Women's brains present hormonal mystery.

A scientific team exploring hormonal influences on the brain and mind has come across an intriguing puzzle. During a drug-induced decline in concentrations of a steroid hormone produced by the ovaries, women given a series of complex problems fail to show surges in the frontal brain activity that has been considered crucial for success on that test. Yet they solve the problems as well as women who possess far greater quantities of the hormone and boast much more frontal brain activity.

Alternate brain networks, which perhaps differ from one woman to another, may pick up the slack when a hormonal deficit blocks the usual cerebral responses to a mental challenge, contend neuroscientist Karen F. Berman of the National Institute of Mental Health in Bethesda, Md., and her coworkers.

Their study, described in the Aug. 5 Proceedings of the National Academy of Sciences, represents the first use of positron emission tomography (PET) imaging to examine the effects of hormones on brain responses evoked by specific mental maneuvers.

"These data are an important start," remarks Barbara B. Sherwin, a psychologist at McGill University in Montreal. "But a clear connection between hormonal influences on neural activity and behaviors or cognition has yet to be made."

Several animal studies have suggested that gonadal steroid hormones affect brain activity and certain cognitive skills, such as the ability to delay learned responses. Little relevant evidence exists regarding people, however.

Berman's team studied 11 women who ranged in age from 27 to 49. Six of the volunteers had no physical or psychological disorders; five were diagnosed with menstruation-related mood disorder.

The researchers took PET scans of the women's brains over 4 to 5 months during each of three treatment phases. First, the women received Lupron, a drug that suppresses the ovaries' production of gonadotropin-releasing hormone. Then they received both Lupron and one of two consecutively administered hormone replacement therapies. Some women, selected at random, received an inactive substance instead of one hormone replacer.

Imaging sessions took place as the women completed a problem-solving test that required them to recall and manipulate recently studied material.

Previous PET investigations had found large increases in blood flow in part of the frontal lobe, known as the prefrontal cortex, when men and women completed this problem-solving test. Comparable brain activity occurred in women given Lupron and either of the hormone-enhancing therapies, but not in women receiving Lupron alone, the scientists hold.

Nonetheless, women in each group (including those with a mood disorder) solved as many complex problems as volunteers in other studies have. Further investigations should employ more powerful brain-scanning instruments and additional mental challenges in a search for brain circuits that may substitute for the prefrontal cortex during times of hormonal drought, Berman's team says.