DHEA
Dehydroepiandrosterone (DHEA) is a steroid hormone naturally produced by the adrenal glands, serving as a precursor to sex hormones like testosterone and estrogen. It plays a role in various physiological processes, including sexual function, muscle and bone health, mood regulation, and immune response. DHEA levels decline with age, prompting interest in supplementation to address conditions like low libido, depression, or age-related decline.
Benefits
Improved Sexual Function
DHEA may enhance libido and sexual performance, particularly in women with low levels, by supporting hormone balance. Studies suggest modest improvements in sexual desire and arousal in postmenopausal women.
Anti-Aging Effects
DHEA levels decline with age, and supplementation may improve skin hydration, reduce wrinkles, and boost energy in some older adults. However, evidence is limited, and long-term effects are unclear.
Muscle and Bone Health
DHEA may support muscle mass and strength, especially in older adults or those with low levels, and could improve bone density, potentially reducing osteoporosis risk. Results are inconsistent across studies.
Mood and Cognitive Support
Some research indicates DHEA may alleviate mild depression, anxiety, or fatigue, possibly by influencing serotonin and other neurotransmitters. It may also support cognitive function in aging populations, though robust evidence is lacking.
Immune Function
DHEA might enhance immune response, potentially aiding in autoimmune conditions or reducing infection susceptibility, but studies are preliminary.
Metabolic Health
Limited evidence suggests DHEA may improve insulin sensitivity and reduce fat accumulation, particularly in older adults, but it’s not a reliable weight-loss aid.
Mechanism of Action
Precursor to Sex Hormones
DHEA serves as a prohormone, converting into androgens (e.g., testosterone, androstenedione) and estrogens (e.g., estradiol) in peripheral tissues via enzymes like 3β-hydroxysteroid dehydrogenase and aromatase. This increases circulating levels of these hormones, influencing sexual function, muscle growth, bone density, and libido.
Neurosteroid Activity
In the brain, DHEA and its sulfate form (DHEA-S) modulate neuronal activity by interacting with neurotransmitter receptors. GABA-A receptors: DHEA may act as an antagonist, promoting excitatory effects. NMDA and sigma-1 receptors: Enhances neuronal excitability and neuroplasticity, potentially supporting mood and cognitive function. These actions may contribute to reported antidepressant and neuroprotective effects.
Anti-Inflammatory and Immune Modulation
DHEA may reduce inflammation by inhibiting pro-inflammatory cytokines (e.g., IL-6, TNF-α) and promoting anti-inflammatory pathways. It may also enhance immune function by supporting T-cell activity, though mechanisms are not fully clear.
Metabolic Effects
DHEA may improve insulin sensitivity and lipid metabolism by influencing enzymes like 11β-hydroxysteroid dehydrogenase, which regulates cortisol activity. This can affect fat distribution and glucose uptake in tissues.
Antioxidant Properties
DHEA may reduce oxidative stress by scavenging free radicals or upregulating antioxidant enzymes, potentially protecting cells from age-related damage.
Direct Receptor Interactions
While no specific DHEA receptor is confirmed, it may bind to or influence nuclear receptors (e.g., peroxisome proliferator-activated receptors, PPARs) or membrane receptors, affecting gene expression related to metabolism, inflammation, and cell growth.
Clinical Trials
A Dose-Response and Meta-Analysis of Dehydroepiandrosterone (DHEA) Supplementation on Testosterone Levels: Perinatal Prediction of Randomized Clinical Trials
Study: A systematic review and meta-analysis of 42 randomized controlled trials (RCTs) with 55 arms, involving 793 subjects, conducted up to February 2020. The study examined the effect of oral DHEA supplementation on testosterone levels, using weighted mean differences (WMD) to calculate effect sizes. Subgroup analyses explored sources of heterogeneity.
Findings: DHEA supplementation significantly increased testosterone levels (WMD: 28.02 ng/dl, 95% CI: 21.44–34.60, p = 0.00), with greater effects at doses >50 mg/day. The magnitude of increase varied across subgroups (e.g., age, sex, health status). More research is needed for pregnant women and miscarriage outcomes due to limited data.
Link: https://pubmed.ncbi.nlm.nih.gov/33045358/
The Effects of Dehydroepiandrosterone (DHEA) Supplementation on Body Composition and Blood Pressure: A Meta-Analysis of Randomized Clinical Trials
Study: A meta-analysis of RCTs based on PRISMA guidelines, including 11 trials with 489 participants for lean body mass (LBM) and 11 trials with 428 participants for fat mass (FM). The study assessed DHEA’s impact on body composition (LBM, FM, body weight, BMI) and blood pressure.
Findings: DHEA supplementation significantly increased LBM (WMD: 0.45 kg, 95% CI: 0.15–0.75, p = 0.004) and decreased FM (WMD: -0.85%, 95% CI: -1.18 to -0.51, p = 0.000). No significant changes were observed in body weight, BMI, or blood pressure (systolic or diastolic). The clinical significance of body composition changes remains debated due to modest effect sizes.
Link: https://pubmed.ncbi.nlm.nih.gov/32675010/
The Effect of Dehydroepiandrosterone (DHEA) Supplementation on Estradiol Levels in Women: A Dose-Response and Meta-Analysis of Randomized Clinical Trials
Study: A meta-analysis of RCTs conducted up to August 2020, analyzing DHEA’s effect on estradiol levels in women. The study included data from four databases (EMBASE, PubMed/MEDLINE, Scopus, Web of Science) and reported results as weighted mean differences.
Findings: DHEA supplementation significantly increased estradiol levels in women, with dose-dependent effects. The study supports DHEA’s role as a precursor to estrogens, potentially benefiting conditions like vaginal atrophy or low libido, but specific effect sizes were not detailed in the source. Further research is needed to confirm clinical applications.
Link: https://pubmed.ncbi.nlm.nih.gov/34246664/
Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression
Study: A randomized, double-blind, placebo-controlled trial by Schmidt et al. (2005) involving 46 individuals (23 men, 23 women) aged 45–65 with depression. Participants received 6 weeks of DHEA supplementation or placebo, with depression scores measured.
Findings: Six weeks of DHEA supplementation (doses up to 90 mg/day) significantly improved depressive symptoms compared to placebo, with notable reductions in depression scores. The study suggests DHEA may have a role as a third-line treatment for depression, though evidence quality is low due to small sample size and heterogeneity.
Link: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/209107
The Dehydroepiandrosterone And WellNess (DAWN) Study: Research Design and Methods
Study: A double-blind, placebo-controlled, crossover trial by von Mühlen et al. (2007) involving 16 healthy, non-obese adults aged 50–65. Participants received 100 mg/day DHEA or placebo for 6 months each, assessing circulating sex steroids, body composition (via DEXA), and muscle strength (via MedX).
Findings: DHEA (100 mg/day) increased circulating DHEA, DHEA-S, and insulin-like growth factor-I (IGF-I) levels in both genders. In women, it raised androgen levels slightly above normal ranges, but not in men. Men showed increased muscle strength and reduced fat mass, while women showed no significant changes, possibly due to estrogen replacement therapy confounding results.
Link: https://pubmed.ncbi.nlm.nih.gov/16784898/
Effect of DHEA Therapy on Cognitive Performance Among Postmenopausal Women: A Systematic Review of Randomized Clinical Trial Data
Study: A systematic review published in 2023, analyzing RCTs on DHEA’s effect on cognitive performance in postmenopausal women. The review included trials with varying doses and durations, focusing on cognitive outcomes.
Findings: DHEA supplementation showed no consistent beneficial effects on cognitive performance in healthy postmenopausal women. Some trials reported subjective memory improvements, but objective measures (e.g., short-term memory tests) showed no significant benefit. Large-scale trials are needed to clarify DHEA’s role in cognition.
Link: https://pubmed.ncbi.nlm.nih.gov/37792632/
Dehydroepiandrosterone (DHEA) in Metastatic Castration-Resistant Prostate Cancer (mCRPC): Preliminary Results from the SU2C/PCF/AACR West Coast Dream Team (WCDT)
Study: An exploratory analysis from a 2016 trial by Kim et al., assessing DHEA levels as a potential biomarker in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide versus chemotherapy.
Findings: There was significant heterogeneity in the relationship between DHEA levels and prostate-specific antigen (PSA) response. No significant correlation was found between DHEA and androgen receptor variants. The study suggests DHEA may serve as a biomarker in mCRPC, but larger studies are needed to confirm this.
Link: https://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.e16598
Potential Side Effects
Hormonal Imbalances
Women may experience acne, facial hair growth (hirsutism), deepening of voice, menstrual irregularities.
Men may experience breast enlargement (gynecomastia), testicular atrophy, reduced sperm count. Due to conversion to estrogens and androgens, which can disrupt natural hormone levels.
Liver Effects
Elevated liver enzymes or liver strain, especially with high doses or long-term use. Rare cases of liver damage reported, though causality is not fully established.
Cardiovascular Risks
May lower HDL ("good") cholesterol and alter lipid profiles, potentially increasing heart disease risk. Limited evidence suggests possible blood pressure changes (increases or decreases).
Psychological Effects
Mood swings, irritability, or anxiety in some users. Rarely, mania or aggression, particularly at high doses.
Skin and Hair
Oily skin, acne, or scalp hair thinning (androgenic alopecia). Increased body hair in some individuals.
Gastrointestinal Issues
Nausea, abdominal discomfort, or bloating in some cases.
Potential Cancer Risk
Theoretical risk of promoting hormone-sensitive cancers due to increased estrogen or androgen levels, though direct evidence is limited.