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Neurology Today:
doi: 10.1097/01.NT.0000280862.16701.43
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Misrepresenting the ‘Female’ Brain

Toran-Allerand, C. Dominique MD

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Dr. Toran-Allerand is professor of anatomy and cell biology at the Columbia University College of Physicians & Surgeons in New York City.

The Female BrainBy Louann Brizendine, MD ▪ 279 Pages ▪Morgan Road Books 2006

In her book The Female Brain, Louann Brizendine, MD, attempts, albeit with obvious sympathy but little valid scientific evidence, to advance a particularly rigid view that prenatal exposure to hormones ‘hard-wires’ the brain for sexually differentiated patterns of behavior, cognitive performance, and emotion that persist throughout life.

Dr. Brizendine, clinical professor of psychiatry and director of the Women's Mood and Hormone Clinic at the University of California-San Francisco, presents a populist view of the neurobiology, neuroendocrinology, and neuropharmacology of sex differences of the human brain. She contends that hormones and brain structure play a role in gender differences.

While entertaining in its breezy style, and with its interesting case histories and anecdotes about her patients and their problems, as well as about her own personal life, this non-technical book is surprisingly replete with scientific inaccuracies, misrepresentations, assumptions, and false statements. The 78 pages of references (at the back of the book) are not cited specifically in the text, making it virtually impossible to find the source of the serious scientific inaccuracies.

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‘THE MALE HORMONE’

What is really gained by criticizing the generally held view that testosterone is a “male hormone,” only to then refer to testosterone as the “sex and aggression hormone”? In particular, why emphasize and glorify testosterone, as “the fast assertive, focused, all-consuming, forceful seducer, aggressive and unfeeling hormone” for sexual differentiation of the brain?

In fact, sexual differentiation of the male brain depends not on direct exposure to testosterone per se, but on the conversion of testosterone to its metabolite, estrogen. In the brain, many actions of testosterone and other androgens are the result of their conversion to estrogen through the actions of the enzyme aromatase.

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PERIMENOPAUSE

Furthermore, what is the scientific basis for saying that, during the perimenopause, “the brain for some reason starts to become less sensitive to estrogen, and the precisely timed dialogue between the ovaries and brain begins to get garbled”? The brain does not get less sensitive to estrogen during the perimenopause. On the contrary, since the circulating levels of estrogen decrease during that physiological period, estrogen becomes less available to the brain. This has nothing to do with loss of sensitivity to estrogen or to “a garbled dialogue” between the ovaries and brain but represents the normal responses of the brain in the face of dwindling perimenopausal levels of estrogen.

If loss of sensitivity during the perimenopause were really the issue, then estrogen replacement would have no beneficial effects. The focus should not be on a purported loss of estrogen sensitivity by the brain, for which there is no evidence, but on the loss of the circulating levels of estrogen itself, which characterizes the perimenopausal period.

Further distortions of scientific fact abound. When addressing the question of hormone replacement, which has become a subject of both considerable anxiety and controversy for many perimenopausal women, Dr. Brizendine unfortunately focuses only on the hormones estrogen and progesterone. She totally disregards important aspects of their biology, including the regulatory interactions of these hormones with their receptor systems, and the negative consequences of continuous, as opposed to cyclical, exposure to estrogen for receptor expression, the regimen which she seems to favor.

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FAULTY CLINICAL ADVICE

Figure. Dr. Toran-Al...
Figure. Dr. Toran-Al...
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Moreover, given the importance the author places on the need for replacement with progesterone in postmenopausal women with an intact uterus who are taking estrogen, it is surprising that the author provides faulty clinical advice by failing to distinguish between progesterone, the physiological hormone, which belongs to a class of hormones called progestagens, and Provera, which is a synthetically produced progestagen, commonly referred to as a progestin.

Progesterone is synthesized in numerous sites including the adrenal glands, the corpus luteum of the ovary, the brain, and the placenta, and is the major naturally occurring human progestagen. Progesterone should not be confused with the progestin Provera. Provera, not progesterone, as erroneously stated by the author, “seems to counter some of the positive effects of estrogen in the female brain.”

Unlike Provera, progesterone does act synergistically with estradiol, and like estradiol, in humans, progesterone is neuroprotective and memory enhancing; it also has sedative, hypnotic, anesthetic, sleep modulating, anti-anxiety, anti-convulsant, anti-depressant, and anti-psychotic effects.

The progestin Provera exhibits none of these properties. Moreover, not only is Provera an ineffective neuroprotectant, but it actually antagonizes estrogen-induced neuroprotection, while exhibiting none of progesterone's beneficial properties for the brain.

What is particularly disconcerting about this book is the author's attempt to characterize the female brain almost as if it belonged to a different species from that of the male. While perhaps politically correct in the current climate, it is really inaccurate scientifically to assume that structural and functional differences in the brain form the basis for all the purported observed sex differences in behavior and cognition.

The differences observed at the individual level are small, and there is a great deal of overlap between the sexes. Inconsistencies abound. For example, there is simply no scientific basis for the author's assumption that there is a connection between brain size and brain function. She states that males have larger brains than females, and proposes that this is not due to gender differences in cell numbers, but that the female brain is smaller because the female brain cells are packed more densely.

Although hormones and brain structure do play a role in gender differences, they represent only part of the story. Sadly lacking are references to the inextricable linkage of biology to the environment. In essence, Dr. Brizendine provides little empirical support for many of her pseudoscientific theories on what makes the female brain unique.

©2007 American Academy of Neurology

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