Dihydroepiandrosterone (DHEA) is a natural hormone secreted by the adrenal gland. It is the building block of several human hormones including the male sex hormone testosterone and the female sex hormone oestrogen.

Due to its chemical structure, DHEA belongs to the class of drugs known as steroids. It may be taken to supplement the bodys own production of steroid hormones but DHEA is not a muscle-building (anabolic) steroid. DHEA has been studied as a potential treatment for many conditions including cancer, diabetes, obesity, aging and diseases affecting the immune system.

It is a licensed drug in Italy and Japan for the treatment of menopause and depression. It is also available in the United States through buyers clubs, which tend to be cheaper than internet sales.

DHEA is also known as dehydroisoandrosterone.

DHEA and the endocrine system

The endocrine or hormonal system of the body is made up of various organs that secrete hormones. For example, the adrenal gland, the pituitary gland, the thyroid and parathyroid glands, and the testes and the ovaries all produce hormones which regulate metabolism and other bodily functions.

DHEA reaches peak levels in the blood around during early adulthood, then gradually declines gradually.

DHEA in people with HIV

Natural DHEA levels tend to decline in people with HIV as the disease progresses. This may indicate that DHEA inhibits HIV, or simply reflect HIV's damage to the adrenal gland.

It has been suggested that the under-production of DHEA in people with AIDS may be a cause of wasting, but a pilot study of DHEA in people with AIDS found no consistent effect on their weight. Some studies suggest that, like anabolic steroids, it increases muscle and reduces fat, although other studies disagree.

Most recently, low DHEA levels have been observed in men with highly active antiretroviral therapy (HAART)-related lipodystrophy. This has led to the theory that lipodystrophy may be caused by hormonal abnormalities due to HIV.

Test tube studies have found that DHEA has a moderate anti-HIV effect and may inhibit HIV infection of macrophages or HIV production from infected macrophages.

DHEA and immune regulation

DHEA stimulates the production of the cytokine interleukin-2 (IL-2), which is required for the production and functioning of CD4 T-cells. A low level of DHEA may inhibit the production of IL-2, contributing to depressed levels of CD4 cells. It has been suggested that DHEA treatment may have the same effect as treatment with IL-2. This theory has not been tested.

Tests in animals indicate that DHEA may act as an immune modulator, by restraining auto-immune responses. DHEA is currently being tested for the treatment of the auto-immune disease lupus in humans, following research which showed that DHEA treatment stablised or improved the condition, whilst those receiving a placebo suffered worsening lupus.

Current use

DHEA is an unlicensed, experimental drug. Clinical trials have failed to show any benefits so far, but further studies with higher doses are under way.

Anecdotal reports from doctors who have used DHEA widely in their clinical practice suggest that DHEA seems to have more effect on symptoms such as fatigue, depression and chronic malaise than on markers such as viral load or CD4 cell count. Nevertheless, a study in Texas suggested that DHEA reduced the viral load of people with CD4 cell counts between 50 and 300 cells/mm³.

Patients considering trying DHEA should consult their doctor. Natural DHEA levels should be measured before commencing supplements.

The most frequent side-effect of DHEA is acne, which is particularly common among women. Irregular heart beat and heart palpitations have also be reported among individuals on DHEA.

Dose recommendations vary depending on the source. The United States-based Direct Access Alternative Information Resource (DAAIR) website recommends 25 to 100mg for men and 15 to 50mg for women daily. Clinical trials have used doses up to 500mg per day. However, the alternative medicine website warns that these high doses may increase the risk of side-effects. Instead, doses between 2 and 15mg are recommended every second day, or for two or three weeks out of every month.

Use in combination

One test tube study found that DHEA was antagonistic to AZT (zidovudine, Retrovir) i.e. it lessens the drug's anti-HIV effects. However, the manufacturer reports that its in vitro tests showed that DHEA and AZT are synergistic.

Getting it

DHEA is available in the United States, but is a controlled substance in the United Kingdom. Mail order of this susbstance from the United States does not appear to be illegal, and an internet search will turn up a vast array of suppliers, although quality may vary.

Key research

Piketty conducted a randomised, double-blind study of DHEA in 32 HIV-infected patients. Dosage was 50 mg DHEA per day for 4 months (n = 14) or a matching placebo (n = 18). The mean CD4 cell count at baseline was 32.5 and the mean DHEA plasma level at baseline was 5.23 micromol/l. Levels of DHEA increased significantly in the treated group throughout the study (P < 0.01). A significant improvement in the Mental Health and Health Distress dimension of the Medical Outcomes Study HIV Health Survey (MOS-HIV) quality-of-life scale was observed in the DHEA treated group. CD4 cell counts did not change significantly.

Sonnabend and Merril reported that DHEA levels are lower in HIV-infected individuals than in healthy HIV-negative people. Jacobson and Mulder described an association between HIV disease progression and decreased levels of DHEA in HIV-infected men with CD4 counts between 200 and 500. This may indicate that DHEA has an inhibitory effect on HIV; or DHEA levels may simply be a marker reflecting HIV-induced damage to the adrenal glands. In vitro studies of DHEA in HIV-infected lymphocytes and macrophages demonstrated a moderately selective inhibitory effect on HIV replication. The exact mechanism of action is unclear. In vitro, the combination of DHEA and AZT is antagonistic.

Henderson reported that treatment with DHEA or its novel synthetic analogues 8354 or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohaemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts.

Dyner enrolled 31 HIV-positive asymptomatic individuals (CD4 cell count range 250-600) in an open-label dose-ranging trial of DHEA (three times daily in doses ranging from 750 mg/day to 2250 mg/day for 16 weeks). The drug was well tolerated and no dose-limiting side-effects were noted. Dose proportionality was evidenced neither by the serum DHEA nor by DHEA-S time-concentration curves for the three dosing groups. However, the study cohort appeared to consist of two subpopulations with markedly different bioavailability for a given DHEA dose. No sustained improvements in CD4 counts nor decreases in serum p24 antigen or beta₂-microglobulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at week 8 compared with baseline in all dosing groups.

Salvato treated 20 adults with CD4 counts between 50 and 300 with DHEA (300 mg or 600 mg twice daily). After 28 days, the 600 mg dose group had experienced a 1 log reduction in plasma viral load and a greater than 1 log reduction in PBMC viral culture.

At the Community Research Initiative (CRI) in New York, 10 people with AIDS completed a 16-week phase I toxicity study of DHEA (1 gm by mouth once daily). Neither side-effects nor clinical improvement was observed.

References

Dyner TS et al. An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease. Journal of AIDS 6(5):459-465, 1993.

Henderson E et al. Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. AIDS Research and Human Retroviruses 8(5):625-631, 1992.

Jacobson MA et al. Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 counts of 200-499. Journal of Infectious Diseases 164:864-868, 1991.

Merril CR et al. Plasma dehydroepiandrosterone levels in HIV infection (letter). Journal of the American Medical Association 261(8):1149, 1989.

Mulder JW et al. Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men. Journal of Infectious Diseases 165(3):413-418, 1992.

Piketty C et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clinical Endocrinology (Oxf) 55(3):325-30, 2001.

Salvato P et al. Viral load response to augmentation of natural dehydroepiandrosterone (DHEA). Eleventh International Conference on AIDS, Vancouver, abstract We.B.3385, 1996.

Sonnabend J et al. DHEA and DHEAS in AIDS. Fifth International Conference on AIDS, Stockholm, abstract C 602, 1989.

Suzuki T et al. Low serum levels of dehdroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Clinical and Experimental Immunology 99(2):251-55, 1995.

Wisniewski TL et al. The relationship of serum DHEA-S and cortisol levels to measures of immune function in human immunodeficiency virus-related illness. American Journal of the Medical Sciences 305(2): 79-83, 1993.

Yang JY et al. Inhibition of HIV-1 latency reactivation by DHEA and an analogue of DHEA. AIDS Research and Human Retroviruses 9(8):747-754, 1993.