Hormones make all the difference

Scientists are uncovering increasing evidence that the brain not only responds to hormones produced by the reproductive system, but that these hormones--the so-called "female hormones" estrogen and progestin and the "male" androgens, such as testosterone--play an important role in the development of differences between male and female brains.

"Understanding the impact of hormones on sex differences in the brain is important for understanding human health and disease," maintains biopsychologist Jill Becker of the University of Michigan, Ann Arbor. "Some conditions--persistent pain syndromes, such as fibromyalgia and TMJ [temporomandibular joint syndrome], for example--are more frequently diagnosed in women than in men. More women than men also suffer from mood disorders, such as major depression, and anxiety.... On the other hand, more men than women develop alcoholism and abuse drugs."

Straightforward comparisons of males and females are not possible because of the cyclical nature of reproductive hormone production in females, Becker points out. The menstrual cycle in humans and other primates and the estrous cycle in rats and mice involve constantly changing levels of reproductive hormones in the blood and brain. Furthermore, although brain development begins before birth, it continues well into young adulthood, and there is increasing evidence that parts of the brain continue to grow, die back, and change throughout an individual's lifespan.

"Reproductive hormones have effects on all of these stages of brain growth and development," Becker reports. "For these and other reasons, the study of sex differences in the brain is both complicated and fascinating." For example, the linking of pain sensitivity and regulation to hormones--particularly estrogen-makes some "evolutionary" sense. Women require more flexible, adaptive mechanisms to protect themselves from injury during their reproductive years to preserve the reproductive function of the species. At the same time, women also have to adapt to the body changes and pain that take place during pregnancy and childbirth--a time when reproductive hormones are at an all-time high.

There also is the role that estrogen and other hormones may play in gender differences in depression. Women are two to three times more likely than men to experience a major depressive episode during their lifetime.

"The underlying cause of the gender difference in depression and other mood disorders is not entirely clear," says researcher Max Steiner of McMaster University, Ontario, Canada, "but the differences, which begin rather dramatically at puberty and become less marked after menopause, strongly suggest a link to fluctuating estrogen and progesterone levels."

Although hormone levels vary in men and women, the fluctuations are much more pronounced in females, particularly around their menstrual cycles, during the weeks immediately after pregnancy (postpartum), and in the period leading up to menopause (perimenopause). These fluctuations, Steiner proposes, cause disturbances along the hypothalamic-pituitary-adrenal axis, a part of the neuroendocfine system that is believed to play a primary role in the body's reaction to stress.

Because hormonal fluctuations occur in all women, yet not all women experience clinical depression, it is likely that those who develop hormone-related depression and mood disorders have a genetic predisposition to them, Steiner concludes.

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