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 |
