August 2, 2004

Synthetic hormone has ill effects on monkeys


By Poul Olson

Medroxyprogesterone acetate (MPA), a synthetic form of the naturally occurring steroid hormone progesterone--widely used in contraceptives and hormone replacement therapy (HRT)--increases aggression and anxiety and reduces sexual activity in female monkeys, according to a study published in the June edition of The Journal of Clinical Endocrinology and Metabolism .

The investigators, from the Yerkes National Primate Research Center and the Center for Behavioral Neuroscience (CBN), say the findings may explain anecdotal reports of mood changes, depression and loss of libido in some women who use MPA for contraception and HRT.

In the counterbalanced-designed study, Yerkes and CBN postdoctoral fellow Karen Pazol compared aggression, anxiety and sexual behavior in six female pigtail macaques that received one week each of three different treatments: estrogen only, estrogen plus natural progesterone and estrogen plus MPA.

Monkeys displayed significantly more aggressive and anxious behaviors when they received the estrogen/MPA combination as compared to the other two treatments. Pazol also noted a marked reduction in sexual activity during the estrogen/MPA treatment period.

"Our findings suggest MPA may be affecting certain neuroendocrine systems in a very different way than natural progesterone," Pazol said. "In comparison to natural progesterone, MPA binds to glucocorticoid receptors with a much higher affinity and may have a greater impact on the brain's stress system."

Unlike natural progesterone, Pazol said, MPA cannot be converted to the mood-regulating chemical allopregnanolone. Changes in allopregnanolone levels have been associated with depression, anxiety disorders and premenstrual mood disorders in women.

To identify MPA's behavioral effects over a longer period, Pazol also is examining aggression, anxiety and sexual activity in monkeys that receive the estrogen/MPA regimen for 21 days, the standard cycle for women who take contraceptives.

"Dr. Pazol's animal studies provide a critical link to better understanding of HRT and its behavioral-related effects," said Mark Wilson, a study coauthor and chief of Yerkes' psychobiology division. "Few reliable clinical studies of MPA's behavioral effects have been conducted because of the variability in hormone levels among women and the subjective nature of reports on mood and libido."

A third coauthor of the study is Kim Wallen, Samuel Candler Dobbs Professor of Psychology and Behavioral Neuroendocrinology