Research In Monkeys Suggests Estrogen Therapy May Lower Androgens In Postmenopausal Women

"Our findings suggest that it might be important for women taking estrogen after menopause to also take androgen supplements – which can include testosterone," said Charles E. Wood, D.V.M., lead researcher, from Wake Forest University Baptist Medical Center. The research is reported in the current issue of The Journal of Clinical Endocrinology & Metabolism.

The adrenal glands are the primary source of androgen hormones in women. While aging is associated with a marked decline in androgens, others factors involved in adrenal androgen production are not well-known. Regulation of androgen levels may be particularly important in postmenopausal women because observational studies have shown that older women who have higher levels tend to be healthier.

"Recently, there has been increased interest in supplementing androgens in older women and research is underway to understand more about these hormones," said Wood. "Our study makes the point that estrogen reduces the adrenal gland's production of androgens."

Wood and colleagues studied both premenopausal and postmenopausal estrogen treatment and the effects on androgen levels in a large group of female cynomolgus monkeys. Half of the monkeys were given oral contraceptives, which contain estrogen, in their diets for 26 months. All animals then had their ovaries removed to make them menopausal.

For the next three years, the animals were divided into three groups based on diet. One group ate soy that didn't contain isoflavones, which are natural plant estrogens; one group ate soy with the isoflavones intact, and one group's diet was soy without isoflavones and Premarin, or estrogen therapy, added.

Blood samples from the monkeys showed that androgen concentrations – both before and after menopause – were comparable to those found in women. They also showed that the monkeys given estrogen supplements had markedly lower levels of androgens.

"It appears that estrogen therapy can suppress adrenal androgen production," said Wood.

The researchers measured levels of the major androgens, which include dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A4), and testosterone. Monkeys who took the oral contraceptives before menopause had DHEA-S levels that were 27 percent lower than the monkeys who didn't take contraceptives. Levels of A4 were 53 percent lower, and levels of testosterone were 50 percent lower. These effects did not continue into menopause.

In the postmenopausal phase of the study, treatment with soy plus Premarin resulted in DHEA-S levels that were 29 percent lower than the monkeys who ate soy without isoflavones (control group) and 35 percent lower than the group eating soy with isoflavones. Total levels of testosterone were 52 percent lower than the control group and 41 percent lower than the group eating soy with isoflavones.

The researchers had suspected that the plant estrogens would also suppress androgen production. While this didn't prove true, they did find that these monkeys had smaller adrenal glands than monkeys that didn't consume the isoflavones.

The adrenal gland, located near the kidneys, uses cholesterol to make the androgen hormones and to make cortisol, a hormone associated with high levels of stress. The researchers found that while estrogen treatment lowered levels of androgen hormones, levels of cortisol increased.

"This may explain the mechanism for how estrogen suppresses androgen production," said Wood.

Other researchers in the study included J. Mark Cline, Mary S. Anthony, Thomas C. Register and Jay R. Kaplan, all from Wake Forest Baptist.

The research was funded by grants from the National Institutes of Health.