DHEA

DHEA (dehydroepiandrosterone) is the most abundant steroid hormone in your body. Your adrenal glands make it, and it sits one step upstream of both testosterone and oestrogen, so it's the raw material your body uses to top up either side depending on what it needs. You produce a lot of it in your 20s, and then it falls off a cliff, by 70 most people are running at around 10-20% of their peak levels. This decline is one of the cleanest, most predictable curves in human endocrinology.

The simplest way to think about DHEA: it's the background hormone that keeps the lights on. Your testes or ovaries handle the big, dramatic stuff (puberty, fertility, your main testosterone or oestrogen levels). DHEA handles the quieter day-to-day signalling in skin, brain, bone, and immune tissue. Most of it gets converted locally inside those tissues into whatever they need, a bit of testosterone here, a bit of oestrogen there, so it acts like a buffer your body draws from to keep everything topped up. When DHEA drops with age, things don't break, they just get a bit duller. Skin thins, mood flattens, libido fades, recovery slows. That's the gap people are trying to fill when they supplement.

Most people take it as a low-dose hormone replacement strategy after 40 or 50, when adrenal output has dropped enough to noticeably affect energy, mood, libido, skin quality, and recovery. It's also used in women with low ovarian reserve, premature ovarian insufficiency, or adrenal insufficiency, where the standard dose can meaningfully restore androgens. The intravaginal form (prasterone) is an FDA-approved treatment for postmenopausal vaginal atrophy and pain with sex. If you're 25 and feeling fine, this isn't for you. If you're 50 and your bloodwork shows DHEA-S in the bottom third of the reference range, this is one of the cheapest, most defensible interventions you can run.

DHEA behaves very differently in men and women. In men, most of an oral dose gets shunted toward oestrogen, with only a modest bump in testosterone. In women, it can substantially raise both androgens and oestrogens, so the same 25-50 mg dose that feels mild in a 55-year-old man can be too much for a 45-year-old woman. Dose accordingly.

If you're on TRT, this is also worth paying attention to. Exogenous testosterone suppresses your HPG axis (LH, FSH, and downstream testicular output), but it also tends to drag DHEA-S down over time, partly through reduced ACTH stimulation and partly through changes in adrenal steroidogenesis. Most long-term TRT users end up with DHEA-S in the bottom quartile of the reference range even though their total testosterone looks great on paper. This is a common reason men on TRT still feel flat on mood, libido, or sense of well-being despite "perfect" T numbers. Adding back 25-50 mg of DHEA in the morning is one of the simpler fixes, just be aware that on a TRT base the oestrogen conversion stacks on top of whatever aromatisation you're already managing, so watch E2 and adjust your AI (or your dose) accordingly.

Deep-dive

DHEA is synthesised in the zona reticularis of the adrenal cortex from pregnenolone, which itself comes from cholesterol. It circulates mostly as DHEA-sulphate (DHEA-S), the storage form, which has a half-life of around 10-20 hours compared to free DHEA's 15-30 minutes. DHEA-S is what gets measured on standard bloodwork because it's stable across the day, whereas free DHEA fluctuates with cortisol's diurnal rhythm.

From DHEA, the body can go two ways. Through 3β-hydroxysteroid dehydrogenase and 17β-HSD, it converts to androstenedione and then testosterone. Through aromatase, testosterone (or androstenedione directly) converts to oestradiol and oestrone. The split between these pathways depends on tissue, sex, body fat (more adipose tissue means more aromatase, so more conversion to oestrogen), and age. This is why DHEA is sometimes called an intracrine hormone, the conversion happens locally inside target tissues like skin, brain, bone, and the vagina rather than only in the gonads. That's also why intravaginal DHEA can restore local tissue health without large systemic hormone changes.

Levels peak around age 25-30 and then fall progressively, roughly 2-3% per year. By 70-80, DHEA-S is typically 10-20% of peak. This is called "adrenopause," and the steepness of the decline (much sharper than for cortisol, which stays stable or rises with age) is what makes DHEA a candidate for replacement. The hypothesis is straightforward: if levels drop this much and the hormone has clear physiological roles, putting it back should help. The evidence for that hypothesis is mixed and dose-dependent, which we'll get to.

Mood, well-being, and depression. This is one of the better-supported uses. A 6-week trial in 46 men and women aged 45-65 with midlife-onset major or minor depression found 90 mg/day of DHEA produced a significant antidepressant effect compared to placebo, with about half of treated subjects achieving 50% improvement on Hamilton ratings. An earlier trial in midlife dysthymia showed similar improvements at 30-90 mg/day. The effect appears most robust in people with measurably low baseline DHEA-S, less consistent in people with normal levels. There's also reasonable evidence in adrenal insufficiency where 50 mg/day in women with Addison's improved well-being, mood, and sexuality scores in a placebo-controlled trial.

Bone density. In older women, DHEA at 50 mg/day for 12 months modestly increased spine bone mineral density and improved bone turnover markers compared to placebo, an effect mediated through the rise in oestrogen and IGF-1. In older men the bone effect is smaller and less consistent.

Libido, sexual function, and vaginal health. In postmenopausal women, intravaginal DHEA (prasterone, 6.5 mg/day) is FDA-approved for moderate-to-severe dyspareunia and consistently improves vaginal cell maturation, lubrication, and pain with sex without raising systemic oestradiol meaningfully above postmenopausal levels. Oral DHEA in older women has shown modest improvements in libido at 50 mg/day. In men, the libido signal is weaker and less consistent, in part because most of the dose goes to oestrogen rather than testosterone.

Fertility (women with diminished ovarian reserve). This is a niche but real use case. Multiple trials of 75 mg/day DHEA for 6-16 weeks before IVF in women with poor ovarian response have shown improvements in oocyte yield, embryo quality, and live birth rates, though the evidence base is heterogeneous and a Cochrane-style review notes the trials are small. If you're a woman in your late 30s or 40s preparing for IVF with poor response history, this is something to discuss with a fertility specialist.

Body composition, strength, and "anti-aging" claims. This is where the hype outruns the data. The DHEAge trial in 280 older adults found 50 mg/day for a year produced small improvements in skin parameters and libido in women but no meaningful change in muscle, strength, or insulin sensitivity. A Mayo Clinic trial in older men and women similarly found 75-50 mg/day for 2 years did not improve body composition, strength, or quality of life. DHEA is not testosterone, and treating it as a stealth testosterone replacement in healthy older men will mostly disappoint you. If you want androgenic effects on muscle in a man, TRT is the actual tool. DHEA's case rests on mood, skin, bone, sexual function, and immune signalling, not gym performance.

Skin. Both oral and topical DHEA produce visible improvements in older skin. A 4-month trial of 50 mg/day oral DHEA in postmenopausal women improved skin thickness, hydration, and sebum production. Topical DHEA shows similar effects in the treated area. This is consistent with what you'd expect from restoring sex steroid signalling to skin, which is a major intracrine target tissue.

Immune and metabolic markers. DHEA modulates a number of immune pathways and tends to lower IL-6 and other inflammatory markers in older adults. The clinical relevance of this is unclear, it's more of a "general restoration of a youthful endocrine background" effect than a specific therapeutic lever.

Men vs women, what to actually expect. In men, oral DHEA mostly raises oestradiol, with a modest bump in testosterone. This is why men often notice mood and well-being effects but rarely the lean mass or libido changes they were hoping for, and why men prone to gynecomastia or oestrogen-sensitive issues should be cautious or run alongside something like

DIM (Diindolylmethane) to support oestrogen clearance. In women, the same dose can raise androgens (testosterone, free testosterone, androstenedione) significantly along with oestrogens, which is why women often notice libido, mood, skin, and energy changes more reliably than men, but also why side effects like acne, oiliness, and unwanted hair growth show up more in women. Postmenopausal women in particular get the most consistent benefit, both because their baseline is lowest and because their tissues are oestrogen-starved.

Older adults. This is the population where DHEA makes the most sense. Roughly: if you're over 50, have measurably low DHEA-S, and have symptoms (low mood, low energy, low libido, thinning skin), a 3-6 month trial at the appropriate dose is reasonable. If you're under 40 with normal levels, there's no good reason to be taking this.

Limits of the evidence. Most trials are 3-12 months, small (under 100 subjects), and use different endpoints. Long-term safety data beyond 2 years is thin. There is no good evidence DHEA extends lifespan or prevents age-related disease, only that it can improve specific symptoms in specific populations. Concerns about hormone-sensitive cancers (prostate, breast) are theoretical but not negligible, since DHEA does raise oestrogen and androgen levels, so it's contraindicated in anyone with active or history of hormone-sensitive cancer.

Dosage:

Women, general low-dose replacement: 10-25 mg/day, oral, in the morning. Start at 10 mg and titrate up based on response and bloodwork at 8-12 weeks. Most women don't need more than 25 mg

Men, general low-dose replacement: 25-50 mg/day, oral, in the morning. Men typically need a higher dose to move levels meaningfully because conversion is more diffuse. Start at 25 mg

Adrenal insufficiency or measurably very low DHEA-S with symptoms: 25-50 mg/day in women, 50 mg/day in men. This is the dose used in most clinical trials for Addison's and depression

Women preparing for IVF with poor ovarian response: 75 mg/day, split into 25 mg three times daily, for 6-16 weeks before cycle. Run under the care of a fertility specialist, not solo

Postmenopausal vaginal atrophy: intravaginal DHEA (prasterone) 6.5 mg as a suppository, once daily at bedtime. This is the prescription product (Intrarosa) and acts locally with minimal systemic absorption. Better tolerated than oral DHEA for women whose symptoms are mainly vaginal

Timing: Take in the morning. DHEA naturally peaks in the morning and dosing this way matches the diurnal rhythm. Evening dosing can cause mild stimulation that interferes with sleep in some people

With or without food: Either works. Fat with the dose may marginally improve absorption since DHEA is lipophilic

What not to do: Don't take 100+ mg/day as a "natural testosterone booster" if you're a healthy young man. You'll mostly raise oestrogen, suppress your own DHEA production through feedback, and accomplish nothing useful. If you want higher testosterone, get bloodwork and consider whether actual TRT is the right call

7-keto-DHEA (no page yet, flag this) is a metabolite that doesn't convert to sex hormones. It's marketed for thermogenesis and weight loss with weak evidence. It's a different compound from DHEA and not a substitute if you want the hormonal effects

Here's what you can expect:

In the right context (low baseline DHEA-S, symptoms of low mood, energy, libido, or skin quality), you should notice gradual improvements in mood and sense of well-being within 2-4 weeks, with skin, libido, and energy changes building over 2-3 months. The effect is restorative rather than stimulating. It's not a hit you feel, it's more that the floor of your daily energy and mood comes up a notch.

Women, particularly postmenopausal women, tend to notice changes faster and more clearly than men, both because their baseline is lower and because the androgen conversion is more impactful.

In the wrong context, you won't feel much except possibly some mild stimulation, acne, or oiliness. Your endogenous DHEA production will downregulate. This is the most common reason people abandon it: they took it because they read it was anti-aging, didn't actually need it, and felt nothing or felt slightly worse.

If you're going to do this, get bloodwork first, dose to the bottom-half of your sex-and-age reference range, and reassess at 3 months. Don't run it indefinitely without rechecking.

Side effects & risks:

Androgenic side effects, especially in women: acne, oily skin, scalp hair thinning, unwanted facial or body hair, deepened voice (rare and at higher doses). These are dose-dependent and reversible at lower doses or with discontinuation. If you're a woman noticing acne or oiliness on 25 mg, drop to 10-15 mg

Oestrogenic side effects, especially in men: breast tenderness, gynecomastia, water retention, mood changes from oestradiol rising too high. More likely at doses above 50 mg/day and in men with higher body fat. DIM can help with clearance, or just lower the dose

Insomnia and mild stimulation if dosed in the evening. Move it to morning

Liver: oral DHEA is processed hepatically. No serious liver toxicity in clinical trials at standard doses, but worth tracking ALT/AST if running 50+ mg/day chronically

Lipids: DHEA tends to lower HDL modestly in women (similar to what testosterone does), with little effect on LDL. Worth tracking on a lipid panel if you're already managing cardiovascular risk

Hormone-sensitive cancers: DHEA is contraindicated in anyone with current or history of breast, prostate, ovarian, or other hormone-sensitive cancers. Because it raises both androgens and oestrogens, it's a hard avoid in this population

PCOS: women with PCOS often already have elevated DHEA-S and adding more is the opposite of what you want. Skip unless guided by a specialist

Pregnancy and breastfeeding: Skip it. It changes the hormonal environment and isn't appropriate during these periods

Drug interactions: DHEA can interact with hormone therapies, aromatase inhibitors, and some antidepressants. If you're on any of these, run it past your prescriber

Suppression of endogenous production: chronic exogenous DHEA, like any hormone, will downregulate your body's own production. This isn't a major issue at low replacement doses in older adults whose production is already low, but it's a reason not to run high doses in young people with intact adrenal output

Quality control: DHEA is sold OTC in the US but is a controlled substance or prescription-only in many countries (UK, Canada, Australia). Independent analyses of commercial products have historically found significant variability between labelled and actual content. Use a reputable brand with third-party testing

Long-term safety data is limited. The longest well-controlled trials run 1-2 years. Decades of use data don't exist

🩸

Blood markers

DHEA-S, baseline before starting. This is the single most important number. Reference ranges are sex- and age-specific, and the goal isn't to push to the top of the range but to restore to roughly the middle of a young-adult range for your sex. Recheck at 8-12 weeks on a stable dose, drawn in the morning before that day's dose.

Total testosterone, free testosterone, and SHBG, baseline and at 12 weeks. Particularly important in women, where DHEA can meaningfully raise androgens. In men, you want to confirm whether T is moving and by how much, since the answer is often "not much."

Oestradiol (E2), baseline and at 12 weeks. Important in both sexes. In men this is the main metabolite of DHEA and a high E2 explains most of the side-effect profile. In postmenopausal women a modest rise is expected and usually fine.

Lipid panel, baseline and at 6 months. Watch HDL especially in women.

Liver enzymes (ALT, AST), baseline if running 50+ mg/day chronically.

PSA (men over 40), baseline before starting. Not because DHEA causes prostate cancer, but because if you have an undetected hormone-sensitive prostate issue, you want to know before adding substrate to it.

The people who actually need this bloodwork are anyone over 40 considering chronic use, anyone using doses above 25 mg/day, women on any dose, and anyone with a history that touches hormone-sensitive tissue. Symptom-only dosing without bloodwork is a bad idea here in a way it isn't for, say, magnesium.

Sold OTC as a dietary supplement in the US. Prescription-only or controlled in the UK, Canada, Australia, and much of the EU. The intravaginal form (prasterone, Intrarosa) is prescription everywhere.