Study uncovers clue to severe PMS, scientists seek more N.C. volunteers

CHAPEL HILL - Unlike most women, those who experience an especially debilitating form of premenstrual syndrome -- a medical condition called premenstrual dysphoric disorder -- show abnormal responses to stress, according to new University of North Carolina at Chapel Hill research.

The study found that healthy women responded to stress during the second half of their monthly cycles by producing more allopregnanolone, a hormone metabolite of the female hormone progesterone, UNC School of Medicine researchers say. Those with the disorder, however, produced less of it during stress.

The new observation could be an important clue as to why such people face such severe symptoms every month, they add. It could also contribute to more effective treatments one day.

"We're not talking about the majority of women who experience normal premenstrual symptoms such as mood changes, bloating, irritability, etc. but the 5 to 10 percent who meet strict psychiatric criteria for this disorder," said Dr. Susan S. Girdler, assistant professor of psychiatry. "During the second half of their menstrual cycle, they can be clinically depressed, anxious or irritable enough that it interferes with their ability to function and their interpersonal relationships."

A report on the findings -- the first in humans to examine the stress responsiveness of allopregnanolone -- appears in the May issue of Biological Psychiatry, a professional journal. Besides Girdler, authors include Drs. Kathleen Light and A. Leslie Morrow, professor and associate professor of psychiatry, respectively, at UNC.

The study involved measuring allopregnanolone levels in women diagnosed as having premenstrual dysphoric disorder and also in others known not to have it. Researchers subjected participants to mildly stressful situations and again measured the hormone levels and symptoms resulting from the artificially induced stress.

"Among the PMDD women, lower allopregnanolone levels were related to more severe premenstrual anxiety and irritability," Girdler said. "A similar pattern was seen for depression, but the numbers there were not statistically significant."

Because the study involved a relatively small group of 24 women with the condition and 12 others serving as controls, results should be considered preliminary, she said. Still, the work is an important first look at the stress responsiveness of this neurosteroid hormone and its effects on women with PMDD.

Girdler and colleagues are looking for women with severe premenstrual emotional symptoms to participate in a new National Institutes of Health-funded investigation of the hormone. Volunteers will receive $500 for completing the study and useful diagnostic feedback from study investigators.

Anyone wishing more information can call (919) 966-8029 and ask for Heidi.

"Many of these women are frustrated dealing with the medical community because PMDD is still a very misunderstood disorder," Girdler said. "Many doctors just say, 'This is normal PMS, just go home, take a break and take some Midol.' This disorder is much stronger than PMS, however, and we need to help these women if we can."

Researchers have known for years that the condition relates in some way to female sex hormones, but they also have shown that it is not a simple matter of the women having too much estrogen or progesterone, she said. Allopregnanolone strongly affects mood receptors in the brain and is some 200 times more powerful than typical anti-anxiety pills at those receptors.

"It may be that the abnormal stress response of allopregnanolone among women with PMDD contributes to a worsening of symptoms during stress, but that's speculation because we haven't measured that directly yet," Girdler said.

Note: Girdler can be reached at (919) 966-2544.