of hormones; bone turnover improved in women over 70 years old, as did libido measures in these older women ^[13].

The DHEA and Well-Ness (DAWN) trial gave 110 men and 115 women aged 55 to 85 either 50 mg a day of DHEA or placebo for 1 year and found no benefit for thinking, mood, quality of life or sexual function ^[14].

Nair and colleagues gave DHEA or placebo for 2 years to 87 older men and 57 older women with low DHEA-S. DHEA did not change body composition, fitness, strength, insulin sensitivity or quality of life, although women taking DHEA gained bone density at the wrist ^[15].

Skin effects: In the DHEAge study, skin hydration, thickness, sebum production and pigmentation improved, particularly in women ^[13].

Immune function: An early study in people above age 65 suggested that DHEA sulfate taken before a flu vaccine might improve the antibody response ^[16]. A later randomized trial in 71 people aged 61-89 found that 50 mg of DHEA did not improve the flu vaccine response; among people with low starting antibody levels, fewer reached protective levels on DHEA than on placebo (52% vs 84%) ^[18]. In 50 men and 50 women given the Oxford-AstraZeneca COVID-19 vaccine, blood DHEA-S levels were not linked to the immune response ^[17].

Bone Mineral Density

Positive evidence in women: Weiss and colleagues gave 55 men and 58 women aged 65-75 either 50 mg a day of DHEA or placebo for a year, then DHEA to everyone for a second year; all took vitamin D (16 micrograms a day) and calcium (700 mg a day). In women, spine bone density rose by 1.7% in the first year on DHEA; it did not change in men, and hip bone density did not change ^[19].

DHEA cream for bone density: In the small, uncontrolled cream study, hip bone density rose after 12 months ^[11]. The lack of a placebo group limits what this shows.

Adrenal insufficiency: Trials in women with adrenal failure have not shown bone benefits. A crossover trial of 50 mg a day for 6 months in ten women found no significant change in bone mineral content or most bone markers ^[21], and a trial of 25 mg a day for 9 months found no change in markers of bone metabolism ^[34].

Lupus-related osteoporosis: In women with lupus taking glucocorticoids, 200 mg a day of prasterone for 1 year raised spine and hip bone density, while bone density fell on placebo ^[22]. A small crossover pilot study in premenopausal women did not support DHEA for preventing osteoporosis in mild lupus ^[23].

Depression

Small trials suggest DHEA may help some people with depression ^{[25, 26, 46]}.

HIV/AIDS-associated depression: In a trial of 145 people with HIV and mild but persistent depression, participants took DHEA (100-400 mg a day) or placebo for 8 weeks. The response rate was 56% on DHEA and 31% on placebo ^[26].

Midlife depression: Schmidt and colleagues treated 23 men and 23 women aged 45 to 65 years with midlife-onset major or minor depression, none on antidepressants, in a crossover trial: 90 mg a day for 3 weeks, then 450 mg a day for 3 weeks. Depression scores improved more on DHEA than on placebo; 23 people had at least a 50% drop in scores on DHEA, against 13 on placebo ^[25].

Mechanism: DHEA and DHEA-S are also made in the brain; proposed actions include protecting nerve cells and opposing the effects of glucocorticoids ^[24].

Synthesis: The trials are small and short, and one used 450 mg a day ^[25]. In a third trial, of 22 people with major depression, DHEA at a maximum dose of 90 mg a day for 6 weeks lowered depression scores more than placebo, and the authors called for larger trials ^[46].

Systemic Lupus Erythematosus (SLE)

Lupus (SLE) is an autoimmune disease, and DHEA (as prasterone) has been tested as an add-on treatment in women with it ^{[28, 63]}.

Corticosteroid dose reduction: In a trial of 191 women with lupus taking prednisone, 200 mg of prasterone a day for 7-9 months let 55% reduce prednisone to 7.5 mg a day or less, against 41% on placebo; the difference was significant only in women with active disease (51% vs 29%) ^[28]. A trial of 381 women with active lupus found that 200 mg a day improved or stabilized the disease in 58.5% of women with clinically active disease, against 44.5% on placebo ^[63]. An earlier open-label study of 50 women also reported lower prednisone doses ^[29].

Osteoporosis prevention in SLE: A 1-year trial found bone density gains on prasterone ^[22], while a small pilot study did not support it ^[23].

Larger context: The FDA did not approve prasterone for lupus ^[74].

Sexual Function and Erectile Dysfunction

Erectile dysfunction in men with low DHEA: In a trial of 40 men with erectile dysfunction and low DHEA-S, 50 mg of DHEA a day for 6 months gave higher erectile function scores than placebo; the authors judged the sample too small for firm statistics ^[30]. A meta-analysis of trials in older men found no effect on sexual function ^[44].

Vulvovaginal atrophy in postmenopausal women: The 6.5 mg vaginal insert is the best-established medical use of DHEA ^{[61, 62]}. Oral DHEA did not significantly improve libido or sexual function in postmenopausal women with normal adrenal function ^[31].

Mechanism in women: Vaginal DHEA is converted inside vaginal tissue to active hormones, while blood steroid levels stay in the normal postmenopausal range ^[62].

Schizophrenia (Adjunctive Therapy)

A few small trials have tested DHEA added to antipsychotic medicines for schizophrenia.

Nachshoni and colleagues added 100 mg of DHEA a day or placebo to antipsychotic treatment in inpatients with schizophrenia; DHEA improved movement side effects of the medicines, especially parkinsonism ^[32].

In a 12-week crossover trial, 200 mg a day of DHEA did not improve symptoms, side effects or quality of life compared with placebo, though attention and movement skills improved ^[33]. A later 8-week trial using 400 mg a day found that movement side effects improved more than on placebo, but general symptoms improved less ^[64].

The results are small and mixed, and need replication before clinical recommendations can be made.

Adrenal Insufficiency

People with adrenal insufficiency lack DHEA. Unlike cortisol and aldosterone, DHEA is not considered essential for life, so it is not routinely replaced ^[65].

Primary adrenal insufficiency (Addison's disease): Results are mixed. In a crossover trial of 24 women with adrenal insufficiency, 50 mg a day for four months improved well-being, depression and anxiety scores and sexual interest compared with placebo ^{[8, 35]}. A trial of 25 mg a day for 9 months in 39 women with adrenal failure found no benefit for well-being or sexuality, and 89% of women on DHEA had side effects, mainly stronger sweat odour and an itchy scalp ^[34]. A trial of 50 mg a day for 6 months in ten women found no effect on muscle, fat or bone, and 60% reported oily-skin side effects ^[21].

Pituitary insufficiency (hypopituitarism): Brooke and colleagues added 50 mg of DHEA or placebo for 6 months in people with hypopituitarism on growth hormone, analysing 26 women and 18 men. Quality of life improved modestly in women, with small gains in self-esteem and mood in men ^[36].

Current guidelines: The evidence on DHEA replacement is inconsistent, it is unclear which patients are most likely to benefit, and recent trials are few ^[65].

Fertility and IVF

DHEA has been used before in-vitro fertilization (IVF) in women with low ovarian reserve; a review reported that about one third of IVF centres used it ^[38].

Mechanism: The idea is that androgens made from DHEA support early follicle growth ^{[38, 39]}.

Evidence: Early case series reported better responses to ovarian stimulation, such as a series of five women given 80 mg a day of DHEA for 2 months ^[39], and a review of this early work suggested 50-75 mg a day for at least 4 months ^[40]. These reports were small and uncontrolled.

A Cochrane review of 17 trials (1496 women) linked DHEA before IVF with higher live birth or ongoing pregnancy rates, but the effect was no longer significant when trials at high risk of bias were removed, and there was too little evidence to judge safety ^[42]. Its update, with 28 trials, found that DHEA likely makes little or no difference to live birth or ongoing pregnancy rates (OR 1.30, 95% CI 0.95 to 1.76) ^[66].

The largest single trial, of 821 poor responders in China, found live births in 8.8% of women on DHEA and 9.0% on placebo (relative risk 0.98, 95% CI 0.63 to 1.51) ^[41].

Synthesis: The best recent evidence finds little or no benefit from DHEA before IVF ^{[41, 66]}.

Athletic Performance and Body Composition

Most trials of DHEA for exercise performance or body composition have found no benefit ^{[6, 43, 44]}.

Negative evidence: In young, recreationally trained women, taking 100 mg a day of DHEA for 28 days left sprint performance and body composition unchanged, despite large rises in DHEA and testosterone ^[6]. In sedentary postmenopausal women, 50 mg a day for 12 weeks added nothing to the gains from endurance and resistance training ^[43].

A meta-analysis of 25 trials in older men found a small fall in fat mass, which disappeared after adjusting for rises in testosterone and estradiol ^[44].

Weight loss: DHEA did not change body composition in long-term trials ^[15]. Its relative 7-keto DHEA raised resting metabolic rate in one short trial in dieters ^[7].

Banned status: WADA bans DHEA, although its effect on performance in female athletes had not been studied before the trial above ^[6].

Chronic Fatigue Syndrome

Early, uncontrolled evidence suggests DHEA might help chronic fatigue syndrome (CFS). In an uncontrolled 6-month study of 23 women aged 35 to 55 with low DHEA-S, oral DHEA starting at 25 mg was followed by less fatigue and pain ^[45]. The authors called for controlled trials ^[45].

Cognitive Function

DHEA is made in the brain ^[24], but trials in healthy older adults have not shown cognitive benefits ^[14].

In the DAWN trial, 50 mg a day for 1 year did not change performance on six cognitive tests ^[14]. In women with adrenal insufficiency, DHEA did not change cognitive performance either ^[35].

In schizophrenia, one trial found DHEA improved attention and movement skills ^[33].

Synthesis: DHEA does not appear to improve thinking in healthy older adults ^[14].

Cardiovascular Effects

The effects of DHEA on the heart and blood vessels are uncertain.

Epidemiological associations: In a 12-year study of 242 men aged 50 to 79 years, lower DHEA-S levels were linked with higher death rates from heart disease ^[47]. An association like this does not show that taking DHEA protects the heart.

HDL cholesterol reduction: A meta-analysis of 23 studies found that DHEA lowered HDL ("good") cholesterol by 3.1 mg/dL on average, with the fall seen in women (5.1 mg/dL) but not in men; total cholesterol, LDL and triglycerides did not change ^[67]. HDL also fell in trials in women with adrenal insufficiency ^[8] and lupus ^{[23, 63]}.

Foam cell formation and atherosclerosis: In a laboratory study, DHEA increased foam cell formation by human macrophages, a possible early step in artery plaque ^[49]. This was a cell study, not evidence of harm in people.

Triglycerides: Pooled trials show no change in triglycerides ^[67]. In ten women with adrenal failure, 50 mg a day for 6 months did not change heart function, blood pressure or blood vessel function ^[20].

Synthesis: DHEA may lower HDL cholesterol, especially in women ^[67], and trials have not shown heart benefits ^[20].

4. Recommended Dosing

Dosing by Indication

Doses in trials vary with the condition, from 25 mg a day in adrenal failure ^[34] to 200 mg a day in lupus ^[28] and 450 mg a day in depression ^[25]. These are trial doses, not recommendations.

General Guidance

Many trials used 50 mg a day ^{[8, 13, 19]}. In older adults this dose restored DHEA-S to young-adult levels, with small rises in testosterone and estradiol, mostly in women ^[13].

When using DHEA:

• Use it under medical supervision
• Expect a stronger androgen effect in women: at 100 mg a day, androgens in women rose above the young-adult range, while men's did not change ^[48]

Important Considerations

DHEA is a hormone precursor, not a typical dietary supplement. Self-dosing without medical advice is not recommended because:

• The conversion of DHEA to testosterone and estrogen differs between men and women ^[48]
• Safety data for DHEA therapy are lacking ^[4]
• Prasterone doses of 100-200 mg a day, as used in lupus trials, produced hormone levels above the normal range ^[74]

5. Safety and Side Effects

General Safety Profile

In a year-long trial of 50 mg of DHEA a day in older adults, blood tests showed no harmful build-up of hormones ^[13]. Meta-analyses found no increase in serious adverse effects in postmenopausal women ^[31] and no change in liver enzymes ^[72]. Long-term safety data are lacking ^[4], and because DHEA is a hormone precursor, its side effects differ from those of most supplements.

Androgenic Side Effects (Primarily in Women)

DHEA can raise testosterone, particularly in women ^{[13, 48]}, leading to:

• Acne: the most common side effect in lupus trials, in 33% of women on 200 mg a day against 14% on placebo ^[63]
• Hirsutism (excess facial or body hair): 16% against 2% in the same trial ^[63]
• Oily skin and stronger sweat odour: 60% reported oily-skin effects at 50 mg of DHEA a day in one small trial ^[21], and 89% had side effects such as sweat odour and scalp itching at 25 mg of DHEA a day in another ^[34]

Most acne and hair growth in the lupus trial was mild and did not require stopping treatment ^[63]. Women are more sensitive because DHEA raises their androgen levels more than men's ^[48].

Estrogenic Concerns

Because DHEA is converted to estrogen ^[4]:

• A review advises caution with DHEA supplements, particularly in obese postmenopausal women, because DHEA could encourage breast cancer growth ^[68]. The prescription label for vaginal prasterone notes that estrogen is one of its breakdown products, that estrogen is contraindicated in women with a known or suspected history of breast cancer, and that the insert has not been studied in these women ^[76]. Women who have had breast cancer should ask their specialist before using DHEA
• There is not enough evidence to confirm that vaginal DHEA is safe for women with breast cancer ^[70]

Cardiovascular Risks

• HDL cholesterol reduction: pooled trials show a fall in HDL, mainly in women ^[67]
• Triglycerides: no change in pooled trials ^[67]
• Foam cell formation: a laboratory study found DHEA increased foam cell formation by human macrophages ^[49]

Cancer Associations

Observational and laboratory findings link DHEA with some hormone-related cancers:

• Prostate cancer: whether DHEA promotes or prevents prostate cancer is an open question ^[52]
• Ovarian cancer: in a blood-bank study, women who later developed ovarian cancer had higher DHEA levels before diagnosis than controls (15.9 nmol/L vs 9.7 nmol/L) ^[53]
• Breast cancer: postmenopausal women who later developed breast cancer had higher DHEA levels at least 9 years earlier than controls ^[51]

These are associations and laboratory findings, not proof that DHEA supplements cause cancer. They still warrant caution in anyone with a history of hormone-sensitive cancer ^[68].

Metabolic Effects

Pooled trials in postmenopausal women and in older men found no effect on blood glucose ^{[31, 44]}. The effect of DHEA in people with type 2 diabetes has not been fully worked out ^[54], so people with diabetes should check their glucose and talk with their doctor before using it.

Psychiatric Effects

A case report describes mania starting while a person was using DHEA ^[69].

Other Reported Side Effects

Prasterone trials have also reported ^[74]:

• High blood pressure
• Blood in the urine
• A rise in serum creatinine (a kidney blood test)

Liver enzymes did not change in pooled trials ^[72].

Special Populations

Pregnancy and nursing: The prescription label for vaginal prasterone covers only postmenopausal women; it has no data on use in pregnancy and no information on whether prasterone passes into breast milk ^[76]. With no safety data, it is safest to avoid DHEA during pregnancy or breastfeeding unless a doctor prescribes it ^[76].

Severe liver or kidney disease: The vaginal prasterone label says the effect of kidney or liver impairment on how the body handles prasterone has not been studied ^[76].

Children and adolescents: The vaginal prasterone label says its safety and effectiveness have not been established in children ^[76].

Duration of Use

Long-term safety data for DHEA are lacking ^[4]. The 2-year trial by Nair and colleagues is among the longest placebo-controlled trials ^[15]. The safety of DHEA supplementation beyond 2 years is unknown.

6. Drug Interactions

Cytochrome P450 3A4 Interactions

In human liver cells grown in the laboratory, DHEA increased the activity of CYP3A4 and several other drug-processing enzymes, and the authors warned of possible drug interactions ^[75]. Whether this changes medicine levels in people taking DHEA is unknown. If you take prescription medicines, check with your doctor or pharmacist before starting.

Hormonal Medications

Because DHEA is converted to both androgens and estrogens ^[4], a drug review lists possible interactions with 5-alpha reductase inhibitors and additive or opposing effects with androgens, estrogens, oral contraceptives and progestins ^[74]:

• Hormone replacement therapy (HRT): possible additive estrogen or androgen effects ^[74]
• Oral contraceptives: possible additive or opposing hormonal effects ^[74]
• Aromatase inhibitors (e.g., anastrozole, letrozole): DHEA can be converted to estrogen ^[4], so it may work against these breast cancer drugs
• 5-alpha reductase inhibitors (e.g., finasteride): a possible interaction ^[74]
• Testosterone therapy: additive androgen effects are possible ^[74]

Insulin and Hypoglycemic Agents

The effect of DHEA on glucose in people with type 2 diabetes has not been fully worked out ^[54]. If you take insulin or other glucose-lowering medicines, check your glucose more often and talk with your doctor.

Anticoagulants

An effect of DHEA on warfarin or other anticoagulants has not been shown. If you take an anticoagulant, check with your doctor or pharmacist before starting.

Corticosteroids

In a lupus trial, prasterone let more women with active disease lower their prednisone dose ^[28]. Any change to steroid doses should be managed by a specialist.

Summary of Key Interactions

7. Dietary Sources

DHEA is not found in food in meaningful quantities. The body makes it, mainly in the adrenal glands ^[47].

Wild Yam and Soy: Common Misconceptions

Yam extracts are used to make commercial steroids ^[73]. Taking a yam extract does not raise DHEA: in older adults, 3 weeks of a yam extract (dioscorea) left blood DHEA-S unchanged, while 85 mg a day of DHEA raised blood DHEA ^[73].

Products sold as "wild yam" or "natural DHEA" that contain only yam extract are unlikely to raise DHEA levels ^[73].

Supporting Natural DHEA Production

While no food directly provides DHEA, some lifestyle factors are linked with DHEA levels:

• Exercise: A single bout of resistance exercise raised DHEA in women aged 19-69 years ^[56], and a treadmill test raised DHEA in older adults ^[57]
• Stress management: People who reported stress at work had 23% lower DHEA-S levels than those who did not ^[58]

Nutrients That Support Adrenal Health

The adrenal glands hold high levels of vitamin C, a cofactor for hormone production; the evidence comes mostly from animal and cell studies ^[59].