What is DHEA?
The body produces 5–8 mg of DHEA every day, mostly in the adrenal glands. DHEA is made from another steroid hormone, pregnenolone, which itself is made from cholesterol.[5] In humans, DHEA is the second most abundant steroid after its sulfate ester, DHEA-S.[6] Rather than DHEA levels, blood tests usually measure DHEA-S levels, which are about a hundred times higher and fluctuate less during the day.[5]
The secretion of DHEA or supplementation with DHEA leads to increased levels of DHEA-S, a hydrophilic storage form of DHEA that stays in circulation. DHEA is the form that is transported into the tissues to be converted into the sex hormones (e.g., androgens and estrogens). Both DHEA and DHEA-S decrease significantly with age, with people in their 70s having less than 20% of the peak DHEA-S levels of young adults.[6][7][8][9] Since DHEA and DHEA-S are the most abundant circulating steroids in the body, and they decline with age, there is speculation that supplementation with DHEA and/or DHEA-S may reduce age-related declines in health.[6][10]
What are DHEA’s main benefits?
The strongest evidence for DHEA is for increasing estrogens and androgens (e.g., testosterone) in women over 60, and for improving postmenopausal symptoms.[2][3][11] However, DHEA might also increase testosterone levels in younger (<60 years old) populations.[2] While the evidence that DHEA supplementation increases androgens is fairly consistent,[12][11][5][4] the evidence that DHEA supplementation increases estrogens is as consistent, if not more so.[11][5][4] However, these androgen and estrogen increases tend to be small; DHEA supplementation has had no clinical effect on muscle strength, muscle size, fat loss,[13][14][1] or sexual function in older men.[5]
What are DHEA’s effects in older women?
What are DHEA’s effects in older men?
What are DHEA’s effects on aging and cognition?
What are DHEA’s effects on stress and mood?
What are DHEA’s effects on body composition and performance?
What are DHEA’s effects on fertility?
What are DHEA’s effects on cardiovascular disease?
What are DHEA’s main drawbacks?
DHEA is well-tolerated, but may cause side effects by increasing estrogen or testosterone levels. For example, in a study of postmenopausal women, 3 of 38 women in the DHEA group experienced acne, and 2 of 38 experienced facial hair growth.[15] In another study, the researchers noted an increase in voice lowering, another common effect of testosterone supplementation in women, among the DHEA group as compared to the placebo group.[16]
Supplementation with testosterone itself may adversely affect cardiovascular risk factors.[17] However, trials examining cardiovascular-risk-related outcomes (blood pressure[1] and liver enzymes[18]) have found no change after DHEA supplementation.
There are commonly occurring associations between sex hormones and the risk of certain types of cancer. For example, supplemental estrogen may increase the risk of some breast and gynecological cancers, and supplemental testosterone and its metabolite, dihydrotestosterone (DHT), may increase the risk of prostate cancer. For instance, one meta-analysis reported a 23% increased risk of breast cancer in participants who had used hormone replacement therapy (HRT).[19] Another meta-analysis examined exercise, HRT, and breast cancer risk. This study found that women who exercised the most reduced their risk of breast cancer—with the exception of women who also used HRT, who saw no exercise-related reduction in their breast cancer risk.[20] Furthermore, an increased risk of breast cancer recurrence was associated with HRT in hormone-receptor-positive breast cancer survivors.[21]
With regard to DHEA and gynecological cancers, the evidence is less clear. One study reported that in participants with endometrial cancer, increased DHEA and DHEA-S levels were noted in participants who survived longer, compared to participants with shorter survival duration.[22] Larger, stronger studies note that the evidence linking estrogen-containing HRT with endometrial cancer is so weak that it does not suggest significant harm, though the researchers noted a lack of high-quality evidence in certain areas.[23][24][25][26]
One meta-analysis reported no association between the risk of prostate cancer and DHEA-S levels, and also found no association with other androgens such as testosterone and DHT,[27] which have sometimes, but not consistently, been found to be associated with prostate cancer risk.[28] Furthermore, while this meta-analysis did find a relationship between sex hormone binding globulin (SHBG) and prostate cancer risk, DHEA does not tend to affect SHBG levels.[29][12]
Based on the possible increased risks of breast cancer, anyone supplementing with DHEA should discuss their plans with their doctor, with whom the benefits and risks of DHEA supplementation, and the resultant possible changes in sex hormones, can be appropriately evaluated for their individual situation.
How does DHEA work?
DHEA is believed to work indirectly by being converted to androgens or estrogens in peripheral target cells, and might theoretically also work directly by stimulating neurotransmitter receptors in the brain.[7]
Dosage information
DHEA has been studied at dosages of 25–200 mg/day, with dosages of 50–100 mg/day being more frequently examined.[1][2][3]
A subgroup analysis in one meta-analysis of randomized controlled trials found that dosages of over 50 mg/day resulted in higher testosterone levels than less than 50 mg/day.[2] However higher dosages of DHEA are likely to result in higher levels of estrogens as well.[4]
Examine Database: DHEA
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Frequently asked questions
The body produces 5–8 mg of DHEA every day, mostly in the adrenal glands. DHEA is made from another steroid hormone, pregnenolone, which itself is made from cholesterol.[5] In humans, DHEA is the second most abundant steroid after its sulfate ester, DHEA-S.[6] Rather than DHEA levels, blood tests usually measure DHEA-S levels, which are about a hundred times higher and fluctuate less during the day.[5]
The secretion of DHEA or supplementation with DHEA leads to increased levels of DHEA-S, a hydrophilic storage form of DHEA that stays in circulation. DHEA is the form that is transported into the tissues to be converted into the sex hormones (e.g., androgens and estrogens). Both DHEA and DHEA-S decrease significantly with age, with people in their 70s having less than 20% of the peak DHEA-S levels of young adults.[6][7][8][9] Since DHEA and DHEA-S are the most abundant circulating steroids in the body, and they decline with age, there is speculation that supplementation with DHEA and/or DHEA-S may reduce age-related declines in health.[6][10]
The strongest evidence for DHEA is for increasing estrogens and androgens (e.g., testosterone) in women over 60, and for improving postmenopausal symptoms.[2][3][11] However, DHEA might also increase testosterone levels in younger (<60 years old) populations.[2] While the evidence that DHEA supplementation increases androgens is fairly consistent,[12][11][5][4] the evidence that DHEA supplementation increases estrogens is as consistent, if not more so.[11][5][4] However, these androgen and estrogen increases tend to be small; DHEA supplementation has had no clinical effect on muscle strength, muscle size, fat loss,[13][14][1] or sexual function in older men.[5]
During the perimenopausal period, there are large reductions in estrogens and progesterones. By the time menopause begins, DHEA and testosterone levels have also reduced by 55%–60%.[30] DHEA has been studied as a potential therapeutic for postmenopausal women. A systematic review found that in postmenopausal women, supplementation with vaginal DHEA, testosterone, and estrogen were all associated, in a dose-response manner, with improvements in genitourinary complaints such as vaginal atrophy and sexual function.[31] Like other androgens, DHEA supplementation increases testosterone in postmenopausal women, but it is unique among supplemental androgens in also increasing estrogens.[30]
In addition, another systematic review found that in older women without health conditions, DHEA supplementation may have small benefits for bone mineral density; however, the benefits did not extend to men.[32] Although that meta-analysis did not evaluate fracture risk, one Mendelian randomization study found that women with genes predicting higher DHEA-S serum levels had higher bone mineral density and less risk of lower back and forearm fractures (but not hip or femoral fractures).[10]
A 2013 meta-analysis found that men over 50 taking DHEA had mild decreases in fat mass, but not after controlling for testosterone and estradiol levels. In other words, DHEA worked to increase testosterone (which may have reduced fat mass), but did not have any effects on fat mass on its own. Also, DHEA had no impact on lipids, glycemic metabolism, sexual function, or quality of life in older men.[5] In terms of muscle strength and physical function, one systematic review reported no consistent effects in men over 60.[14]
A small clinical trial in older men without health conditions, but with blood levels of DHEA-S below the normal range for younger men (and within the normal range for older men), confirmed that DHEA supplementation can raise DHEA-S levels effectively. It found that supplementation with a single dose of 50 mg of DHEA led to blood levels of DHEA-S levels similar to the average for young adult men, and supplementation with a single dose of 100 mg led to a higher average level than that seen in most young men. Testosterone and DHT levels remained unchanged at both doses compared to baseline, whereas estrogens increased in a dose-dependent way at both doses.[4]
As the body ages, in addition to DHEA levels decreasing, the catabolic (i.e., breakdown-causing) hormone cortisol generally increases, which can negatively affect cognition.[33] Fortunately, regular exercise seems to increase DHEA-S levels and decrease cortisol levels in adults 65 and older.[34]
Despite DHEA decreasing with age, cortisol increasing with age, and DHEA levels being higher in the central nervous system (suggesting a higher need for DHEA in the brain),[35][11] DHEA supplementation does not appear to benefit cognitive function in adults over 50.[36][11]
Cortisol, and perhaps DHEA, increase after exposure to situations that a person interprets as stressful.[37][38] It has been hypothesized that DHEA may counteract some of the effects of cortisol,[39] and that having higher levels of cortisol and lower levels of DHEA after stressful situations increases the risk of negative mood states, such as depression, anxiety, or anger.[39] It does appear that DHEA supplementation decreases cortisol,[18] though its effects on subjective stress levels or mood seem less consistent. For instance, a study of DHEA supplementation in military men undergoing 12-day survival training found that supplementation of 50–75 mg per day of DHEA did not affect participants’ subjective distress ratings.[40] In another study, the researchers found that low DHEA was associated with a higher risk of negative mood mood in men during and after a social stress test. However this only reflects internal DHEA production, and does not reflect supplementation with DHEA.[37]
In a randomized, placebo-controlled trial examining the broader implications of DHEA supplementation in twenty men and women with Addison’s disease (who have damaged adrenal glands, and as a result both produce very little cortisol and typically have lower levels of DHEA and androgens), participants took either placebo or 50 mg per day of DHEA for 4 months. Even in this unique population, DHEA supplementation did not show any significant effects on mood or on ratings of wellbeing. Besides mood, participating women saw increases in testosterone, participating men saw decreases in sex hormone binding globulin (which binds to and inactivates testosterone), and participants of both sexes saw decreases in body fat mass percentage (4% on average). No side effects were observed.[29] However, the applicability of these results to people without Addison’s disease is low.
Although DHEA supplementation increases androgens, these small increases may only prompt zero-to-small changes to muscle size and strength: a 2018 systematic review of randomized controlled trials (RCTs) concluded that supplementation with DHEA had no effects on muscle size or strength,[13] and a 2020 meta-analysis of RCTs found small benefits (often at doses 50–100 mg) to body composition: increased lean body mass (0.99 lbs) and decreased fat mass (-1%).[1]
The evidence for DHEA and fertility outcomes is inconsistent. It might help outcomes in women with poor ovarian response undergoing in vitro fertilization (IVF),[41][42] but one meta-analysis of randomized controlled trials in women with poor/diminished ovarian response found that while DHEA supplementation increased follicle count, ultimately there was no significant improvement in live birth rates.[43]
While lower DHEA-S levels have some associations with worsened health outcomes, such as cardiovascular disease,[44] supplementation with DHEA has not been shown to improve most of the biomarkers associated with negative cardiovascular outcomes. For example, supplementation with DHEA mostly has no effect on blood lipids, though researchers did note one negative effect: a reduction in high-density lipoprotein cholesterol, with a stronger effect noted in women.[45] Similarly, a meta-analysis found that DHEA does not appear to have any effect on glycemic markers, except by decreasing fasting glucose in a subgroup of adults over 60 who had taken less than 50 mg of DHEA per day for less than 12 weeks.[46] Furthermore, one randomized controlled trial (RCT) found that supplementation with testosterone and 50 mg of DHEA had no effect on systemic lipolysis (fat metabolism) in adults over 60.[47] However, one RCT did find that DHEA supplementation decreased (improved) arterial stiffness in men and women over 65 (and increased their estradiol).[48]
DHEA is well-tolerated, but may cause side effects by increasing estrogen or testosterone levels. For example, in a study of postmenopausal women, 3 of 38 women in the DHEA group experienced acne, and 2 of 38 experienced facial hair growth.[15] In another study, the researchers noted an increase in voice lowering, another common effect of testosterone supplementation in women, among the DHEA group as compared to the placebo group.[16]
Supplementation with testosterone itself may adversely affect cardiovascular risk factors.[17] However, trials examining cardiovascular-risk-related outcomes (blood pressure[1] and liver enzymes[18]) have found no change after DHEA supplementation.
There are commonly occurring associations between sex hormones and the risk of certain types of cancer. For example, supplemental estrogen may increase the risk of some breast and gynecological cancers, and supplemental testosterone and its metabolite, dihydrotestosterone (DHT), may increase the risk of prostate cancer. For instance, one meta-analysis reported a 23% increased risk of breast cancer in participants who had used hormone replacement therapy (HRT).[19] Another meta-analysis examined exercise, HRT, and breast cancer risk. This study found that women who exercised the most reduced their risk of breast cancer—with the exception of women who also used HRT, who saw no exercise-related reduction in their breast cancer risk.[20] Furthermore, an increased risk of breast cancer recurrence was associated with HRT in hormone-receptor-positive breast cancer survivors.[21]
With regard to DHEA and gynecological cancers, the evidence is less clear. One study reported that in participants with endometrial cancer, increased DHEA and DHEA-S levels were noted in participants who survived longer, compared to participants with shorter survival duration.[22] Larger, stronger studies note that the evidence linking estrogen-containing HRT with endometrial cancer is so weak that it does not suggest significant harm, though the researchers noted a lack of high-quality evidence in certain areas.[23][24][25][26]
One meta-analysis reported no association between the risk of prostate cancer and DHEA-S levels, and also found no association with other androgens such as testosterone and DHT,[27] which have sometimes, but not consistently, been found to be associated with prostate cancer risk.[28] Furthermore, while this meta-analysis did find a relationship between sex hormone binding globulin (SHBG) and prostate cancer risk, DHEA does not tend to affect SHBG levels.[29][12]
Based on the possible increased risks of breast cancer, anyone supplementing with DHEA should discuss their plans with their doctor, with whom the benefits and risks of DHEA supplementation, and the resultant possible changes in sex hormones, can be appropriately evaluated for their individual situation.
DHEA is believed to work indirectly by being converted to androgens or estrogens in peripheral target cells, and might theoretically also work directly by stimulating neurotransmitter receptors in the brain.[7]
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References
Examine Database References
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- Estrogen - Kenny AM, Boxer RS, Kleppinger A, Brindisi J, Feinn R, Burleson JADehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older womenJ Am Geriatr Soc.(2010 Sep)
- Power Output - Percheron G, Hogrel JY, Denot-Ledunois S, Fayet G, Forette F, Baulieu EE, Fardeau M, Marini JF; Double-blind placebo-controlled trialEffect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trialArch Intern Med.(2003 Mar 24)
- Testosterone - Stomati M, Monteleone P, Casarosa E, Quirici B, Puccetti S, Bernardi F, Genazzani AD, Rovati L, Luisi M, Genazzani ARSix-month oral dehydroepiandrosterone supplementation in early and late postmenopauseGynecol Endocrinol.(2000 Oct)
- Testosterone - Igwebuike A, Irving BA, Bigelow ML, Short KR, McConnell JP, Nair KSLack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal womenJ Clin Endocrinol Metab.(2008 Feb)
- Testosterone - Alessandro D Genazzani, Massimo Stomati, Francesca Bernardi, Matteo Pieri, Lucio Rovati, Andrea R GenazzaniLong-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroidsFertil Steril.(2003 Dec)
- Testosterone - Genazzani AR, Pluchino N, Begliuomini S, Stomati M, Bernardi F, Pieri M, Casarosa E, Palumbo M, Genazzani AD, Luisi MLong-term low-dose oral administration of dehydroepiandrosterone modulates adrenal response to adrenocorticotropic hormone in early and late postmenopausal womenGynecol Endocrinol.(2006 Nov)
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- Menopausal Symptoms - Ma H, Sullivan-Halley J, Smith AW, Neuhouser ML, Alfano CM, Meeske K, George SM, McTiernan A, McKean-Cowdin R, Baumgartner KB, Ballard-Barbash R, Bernstein LEstrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study reportBMC Complement Altern Med.(2011 Nov 8)
- Muscle Mass - Abrams DI, Shade SB, Couey P, McCune JM, Lo J, Bacchetti P, Chang B, Epling L, Liegler T, Grant RMDehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled studyAIDS Res Hum Retroviruses.(2007 Jan)
- Stress Signs and Symptoms - Taylor MK, Padilla GA, Stanfill KE, Markham AE, Khosravi JY, Ward MD, Koehler MMEffects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field studyStress.(2012 Jan)
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- Estrogen - Ostojic SM, Calleja J, Jourkesh MEffects of short-term dehydroepiandrosterone supplementation on body composition in young athletesChin J Physiol.(2010 Feb 28)
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- Testosterone - Morales A, Black A, Emerson L, Barkin J, Kuzmarov I, Day AAndrogens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiencyAging Male.(2009 Dec)
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- Fertility - David Barad, Norbert GleicherEffect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVFHum Reprod.(2006 Nov)
- Fertility - Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman AAddition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective studyHum Reprod.(2010 Oct)
- Fertility - Wang J, Liu B, Wen J, Qu BThe Role of Dehydroepiandrosterone in Improving Fertilization Outcome in Patients with DOR/POR: A Systematic Review and Meta- Analysis.Comb Chem High Throughput Screen.(2023)