Is DHEA safe?

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Safety of Dehydroepiandrosterone (DHEA)

Introduction to DHEA Safety

Dehydroepiandrosterone (DHEA) is a hormone that serves as a precursor to androgens and estrogens. It is widely used as a supplement, particularly among aging populations, to counteract the decline in natural hormone levels. However, the safety of DHEA supplementation has been a topic of extensive research and debate.

Short-Term Safety in Elderly Populations

Several studies have investigated the short-term safety of DHEA supplementation in elderly populations. A study involving 24 healthy elderly men and women found that daily oral administration of DHEA (25/50 mg) for 8 days did not result in the accumulation of steroids or worrying transformations to androgens and estrogens, suggesting that it is safe for short-term use in elderly subjects . Another study involving postmenopausal women over a 52-week period found that a daily dose of 50 mg DHEA did not significantly alter lipid profiles, insulin sensitivity, or adversely affect the endometrium, further supporting its short-term safety .

Cardiovascular Risk Factors

Research on the impact of DHEA on cardiovascular risk factors has shown mixed results. A study on older women with frailty characteristics found significant changes in hormone levels but no significant changes in cardiovascular risk factors such as lipid profiles, body fat, fasting glucose, or blood pressure after 6 months of DHEA supplementation . This suggests that short-term DHEA therapy may be safe concerning cardiovascular risk factors in older women.

Sexual Function and Menopausal Symptoms

DHEA has been studied for its effects on sexual function and menopausal symptoms. Intravaginal DHEA has been shown to improve sexual dysfunction in women with vulvovaginal atrophy and dyspareunia, with no significant adverse effects reported . However, a meta-analysis concluded that DHEA does not significantly improve menopausal symptoms or sexual function compared to placebo and may increase androgenic side effects such as acne and hirsutism .

Neurotoxicity and High-Dose Concerns

While DHEA is generally considered safe at recommended doses, high concentrations have been associated with neurotoxicity. Animal studies have shown that high doses of DHEA can inhibit mitochondrial respiration and lead to neuronal death, particularly under hypoglycemic conditions . This highlights the importance of adhering to recommended dosages to avoid potential neurotoxic effects.

COVID-19 Considerations

During the COVID-19 pandemic, concerns have been raised about the use of DHEA due to its potential to exacerbate the severity of the disease. DHEA is an inhibitor of Glucose-6-phosphate Dehydrogenase (G6PD), and G6PD-deficient cells are more susceptible to coronavirus infection. The unrestricted availability of DHEA as a dietary supplement in the U.S. has led to calls for more stringent regulation and clinical trials to ensure its safety during the pandemic .

Conclusion

Overall, DHEA appears to be safe for short-term use in elderly populations and for improving sexual function in women with specific conditions like vulvovaginal atrophy. However, its long-term safety, particularly at high doses, remains a concern due to potential neurotoxic effects. Additionally, the role of DHEA in exacerbating COVID-19 severity warrants further investigation. Users should adhere to recommended dosages and consult healthcare providers before starting DHEA supplementation.

Sources and full results

Most relevant research papers on this topic

Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects.

Daily oral administration of DHEA (25/50 mg) is safe in elderly subjects, with no accumulation of steroids or concerns about androgen and estrogen transformation.

RCTHighly Cited

2000·

105citations

·Sylvie Legrain et al.

The safety of 52 weeks of oral DHEA therapy for postmenopausal women.

Oral DHEA 50mg daily for 52 weeks did not significantly alter lipid profile, insulin sensitivity, or adversely affect the endometrium in postmenopausal women.

RCT

2009·

60citations

·M. Panjari et al.

Effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics.

Short-term DHEA therapy is safe for older women with frailty, but does not significantly affect cardiovascular risk factors.

RCTRigorous Journal

2010·

47citations

·R. Boxer et al.

Efficacy of intravaginal dehydroepiandrosterone (DHEA) for symptomatic women in the peri- or postmenopausal phase.

Intravaginal DHEA is a safe and effective treatment for menopausal vulvovaginal atrophy and dyspareunia in most women, but further studies are needed for women with a history of thrombosis, cardiovascular disease, or hormone-sensitive neoplasms

Systematic Review

2018·

22citations

·Ulrike Sauer et al.

DHEA on sexual function in Sheehan Syndrome: A randomized double-blind placebo-controlled cross-over trial.

Short-duration DHEA supplementation is efficacious and safe for improving female sexual dysfunction in women with Sheehan syndrome.

RCTVery Rigorous Journal

2022·

2citations

·Soumita Mandal et al.

Alert to US physicians: DHEA, widely used as an OTC androgen supplement, may exacerbate COVID-19.

DHEA, widely used as an OTC androgen supplement in the US, may exacerbate COVID-19 due to its unrestricted availability and potential for adverse events without proof of safety.

2020·

10citations

·J. Nyce

Review: In peri- or postmenopausal women, DHEA does not improve symptoms and increases androgenic side effects

DHEA does not improve menopausal symptoms and increases androgenic side effects in peri- or postmenopausal women compared to placebo or no treatment.

Meta-AnalysisRigorous Journal

2015·

1citation

·D. Fedorkow

Dehydroepiandrosterone inhibits complex I of the mitochondrial respiratory chain and is neurotoxic in vitro and in vivo at high concentrations.

High concentrations of dehydroepiandrosterone inhibit complex I of the mitochondrial respiratory chain and are neurotoxic in vitro and in vivo, leading to neuronal death and motor impairment.

Non-RCTAnimal Study

2006·

42citations

·Dzhamilja Safiulina et al.

DHEA for postmenopausal women: a review of the evidence.

Oral DHEA therapy for postmenopausal women shows limited benefits, while vaginally administered DHEA may improve vaginal atrophy and sexual function in estrogen deficient women.

Systematic ReviewHighly Cited

2010·

96citations

·M. Panjari et al.

Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity.

DHEA and DHEAS protect hippocampal neurons from neurotoxicity caused by excitatory amino acids, suggesting that decreased DHEA levels may contribute to increased vulnerability in aging or stressed human brains.

In Vitro StudyHighly Cited

1998·

440citations

·V. G. Kimonides et al.

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