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]