A synthetic progesterone causes anxiety in mice; allopregnanolone involved?

Kofi kofi at anon.un
Wed Jun 16 07:49:23 EST 2004

A few months back in the context of a male contraceptive, I wondered if 
the synthetic progesterone used might not cause problems in men similar 
to the problems women experience on birth control pills.  I also 
mustered support for a hypothesis that the artificial progesterone used 
in hormone replacement caused these problems by interfering in the 
pathway for allopregnanolone synthesis.  Here's the first experimental 
evidence I've found in support of this.



   Emory University Health Sciences Center

Print this page
Email to friend
Synthetic Hormone Used In Contraceptives And HRT Produces Negative 
Effects In Monkey Studies

ATLANTA -- 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. 


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.

Editor's Note: The original news release can be found here.


This story has been adapted from a news release issued by Emory 
University Health Sciences Center.

More information about the Neur-sci mailing list

Send comments to us at biosci-help [At] net.bio.net