Cancer Prevention
Administration of DHEA inhibited tumor formation in a strain of mice that develops spontaneous breast cancer.5 DHEA also has been shown to prevent chemically-induced colon and liver cancers, as well as skin papillomas in mice.6,7,8 Premenopausal women with breast cancer had significantly lower plasma levels of DHEA than age-matched controls without breast cancer, whereas postmenopausal women with breast cancer had significantly higher DHEA levels than age-matched controls.9 In another study, women with DHEA levels in the highest tertile were 60% less likely to develop breast cancer than were women in the lowest tertile.10 In a prospective case-control study, serum DHEA and DHEA-S levels were significantly lower in individuals who subsequently developed bladder cancer than in those who did not.11
These findings suggest that DHEA has anti-cancer activity and that low DHEA levels might be a risk factor for cancer. However, additional research must be done before guidelines can be developed regarding DHEA therapy and cancer. The observation that some postmenopausal women with breast cancer have elevated DHEA levels, and the fact that DHEA is converted in part to estrogen and testosterone should be cause for concern. It is not known whether the possible anti-cancer effects of DHEA might be stronger than the prostate cancer-promoting effects of additional testosterone or the breast cancer-promoting effects of additional estrogen. Until those questions can be answered, DHEA therapy should be approached with caution in patients who are at risk for developing hormone-dependent cancers.
Effects on Immune Function
DHEA exerts a number of different effects on the immune system. Some of these effects appear to result from the anti-glucocorticoid actions of DHEA. For example, in mice DHEA antagonized the suppressive effects of dexamethasone on lymphocyte proliferation and prevented glucocorticoid-induced thymic involution.12,13 Administration of DHEA also has been shown to preserve immune competence in burned mice, an effect that extends beyond its anti-glucocorticoid action.14,15 Administration of DHEA also protected against acute lethal infections with coxsackie virus B4 and herpes simplex type 2 encephalitis in mice. DHEA appeared to act by preventing the suppression of immune competence caused by the viral infections.16
DHEA has also been shown to influence immune function in humans. In a double-blind study, administration of 50 mg per day of DHEA to postmenopausal women (mean age, 56.1 years) produced a two-fold increase in natural killer cell activity and a 6% decrease in the proportion of helper T cells.17 While the increase in natural killer cell activity might be expected to enhance immune surveillance against cancer and viral infections, the decline in helper T cells could have adverse consequences. On the other hand, since DHEA is known to mediate T cell responses,18 the decline in helper T cells merely could be a reflection of enhanced T cell function. Although the implications of these changes in immune function are not entirely clear, it should be noted that 50 mg per day of DHEA has been shown to produce supraphysiologic serum levels in postmenopausal women.19 Lower doses may therefore be more appropriate and might result in more clear-cut improvements in immune function.
