Highs and lows

PREMENSTRUAL syndrome or PMS is an inseparable part of every woman's life. Involving both physical as well as emotional symptoms, it occurs regularly in relation to the menstrual cycle. PMS, according to experts, usually sets in about five to eleven days before the menses and subsides either with menses or shortly thereafter. It can occur with apparently normal ovarian function (regular ovulatory cycles). An estimated 70 to 90 per cent of women are affected by PMS during their child-bearing I years. Over 30 to 40 per cent of them are thought to have symptoms severe enough to interfere with daily activities, and some 10 per cent face symptoms so severe that they are considered "disabling".

The symptoms associated with PMS range in severity from compulsive behaviour such as cravings of certain types of food or alcohol, to migraines and exhaustion. From mood swings to child battering, there are about 150 recorded symptoms of PMS. Patients, however, report oniy 30 to 40 multi-symptom complaints during a single cycle.

Experts believe the body's inability to properly metabolise fatty acids causes these syndromes. The resultant build-up of unmetabolised fatty acids alters normal cellular functions causing these physical and mental syndromes. In its more severe manifestations, women are unable to maintain jobs or even relationships because of cyclical anger. In some, PMS is so severe that it induces strong feelings of suicide. Experts now have an idea as to the functioning of PMS-related disorders. PMS resembles symptoms of alcohol or drug withdrawal (Nature, Vol 392, No 6679).

The culprit could be the same in both cases - increased levels of a protein that blocks a neurotransmitter from calming the brain. Near the end of a menstrual cycle, the female body produces copious amounts of progesterone, a hormone. Two weeks before menstruation, however, progesterone levels plummet. A team led by Sheryl Smith of the Allegheny University of the Health Sciences in Philadelphia, USA, found rats which experienced this hormonal plunge had similar symptoms.

Now, Smith thinks they may have discovered how this works. To mimic the conditions that lead to PMS, the researchers fed rats large doses of progesterone and then abruptly stopped the dosage. After being denied proges-terone, they found, the rats produced increased levels of a protein called alpha 4 subunit. This protein is a receptor for GABA, a neurotransmitter that reduces anxiety. Because people suffering from alcohol or Valium withdrawal tend to have high levels of alpha 4 subunit, Smith's group suspected that the protein might somehow prevent GABA from maintaining mental peace. To see if alpha 4 subunit is really responsible for disturbing this mental peace, the researchers injected a chemical that prevented alpha 4 subunit production. As soon as the protein levels had dropped, the rats regained their calm, supporting the researcher's theory.

Blocking alpha 4 subunit production may some day be an effective treatment for PMS, alcohol dependence, and perhaps even for people who simply feel stressed, says Smith. Karen T Britton, a psychiatrist at the University of California, San Diego, agrees: "This is exciting, because it shows that there is a biological foundation to the symptoms of PMS which may lead to pharmacological treatments in the future," she says, "but there is still a ton of work to be done." In fact, the commentators predict that Smith's work may eventually help us unravel the differences between men and women as far as anxiety and mood disorders are concerned.

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