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New Theory on Body Fat Changes:
Hormone Disruption by Protease Inhibitors May be the Root of Syndrome

by Guy Pujol

March 2000

According to a group of French researchers, disrupted production of the steroid hormones cortisol and DHEA may be at the root of body fat and metabolic changes in people taking protease inhibitors. A team from the Pasteur Institute found a significant correlation between lipid alterations, body fat changes and levels of the steroid hormone DHEA. The team suggests that steroid hormone production may be disrupted by the effects of protease inhibitors on cytochrome p450, a liver enzyme involved in the production of the steroid hormones. The group tested 37 men on antiretroviral therapy and 20 HIV-negative patients for a variety of immunological, metabolic and body fat changes, and found:


What Do These Findings Mean?

DHEA acts as an anti-glucocorticoid, controlling levels of cortisol. The authors of the report suggest that if DHEA levels are suppressed, then cortisol levels will be permitted to rise, encouraging an increase in lipid production. DHEA is also involved in the regulation of lipid production, and has been shown to reduce serum cholesterol and body fat in healthy men. DHEA also regulates insulin secretion. A decline in DHEA levels could become self-perpetuating because such a decline will also allow increased insulin secretion, an increase in insulin resistance and the knock-on effect of a further reduction in DHEA levels.

These hormones are involved in the regulation of fat deposits in both peripheral tissues (the arms and the legs) and the central adipose tissue. Elevated cortisol levels could stimulate fat cells in peripheral tissue to release stored fats, while the decline in DHEA levels will block the storage of fat in peripheral tissue. Meanwhile, circulating fat is being mopped up by central fat deposits, leading to the characteristic fat belly.


Cautions

However, it should be borne in mind that changes in the DHEA:cortisol ratio have been observed in people with AIDS prior to HAART, and that this study was conducted only in men. Individuals who developed lipodystrophy tended to have lower CD4 counts before commencing HAART, but similar weight before commencing HAART. Furthermore, hormonal changes in women may differ, and average DHEA levels in women have been observed to be lower. Another puzzle is the relationship seen in this study between strong CD8+ responses and increased lipodystrophy risk: in people with high levels of cytotoxic T-cells and fully suppressed viral load, one would expect to find high DHEA levels as a consequence of improved IL-2 production.

DHEA is already used quite frequently by people with HIV as an antidepressant, an energy booster and an aid to building muscle (it is a precursor of testosterone). This new theory makes it important to tell your doctor if you are using DHEA and also taking antiretroviral therapy, so that any effects of DHEA can be detected in any clinical study you might take part in.

The AIDS Treatment Initiative (ATI) carries DHEA in 50 mg and 250 mg capsules.


Reference

Christeff N. & Gougeon L. et al. "Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations." AIDS 13: 2251-2260, 1999.




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