Written by Dr. Laura Kelly, DAOM, L.Ac, Dipl. OM
In the realm of women’s health, few substances are as underappreciated yet powerful as DHEA (dehydroepiandrosterone). While we have spotlighted DHEA for its local effects on vulvovaginal health, DHEA plays a far more comprehensive role in the body. As a key hormone precursor, DHEA influences a wide array of biological systems—from mood and memory to bone density and immune resilience.
In this article, we go beyond the vaginal applications of DHEA and explore the systemic benefits, with a particular focus on the needs of midlife women. We’ll look at how DHEA supplements support adrenal health, contribute to hormone balance, and offer exciting insights into anti-aging strategies for women over 40.
DHEA for Women: The Mother Hormone
DHEA is one of the most abundant steroid pro-hormones (hormone precursor) in the human body, produced primarily in the adrenal glands, with smaller amounts coming from the ovaries and brain. It serves as the biochemical precursor to both androgens (e.g., testosterone) and estrogens (e.g., estradiol, estrone)—hormones that are essential for maintaining vitality throughout the human system.
DHEA production peaks in a woman’s mid-20s and then begins a steady decline, often dropping by more than 80% by the time she reaches her 60s. This decline parallels the appearance of many age-related conditions: reduced energy, lowered libido, bone loss, mood fluctuations, brain fog, and increased susceptibility to infections.
Because of its central role in the hormonal cascade, DHEA acts as a foundational molecule for maintaining balance throughout the endocrine system. This is especially important in women who are navigating perimenopause or postmenopause, where hormonal variability or deficiency can disrupt everything from metabolism to mood to sexual wellness.
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Introduction to DHEA
DHEA, or Dehydroepiandrosterone, is a hormone produced primarily by the adrenal glands, playing a crucial role in the production of sex hormones such as estrogen and testosterone. As a precursor to these vital hormones, DHEA is essential for maintaining hormonal balance and overall health. Natural DHEA levels peak in early adulthood but begin to decline with age, often leading to symptoms like decreased sexual desire, fatigue, and weight gain. Understanding the importance of DHEA and its effects on the body can help individuals make informed decisions about their health. Considering DHEA supplements or DHEA therapy can be a proactive step towards supporting well-being, especially as natural levels diminish over time.
DHEA vs Cortisol – the battle in the Adrenals
Both DHEA and cortisol are produced in the adrenal gland. Normal adrenal function is crucial for maintaining balanced DHEA and cortisol levels. With age DHEA declines steadily, while cortisol production remains relatively stable or even increases with aggregated stress from the lack of sleep common in the aging process.
DHEA Is an Adrenal Hormone
- DHEA is produced primarily in the zona reticularis of the adrenal cortex.
- It’s secreted alongside cortisol and other adrenal steroids.
- While cortisol is a catabolic hormone (breaks tissue down), DHEA is anabolic (builds tissue up), providing a counterbalance in the body’s stress response.
- DHEA is essential for androgen production, which includes hormones like testosterone.
Stress and the Cortisol–DHEA Imbalance
In states of chronic stress, the adrenal glands often produce excess cortisol and relatively less DHEA. Over time, this can lead to a low DHEA-to-cortisol ratio, which has been associated with:
- Fatigue
- Anxiety or mood instability
- Impaired immunity
- Muscle loss
- Poor sleep
- Decreased resilience to stress
- Mood disorders, including depression
By supplementing with DHEA, some of these effects can be partially reversed or modulated, especially when cortisol levels are chronically high.
HPA Axis Dysregulation
Though “adrenal fatigue” is a debated term in conventional medicine, this term is really describing the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis under chronic stress.
In these models:
- DHEA supplementation (typically 5–25 mg/day for women) is used to replenish low levels, improve mood, and restore energy.
- Monitoring serum concentrations of DHEA can help assess the effectiveness of supplementation.
- It helps re-establish a healthier cortisol:DHEA balance, reducing the catabolic toll of chronic stress on tissues.
Clinical evidence supports this approach in adrenal insufficiency and burnout syndromes:
- Studies show improved energy, well-being, libido, and bone turnover when DHEA is added in adrenal-compromised patients.
Neurosteroid and Mood-Stabilizing Effects
DHEA is also a neurosteroid—it acts on receptors in the brain that modulate mood, including:
- GABA-A antagonism (mildly stimulating)
- NMDA receptor modulation (involved in cognition)
- Positive influence on serotonin and dopamine systems
DHEA’s positive influence on serotonin and dopamine systems can significantly impact mental health.
These effects may help counter the mental exhaustion, anxiety, or apathy often seen in women with HPA axis dysfunction or postmenopausal adrenal decline.
DHEA-S as a Marker of Adrenal Reserve
- DHEA-Sulfate (DHEA-S) is a storage form of DHEA with a longer half-life, and it’s often used as a clinical biomarker of adrenal output.
- Low DHEA-S is common in:
- Chronic stress
- Aging (especially postmenopause)
- Autoimmune conditions
- Chronic infections
Maintaining optimal levels of DHEA is crucial for overall well-being, as it impacts hormonal balance, mood, and skin quality, particularly in women during menopause.
Supplementation can restore DHEA-S to a youthful range (~100–150 μg/dL in women), which is often correlated with better stress tolerance and physical resilience.
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Energy, Mood, and Cognitive Function
Many women report a noticeable improvement in energy, mood, and mental clarity after starting DHEA supplementation. Scientific studies back this up:
- Energy and fatigue: Clinical trials have shown that DHEA can enhance feelings of vigor, particularly in older adults and those with adrenal insufficiency.
- Mood support: DHEA has been studied as an adjunct treatment for mild depression, especially in midlife women and those with low baseline DHEA-S levels. It appears to act on GABA and NMDA receptors, modulating stress and mood. Additionally, DHEA’s impact on serotonin and dopamine can help manage mood disorders.
- Cognitive function: Although evidence is still emerging, some studies suggest that DHEA may support memory and executive function, likely due to its neurosteroid activity in the brain and its conversion to estrogen and testosterone locally within neural tissues. DHEA may support various cognitive functions, including memory and executive function.
Women who are perimenopausal or postmenopausal frequently experience emotional flatness, anxiety, or reduced resilience to stress. Because DHEA levels are closely linked to adrenal output, supplementation may restore a sense of “mental buoyancy” during this transition.
Bone Health and Aging
Osteopenia and osteoporosis are major concerns for women over 50, especially after the drop in estrogen that accompanies menopause. While estrogen replacement therapy is a well-known intervention, DHEA also plays a direct and indirect role in maintaining bone mass.
- Direct effects: DHEA interacts with androgen and estrogen receptors on bone-forming cells (osteoblasts), stimulating bone mineralization.
- Indirect effects: By increasing circulating levels of estradiol and testosterone (especially in women with low baseline levels), DHEA promotes calcium retention and reduces bone resorption by activating the Rank ligand system. Additionally, DHEA may stimulate the expression of insulin-like growth factor 1, which is linked to improvements in bone density.
Clinical studies have found that oral DHEA supplementation (typically 50 mg/day) over a period of 6–12 months can improve bone density in the lumbar spine and hip, particularly in women with adrenal insufficiency or those not using estrogen therapy.
This makes DHEA a promising adjunct for women seeking to preserve skeletal strength without committing to full-dose estrogen therapy.
Immune System Modulation
Less well known—but equally fascinating—are DHEA’s effects on the immune system. As an immunomodulator, DHEA helps maintain immune vigilance while preventing excessive inflammation.
- It enhances the activity of natural killer (NK) cells and T lymphocytes, are our main cells for immune surveillance and active function. DHEA plays a crucial role in enhancing immune function.
- DHEA has been shown to counteract the immunosuppressive effects of cortisol, helping to restore balance in stressed or aging individuals. DHEA modulates immune function, helping to maintain a balanced immune response.
- In autoimmune conditions such as lupus or Sjögren’s syndrome, DHEA has demonstrated mild but significant benefits in symptom reduction and quality of life.
With immune health top of mind for many midlife women, especially in the context of chronic inflammation and infection risk, DHEA may offer subtle but meaningful tool.
DHEA and Menopause
During menopause, women experience a significant decline in estrogen and testosterone levels, leading to a range of symptoms such as hot flashes, vaginal dryness, and decreased sexual desire. DHEA therapy has shown promise in alleviating some of these menopausal symptoms, particularly in postmenopausal women. Studies have demonstrated that DHEA use can improve sexual function, cognitive function, and overall quality of life in postmenopausal women. Additionally, DHEA has been found to offer anti-aging benefits, including improved skin health and a reduced risk of osteoporosis. However, more research is needed to fully understand the effects of DHEA on menopausal symptoms and to determine the optimal dosage and duration of DHEA therapy for each individual.
Adrenal Insufficiency
Adrenal insufficiency is a condition where the adrenal glands do not produce enough hormones, including DHEA. This can result in symptoms such as fatigue, weight loss, and decreased sexual desire. DHEA supplementation has been shown to be effective in treating adrenal insufficiency, particularly in individuals with low DHEA levels. However, it is crucial to work with a healthcare provider to determine the underlying cause of adrenal insufficiency and to develop a personalized treatment plan. DHEA therapy should only be used under medical supervision, as it can have potential side effects, including acne, hair loss, and an increased risk of hormone-sensitive cancers.
Topical vs. Oral DHEA: How They Differ
While vulvar or vaginal DHEA is applied locally and converted within vulvar or vaginal tissues, oral DHEA or body-wide transdermal cream have more systemic effects. Understanding the difference is essential when selecting the best approach.
Additionally, vaginal estrogen is another effective treatment for genitourinary syndrome of menopause (GSM), offering significant improvements for symptoms like vaginal dryness and dyspareunia.
Oral DHEA
- Standard dose: 25–50 mg/day (studies up to 100mg/day)
- Absorption: Enters systemic circulation; partially converted in the liver to DHEA-S.
- Effect profile: Increases serum DHEA-S, testosterone, and estradiol modestly
- Benefits: System-wide support for energy, mood, skin, and bone health, and maybe libido
- Body composition: Oral DHEA can positively impact body composition by influencing fat mass and muscle mass.
Topical DHEA (e.g., creams or transdermal gels, often 20 or 50mg/dose)
- Dose: Varies by formulation; 5–20% concentration used in studies/20-100mg studied)
- Absorption: Variable based on carrier and application site; often lower systemic exposure than oral
- Targeted use: Applied to thin-skin areas (inner thighs, abdomen)
- Benefit: May improve localized tissue tone and androgenic support without systemic peaks found in oral supplementation – slower absorption.
- Muscle mass: Topical DHEA can help maintain muscle mass, particularly in aging women.
In general, oral DHEA is best for whole-body effects, topical body creams for a potentially milder version of systemic effects with increased improvement in localized tissue where applied, while vaginal and vulvar DHEA are ideal for GSM and sexual rejuvenation. Some women use multiple types of DHEA support (under medical guidance) to balance local and systemic support, and in this case all dosages are balanced to achieve one proper dose.
Who Might Benefit from Systemic DHEA Supplementation?
Systemic DHEA may be especially beneficial for:
- Women over 45 experiencing fatigue, brain fog, and decreased resilience to stress
- Individuals with low DHEA-S levels (confirmed via blood test)
- Women with osteopenia or early osteoporosis
- Those with mild autoimmune or inflammatory conditions
- Women seeking natural hormone balance without committing to full hormone replacement therapy (HRT)
- Elderly women to support overall health and vitality
It’s important to note that DHEA isn’t for everyone. Women with hormone-sensitive cancers, polycystic ovarian syndrome (PCOS), or a history of androgenic side effects (acne, hirsutism) should consult their provider before starting supplementation.
A Word on Testing and Safety
Although DHEA is available over the counter in many countries, testing DHEA-S levels before supplementation is a good practice especially if in perimenopause/pre menopause. This gives a baseline to assess whether a woman is truly deficient and allows for monitoring of response. Because DHEA turns into our sex hormones, sometimes a transformation is not occurring as it should – so the effects are not felt, but not because DHEA levels are low.
- Normal postmenopausal DHEA-S levels range from ~30 to 200 µg/dL
- Many clinicians aim to restore levels to the mid-normal range (e.g., 100–150 µg/dL)
Oral doses of up to 50 mg/day are generally well tolerated. Side effects, though uncommon, may include mild acne, oily skin, or facial hair growth—typically dose-related and reversible. If these side effects occur, then the dose it too high for you – work with your provider to find the appropriate dose.
Long-term studies have found no significant impact on liver enzymes, endometrial thickness, or breast density when DHEA is used appropriately.
Risks and Side Effects
While DHEA supplements and DHEA therapy can offer potential health benefits, they also come with risks and side effects. Common side effects of DHEA supplementation include acne, hair loss, and an increased risk of hormone-sensitive cancers. Additionally, DHEA can interact with certain medications, such as blood thinners and diabetes medications. It is essential to work with a healthcare provider to assess the potential risks and benefits of DHEA therapy and to develop a personalized treatment plan. Individuals with a history of breast cancer, polycystic ovary syndrome, or other hormone-sensitive conditions should exercise caution when considering DHEA supplements or therapy. Regular monitoring of DHEA levels, liver function, and other health markers can help minimize the risks associated with DHEA therapy.
Final Thoughts: A Gentle Yet Powerful Ally in Midlife Health
Though typically overshadowed by estrogen and progesterone in hormone discussions, DHEA is a quiet multitasker—one that supports everything from mental sharpness and immunity to libido and bone health. For midlife women navigating the complex transitions of perimenopause and menopause, systemic DHEA benefits – on top of local vulvovaginal benefits – can be an empowering and accessible solution.
DHEA also plays a critical role in women’s health, influencing various aspects such as mood, bone density, and sexual function.
Whether taken orally for full-body support or applied vulvo/vaginally to restore comfort and function, DHEA supplements are a versatile, science-backed option in the landscape of midlife and longevity medicine. With proper guidance, testing, and dose adjustment, DHEA offers a path to restoring energy, balance, and vitality—naturally.
Dr. Laura Kelly, DAOM, L.Ac, Dipl. OM is a double board-certified Doctor of Oriental Medicine and nationally licensed primary care provider based in Topanga, California. She earned her clinical doctorate in Oriental Medicine and integrates traditional Eastern healing practices with modern Western diagnostics, including genetics and advanced clinical testing, to deliver personalized, natural medicine solutions. With a deep commitment to Assisted Self-Healing, Dr. Kelly creates personalized, natural medicine programs that support the body’s innate ability to heal. She is the author of multiple internationally published books, including The Healthy Bones Nutrition Plan and Cookbook, which emphasize nutrition-based treatments for bone health. https://www.instagram.com/dr.laurakelly/
