Premenstrual syndrome, or PMS, is an "abnormal response to normal hormonal
changes," report National Institute of Mental Health (NIMH) researchers
David Rubinow, M.D., and Peter Schmidt, M.D., in the January 22 New England
Journal of Medicine. "Women with PMS have a specific susceptibility for
mood problems triggered by normal monthly cycles," said the researchers.
Their study is the first to directly demonstrate the widely assumed--yet
heretofore unproven--link between female sex hormones and PMS symptoms.
PMS affects 3 to 7 percent of women, causing mood swings and physical
symptoms that can interfere with work and social life.
Women with a history of the disorder experienced a reprieve from mood
problems when their sex hormones were temporarily turned off, but the PMS
symptoms returned when they were given either estrogen or progesterone, the
major female reproductive hormones. A control group of women without PMS
reported no mood shifts during the same hormonal manipulations.
The researchers compared mood ratings of 10 patients whose PMS responded to
leuprolide, a drug that suppresses sex hormones in both men and women, with
those of 15 women without PMS. The hormones were first removed and then
reintroduced one at a time to reveal whether estrogen or progesterone alone
could account for the mood changes.
Each woman was placed on month-long courses of leuprolide alone and
leuprolide in combination with estrogen, progesterone and placebo. Each then
rated her own severity of symptoms nightly on standardized forms that
covered various aspects of mood as well as physical sensations like food
craving, hot flushes and breast pain. Investigators obtained additional
ratings, as well as blood for hormone assays, during biweekly visits to the
Within a week or two after either sex hormone was added back, the women with
PMS began suffering typical symptoms of the disorder--sadness, anxiety,
bloating, irritability and impaired function. The control women reported no
change. Yet, the NIMH researchers found no apparent differences between the
two groups of women--both groups had normal menstrual cycles in terms of
hormone levels and activity.
"Although the female sex hormones need to be present to trigger PMS
symptoms, the hormones themselves are not the cause of the disorder," said
The researchers are pursuing clues to explain what may cause the
susceptibility to PMS in some women but not others. One possibility now
being investigated is genetic differences in the sensitivity of receptors
and related messenger systems that relay sex hormone signals within cells.
Other clues include possible differences in patients' histories of other
mood disorders or in serotonin function.
The NIMH researchers are currently seeking women in the perimenopause, women
with PMS, and men with mid-life depression who might be interested in
participating in ongoing studies aimed at identifying factors responsible
for the differential mood responses to sex hormones.
Also participating the current study were: Linda Adams of NIMH; Merry
Danaceau, R.N., NIH Clinical Center Nursing Department; and Lynnette Nieman,
M.D., National Institute on Child Health and Human Development.
NIMH is a component of the National Institutes of Health, an agency of the
U.S. Department of Health and Human Services.