Louann Brizendine, M.D. ’81, never suspected that her third-year psychiatry rotation would lead to her becoming a best-selling author. Recalling that rotation, she said, “I was stunned by the two-to-one female/male ratio. No one knew why so many patients were suicidally depressed women.”

Over the past 25 years Brizendine, director of the Women’s Mood and Hormone Clinic at the University of California, San Francisco (UCSF), has developed many theories about women’s psychological issues. She finally explained them in The Female Brain (Morgan Road Books, 2006), which sold 80,000 copies in its first four months and has been translated into 18 languages. Brizendine believes that physiological differences between men and women lead to significant psychological differences—for example, oxytocin, “the hormone of intimacy,” causes women to crave social contact far more often than men.

Her interest in women’s mental health continued during a psychiatry residency at Harvard and on into her private practice. Recruited by UCSF in 1988, Brizendine taught psychiatry. “Then I got pregnant, and had all the postpartum hormones,” she said. “Phases of a woman’s life were no longer theoretical.”

She began working with UCSF neuroendocrinologists to explore whether fluctuating hormones could trigger women’s mood disorders. “A progesterone metabolite in the brain decreases at menstruation, causing [symptoms similar to] Valium withdrawal: emotional sensitivity, mood changes, etc.,” observed Brizendine, who had read the literature about hormones, estrogen and neurochemical brain changes in mammals. “Animal models aren’t adequate—you can’t ask a mouse how its mood is today.”

Her new perspective led to an innovative course at UCSF in 1993, “Hormones in Psychiatry,” which quickly evolved into her mood and hormone clinic. The clinic now treats about 600 women annually.

Brizendine’s research into hormones led her to a startling conclusion. “It hit me like a lightning bolt—testosterone causes sexual desire. No one ever thought the problem of frigidity might be biological! I started measuring testosterone and correlating it with sexual interest in females. Levels were often low. Watching patients suffer, knowing other psychiatrists weren’t seeing it the same way, I felt a passion to clarify biological aspects of women’s mental health and hormonal issues,” she said.

Surprisingly, some patients wanted to stay on the antidepressant Prozac, even though one of its side effects is decreased libido. They were choosing better moods over better sex. In early Prozac trials, manufacturer Eli Lilly and Company had found (but not publicized) women’s orgasmic difficulties. “Female sexual problems are treated as just ho-hum,” Brizendine said, “but erection or ejaculation problems are treated as a medical emergency.”

Her book’s provocative claims—including the contention that oxytocin gives females so much pleasure that they crave connections like gossip with friends to get that “rush”—are criticized for exaggerating gender differences or oversimplifying research. Some social scientists say her unflattering, dubious presentation of female behaviors weakens crusades for equal pay and opportunities.

Other colleagues remain unruffled. Bruce McEwen, Ph.D., head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller University, confirmed the biological basis of sex differences in brain and behavior. “Sex hormones and experiences interact over the entire lifespan and alter brain structure and function in both men and women. Brizendine perhaps has not emphasized [these ongoing interactions] as much as she might have.”

He appreciates Brizendine’s efforts to “elucidate biological bases of how many men and women behave. Whether she’s contributed to more prejudice, in spite of the best intentions to educate … is to me the almost inevitable price of writing about this topic.”

Brizendine, ruefully aware of the controversies, had aimed to preclude them. In a mass-market book, she discovered, “you can’t go into details of how and where a study was done. I wrote a more sophisticated section for people in science, so that anyone wanting to know more could go to those 45 pages of notes at the back.” However, determined to shorten the length of The Female Brain, the publisher deleted all of Brizendine’s painstaking explanatory notes during final editing.

How does she endure the negative reactions? “I just breathe deeply,” Brizendine said. “Some days, I need ovaries of steel.”