How Estrogen Can Lead to Addiction

In a recent study, neuroscientists at the University of California, Berkeley, report that hormone fluctuations during a woman’s menstrual cycle may affect the brain as much as do substances such as caffeine, methamphetamines or the popular attention drug Ritalin.

 

Scientists have known for decades that working memory (short-term information processing) is dependent on the chemical dopamine. In fact, drugs like Ritalin mimic dopamine to help people concentrate. Researchers have also had evidence that in rats, estrogen seems to trigger a release of dopamine. The new study from Berkeley, however, is the first to show that cognition is tied to estrogen levels in people—explaining why some women have better or worse cognitive abilities at varying points in their menstrual cycles.

 

The Berkeley team examined 24 healthy women, some of whom had naturally high levels of dopamine and some of whom had low levels, as indicated by genetic testing. As expected, those with the lower levels struggled with complicated working memory tasks, such as repeating a series of five numbers in reverse order. When the test was repeated during ovulation, however, when estrogen levels are highest (usually 10 to 12 days after menstruation), these women fared markedly better, improving their performance by about 10%. Surprisingly, those with naturally high dopamine levels took a nosedive in their ability to do complicated mental tasks at that point in their cycle.

For women with the lowest levels—about 25 percent of the general population—increased dopamine during ovulation will sharpen cognitive functions, whereas for the 25 percent of women with the highest levels, ovulation seems to take them beyond a threshold and to impair thinking. The remaining half of women fall somewhere in between and were not a part of the study.

 

The work has broad implications: it may mean that caffeine, which triggers a dopamine release, and Ritalin-like drugs are less effective—or even detrimental—at certain times of the month for some women, when estrogen is spiking.

 

But the estrogen-dopamine link is showing that this may make women more vulnerable to addictions. Dopamine is a neurotransmitter involved in the perception of rewards such as food, sex and drugs. There is a growing literature on female addiction shows that they are not much like their male counterparts. The studies point to new drug treatments for addiction as well as practical tips for women who want to quit using.

 

The Weaker Sex?


Although scientists have been studying drug use in women on a small scale since the 1970s, progress was relatively meager before 1994, when the National Institutes of Health mandated that most clinical research include women and minorities. As research on gender differences greatly accelerated, investigators uncovered hints that girls and women may be more vulnerable to addiction and substance abuse than men are. Scientists noticed that women more quickly escalate to heavy drug use and more readily succumb to the accompanying social and physical damage. Even female rats obsessively self-administer addictive drugs more readily than male rodents do.

 

Reproductive hormones may underlie this susceptibility. Removing the ovaries of female rats so that the animals no longer produce estrogen can diminish their tendency to seek out stimulants such as cocaine and amphetamine. In addition, giving estrogen to female rats whose ovaries have been removed can shorten the path to addiction. In 2004 neuroscientist Jill Becker of the University of Michigan and her colleagues reported that it took six days for ovary-free rats to start repeatedly helping themselves to infusions of cocaine—in this setup, by poking their noses into a hole. In contrast, rats receiving supplemental estrogen succumbed to the same compulsion after just four days.

 

Researchers believe that estrogen spurs addiction by stimulating the brain’s reward pathways, enhancing the “high” from drugs. Administering estrogen to rats that have had their ovaries removed boosts levels of dopamine.

 

Hormone High


In female mammals, estrogen does not act alone, however. Its hormonal partner, progesterone, appears to oppose estrogen’s ability to promote addictive tendencies. In 2006 Becker’s team reported that giving both estrogen and progesterone to female rats lacking ovaries does not accelerate obsessive cocaine use in the rodents, suggesting that progesterone may be an antidote to estrogen’s pleasure-seeking influence.

 

And more recent work confirms that women’s response to drugs varies across the menstrual cycle, as the relative levels of estrogen and progesterone naturally wax and wane. In a 2007 study clinical neurobiologist Suzette Evans and her colleagues found that stimulants are far more pleasurable to women during the estrogen-dominated ‘follicular phase’ (which occupies the approximately two weeks from the onset of a woman’s period until she ovulates) than during the ‘luteal phase’ after ovulation, when both estrogen and progesterone are high.

 

A woman’s perception of other kinds of rewards—such as money, food and sex—may also vary during her menstrual cycle. In a 2007 study researchers at the NIH scanned women’s brains using functional MRI as the women played slot-machine games. They found that women’s reward circuitry was more active when they won jackpots during the estrogen-governed phase of their cycles than during the progesterone-infused phase that follows. The ebb and flow of female hormones could thus have broad effects on the perception of pleasures and incentives, influencing women’s motivation to engage in a wide variety of behaviors.

 

A Smarter Way to Stop


Artificially boosting progesterone levels in women tempers the “high” they get from drugs. In a 2006 study Evans’s team gave 11 female cocaine users progesterone when their bodies’ natural levels of the hormone were low. The treated women reported feeling a reduced high as compared with the one they got at the same point in their cycles in the absence of additional progesterone. (In contrast, progesterone did not influence the subjective experience of cocaine smoking in the 10 male addicts they tested, although the researchers are not sure why.) If progesterone dampens the pleasure of drugs, it might help treat addiction in women—something Evans is currently testing in female cocaine addicts.

 

Short of a chemical fix, paying attention to the calendar could help women succeed at quitting smoking, drinking or using drugs. In a study published in 2008, Sharon Allen, a family medicine doctor at the University of Minnesota Medical School, and her colleagues asked half of 202 female smokers to try to quit during the second part of their cycles—when progesterone levels are high—and the others to make the attempt earlier in their cycles. The results were stunning: 34 percent of the women in the first group had not smoked 30 days later as compared with only 14 percent of those who tried to stop smoking when progesterone levels were low. When women smoke early in their cycle, they get more of a kick from their nicotine, so it might be harder to quit. In this mix of hormones, brain chemicals and desire—as in many other parts of life—timing may be everything.

 
 
References:

 

Allen SS, Bade T, Center B, et al. Menstrual phase effects on smoking relapse. Addiction (2008), volume 103, issue 5, pages 809-821.   

 

Allen SS, Bade T, Hatsukami D, et al. Craving, withdrawal, and smoking urges on days immediately prior to smoking relapse. Nicotine and Tobacco Research (2008), volume 10, issue 1, pages 35-45.

 

Anthes E. She's Hooked: Allure of Vices Tied to a Woman's Monthly Cycle. Scientific American Mind (2010), volume 21, issue 2, pages 14-15.

 

Cools R, Sheridan M, Jacobs E, D'Esposito M. Impulsive personality predicts dopamine-dependent changes in frontostriatal activity during component processes of working memory. Journal of Neuroscience (2007), volume 27, issue 20, pages: 5506-5514.

 

Evans SM, Foltin RW. Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men. Neuropsychopharmaclogy (2006), volume 31, issue 3, pages 659-674.

 

Evans SM. The role of estradiol and progesterone in modulating the subjective effects of stimulants in humans. Experimental and Clinical Psychopharmacology (2007), volume 15, pages 418-426.  

 

Hu M, Crombag HS, Robinson TE, Becker JB. Biological basis of sex differences in the propensity to self-administer cocaine. Neuropsycholpharmacology (2004), volume 29, issue 1, pages 81-85.

 

Jackson LR, Robinson TE, Becker JB. Sex differences and hormonal influences on acquisition of cocaine self-administration in rats.  Neuropsychopharmaclogy (2006), volume 31, issue 1, pages 129-138.

 

Vance E. Is estrogen the new Ritalin? Scientific American Mind (2010), volume 21, issue 2, page 6.