Severe Premenstrual Syndrome Can Affect Stress Responses

Unlike most women, those who experience an especially debilitating form of premenstrual syndrome — a medical condition called premenstrual dysphoric disorder (PMDD) — show abnormal responses to stress, according to new research from the University of North Carolina at Chapel Hill.

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, the researchers say. Women with the disorder, however, produced less of this hormone during stress.

The new observation could be an important clue as to why some women face severe symptoms every month and might 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 with their interpersonal relationships."

This study was the first to examine the stress responsiveness of allopregnanolone in humans. Allopregnanolone levels were measured in women with a diagnosis of premenstrual dysphoric disorder (PMDD) and in other women who were known not to have it. The 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," Dr. 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.

"Many of these women are frustrated dealing with the medical community because PMDD is still a very misunderstood disorder," Dr. Girdler said. "Many doctors just say, 'This is normal PMS [premenstrual syndrome]; just go home, take a break, and take some [medication].' 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 have also 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 it is almost 200 times more powerful than typical antianxiety medications 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," Dr. Girdler said.

(Source: Biological Psychiatry, May 2001.)

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