5-androsten-3beta-ol-17-one

Other Names

(3β)-3-Hydroxyandrost-5-en-17-one(3β)-3-Hydroxyandrost-5-ene-17-one3-Hydroxyandrost-5-en-17-one3β-Hydroxy-5-androsten-17-one3β-Hydroxyandrost-5-en-17-one3β-Hydroxyandrost-5-ene-17-one5,6-Didehydroepiandrosterone5-DehydroepiandrosteroneAndrost-5-en-17-one, 3-hydroxy-, (3β)-Androst-5-en-17-one, 3β-hydroxy-Androst-5-en-3β-ol-17-oneAndrost-5-ene-3β-ol-17-oneAndrostenoloneD5-Androsten-3β-ol-17-oneDehydro-epi-androsteroneDehydroepiandrosteroneDehydroisoandrosteroneDHEADiandroneDidehydroepiandrosteronePrasteronaPrasteronePsicosteroneTrans-dehydroandrosteroneΔ5-Androsten-3β-ol-17-oneδ5-Epiandrosterone

Synopsis

5-Androsten-3β-ol-17-one (Dehydroepiandrosterone / DHEA): A Comprehensive Reference

1. Identity, Chemical Nomenclature, and Forms

1.1 Chemical Names and Identifiers

Dehydroepiandrosterone (DHEA), also known as 3-beta-hydroxyandrost-5-en-17-one, dehydroisoandrosterone, trans-dehydroandrosterone, Δ5-androsten-3-β-ol-17-one, and prasterone, is a naturally occurring intermediate formed in the course of synthesis of various steroids from cholesterol. The International Union of Pure and Applied Chemistry (IUPAC) name most commonly used in scientific literature is (3β)-3-hydroxandrost-5-en-17-one. DHEA, 5-androsten-3β-ol-17-one, and DHEAS belong to the C19 steroid family. Its molecular formula in free form is C₁₉H₂₈O₂, with a molecular weight of 288.42 g/mol.

Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor and one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain, and functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors.

1.2 Natural Sources and Biosynthesis

Dehydroepiandrosterone (5-androsten-3β-ol-17-one) is a naturally occurring C-19 adrenal steroid derived from cholesterol by a series of cytochrome P450-dependent monooxygenase and hydroxysteroid dehydrogenase catalyzed reactions. DHEA is secreted primarily by the zona reticularis of the adrenal cortex of humans and other primates. DHEA secretion is controlled by adrenocorticotrophin (ACTH) and other pituitary factors. The adrenal cortex daily synthesizes DHEA from cholesterol and secretes 75–90% of the body's DHEA, with the remainder being produced by the testes and ovaries.

The biosynthesis of dehydroepiandrosterone (DHEA) from cholesterol involves only two enzymes, both cytochrome P450s. The conversion of cholesterol to pregnenolone is mediated by cholesterol side-chain cleavage enzyme (CYP11A1), which is found in the mitochondria. The cleavage of pregnenolone to DHEA requires both the 17alpha-hydroxylase and 17,20-lyase activities of CYP17, which is found in the endoplasmic reticulum. DHEA can be further converted to DHEAS by DHEA sulfotransferase (SULT2A1). Levels of DHEA-S in circulation are approximately 250 to 300 times those of DHEA.

Adrenal production of DHEA begins during puberty, peaks at the age of 20 years, and declines with ageing beginning at the age of 25 years. This hormone progressively declines at the rate of 2% per year. After achieving a plateau level during early adulthood (ages 16 to 24), total serum DHEA (DHEA + DHEA-S) declines steadily to about 5 to 10% of peak values by age 60 to 70. This age-related decline is termed adrenopause. DHEA levels decline significantly with age, a phenomenon termed "adrenopause," prompting interest in supplementation to mitigate age-related symptoms.

DHEA and DHEAS are produced de novo in the brain, hence their classification as neurosteroids. In humans, the brain-to-plasma ratios for DHEA and DHEAS are 4–6.5 and 8.5, respectively, indicating a specific neuroendocrine role for these hormones.

1.3 Commercial Sources and Preparations

DHEA and its metabolites are naturally synthesized in the body through the cholesterol–pregnenolone pathway and can also be synthesized from various other sources like diosgenin, genistein, wild yam, soy, and cholesterol in the laboratory. Many nonprescription preparations of DHEA are developed in China and are likely to contain DHEA derived from diosgenin that has been extracted from the root of wild yam (Dioscorea villosa). Other commercial preparations contain synthetically derived DHEA.

Extracts of wild yam — specifically Mexican yam — can be processed in laboratories for the production of DHEA. Yams of various species belonging to the family Dioscoreaceae help in the isolation of diosgenin, which leads to conversion into steroidal compounds. An important distinction applies here: DHEA can also be synthesized from precursors in the wild Mexican yam; however, consumption of wild yam may not be an effective supplement as the body is unable to convert the precursors to DHEA. The laboratory chemical transformation — first developed commercially by chemist Russell Marker — is required; in the 1940s, Marker perfected a method of synthesizing progesterone from a constituent of wild yam called diosgenin; this process involved several chemical transformations carried out in the laboratory.

These supplements are not regulated by the US Food and Drug Administration (FDA) and are exempt from pharmaceutical quality standards; wide variations in DHEA content among products have been described. In contrast, the prescription product Intrarosa (prasterone) is an FDA-approved pharmaceutical. Intrarosa is a prescription vaginal pessary containing 6.5 mg of prasterone (dehydroepiandrosterone, or DHEA) and is used to treat moderate to severe symptoms of vulvovaginal atrophy (VVA) — also known as genitourinary syndrome of menopause (GSM) — in postmenopausal women. Over-the-counter dietary supplement forms include oral capsules and tablets (commonly ranging from 5 mg to 200 mg per dose), topical creams, and sublingual preparations, though these formulations are not FDA-approved for any specific indication.

2. Historical and Traditional Use

2.1 Discovery and Early Research History

DHEA was first isolated by the German biochemist Adolf Butenandt in the 1930s. For several decades after its discovery, DHEA remained a subject of biochemical investigation without widespread human application, as the biological significance of such an abundant circulating steroid was not initially well understood.

Since the Dietary Supplement Health and Education Act of 1994, dehydroepiandrosterone (DHEA, 5-androsten-3β-ol-17-one) has become widely available, and a large and growing market has developed for this "fountain of youth." DHEA has been shown to have significant beneficial effects in animals, which may lead to clinical uses in man. Historically, the U.S. Food and Drug Administration removed DHEA from the over-the-counter market in 1985 because there was no support for the health claims that were made for this product. The FDA banned over-the-counter sales of DHEA in 1985; however, since the passage of the Dietary Supplement Health and Education Act of 1994, DHEA has been widely available and marketed as a dietary supplement.

2.2 Traditional Ethnobotanical Context

DHEA itself — as an isolated steroid — is not part of any traditional herbal or botanical medicine system, as it was only isolated and characterized chemically in the 20th century. The plant from which it is most commonly manufactured commercially, Dioscorea villosa (wild yam), does have a documented history of traditional use, though this is conceptually distinct from the use of purified DHEA. Wild yam was historically used by Native American and Mexican herbalists for menstrual cramps, colic, and digestive discomfort. Wild yam root contains diosgenin — a naturally occurring steroidal saponin that serves as a precursor in the laboratory synthesis of hormones like progesterone and DHEA.

The therapeutic interest in DHEA supplementation itself arose not from traditional herbalism but from 20th-century endocrinology, particularly observations that DHEA declines markedly with age in parallel with the onset of various degenerative changes. Epidemiological evidence in humans and animal studies suggest that DHEA(S) may have cardioprotective, antiobesity, antidiabetic, and immuno-enhancing properties. These observations led to the proposal that restoration of DHEA to young adult levels may have beneficial effects on age-related conditions.

3. Key Constituents, Metabolites, and Mechanisms of Action

3.1 Principal Metabolic Pathways

A number of androgens and estrogens are synthesized in peripheral tissues by enzymes, which enables them to transform from DHEA to sex hormones including testosterone, dihydrotestosterone, androstenedione, and estrogens. DHEA is the physiological precursor in the synthesis of androgens and estrogen via androst-4-ene-3,17-dione (4-adione) in humans. This intracrine conversion — occurring locally within target tissues rather than being centrally delivered by the bloodstream — is considered especially important in postmenopausal women and elderly men, for whom the loss of adrenal androgen precursors results in a significant decrease in peripheral sex hormone levels, and adrenal androgens become the main source of sex hormones due to the natural decline in gonadal steroid production.

3.2 Nuclear Receptor Interactions

DHEA does not bind to or activate the progesterone, glucocorticoid, or mineralocorticoid receptors. Other nuclear receptor targets of DHEA besides the androgen and estrogen receptors include the PPARα, PXR, and CAR. However, whereas DHEA is a ligand of the PPARα and PXR in rodents, it is not in humans. In addition to direct interactions, DHEA is thought to regulate a handful of other proteins via indirect, genomic mechanisms, including the enzymes CYP2C11 and 11β-HSD1 — the latter of which is essential for the biosynthesis of the glucocorticoids such as cortisol and has been suggested to be involved in the antiglucocorticoid effects of DHEA — and the carrier protein IGFBP1.

Activation of the peroxisome proliferators activated receptor alpha (PPARα), pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated, leading to additional mechanisms by which DHEA may exert its biological effects.

3.3 Neurosteroid Mechanisms

DHEA and DHEAS exhibit diverse neuroactive properties through modulation of GABA-A, NMDA, and sigma-1 receptors. These neurosteroids contribute to neuroprotection, synaptic plasticity, and mood regulation. Specifically, the sulfate ester of DHEA (DHEA-S) is particularly potent in antagonizing gamma-aminobutyric acid type A (GABA-A) receptors and potentiating N-methyl-D-aspartate (NMDA) receptor activation through its agonist effects at sigma-1 receptors. DHEA and DHEAS are both non-competitive antagonists towards GABA-A receptors, whereas DHEAS demonstrates a more potent inhibitory tendency.

DHEA and DHEA-S have neuroprotective effects, possibly via effects on glucocorticoid receptors, and can stimulate neurogenesis. DHEA/S stimulates neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis, and secretion. In the brain, DHEA is classified as a neurosteroid and may act as a modulator of GABA-A and glutamate NMDA receptors.

3.4 Immunomodulatory Mechanisms

There is evidence that DHEA has an immunomodulatory effect as well as an androgenic role, both of which may potentially have benefits in people with SLE. In vitro, DHEA reduces circulating inflammatory drivers such as interleukin-6 and up-regulates interleukin-2. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects.

3.5 Complexity of Mechanism

Many studies have been undertaken in attempts to elucidate the mechanism(s) responsible for these effects, but the data available so far indicate that DHEA acts at various sites and levels rather than by a unifying mechanism. The mechanism by which DHEA exerts its pleiotropic effects in humans and rodents is not well understood but may involve metabolism of DHEA into biologically active oxygenated metabolites.

4. Scientific Evidence by Area of Use

4.1 Genitourinary Syndrome of Menopause / Vulvovaginal Atrophy

This is the area with the highest quality clinical evidence and the only indication for which a DHEA-based product has received regulatory approval. Intrarosa is the first agent approved by the Food and Drug Administration (FDA) to treat women experiencing moderate-to-severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. During menopause, vaginal tissue estrogen levels decrease, which may lead to VVA. Intrarosa is the first FDA-approved product containing the active ingredient prasterone, which is also known as dehydroepiandrosterone (DHEA).

Prasterone is approved by the US Food and Drug Administration for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone has been shown to decrease the pain associated with dyspareunia, and to improve vaginal pH, as well as superficial and parabasal cell counts, while maintaining serum hormone levels within the range of those seen in normal postmenopausal women. Prasterone (Intrarosa) is a steroid approved by the US FDA in 2016 at a dose of 6.5 mg and a concentration of 0.50% for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone is administered as a vaginal insert once daily at bedtime, does not carry a boxed warning in its label, and has no restrictions on duration of use.

Particularly in postmenopausal women, DHEA has shown potential benefits in treating genitourinary syndrome of menopause (GSM), including improved vaginal health, lubrication, and sexual function. A pivotal pharmacokinetic study confirmed that intravaginal prasterone provides local action without clinically significant changes in serum concentrations of estrogens or androgens, distinguishing it from systemic hormone therapy.

Strength of evidence: Strong — multiple phase 3 randomized controlled trials (RCTs) supported FDA approval. Evidence is specific to the intravaginal route at 6.5 mg/day; evidence for oral DHEA in GSM is more limited.

4.2 Adrenal Insufficiency and Addison's Disease

In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. In a double-blind trial, 106 subjects (44 males, 62 females) with Addison's disease were randomized to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body and truncal measures. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females, who experienced mild androgenic side effects.

An earlier smaller crossover RCT of 24 women with primary and secondary adrenal insufficiency (double-blind, placebo-controlled, randomized crossover design, with a DHEA dose of 50 mg/d; each patient received four months of treatment with DHEA and four months placebo, with a one-month washout period) found that DHEA treatment significantly improved overall wellbeing as well as scores for depression, anxiety, and their physical correlates; furthermore, DHEA significantly increased both sexual interest and the level of satisfaction with sex. DHEA replacement had no influence on cognitive performance.

Although there is evidence from some randomized, placebo-controlled clinical trials that DHEA replacement therapy has shown significant benefits on mood, sexuality, and quality of life in women with adrenal insufficiency, further studies with prolonged observation periods and dosage adjustments are desirable.

Strength of evidence: Moderate for mood and well-being in women with adrenal insufficiency. Mixed for sexual function, bone, and cognition. Evidence base is limited by small sample sizes and methodological inconsistencies across trials.

4.3 Systemic Lupus Erythematosus (SLE)

Androgens and DHEA are reduced (by approximately 50%) in women with SLE, especially those with active disease, and are further reduced by corticosteroid administration. DHEA has shown promise for the treatment of SLE in three controlled and several uncontrolled clinical trials, including one large multicenter study comprising nearly 200 patients.

A Cochrane-style review of seven RCTs (842 participants) found that DHEA: had little clinical effect on disease activity in those with mild/moderate disease (measured by SLEDAI or SLAM) but one study demonstrated evidence of stabilisation or improvement in 8.3% more patients than those treated with placebo; had a modest but clinically significant improvement in health-related quality of life measured by Patient Global Assessment, estimated as 11.5 mm on a 100 mm scale by meta-analysis; and resulted in a greater number of patients experiencing adverse events, particularly androgenic effects such as acne, where patients' risk was doubled when compared to placebo (RR 2.2; 95% CI 1.65 to 2.83).

The benefits might include an amelioration of disease activity, decreasing corticosteroid requirements, diminished SLE flares, improved cognitive function, and possibly some degree of protection against corticosteroid-induced osteoporosis. Regarding bone outcomes specifically, several studies have examined the use of DHEA (prasterone) at a dose of 200 mg/day in SLE patients; one trial demonstrated that prasterone provided mild protection against bone loss in female SLE patients on chronic steroids. However, in premenopausal women with quiescent SLE, use of DHEA does not have a significant effect on BMD; DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates.

Strength of evidence: Moderate for quality-of-life improvement in SLE; weak-to-moderate for bone protection in glucocorticoid-treated SLE patients. Effects on disease activity are modest and inconsistent.

4.4 Mood and Depression

A National Institute of Mental Health (NIMH) randomized, placebo-controlled crossover trial found that both men and women taking DHEA showed significant improvement on the Hamilton Depression Rating Scale (HAM-D) in depression severity compared to both baseline (p < 0.01) and placebo conditions (p < 0.01). During the placebo phase, there was no significant difference in depressive symptoms from baseline. The researchers also observed beneficial effects on symptoms of loss of libido; DHEA administration resulted in an improvement overall in sexual functioning compared with baseline and placebo, and this improvement was in parallel with improvements in mood.

A separate RCT in HIV/AIDS patients with subsyndromal depression enrolled 145 patients randomized to DHEA or placebo. On the basis of clinicians' ratings, DHEA was superior in the intent-to-treat analysis, where the response rate was 56% for the DHEA group versus 31% for the placebo group. In the completer analysis, the response rate was 62% for the DHEA group, compared to 33% for the placebo group. Nonmajor but persistent depression is common in patients with HIV/AIDS, and DHEA appears to be a useful treatment that is superior to placebo in reducing depressive symptoms.

Strength of evidence: Preliminary to moderate. Evidence from small-to-medium RCTs suggests a mood-improving effect, particularly in individuals with low DHEA/DHEAS levels or specific clinical populations (adrenal insufficiency, HIV-related depression). Evidence in the general population is insufficient.

4.5 Cognitive Function

A review of available clinical trials having cognitive domains as the main or secondary outcome found that although cross-sectional evidence suggests a positive association between DHEA/S and cognitive function, longitudinal studies and RCTs using DHEA oral treatment (50 mg/day) in normal or older adult subjects with or without dementia produced conflicting and inconsistent results. In summary, the current data do not provide clear evidence for the usefulness of DHEA treatment to improve cognitive function in adult–older subjects.

The DHEA and Well-Ness (DAWN) trial, a year-long RCT, confirmed this finding: there were no beneficial effects of DHEA supplementation on quality of life, including mood, perceptions of physical and emotional health, life satisfaction, or sexual function. The results of this year-long clinical trial are in accord with other shorter-term studies with smaller sample sizes that also found no effects of DHEA supplementation on cognitive function. No effects of DHEA were found on cognitive function in a nonclinical sample of 46 men aged 62 to 76 who received 50 mg DHEA daily for 13 weeks; similarly, a clinical trial of 60 symptomatic perimenopausal women aged 45 to 55 randomized to 50 mg/day of DHEA or placebo for 3 months found no differences in cognitive function.

Strength of evidence: Weak. Despite epidemiological associations between higher DHEA/S levels and cognitive performance, RCT evidence does not support a benefit of DHEA supplementation on cognition in the general aging population.

4.6 Sexual Function and Libido

Research about the effects of DHEA for sexual dysfunction is conflicting. In populations with documented adrenal insufficiency, evidence is more consistent: women with adrenal insufficiency treated with oral DHEA replacement demonstrated significant improvement in overall well-being, as well as in frequency of sexual thoughts, sexual interest, and satisfaction. Some early randomized trials that suffered from methodological issues, such as small number of participants, short treatment duration, and supraphysiological doses, demonstrated positive effects of DHEA replacement on sexual function and well-being. However, other studies failed to show any benefit of DHEA replacement on sexual function, well-being, and menopausal symptoms in peri- and postmenopausal women.

In general, postmenopausal women do not benefit from oral DHEA, and women with intact adrenal function do not necessarily benefit from DHEA supplementation.

Strength of evidence: Moderate for women with adrenal insufficiency; weak for the general postmenopausal population using oral DHEA. Strong for intravaginal DHEA in the specific context of dyspareunia associated with GSM (see Section 4.1).

4.7 Bone Mineral Density and Osteoporosis

Evidence on DHEA and bone density exists primarily in three populations: older adults (general population), Addison's disease patients, and SLE patients on corticosteroids. In the Addison's disease RCT, DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites. In postmenopausal and glucocorticoid-treated SLE patients, low serum DHEAS levels, which are associated with low BMD, have been demonstrated in patients with SLE. Studies in postmenopausal and GC-treated SLE patients with active disease have shown that DHEA treatment offers mild protection against bone loss. However, the therapeutic use of this hormonal supplement is limited since DHEA is not approved for the prevention of bone loss in GC-treated SLE patients.

Strength of evidence: Weak-to-moderate and condition-specific. Benefits appear limited to subpopulations with deficiency states (adrenal insufficiency, SLE on steroids). Evidence is insufficient to recommend DHEA for bone protection in the general population.

4.8 General Aging and Well-Being

During the last decades, several epidemiologic and cohort studies have shown the age-related circulating levels of DHEA/DHEAS; these first increase in childhood (adrenarche), peak in the 3rd decade of life, and progressively decrease in midlife (adrenopause). The potential clinical and therapeutic roles of DHEA/DHEAS have been studied extensively, but the data remain controversial and largely inconclusive. Almost all of the biological data was on animals and there was a lack of demonstrated efficacy in humans. Recently there have been a number of small clinical trials in humans but the results have not been as positive as in the animal tests.

Strength of evidence: Weak for the general anti-aging claim. No large, well-designed long-term RCT in healthy older adults has established that DHEA supplementation meaningfully reduces age-related decline across a broad range of outcomes.

4.9 Cardiometabolic Areas

Epidemiological evidence in humans and animal studies suggest that DHEA(S) may have cardioprotective, antiobesity, and antidiabetic properties. In animal models, notable effects on atherosclerosis have been reported. Males with lower DHEA levels had a greater blockage of the arteries of the heart according to the literature, and there is growing evidence that increasing DHEA levels can reduce atherosclerosis and blockage of the arteries of the heart. Experimentally, it was reported that DHEA supplementation reduced atherosclerosis in rabbits by almost 50%. However, robust randomized clinical trial evidence in humans for cardiovascular outcomes is currently insufficient to support clinical recommendations.

5. Body Systems and Health Domains

Endocrine system: DHEA and DHEAS are the most abundant circulating steroid hormones, synthesized in the zona reticularis of the adrenal cortex, in the gonads, and in the brain. These steroid hormones can act as androgens, estrogens, and neurosteroids, and perform many roles in the human body.
Reproductive system: DHEA is a primary precursor for sex steroid biosynthesis via intracrine pathways. Intravaginal DHEA has an FDA-approved role in genitourinary syndrome of menopause.
Central nervous system: DHEA exhibits independent biological effects by binding to a range of nuclear and cell surface receptors. Additionally, DHEA acts as a neurosteroid and modulates neurotrophic factor receptors, making it significant in the central nervous system.
Immune and autoimmune system: There is evidence that DHEA has an immunomodulatory effect as well as an androgenic role, both of which may potentially have benefits in people with SLE.
Musculoskeletal system: Evidence suggests mild bone-protective effects in specific deficiency and corticosteroid-treated populations, as reviewed above.
Metabolic system: DHEA has been studied in relation to insulin sensitivity, body composition, and lipid metabolism, with mixed results in human trials.

6. Dosage Forms and Dosages Reported in Studies

6.1 Prescription Form (Prasterone / Intrarosa)

Prasterone (Intrarosa) is a steroid approved by the US FDA in 2016 at a dose of 6.5 mg and a concentration of 0.50% for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone is administered as a vaginal insert once daily at bedtime, does not carry a boxed warning in its label, and has no restrictions on duration of use.

6.2 Oral Doses Used in Clinical Research

The following doses have been used in the clinical studies described above and are reported here solely as observed in source-cited research:

50 mg daily of micronized DHEA orally for 12 months in a double-blind trial of 106 subjects with Addison's disease.
A DHEA dose of 50 mg/day was used in a crossover adrenal insufficiency trial; each patient received four months of treatment with DHEA and four months of placebo, with a one-month washout period.
50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, was studied in 39 patients with Addison's disease in a randomized, double-blind study.
200 mg/day oral DHEA for 1 year was evaluated in female patients with quiescent systemic lupus erythematosus.
25 mg of DHEA daily for one year was evaluated for mood, fatigue, and joint pain in older men with hormone deficiency.
50 mg/day of DHEA was used in a clinical trial of 60 symptomatic perimenopausal women aged 45 to 55 for 3 months.
One hundred forty-five patients with subsyndromal depression or dysthymia were randomly assigned to receive either DHEA or placebo in an 8-week trial.

Most studies have used doses ranging from 25–200 mg daily, though some have used higher amounts. DHEA is available as a dietary supplement in a wide range of doses. Wide dose variation exists across the research literature and among commercial products.

7. Safety Considerations and Drug Interactions

7.1 Documented Adverse Effects

Common side effects include acne, increased hair growth, and sexual problems. Serious side effects are rare and include hallucinations or psychosis. In adrenal insufficiency trials, minor side effects associated with taking DHEA in these studies include greasy skin, male-pattern hair growth in women, acne, scalp itching, and increased sweating. In SLE trials, DHEA resulted in a greater number of patients experiencing adverse events, particularly androgenic effects such as acne, where patients' risk was doubled compared to placebo (RR 2.2; 95% CI 1.65 to 2.83).

Other side effects may include slight changes in blood cholesterol, insulin, and triglyceride levels. Additional side effects that may occur are skin rash, breast tenderness or enlargement (in both men and women), oily skin, irregular or abnormal menstruation (women only), and lower blood pressure. There is also a possible risk of benign prostatic hyperplasia (BPH) as DHEA has been shown to increase a hormone that may prompt BPH.

Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects.

7.2 Hormone-Sensitive Conditions

DHEA can affect estrogen levels and may worsen hormone-sensitive conditions like breast cancer, ovarian cancer, and endometriosis. Taking high doses of DHEA or using it for a long time might raise the risk of hormone-sensitive cancers, such as prostate and breast cancers, but more research is needed. If you have a type of hormone-sensitive cancer, don't use DHEA. The prescription product Intrarosa similarly carries a warning: based on the fact that there is minimal data on safety in the setting of hormonally sensitive malignancy, the FDA warns against using prasterone if there is a history of or known or suspected breast cancer. While definitive evidence linking DHEA supplements to increased cancer risk is limited, people with a history of hormone-sensitive cancers or those at high risk should avoid DHEA supplementation. The potential for DHEA to stimulate the growth of existing hormone-sensitive tumors is a significant concern.

7.3 Cardiovascular and Metabolic Considerations

Consider avoiding use of DHEA if you have high cholesterol or a condition that affects the supply of blood to the heart (ischemic heart disease). DHEA might reduce high-density lipoprotein (HDL), or "good," cholesterol levels. DHEA can interfere with insulin.

7.4 Neuropsychiatric Considerations

Use of DHEA also might worsen mental health conditions and raise the risk of mania in people who have mood disorders.

7.5 Drug Interactions

DHEA may interact with certain medications, including blood thinners, hormone therapies, certain cancer treatments, and antidepressants. Key specific interactions include:

Anticoagulants and antiplatelet agents: DHEA might slow blood clotting. Taking DHEA along with medications that also slow clotting might increase the chances of bruising and bleeding. Medications that slow blood clotting include aspirin, clopidogrel (Plavix), NSAIDs such as diclofenac, ibuprofen, and naproxen, dalteparin, enoxaparin, heparin, and warfarin, among others.
Aromatase inhibitors: Exemestane (Aromasin) is used to help decrease estrogen in the body. Taking DHEA along with exemestane might decrease the effectiveness of exemestane. Do not take DHEA if you are taking exemestane. Some chemotherapy drugs for postmenopausal women with breast cancer work to lower estrogen levels, including anastrozole (Arimidex). Since DHEA is a precursor for estrogen, it can increase estrogen levels, potentially making anastrozole less effective.
Fulvestrant: Fulvestrant (Faslodex) is used for estrogen-sensitive cancers. DHEA might increase estrogen in the body and decrease the effectiveness of fulvestrant for treating cancer. Do not take DHEA if you are taking fulvestrant.
Herbal compounds with anticoagulant properties: Certain herbs can also slow blood clotting and should be used with caution if you take DHEA; these include angelica, clove, danshen, garlic, ginger, ginkgo, and Panax ginseng.
Hormonal contraceptives and estrogen/testosterone therapies: Interactions are a concern with birth control pills, patches, vaginal rings, implants, injections, or intrauterine devices that contain hormones, as well as exogenous estrogens.

7.6 Regulatory and Quality Considerations

The FDA banned over-the-counter sales of DHEA in 1985; however, since the passage of the Dietary Supplement Health and Education Act of 1994, DHEA has been widely available and marketed as a dietary supplement. Other forms of DHEA are used in dietary supplements that are not approved by the FDA. As with other supplements, DHEA is not regulated by the FDA. As a result, the quality and content of these products can vary. These supplements are exempt from pharmaceutical quality standards, and wide variations in DHEA content among products have been described.

Although its use is prohibited under the World Anti-Doping Code and the National Collegiate Athletic Association, several high-profile athletes have tested positive for DHEA.

References

Health Conditions

Health conditions that 5-androsten-3beta-ol-17-one may help support.

No conditions available.

Body Systems

Body systems that 5-androsten-3beta-ol-17-one may help support.

No body systems available.