DHEA

updated

DHEA (prasterone) is an adrenal steroid precursor that the body converts to androgens and estrogens. FDA approved a vaginal prasterone insert (INTRAROSA) in 2016 for menopausal dyspareunia, but an openFDA query located no oral or systemic DHEA drug, and in older adults oral DHEA raised hormone levels without most outcomes following.

Adrenal steroid precursor (androgen and estrogen precursor)

  • FDA approved INTRAROSA (prasterone vaginal insert) under NDA 208470 on 16 November 2016 for dyspareunia due to menopause; an openFDA query located no oral or systemic DHEA drug.
  • In 14 healthy older men with low DHEA-S, single oral DHEA doses raised estradiol and estrone but not testosterone or dihydrotestosterone.
  • In 20 healthy postmenopausal women, oral DHEA 25 mg/day for 6 months raised androgens including testosterone, while estrogens rose nonsignificantly.
  • In a 2-year trial in 87 older men and 57 older women, DHEA raised DHEA-S but did not change body composition, peak oxygen uptake, strength, insulin sensitivity or quality of life.
  • WADA's Prohibited List names prasterone (DHEA) under S1.1 when administered exogenously, while the Controlled Substances Act excludes DHEA from the federal anabolic steroid definition.
  • A Cochrane review of 28 trials (1273 women) found DHEA did not improve quality of life, may slightly improve sexual function, and was associated with acne (OR 3.77).

What is DHEA, and what has FDA approved?

DHEA (prasterone) is an adrenal steroid precursor. FDA approved a vaginal prasterone insert, INTRAROSA, in 2016 for menopausal dyspareunia, and an openFDA query located no oral or systemic DHEA drug.

Prasterone (dehydroepiandrosterone, DHEA) is C19H28O2 (288.4 g/mol, CAS 53-43-0). Its sulfate, DHEA-S, is C19H28O5S (368.5 g/mol, CAS 651-48-9). 7-keto-DHEA is a different molecule with a similar name and is not covered on this page.

FDA approved INTRAROSA (prasterone 6.5 mg vaginal insert) under NDA 208470 on 16 November 2016 for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. An openFDA Drugs@FDA query for prasterone as an active ingredient returned only this application, so no oral or systemic DHEA drug was located. Approvals outside the United States are not covered here.

In a 12-week trial of 325 women on INTRAROSA and 157 on placebo, dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). That label result is for the local vaginal product, not oral DHEA.

PubChem: DHEA, DHEA-S and 7-keto-DHEA identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5881 (prasterone, dehydroepiandrosterone), CID 12594 (prasterone sulfate, DHEA-S) and CID 193313 (7-keto-DHEA).

Prasterone (dehydroepiandrosterone, DHEA): C19H28O2, 288.4 g/mol, CAS 53-43-0 (the record also lists 105597-37-3). Its sulfate, DHEA-S (prasterone sulfate): CID 12594, C19H28O5S, 368.5 g/mol, CAS 651-48-9. 7-keto-DHEA, a related compound with a similar name, is a different molecule (CID 193313, C19H26O3, 302.4 g/mol, CAS 566-19-8) and is not covered by any other source on this page.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecules
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
INTRAROSA label, version effective 17 July 2026: indication, warning, PK, adverse reactions

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INTRAROSA (prasterone) 6.5 mg vaginal insert, prescribing information, label version effective 17 July 2026. Set ID ada639d4-bac0-2ad0-e053-2a95a90afce7.

The label approves INTRAROSA for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. Because estrogen is a metabolite, it carries a warning for women with current or past breast cancer, in whom it was not studied. In a 12-week trial (325 on INTRAROSA, 157 on placebo), dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials); in a 52-week open-label trial, 14.2% had discharge and 2.1% abnormal Pap smears. After 7 days, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

Participants / model
Postmenopausal women with moderate to severe dyspareunia from vulvar and vaginal atrophy
Treatment
INTRAROSA prasterone 6.5 mg vaginal insert
Follow-up
Label version effective 17 July 2026
Study design
FDA prescribing information
Funding
not stated in the source

This is a local vaginal product. The breast cancer warning belongs to the vaginal product, and the label results do not describe oral DHEA.

Read the original source
Drugs@FDA: INTRAROSA approved 16 November 2016, the only prasterone application

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 208470 (INTRAROSA, prasterone). Date read from the openFDA Drugs@FDA record; an openFDA query for prasterone as an active ingredient returned only this application.

FDA approved INTRAROSA (prasterone) under NDA 208470 on 16 November 2016. An openFDA Drugs@FDA query for prasterone as an active ingredient returned only this application, so no oral or systemic DHEA drug was located.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approval in 2016
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date. The indication comes from the product label.

Read the original source

What do oral DHEA studies show for testosterone and estrogen?

The result depends on sex. In 14 older men, oral DHEA raised estradiol and estrone but not testosterone, while in 20 postmenopausal women it raised mainly androgens including testosterone.

In 14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L, single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

In 20 healthy postmenopausal women given oral DHEA 25 mg/day or placebo for 6 months (7 evaluable on DHEA), DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose and SHBG did not change. In these women, oral DHEA raised mainly androgens.

A meta-analysis of 9 trial arms (793 older women) found DHEA raised testosterone by a weighted mean 17.52 ng/dL (95% CI 6.61 to 28.43) and lowered BMI slightly (WMD -0.39 kg/m2) versus placebo.

Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
Oral DHEA in 20 postmenopausal women for 6 months: androgens rose

Randomized controlled trial

Stanczyk FZ et al. Menopause. 2009;16(2):272-8. PMID 19098687.

DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose, and SHBG did not change. In these women, oral DHEA raised mainly androgens. The study notes that some women use over-the-counter DHEA.

Participants / model
20 healthy postmenopausal women (7 evaluable on DHEA)
Treatment
Oral DHEA 25 mg/day or placebo
Follow-up
6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Only 7 women on DHEA were evaluable.

Read the original source
Meta-analysis: 9 trial arms, 793 older women, testosterone up 17.52 ng/dL

Systematic review and meta-analysis

Hu Y et al. Complement Ther Med. 2021;56:102620. PMID 33220453.

DHEA raised testosterone by a weighted mean 17.52 ng/dL (95% CI 6.61 to 28.43) and lowered BMI slightly (WMD -0.39 kg/m2) versus placebo.

Participants / model
793 older women across 9 trial arms
Treatment
DHEA versus placebo
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 9 trial arms
Funding
not stated in the source

Applies to older women.

Read the original source

Does raising DHEA-S in older adults change body composition, strength or metabolism?

DHEA-S rose, but in a 2-year trial and in meta-analyses, outcomes mostly did not follow: no meaningful change in strength, metabolism, quality of life or cognition, and at most a small fat mass effect in older men.

In a 2-year double-blind trial, 87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo) were randomized. DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects. The abstract does not state the DHEA dose.

A meta-analysis of 25 placebo-controlled trials (1353 older men, mean follow-up 36 weeks) found oral DHEA reduced fat mass slightly (SMD -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rises in testosterone and estradiol. It found no effect on lipid or glucose metabolism, bone health, sexual function or quality of life.

A Cochrane review found only 3 adequate placebo-controlled trials of DHEA for cognition in people over 50 without dementia. None showed a consistent benefit, and one found worse visual-memory recall after a psychosocial stressor. The authors concluded the evidence does not support a benefit on cognitive function.

Two-year trial: 87 older men and 57 older women, DHEA-S rose, outcomes mostly did not

Randomized controlled trial

Nair KS et al. N Engl J Med. 2006;355(16):1647-59. PMID 17050889.

DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects.

Participants / model
87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo)
Treatment
Oral DHEA (dose not stated in the abstract) versus testosterone or placebo
Follow-up
2 years
Study design
Double-blind randomized trial
Funding
not stated in the source

This tests the high-normal DHEA-S idea directly: levels rose, outcomes mostly did not. The DHEA dose is not stated in the abstract.

Read the original source
Older men meta-analysis: 25 trials, 1353 men, small fat mass effect that disappeared on adjustment

Systematic review and meta-analysis

Corona G et al. J Clin Endocrinol Metab. 2013;98(9):3615-26. PMID 23824417.

Oral DHEA reduced fat mass slightly (SMD -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rises in testosterone and estradiol. It had no effect on lipid or glucose metabolism, bone health, sexual function or quality of life.

Participants / model
1353 older men across 25 placebo-controlled trials (mean follow-up 36 weeks)
Treatment
Oral DHEA versus placebo
Follow-up
Mean follow-up 36 weeks
Study design
Systematic review and meta-analysis of 25 placebo-controlled trials
Funding
not stated in the source

Applies to older men.

Read the original source
Cochrane: 3 adequate trials, no consistent cognitive benefit

Systematic review and meta-analysis

Grimley Evans J et al. Cochrane Database Syst Rev. 2006;2006(4):CD006221. PMID 17054283.

The review found only 3 adequate placebo-controlled trials of DHEA for cognition in people over 50 without dementia. None showed a consistent benefit, and one found worse visual-memory recall after a psychosocial stressor. The authors concluded the evidence does not support a benefit of DHEA on cognitive function in non-demented middle-aged or older people.

Participants / model
People over 50 without dementia
Treatment
DHEA or DHEA-S supplementation
Follow-up
Varied by included trial
Study design
Systematic review of 3 placebo-controlled trials
Funding
not stated in the source

Only 3 adequate trials were available.

Read the original source

What did studies in menopausal women find for sexual function and quality of life?

Results were small or null. Systemic DHEA did not significantly improve libido or sexual function in a 23-trial meta-analysis, and a Cochrane review found no quality of life gain and a possible slight sexual function benefit.

A meta-analysis of 23 randomized trials (1188 postmenopausal women with normal adrenal function, moderate to high risk of bias) found systemic DHEA did not significantly improve libido or sexual function (SMD 0.35, 95% CI -0.02 to 0.73). It also found no significant effect on serious adverse effects, lipids, glucose, weight, BMI or bone density. Confidence in the evidence was low.

A Cochrane review of 28 trials (1273 peri- or postmenopausal women) found DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34) and may slightly improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55). Effects on menopausal symptoms were unclear. That review pools DHEA by any route, so it includes more than oral DHEA.

Postmenopausal women meta-analysis: 23 trials, no significant sexual function benefit

Systematic review and meta-analysis

Elraiyah T et al. J Clin Endocrinol Metab. 2014;99(10):3536-42. PMID 25279571.

Systemic DHEA did not significantly improve libido or sexual function (SMD 0.35, 95% CI -0.02 to 0.73) and had no significant effect on serious adverse effects, lipids, glucose, weight, BMI or bone density. Confidence in the evidence was low.

Participants / model
1188 postmenopausal women with normal adrenal function across 23 randomized trials (moderate to high risk of bias)
Treatment
Systemic DHEA versus control
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

Confidence in the evidence was low and the trials were at moderate to high risk of bias.

Read the original source
Cochrane: 28 trials, 1273 women, no quality of life gain, acne increased

Systematic review and meta-analysis

Scheffers CS et al. Cochrane Database Syst Rev. 2015;1(1):CD011066. PMID 25879093.

DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34), may slightly improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55), and was associated with androgenic side effects, mainly acne (OR 3.77, 95% CI 1.36 to 10.4). Effects on menopausal symptoms were unclear.

Participants / model
1273 peri- or postmenopausal women across 28 trials
Treatment
DHEA by any route versus placebo or other treatment
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 28 trials
Funding
not stated in the source

Pools DHEA by any route, so it includes more than oral DHEA.

Read the original source

Does keeping DHEA-S in the high-normal range raise testosterone and help?

The conversion is real and depends on sex: older men made more estrogen and postmenopausal women more androgens. But raising DHEA-S to young-adult levels has not been shown to deliver benefits in the trials reviewed.

Sellers describe DHEA as an adrenal androgen precursor taken to keep DHEA-S in the high-normal range, raising testosterone or estradiol depending on what tissues convert it to. The conversion part is supported and sex-dependent: in older men, oral DHEA raised estradiol and estrone but not testosterone, and in postmenopausal women it raised mainly androgens.

The 2-year trial tests the high-normal DHEA-S idea directly. DHEA-S rose by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo, but body composition, peak oxygen uptake, muscle strength, insulin sensitivity and quality of life did not change. Meta-analyses in older men and postmenopausal women found at most small effects and no meaningful effect on metabolism, pooled bone density, quality of life or cognition.

Two-year trial: 87 older men and 57 older women, DHEA-S rose, outcomes mostly did not

Randomized controlled trial

Nair KS et al. N Engl J Med. 2006;355(16):1647-59. PMID 17050889.

DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects.

Participants / model
87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo)
Treatment
Oral DHEA (dose not stated in the abstract) versus testosterone or placebo
Follow-up
2 years
Study design
Double-blind randomized trial
Funding
not stated in the source

This tests the high-normal DHEA-S idea directly: levels rose, outcomes mostly did not. The DHEA dose is not stated in the abstract.

Read the original source
Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
Oral DHEA in 20 postmenopausal women for 6 months: androgens rose

Randomized controlled trial

Stanczyk FZ et al. Menopause. 2009;16(2):272-8. PMID 19098687.

DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose, and SHBG did not change. In these women, oral DHEA raised mainly androgens. The study notes that some women use over-the-counter DHEA.

Participants / model
20 healthy postmenopausal women (7 evaluable on DHEA)
Treatment
Oral DHEA 25 mg/day or placebo
Follow-up
6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Only 7 women on DHEA were evaluable.

Read the original source
Older men meta-analysis: 25 trials, 1353 men, small fat mass effect that disappeared on adjustment

Systematic review and meta-analysis

Corona G et al. J Clin Endocrinol Metab. 2013;98(9):3615-26. PMID 23824417.

Oral DHEA reduced fat mass slightly (SMD -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rises in testosterone and estradiol. It had no effect on lipid or glucose metabolism, bone health, sexual function or quality of life.

Participants / model
1353 older men across 25 placebo-controlled trials (mean follow-up 36 weeks)
Treatment
Oral DHEA versus placebo
Follow-up
Mean follow-up 36 weeks
Study design
Systematic review and meta-analysis of 25 placebo-controlled trials
Funding
not stated in the source

Applies to older men.

Read the original source
Postmenopausal women meta-analysis: 23 trials, no significant sexual function benefit

Systematic review and meta-analysis

Elraiyah T et al. J Clin Endocrinol Metab. 2014;99(10):3536-42. PMID 25279571.

Systemic DHEA did not significantly improve libido or sexual function (SMD 0.35, 95% CI -0.02 to 0.73) and had no significant effect on serious adverse effects, lipids, glucose, weight, BMI or bone density. Confidence in the evidence was low.

Participants / model
1188 postmenopausal women with normal adrenal function across 23 randomized trials (moderate to high risk of bias)
Treatment
Systemic DHEA versus control
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

Confidence in the evidence was low and the trials were at moderate to high risk of bias.

Read the original source

How does the body convert DHEA?

The INTRAROSA label calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens. The studies show the balance differs by sex, and tissue-specific conversion beyond the label statement is not established here.

The INTRAROSA label calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. After 7 days of the vaginal insert, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

For oral DHEA, the balance differs by sex in the studies reviewed: estradiol and estrone rose with dose in older men without a change in testosterone, while androgens rose mainly in postmenopausal women. Tissue-specific conversion beyond the label's statement was not examined against a primary human source here.

INTRAROSA label, version effective 17 July 2026: indication, warning, PK, adverse reactions

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INTRAROSA (prasterone) 6.5 mg vaginal insert, prescribing information, label version effective 17 July 2026. Set ID ada639d4-bac0-2ad0-e053-2a95a90afce7.

The label approves INTRAROSA for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. Because estrogen is a metabolite, it carries a warning for women with current or past breast cancer, in whom it was not studied. In a 12-week trial (325 on INTRAROSA, 157 on placebo), dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials); in a 52-week open-label trial, 14.2% had discharge and 2.1% abnormal Pap smears. After 7 days, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

Participants / model
Postmenopausal women with moderate to severe dyspareunia from vulvar and vaginal atrophy
Treatment
INTRAROSA prasterone 6.5 mg vaginal insert
Follow-up
Label version effective 17 July 2026
Study design
FDA prescribing information
Funding
not stated in the source

This is a local vaginal product. The breast cancer warning belongs to the vaginal product, and the label results do not describe oral DHEA.

Read the original source
Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
Oral DHEA in 20 postmenopausal women for 6 months: androgens rose

Randomized controlled trial

Stanczyk FZ et al. Menopause. 2009;16(2):272-8. PMID 19098687.

DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose, and SHBG did not change. In these women, oral DHEA raised mainly androgens. The study notes that some women use over-the-counter DHEA.

Participants / model
20 healthy postmenopausal women (7 evaluable on DHEA)
Treatment
Oral DHEA 25 mg/day or placebo
Follow-up
6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Only 7 women on DHEA were evaluable.

Read the original source

Is DHEA banned in sport or controlled under US law?

WADA prohibits exogenous DHEA at all times under S1.1. The US Controlled Substances Act excludes DHEA from its anabolic steroid definition.

WADA's Prohibited List, as read online on 9 October 2026, lists prasterone (DHEA) under S1.1 anabolic androgenic steroids when administered exogenously. The list marks S1 anabolic agents as prohibited at all times and as non-Specified Substances.

The Controlled Substances Act defines anabolic steroid as a drug or hormonal substance chemically and pharmacologically related to testosterone, other than estrogens, progestins, corticosteroids and dehydroepiandrosterone, so DHEA is excluded from the federal anabolic steroid definition. National anti-doping and military rules beyond the WADA list are not covered here.

WADA Prohibited List: prasterone prohibited at all times when administered exogenously

Regulatory record

World Anti-Doping Agency. Prohibited List, as read online on 9 October 2026 (the page carries the 2026 Monitoring Program).

WADA's Prohibited List lists prasterone (dehydroepiandrosterone, DHEA, 3beta-hydroxyandrost-5-en-17-one) under S1.1 anabolic androgenic steroids when administered exogenously. The list marks S1 anabolic agents as prohibited at all times and as non-Specified Substances.

Participants / model
Athletes subject to the World Anti-Doping Code
Treatment
Exogenous DHEA by any route
Follow-up
Read on 9 October 2026
Study design
Official anti-doping list
Funding
not stated in the source

National anti-doping and military rules beyond the WADA list are not covered.

Read the original source
21 U.S.C. 802(41)(A): DHEA excluded from the federal anabolic steroid definition

Regulatory record

United States Code, Title 21, section 802(41)(A), 2024 edition. U.S. Government Publishing Office, govinfo.gov.

The Controlled Substances Act defines anabolic steroid as any drug or hormonal substance chemically and pharmacologically related to testosterone, other than estrogens, progestins, corticosteroids and dehydroepiandrosterone. DHEA is therefore excluded from the federal anabolic steroid definition.

Participants / model
Not a clinical population
Treatment
Statutory definition
Follow-up
2024 edition of the US Code
Study design
Federal statute
Funding
not stated in the source

This is US federal controlled-substance status. It says nothing about efficacy or safety.

Read the original source

What warnings and side effects are reported?

Acne was the consistent side effect of DHEA in a Cochrane review (OR 3.77). The vaginal product's label warns about women with current or past breast cancer, and long-term breast and prostate cancer risk with systemic DHEA is not established here.

A Cochrane review of 28 trials found DHEA associated with androgenic side effects, mainly acne (OR 3.77, 95% CI 1.36 to 10.4). A meta-analysis of 23 trials in postmenopausal women found no significant effect of systemic DHEA on serious adverse effects, lipids, glucose, weight, BMI or bone density, and the 2-year trial in older adults reported no major adverse effects. In older men, estradiol and estrone rose with oral DHEA while staying within the upper normal male range.

For the vaginal product, the INTRAROSA label carries a warning for women with current or past breast cancer, in whom it was not studied, because estrogen is a metabolite. Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials), and in a 52-week open-label trial 14.2% had discharge and 2.1% abnormal Pap smears. That breast cancer warning belongs to the vaginal product.

No primary source reviewed quantifies long-term breast or prostate cancer risk with systemic DHEA, so that risk is not established here.

Cochrane: 28 trials, 1273 women, no quality of life gain, acne increased

Systematic review and meta-analysis

Scheffers CS et al. Cochrane Database Syst Rev. 2015;1(1):CD011066. PMID 25879093.

DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34), may slightly improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55), and was associated with androgenic side effects, mainly acne (OR 3.77, 95% CI 1.36 to 10.4). Effects on menopausal symptoms were unclear.

Participants / model
1273 peri- or postmenopausal women across 28 trials
Treatment
DHEA by any route versus placebo or other treatment
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 28 trials
Funding
not stated in the source

Pools DHEA by any route, so it includes more than oral DHEA.

Read the original source
Postmenopausal women meta-analysis: 23 trials, no significant sexual function benefit

Systematic review and meta-analysis

Elraiyah T et al. J Clin Endocrinol Metab. 2014;99(10):3536-42. PMID 25279571.

Systemic DHEA did not significantly improve libido or sexual function (SMD 0.35, 95% CI -0.02 to 0.73) and had no significant effect on serious adverse effects, lipids, glucose, weight, BMI or bone density. Confidence in the evidence was low.

Participants / model
1188 postmenopausal women with normal adrenal function across 23 randomized trials (moderate to high risk of bias)
Treatment
Systemic DHEA versus control
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

Confidence in the evidence was low and the trials were at moderate to high risk of bias.

Read the original source
Two-year trial: 87 older men and 57 older women, DHEA-S rose, outcomes mostly did not

Randomized controlled trial

Nair KS et al. N Engl J Med. 2006;355(16):1647-59. PMID 17050889.

DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects.

Participants / model
87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo)
Treatment
Oral DHEA (dose not stated in the abstract) versus testosterone or placebo
Follow-up
2 years
Study design
Double-blind randomized trial
Funding
not stated in the source

This tests the high-normal DHEA-S idea directly: levels rose, outcomes mostly did not. The DHEA dose is not stated in the abstract.

Read the original source
Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
INTRAROSA label, version effective 17 July 2026: indication, warning, PK, adverse reactions

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INTRAROSA (prasterone) 6.5 mg vaginal insert, prescribing information, label version effective 17 July 2026. Set ID ada639d4-bac0-2ad0-e053-2a95a90afce7.

The label approves INTRAROSA for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. Because estrogen is a metabolite, it carries a warning for women with current or past breast cancer, in whom it was not studied. In a 12-week trial (325 on INTRAROSA, 157 on placebo), dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials); in a 52-week open-label trial, 14.2% had discharge and 2.1% abnormal Pap smears. After 7 days, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

Participants / model
Postmenopausal women with moderate to severe dyspareunia from vulvar and vaginal atrophy
Treatment
INTRAROSA prasterone 6.5 mg vaginal insert
Follow-up
Label version effective 17 July 2026
Study design
FDA prescribing information
Funding
not stated in the source

This is a local vaginal product. The breast cancer warning belongs to the vaginal product, and the label results do not describe oral DHEA.

Read the original source

Why does DHEA sit in B tier?

The conversion to sex steroids is documented and a local vaginal product is FDA-approved, but systemic oral DHEA mostly did not change outcomes in older adults.

The B reflects a mechanism that checks out and outcomes that do not. DHEA's conversion to sex steroids is documented, and FDA approved a local prasterone product in 2016 for menopausal dyspareunia, a narrow use. Systemic oral DHEA raises DHEA-S, estrogens in older men and androgens in postmenopausal women.

In older adults the outcomes mostly do not follow: a 2-year trial and meta-analyses found at most small effects on body composition and no meaningful effect on strength, metabolism, pooled bone density, quality of life or cognition, with a small sexual-function signal in women in one review and acne as the consistent side effect. DHEA is prohibited at all times under the World Anti-Doping Code.

INTRAROSA label, version effective 17 July 2026: indication, warning, PK, adverse reactions

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INTRAROSA (prasterone) 6.5 mg vaginal insert, prescribing information, label version effective 17 July 2026. Set ID ada639d4-bac0-2ad0-e053-2a95a90afce7.

The label approves INTRAROSA for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. Because estrogen is a metabolite, it carries a warning for women with current or past breast cancer, in whom it was not studied. In a 12-week trial (325 on INTRAROSA, 157 on placebo), dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials); in a 52-week open-label trial, 14.2% had discharge and 2.1% abnormal Pap smears. After 7 days, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

Participants / model
Postmenopausal women with moderate to severe dyspareunia from vulvar and vaginal atrophy
Treatment
INTRAROSA prasterone 6.5 mg vaginal insert
Follow-up
Label version effective 17 July 2026
Study design
FDA prescribing information
Funding
not stated in the source

This is a local vaginal product. The breast cancer warning belongs to the vaginal product, and the label results do not describe oral DHEA.

Read the original source
Drugs@FDA: INTRAROSA approved 16 November 2016, the only prasterone application

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 208470 (INTRAROSA, prasterone). Date read from the openFDA Drugs@FDA record; an openFDA query for prasterone as an active ingredient returned only this application.

FDA approved INTRAROSA (prasterone) under NDA 208470 on 16 November 2016. An openFDA Drugs@FDA query for prasterone as an active ingredient returned only this application, so no oral or systemic DHEA drug was located.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approval in 2016
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date. The indication comes from the product label.

Read the original source
Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
Oral DHEA in 20 postmenopausal women for 6 months: androgens rose

Randomized controlled trial

Stanczyk FZ et al. Menopause. 2009;16(2):272-8. PMID 19098687.

DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose, and SHBG did not change. In these women, oral DHEA raised mainly androgens. The study notes that some women use over-the-counter DHEA.

Participants / model
20 healthy postmenopausal women (7 evaluable on DHEA)
Treatment
Oral DHEA 25 mg/day or placebo
Follow-up
6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Only 7 women on DHEA were evaluable.

Read the original source
Two-year trial: 87 older men and 57 older women, DHEA-S rose, outcomes mostly did not

Randomized controlled trial

Nair KS et al. N Engl J Med. 2006;355(16):1647-59. PMID 17050889.

DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects.

Participants / model
87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo)
Treatment
Oral DHEA (dose not stated in the abstract) versus testosterone or placebo
Follow-up
2 years
Study design
Double-blind randomized trial
Funding
not stated in the source

This tests the high-normal DHEA-S idea directly: levels rose, outcomes mostly did not. The DHEA dose is not stated in the abstract.

Read the original source
Older men meta-analysis: 25 trials, 1353 men, small fat mass effect that disappeared on adjustment

Systematic review and meta-analysis

Corona G et al. J Clin Endocrinol Metab. 2013;98(9):3615-26. PMID 23824417.

Oral DHEA reduced fat mass slightly (SMD -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rises in testosterone and estradiol. It had no effect on lipid or glucose metabolism, bone health, sexual function or quality of life.

Participants / model
1353 older men across 25 placebo-controlled trials (mean follow-up 36 weeks)
Treatment
Oral DHEA versus placebo
Follow-up
Mean follow-up 36 weeks
Study design
Systematic review and meta-analysis of 25 placebo-controlled trials
Funding
not stated in the source

Applies to older men.

Read the original source
Cochrane: 28 trials, 1273 women, no quality of life gain, acne increased

Systematic review and meta-analysis

Scheffers CS et al. Cochrane Database Syst Rev. 2015;1(1):CD011066. PMID 25879093.

DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34), may slightly improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55), and was associated with androgenic side effects, mainly acne (OR 3.77, 95% CI 1.36 to 10.4). Effects on menopausal symptoms were unclear.

Participants / model
1273 peri- or postmenopausal women across 28 trials
Treatment
DHEA by any route versus placebo or other treatment
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 28 trials
Funding
not stated in the source

Pools DHEA by any route, so it includes more than oral DHEA.

Read the original source
WADA Prohibited List: prasterone prohibited at all times when administered exogenously

Regulatory record

World Anti-Doping Agency. Prohibited List, as read online on 9 October 2026 (the page carries the 2026 Monitoring Program).

WADA's Prohibited List lists prasterone (dehydroepiandrosterone, DHEA, 3beta-hydroxyandrost-5-en-17-one) under S1.1 anabolic androgenic steroids when administered exogenously. The list marks S1 anabolic agents as prohibited at all times and as non-Specified Substances.

Participants / model
Athletes subject to the World Anti-Doping Code
Treatment
Exogenous DHEA by any route
Follow-up
Read on 9 October 2026
Study design
Official anti-doping list
Funding
not stated in the source

National anti-doping and military rules beyond the WADA list are not covered.

Read the original source

Studies and sources

PubChem: DHEA, DHEA-S and 7-keto-DHEA identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5881 (prasterone, dehydroepiandrosterone), CID 12594 (prasterone sulfate, DHEA-S) and CID 193313 (7-keto-DHEA).

Prasterone (dehydroepiandrosterone, DHEA): C19H28O2, 288.4 g/mol, CAS 53-43-0 (the record also lists 105597-37-3). Its sulfate, DHEA-S (prasterone sulfate): CID 12594, C19H28O5S, 368.5 g/mol, CAS 651-48-9. 7-keto-DHEA, a related compound with a similar name, is a different molecule (CID 193313, C19H26O3, 302.4 g/mol, CAS 566-19-8) and is not covered by any other source on this page.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecules
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
INTRAROSA label, version effective 17 July 2026: indication, warning, PK, adverse reactions

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INTRAROSA (prasterone) 6.5 mg vaginal insert, prescribing information, label version effective 17 July 2026. Set ID ada639d4-bac0-2ad0-e053-2a95a90afce7.

The label approves INTRAROSA for moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It calls prasterone an inactive endogenous steroid that is converted into active androgens and/or estrogens and says its mechanism in this use is not fully established. Because estrogen is a metabolite, it carries a warning for women with current or past breast cancer, in whom it was not studied. In a 12-week trial (325 on INTRAROSA, 157 on placebo), dyspareunia severity fell 1.42 versus 1.06 points (difference -0.35, p=0.0002). Vaginal discharge was the most common adverse reaction (5.71% versus 3.66% in 12-week trials); in a 52-week open-label trial, 14.2% had discharge and 2.1% abnormal Pap smears. After 7 days, mean prasterone Cmax was 4.4 ng/mL and AUC0-24 56.2 ng.h/mL, with testosterone and estradiol slightly higher than on placebo.

Participants / model
Postmenopausal women with moderate to severe dyspareunia from vulvar and vaginal atrophy
Treatment
INTRAROSA prasterone 6.5 mg vaginal insert
Follow-up
Label version effective 17 July 2026
Study design
FDA prescribing information
Funding
not stated in the source

This is a local vaginal product. The breast cancer warning belongs to the vaginal product, and the label results do not describe oral DHEA.

Read the original source
Drugs@FDA: INTRAROSA approved 16 November 2016, the only prasterone application

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 208470 (INTRAROSA, prasterone). Date read from the openFDA Drugs@FDA record; an openFDA query for prasterone as an active ingredient returned only this application.

FDA approved INTRAROSA (prasterone) under NDA 208470 on 16 November 2016. An openFDA Drugs@FDA query for prasterone as an active ingredient returned only this application, so no oral or systemic DHEA drug was located.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approval in 2016
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date. The indication comes from the product label.

Read the original source
21 U.S.C. 802(41)(A): DHEA excluded from the federal anabolic steroid definition

Regulatory record

United States Code, Title 21, section 802(41)(A), 2024 edition. U.S. Government Publishing Office, govinfo.gov.

The Controlled Substances Act defines anabolic steroid as any drug or hormonal substance chemically and pharmacologically related to testosterone, other than estrogens, progestins, corticosteroids and dehydroepiandrosterone. DHEA is therefore excluded from the federal anabolic steroid definition.

Participants / model
Not a clinical population
Treatment
Statutory definition
Follow-up
2024 edition of the US Code
Study design
Federal statute
Funding
not stated in the source

This is US federal controlled-substance status. It says nothing about efficacy or safety.

Read the original source
WADA Prohibited List: prasterone prohibited at all times when administered exogenously

Regulatory record

World Anti-Doping Agency. Prohibited List, as read online on 9 October 2026 (the page carries the 2026 Monitoring Program).

WADA's Prohibited List lists prasterone (dehydroepiandrosterone, DHEA, 3beta-hydroxyandrost-5-en-17-one) under S1.1 anabolic androgenic steroids when administered exogenously. The list marks S1 anabolic agents as prohibited at all times and as non-Specified Substances.

Participants / model
Athletes subject to the World Anti-Doping Code
Treatment
Exogenous DHEA by any route
Follow-up
Read on 9 October 2026
Study design
Official anti-doping list
Funding
not stated in the source

National anti-doping and military rules beyond the WADA list are not covered.

Read the original source
Oral DHEA in 14 older men: estradiol and estrone rose, testosterone did not

Human study

Arlt W et al. J Clin Endocrinol Metab. 1999;84(6):2170-6. PMID 10372727.

Single oral doses of 50 mg DHEA raised DHEA-S to mean young-adult male levels, and 100 mg produced supraphysiological levels. Testosterone and dihydrotestosterone did not change, while estradiol and estrone rose with dose (estradiol AUC 510, 635 and 700 pmol/L x h for placebo, 50 mg and 100 mg), staying within the upper normal male range. In these men, oral DHEA raised estrogens, not testosterone.

Participants / model
14 healthy men (mean age 58.8) with serum DHEA-S below 4.1 micromol/L
Treatment
Single oral DHEA 50 or 100 mg versus placebo
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

Single doses in 14 older men with low DHEA-S.

Read the original source
Oral DHEA in 20 postmenopausal women for 6 months: androgens rose

Randomized controlled trial

Stanczyk FZ et al. Menopause. 2009;16(2):272-8. PMID 19098687.

DHEA, DHEA-S, androstenedione, testosterone (17.9 to 28.7 ng/dL by month 3), dihydrotestosterone and androstanediol glucuronide rose significantly, while estrone and estradiol rose nonsignificantly. Free testosterone rose, and SHBG did not change. In these women, oral DHEA raised mainly androgens. The study notes that some women use over-the-counter DHEA.

Participants / model
20 healthy postmenopausal women (7 evaluable on DHEA)
Treatment
Oral DHEA 25 mg/day or placebo
Follow-up
6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Only 7 women on DHEA were evaluable.

Read the original source
Meta-analysis: 9 trial arms, 793 older women, testosterone up 17.52 ng/dL

Systematic review and meta-analysis

Hu Y et al. Complement Ther Med. 2021;56:102620. PMID 33220453.

DHEA raised testosterone by a weighted mean 17.52 ng/dL (95% CI 6.61 to 28.43) and lowered BMI slightly (WMD -0.39 kg/m2) versus placebo.

Participants / model
793 older women across 9 trial arms
Treatment
DHEA versus placebo
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 9 trial arms
Funding
not stated in the source

Applies to older women.

Read the original source
Two-year trial: 87 older men and 57 older women, DHEA-S rose, outcomes mostly did not

Randomized controlled trial

Nair KS et al. N Engl J Med. 2006;355(16):1647-59. PMID 17050889.

DHEA raised DHEA-S by a median 3.4 mcg/mL in men and 3.8 mcg/mL in women versus placebo but did not change body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Men on DHEA gained femoral-neck bone mineral density and women ultradistal-radius bone mineral density. There were no major adverse effects.

Participants / model
87 older men with low DHEA-S and bioavailable testosterone (29 DHEA, 27 testosterone, 31 placebo) and 57 older women with low DHEA-S (27 DHEA, 30 placebo)
Treatment
Oral DHEA (dose not stated in the abstract) versus testosterone or placebo
Follow-up
2 years
Study design
Double-blind randomized trial
Funding
not stated in the source

This tests the high-normal DHEA-S idea directly: levels rose, outcomes mostly did not. The DHEA dose is not stated in the abstract.

Read the original source
Older men meta-analysis: 25 trials, 1353 men, small fat mass effect that disappeared on adjustment

Systematic review and meta-analysis

Corona G et al. J Clin Endocrinol Metab. 2013;98(9):3615-26. PMID 23824417.

Oral DHEA reduced fat mass slightly (SMD -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rises in testosterone and estradiol. It had no effect on lipid or glucose metabolism, bone health, sexual function or quality of life.

Participants / model
1353 older men across 25 placebo-controlled trials (mean follow-up 36 weeks)
Treatment
Oral DHEA versus placebo
Follow-up
Mean follow-up 36 weeks
Study design
Systematic review and meta-analysis of 25 placebo-controlled trials
Funding
not stated in the source

Applies to older men.

Read the original source
Postmenopausal women meta-analysis: 23 trials, no significant sexual function benefit

Systematic review and meta-analysis

Elraiyah T et al. J Clin Endocrinol Metab. 2014;99(10):3536-42. PMID 25279571.

Systemic DHEA did not significantly improve libido or sexual function (SMD 0.35, 95% CI -0.02 to 0.73) and had no significant effect on serious adverse effects, lipids, glucose, weight, BMI or bone density. Confidence in the evidence was low.

Participants / model
1188 postmenopausal women with normal adrenal function across 23 randomized trials (moderate to high risk of bias)
Treatment
Systemic DHEA versus control
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

Confidence in the evidence was low and the trials were at moderate to high risk of bias.

Read the original source
Cochrane: 28 trials, 1273 women, no quality of life gain, acne increased

Systematic review and meta-analysis

Scheffers CS et al. Cochrane Database Syst Rev. 2015;1(1):CD011066. PMID 25879093.

DHEA did not improve quality of life (SMD 0.16, 95% CI -0.03 to 0.34), may slightly improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55), and was associated with androgenic side effects, mainly acne (OR 3.77, 95% CI 1.36 to 10.4). Effects on menopausal symptoms were unclear.

Participants / model
1273 peri- or postmenopausal women across 28 trials
Treatment
DHEA by any route versus placebo or other treatment
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 28 trials
Funding
not stated in the source

Pools DHEA by any route, so it includes more than oral DHEA.

Read the original source
Cochrane: 3 adequate trials, no consistent cognitive benefit

Systematic review and meta-analysis

Grimley Evans J et al. Cochrane Database Syst Rev. 2006;2006(4):CD006221. PMID 17054283.

The review found only 3 adequate placebo-controlled trials of DHEA for cognition in people over 50 without dementia. None showed a consistent benefit, and one found worse visual-memory recall after a psychosocial stressor. The authors concluded the evidence does not support a benefit of DHEA on cognitive function in non-demented middle-aged or older people.

Participants / model
People over 50 without dementia
Treatment
DHEA or DHEA-S supplementation
Follow-up
Varied by included trial
Study design
Systematic review of 3 placebo-controlled trials
Funding
not stated in the source

Only 3 adequate trials were available.

Read the original source

Why is DHEA in B tier?

B fits a precursor whose conversion to sex steroids is well documented and which has a narrow FDA-approved local use, but whose systemic oral use mostly shows no outcome benefit in older adults. The mechanism checks out and the outcomes do not.