DHEA is a steroid prohormone produced by the adrenal glands and transformed in target tissue to androgens or estrogens. Plasma DHEA levels decline with age. By the age of 70–80 years, levels may be as low as 10%–20% of those encountered in young individuals.
Dehydroepiandrosterone (DHEA) is a steroid hormone produced by the adrenal glands in men and women. The adrenal glands are located on top of the kidneys.
DHEA is the most common steroid in humans. It can be transformed in the body into testosterone (the primary male sex hormone), estrogen (an important female sex hormone), or other steroids. However, DHEA supplements have been shown not to increase testosterone in men (this effect is only seen in women).
DHEA has not demonstrated the same effects as anabolic (muscle-building) steroids, but the Food and Drug Administration has already examined the possibility of classifying DHEA as a Schedule III drug. If this happens, it will be extremely difficult to get DHEA. Right now, DHEA can be obtained in over-the-counter supplements in the United States (a prescription is required in many countries).
In normal adults, DHEA levels are highest at about age 20, and then decrease steadily. HIV patients with visceral fat accumulation have very low levels of DHEA.
People with various diseases have levels of DHEA that are unusually low. DHEA has been used in the last thirty years or so to treat obesity, diabetes, and lupus. It has also been found to improve sleep. Many people who have taken DHEA report improved energy levels and a better sense of well being.
Some people with HIV take DHEA in amounts designed to restore normal levels. This might help improve their energy levels. Several studies have found that DHEA increases the levels of IL-2, a chemical messenger that increases the production of CD4 (T-helper) cells. DHEA also improves the ability of CD8 (T-killer) cells to destroy infected cells. DHEA may help normalize the immune system. A recent study shows that DHEA can reduce in people with HIV.
DHEA is available in “regular” form or as DHEA-S (DHEA sulfate). The body can convert DHEA into DHEA-S and back again.
One approach to using DHEA is to maintain normal blood levels for young adults. This usually means taking 25-100 milligrams of DHEA either once or twice a day.
Blood levels of DHEA-S determine the need for potentially supplementing this hormone, but we are lacking studies in HIV that prove its clinical benefit.
DHEA is not recommended for children or adolescents with HIV. Its use might interfere with normal hormone balance.
There are few documented side effects of DHEA at doses up to 2,500 mg per day. However, there are reports of increases in acne and facial hair, and decreases in high-density lipoprotein (“good” cholesterol) and increases in liver enzymes and estrogen.
There are no documented interactions of DHEA with other therapies. Because DHEA occurs naturally in the body, interactions are unlikely. It is possible that DHEA could affect the processing of drugs by the liver, but this has not been studied.
There is continuing scientific interest in DHEA, with well over 100 scientific articles written in each of the last four years. However, there have not been many studies that document health benefits in humans, and some initial good results have not been confirmed in follow-up studies.
There is not good scientific support for taking DHEA supplements (that is, getting more than normal amounts in your body). However, some health care providers recommend DHEA replacement, which means taking enough DHEA to bring your levels back into the normal range.
The importance of DHEA in steroid hormone production increases with age. Indeed, in postmenopausal women, production of estrogens by the ovaries declines dramatically, making the adrenals the only source of steroid hormones through DHEA. In men, although T secretion by the testicles continues late into life, T levels progressively decline, and DHEA’s importance in steroid hormone production is also higher with increasing age. DHEA’s effect is mostly through its hormone end products.
Effects of DHEA decline on the aging process and age-related diseases
DHEA decline with age is clinically relevant and has been related to a variety of age-related conditions. A positive relationship between DHEA levels and muscle mass, muscle strength, as well as mobility and a lower risk for falls, has been described in elderly individuals. Moreover, a positive effect of DHEA on bone mineral density (BMD) through transformation to estrogens (in vitro human osteoblasts present an aromatase activity),but also directly through mitogen-activated protein kinase signaling pathways, has been suggested. Indeed, DHEA levels have been positively related to BMD in women and men.
Concerning neuropsychiatric diseases, the relationship between DHEA and cognitive disorders has not been studied sufficiently in order to formally conclude on its effect on dementia onset and progression. On the other hand, the relationship between DHEA levels and mood disorders seems clearer. Low levels of DHEA have been related to depression symptoms.
The relationship between DHEA levels and cardiovascular disease risk factors such as cholesterol and glucose tolerance is inconsistent. Nevertheless, studies have shown that low DHEA levels are related to a higher risk for atherosclerosis, heart failure, cardiovascular complications, and overall mortality.
DHEA seems to play a rather important role in sexual function for both sexes. Low levels of DHEA have been linked to a higher risk for erectile dysfunction in men and low sexual responsiveness in women.
Efficiency and safety of DHEA supplementation
DHEA administration has had positive effects on muscle mass and strength, as well as physical performance parameters. Also, DHEA has had positive effects on BMD both in women and in men. Furthermore, DHEA supplementation has shown positive effects on mood as well as sexual function both for men and for women. However, no positive effects on erectile function were found when conditions such as diabetes or neurological disorders were present. Finally, DHEA supplementation has improved menopause symptoms in perimenopausal and early postmenopausal women. Also, intravaginal formulations have had a positive effect in reversing vaginal mucosa atrophy in postmenopausal women.
Most studies show a very satisfying safety profile for DHEA supplementation. Only minimal effects such as mild acne, seborrhea, facial hair growth, and ankle swelling have been reported in women. Otherwise, DHEA supplementation has had a rather positive effect on skin. No significant effect has been reported on hormone-dependent tumors such as breast and prostate cancer. On the contrary, animal studies showed that DHEA inhibits tumors of lymphatic tissue, lung, colon, breast, liver, and skin. Nevertheless, to our knowledge, the longest study durations for DHEA supplementation did not exceed 2 years. Consequently, no data exist on treatment safety regarding hormone-dependent tumors (breast, prostate, and endometrium), cardiovascular risk, or mortality for longer treatments.
DHEAS was the only hormone significantly negatively correlated to the prevalence of erectile dysfunction among 17 investigated hormones, including testosterone and E2, in the Massachusetts Male Aging Study . In addition, Basar et al , in a consecutive series of 348 male patients, reported that that DHEAS and free testosterone levels were significantly lower in men with sexual dysfunction, as determined by the IIEF-15 score. However, evidence of positive effects of DHEA in improving sexual function in men is unconvincing, scanty, and/or conflicting. Only 4 placebo-controlled studies were available. By meta-analyzing these data we did not observe any difference for total IIEF and IIEF-erectile function or IIEF-sexual desire domain score. The limited effect of DHEA on male sexual function is not surprising. In fact, the specific DHEA contribution to overall circulating testosterone level in men is marginal, if not negligible
Future perspectives of DHEA supplementation
DHEA has the status of a dietary supplement and is sold over the counter in the US. In Europe, in most countries it is either forbidden (France) or subject to medical prescription (Switzerland). DHEA is widely used in antiaging medicine and is considered as a “fountain of youth” hormone by some. As it is a prohormone, it is also used as a “hormone regulator”, permitting the body to reach a hormone equilibrium. DHEA is indeed a prohormone with positive effects on several age-related diseases. Supplementing a prohormone is also extremely interesting, as it would theoretically provide the organism with the possibility to use it and transform it according to local and general hormone needs. For the future, the role of DHEA supplementation in specific indications such as sarcopenia, falls and rehabilitation protocols, osteoporosis, mood and cognitive disorders, and also sexual well- being needs to be better studied in longer and larger studies. Finally, physicians prescribing DHEA should consider and inform their patients of the fact that long-term effects concerning efficiency, but also safety, are still uncertain.
1- Off-label use of hormones as an antiaging strategy: a review. Nikolaos Samaras et al. Clinical Interventions in Aging 2014:9 1175–1186
2- Vergel, Nelson. Testosterone: A Man’s Guide.
3- DHEA studies