Estrogen May Protect Against Cocaine-Induced Brain Dysfunction

Researchers have known that women are less inclined to be a victim of vascular disorders caused by chronic use of the drug. What the scientific community did not know was why. Now, a team of medical researchers affiliated with Harvard University Medical School has found that during the first half of a women’s menstrual cycle, the susceptibility to vascular dysfunction may be lower than the corresponding propensity for male users. Only in the latter stages of the menstrual cycle did women experience a significant degree of vasoconstriction (restriction of blood flow to the brain).

"Cocaine-Induced Cerebral Vasoconstriction Differs as a Function of Sex and Menstrual Cycle Phase" is the subject of a study recently conducted by Marc J. Kaufman, Jonathan M. Levin, Luis C. Maas, Thellea J. Kukes, Rosemond A. Villafuerte, Kerstin Dostal, Scott E. Lukas, Jack H. Mendelson, Bruce M. Cohen and Perry F. Renshaw. Their findings, published in the May 1, 2001 edition of Biological Psychiatry, are being presented at the upcoming conference, Genomes and Hormones: An Integrative Approach to Gender Differences in Physiology, sponsored by the American Physiological Society (APS) October 17-20, 2001, at the Westin Convention Center, Pittsburgh, Pa.

Methodology

Lead researcher Marc Kaufman and his colleagues first established the rate of blood flow to the brain in male and female occasional cocaine users. An intravenous dose of cocaine (0.4 mg/kg) was administered to nine men and 13 women. Men were studied once while women were examined during different phases of their menstrual cycle phases (days 3-8, follicular phase and 18-24, leutial phase) after the beginning of menstruation.

Reduction in blood flow to the brain was measured with Dynamic Susceptibility Contrast functional magnetic resonance imaging (MRI), which uses a magnetic resonance contrast agent to detect changes in blood flow.

Results

In the follicular phase, when estrogen levels are high and progesterone levels are low, cocaine did not alter the amount of blood in the brain. By contrast, a 10 percent reduction in blood was found in women during their luteal menstrual cycle phase, when progesterone levels rise; male subjects incurred a 20 percent loss. These findings suggest that cocaine’s effects on blood vessels in the brain differ as a function of sex and menstrual cycle phase, and imply that progesterone in women and testosterone in men may enhance cocaine-induced vasoconstriction, while estrogen in women may blunt cocaine’s vascular effects.

Significance of Findings

Previous studies have asserted that chronic cocaine users are found to be more prone to strokes than non-abusers of the drug. Abusers have also been found to suffer damage to electrical activity of the brain, which may be secondary to reduced blood flow.

Estrogen, or a synthetic estrogen-like compound, could be helpful in treating the two percent of Americans needing relief from cocaine addiction, by reducing damage caused to the brain by the addictive drug. Such benefits could extend beyond drug using populations. For example, treatments that improve brain blood flow might also benefit the elderly, many of whom experience reductions of blood flow to the brain as a result of aging.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.