Synthetic hormone used in contraceptives and HRT produces negative effects in monkey studies

Findings may explain mood and behavior changes in women

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 of Emory University and the Center for Behavioral Neuroscience (CBN) in Atlanta, 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 counter balanced-designed study, Yerkes and CBN post-doctoral fellow Karen Pazol, PhD, 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 when they received the estrogen only or the estrogen/progesterone combination. Dr. 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,” explained Dr. Pazol. “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.”

Moreover, according to Dr. Pazol, unlike natural progesterone, 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 humans.

To identify MPA’s behavioral effects over a longer period, Dr. 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 Yerkes-based animal studies provide a critical link to better understanding of HRT and its behavioral-related effects,” says Mark Wilson, PhD, a study co-author 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.”

Kim Wallen, PhD, Dobbs Professor of Psychology and Behavioral Neuroendocrinology at Emory University, also is a study co-author.

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The Yerkes National Primate Research Center of Emory University is one of eight National Primate Research Centers funded by the National Institutes of Health. The Yerkes Research Center is a multidisciplinary research institute recognized as a leader in biomedical and behavioral studies with nonhuman primates. Yerkes scientists are on the forefront of developing vaccines for AIDS and malaria, and treatments for cocaine addiction and Parkinson’s disease. Other research programs include cognitive development and decline, childhood visual defects, organ transplantation, the behavioral effects of hormone replacement therapy and social behaviors of primates. Leading researchers located worldwide seek to collaborate with Yerkes scientists.

The Center for Behavioral Neuroscience, a National Science Foundation Science and Technology Center consisting of more than 90 neuroscientists at eight metro Atlanta colleges and universities, conducts research on the basic neurobiology of complex social behaviors. Its programs have led to a breakthrough treatment for anxiety-related disorders and new understanding of the potential roles of the neurochemicals vasopressin and oxytocin in autism. CBN’s workforce training programs also have contributed significantly to enhancing the diversity of Georgia’s burgeoning biotechnology industry.