DHEA and Pregnenolone: What to Know Before Taking Hormone Supplements

In the world of health videos, DHEA and pregnenolone are often called "the mother of all hormones" or "anti-ageing hormones". They sound worth trying, especially when you feel more tired as you get older. I understand the appeal, but as a doctor whose job is to explain the evidence honestly, I have to say the picture is much more complicated than the adverts suggest.

What is DHEA?

DHEA (dehydroepiandrosterone) is the steroid hormone produced in the greatest amount by the adrenal glands. The body uses it as a building block to make both male and female sex hormones in various tissues. In the blood, most of it circulates as DHEA-S.

DHEA levels peak between the ages of 20 and 30 and then fall steadily. By 70–80, they may be only about 10–20% of young-adult levels. This fact led to the idea that topping it back up might slow ageing.

Evidence from studies in people

The early studies that are often quoted, such as work from around 1994 or 2000 that found people felt better or had higher hormone levels, were small or short. Larger, longer studies later did not confirm those results.

Advertised claims

• More muscle, less fat in older people
• More energy, quality of life
• Better memory and brain function
• Better sex life

What studies found

• No meaningful benefit (NEJM 2006)
• No clear benefit
• Cochrane: no evidence it helps
• Inconsistent; not recommended as treatment

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Medical exceptions exist, e.g. vaginal DHEA for menopausal vaginal dryness.

Where DHEA has a medical role

• Vaginal DHEA (prasterone) is approved in several countries to treat pain during sex caused by menopausal vaginal dryness. It acts locally (read vaginal dryness and GSM).
• Women with adrenal insufficiency: in some who still have symptoms despite full replacement of the main hormones, a doctor may try it for a short period and assess the effect.
• Fertility treatment: it has been studied in some groups, but the evidence is still unclear, and it is used only in a specialist setting.

Apart from these, DHEA should not be used instead of treating diagnosed testosterone deficiency in men. If testosterone is genuinely low, the evidence-based treatment is TRT, as a doctor assesses. For women with reduced sexual desire, there are specific guidelines; read testosterone in women.

Side effects and risks of DHEA

• Acne, oily skin, hair thinning
• In women: excess hair growth, a hoarse or deeper voice, irregular periods
• In men: some is converted to oestrogen, which can cause breast enlargement or tenderness (see hormone imbalance in men)
• HDL ("good" cholesterol) may fall
• Concerns in people who have or have had hormone-sensitive cancers, such as breast or prostate cancer
• Irritability and insomnia; some people with bipolar disorder have had mania-like symptoms
• It is on the World Anti-Doping Agency (WADA) prohibited list, so athletes who are drug-tested need to be careful

Another problem is product quality. Testing of DHEA products on the US market (JAMA 1998) found that the actual content ranged from almost none to more than the label stated. The dose in products bought online is therefore unpredictable.

What is pregnenolone?

Pregnenolone is made from cholesterol and is the starting point of the pathway that produces almost every steroid hormone: cortisol, aldosterone and the sex hormones. It also acts as a messenger in the brain (a neurosteroid). So the phrase "mother of all hormones" is correct biochemically.

What the adverts usually do not tell you is that when you swallow pregnenolone, your body does not necessarily convert it into the hormone you want, and you cannot control which way it goes.

Evidence in people:

• There are small studies in psychiatric conditions, for example as an add-on in schizophrenia or bipolar depression. Results are inconsistent and it is not a standard treatment.
• There is no good evidence that it helps energy, memory or sexual function in the general population.
• No dose has been proven safe for long-term use.

The cautions are similar to DHEA: it may affect sex hormones, it should not be used in pregnancy, while breastfeeding or with hormone-sensitive cancers, and it may cause insomnia and irritability.

If you feel tired and drained, where to start instead

1. Look for treatable causes, such as thyroid problems, anaemia, diabetes, sleep apnoea or depression.
2. Have your testosterone tested properly if you have symptoms (read symptoms of low testosterone).
3. Sort out the basics: sleep, exercise, weight and alcohol (see supporting testosterone through sleep, diet and exercise).
4. If you want to take any supplement, show the product to a doctor or pharmacist first.

1. 1Find treatable causesThyroid, anaemia, diabetes, sleep apnoea, depression
2. 2Test hormones properlyIf symptomatic, test in the morning per guidelines
3. 3Cover the basicsSleep, exercise, weight, alcohol
4. 4Have a doctor review productsAsk your doctor or pharmacist before any supplement

When to see a doctor, and how the clinic can help

See a doctor if you are taking DHEA or pregnenolone and develop marked acne, excess hair growth, a change in your voice, breast enlargement, irregular periods or insomnia, or if you have a history of hormone-sensitive cancer.

At Dr. Kris Clinic, I give evidence-based advice on hormones and supplements, look for the causes of tiredness or reduced sexual desire, and recommend safer options. Consultations are available at the clinic or online, in English.