What is the clinical significance of Dehydroepiandrosterone (DHEA)?

From the Guidelines

DHEA should be used with caution in survivors of hormonally mediated cancers, particularly those receiving aromatase inhibitor therapy, due to its potential to increase levels of circulating androgens and impact treatment efficacy. When considering DHEA for vaginal dryness or pain with sexual activity, it is essential to weigh the potential benefits against the limited safety data available, especially in survivors of estrogen-dependent cancers 1.

Key Points to Consider

• DHEA has been shown to be effective in reducing dyspareunia in postmenopausal individuals, but its impact on vaginal dryness is less clear 1.
• A randomized controlled trial of 464 survivors of breast or gynecologic cancer found that vaginal DHEA led to significant improvements in sexual desire, arousal, pain, and overall sexual function, although a plain moisturizer also improved symptoms 1.
• The safety of vaginal hormones, including DHEA, has not been firmly established in survivors of estrogen-dependent cancers, making cautious use and close monitoring crucial 1.

Alternatives and Considerations

• Vaginal estrogen is the most effective treatment for vaginal dryness leading to sexual dysfunction and has been shown to be safe in postmenopausal survivors of hormone receptor-positive breast cancer receiving aromatase inhibitor therapy 1.
• Ospemifene, an FDA-approved selective estrogen receptor modulator, is an option for dyspareunia in survivors without a history of estrogen-dependent cancers, with data showing improvements in vaginal health and function, sexual activity, and quality of life 1.
• Flibanserin, an FDA-approved medication for acquired, generalized hypoactive sexual desire disorder, may also be considered for survivors, offering another potential treatment option for sexual dysfunction 1.

From the FDA Drug Label

INDICATIONS: Temporarily supports the body to rebalance Adrenal and DHEA output. Symptoms of imbalanced Adrenal and DHEA may include: low energy, depression, anxiety, dry eyes, skin, and hair, loss of head hair. The indications for DHEA (PO) include temporarily supporting the body to rebalance Adrenal and DHEA output, with symptoms of imbalance including:

• Low energy
• Depression
• Anxiety
• Dry eyes, skin, and hair
• Loss of head hair 2

From the Research

DHEA Overview

• Dehydroepiandrosterone (DHEA) is an androgen produced by the zona reticularis of the adrenal gland 3, 4.
• DHEA levels increase in early puberty, peak in the second and third decade, and decline thereafter, independent of menopausal status 3.
• DHEA deficiency is associated with morbidity, including adverse impacts on metabolic function, quality of life, and sexuality in multiple studies 4, 5.

Benefits of DHEA Supplementation

• DHEA supplementation has been shown to have beneficial effects on quality of life, body composition, bone health, and metabolic markers in patients with primary and secondary adrenal insufficiency 4, 6.
• DHEA may also improve physical and psychological well-being, muscle strength, and bone density, and reduce body fat and age-related skin atrophy in the elderly 5.
• In women, DHEA may improve sexual satisfaction, fertility, and age-related vaginal atrophy 5, 6.

Risks and Side Effects of DHEA Supplementation

• High physiologic or pharmacologic use of DHEA may lead to androgenic and estrogenic side effects, which are of concern for long-term administration 3.
• Side effects of DHEA replacement in women may include increased sebum production, facial acne, and changes in hair status 6.

DHEA Supplementation in Adrenal Insufficiency

• DHEA supplementation may be beneficial for patients with adrenal insufficiency, particularly those with impaired well-being 4, 6.
• However, the role of DHEA replacement in adrenal insufficiency remains unclear, and large-scale randomized controlled trials are needed to inform on optimal dose and duration of DHEA replacement 4, 6.

Current Recommendations

• DHEA supplementation is not considered essential for life and is not routinely replaced in adrenal failure 4.
• Compassionate use of DHEA in individual patients with adrenal insufficiency and impaired well-being may be justified, but DHEA cannot be considered part of standard replacement in adrenal insufficiency until further research is conducted 6.