Drugs, sex, alcohol, estrogen.
Estrogen may not be the word that springs to mind when you think of the other three. But if you're a woman, researchers say, knowing how they're connected could keep you from falling prey to an addiction.
Fluctuations in estrogen levels every month may have an impact on areas of a woman's brain that control addictive behaviors, particularly addiction to drugs like cocaine, says a study on rats presented at the recent annual Society for Neuroscience conference in San Diego.
"Since estrogen enhances sensitization, and sensitization has been shown to be related to craving, one would predict that women would be more likely to want more cocaine and to take more cocaine if it is available during the early luteal phase of the cycle, compared to other times in their cycle," says study author Jill Becker, a psychiatry professor at the University of Michigan, where the study was conducted. The luteal phase is the two weeks that follow ovulation, when estrogen levels are highest.
The study results also indicate that once a woman is sensitized to drugs when her estrogen level is high, the increased sensitivity remains even when the estrogen is taken away, Becker says.
Not everyone agrees with these findings, however. One researcher who has done similar studies on women says that, more times than not, what's true in rats is not true in humans.
Becker says the study also shows that women who start using cocaine during the second half of their menstrual cycle will be "more likely to become addicted and will find it more difficult to quit than women who experiment with cocaine during phases in the cycle when estrogen is low."
And she believes that women who begin using cocaine or other addictive drugs while on hormone replacement therapy (HRT), when the flow of estrogen is constant, may also be more vulnerable to addiction.
Becker's conclusions are based on animal data, not human data, and therein lies the problem, says researcher Suzette Evans.
Evans, who has done similar studies on women, says there are too many differences between rats and people to jump to any conclusions about this study.
"The rat's reproductive biology is totally different from that of a woman; for one, they only have a four-day cycle, as compared to 28 days in most women," says Evans, the director of the Woman's Research Center, Substance Use Research Division, New York
State Psychiatric Institute of Columbia University.
Moreover, she adds, although it's clear from her own work that reproductive hormones do affect the area of the brain linked to addiction, there is no proof that estrogen alone holds the key.
"It could just as easily be the effects of progesterone as estrogen, or even some other chemical that is stimulated by the rise and fall of the reproductive hormones. Based on rat data, I don't think we can say it is absolutely estrogen that is having this effect in women," says Evans.
Becker, however, cited previous studies she has done that looked at responses to amphetamine in relation to both estrogen and progesterone.
"I have looked at the effects of estrogen plus progesterone vs. estrogen alone on the acute behavioral and neurochemical responses to amphetamine, and I do not find a difference when these groups are compared. Therefore, I do not think that the absence of progesterone is a factor," she says.
The latest study involved 200 rats, half male, half female, all of which were exposed to cocaine over the course of three weeks. Half the male rats were castrated. All the female rats had their ovaries removed, and half were given controlled daily doses of estrogen to produce serum concentrations equivalent to the surges of estrogen seen during the human menstrual cycle.
The cocaine was given once a day for four days. The rats on the hormone received it 30 minutes before the cocaine. All the rats were then withdrawn from the cocaine for three days; those on the hormone stopped getting it for the three days. The whole procedure was done three times.
The result: The female rats who were given estrogen were 20 percent to 50 percent more sensitized to the cocaine than either the female rats who received no estrogen, or the male rats. The researchers measured sensitivity by the number of repetitive movements the rats made, as well as their inclination to turn in circles.
The result, Becker says, tells the story of estrogen's link to addiction.
"My data indicates that estrogen exacerbates the neural changes that occur during exposure to drugs of abuse," says Becker.
Among those effects, she says, is the ability to impact brain chemicals that are linked to inhibition, which in turn affects craving and sensitivity to addictive substances as well as sexual desire and function.
Becker points out that the ability of estrogen to enhance sexual motivation may well be the link between estrogen and drug sensitization or the increased risk of addiction.
Evans says the research is important because "the more we learn about the effects of hormones on brain chemistry, the closer we come to unraveling a lot of mysteries that can have important health implications for women."
"However," she adds "we also have to be careful not to jump to conclusions too quickly without having the human data to back up the animal findings -- and not all of what has been found true in terms of rats will necessarily apply to humans."
What To Do
Experts say women who have more cravings during the two weeks leading up to each monthly cycle should be careful about starting any substance use that could become addictive.
Additionally, Evans says, women thinking about giving up an addiction might note that it could be harder to stick to a detoxification program -- for quitting smoking, for instance -- if the process is started during the high-estrogen part of the menstrual cycle.
For more information on addictions in women, visit the Women's Addiction Foundation.
Or you can visit the National Institute on Drug Abuse for facts on women's health and drug use.