Estrogen Helps Fight Pain

by Colette Bouchez

A woman's tolerance of pain may have more to do with the power of her reproductive hormones than the strength of her muscles.

That's the theory a group of Michigan researchers presented Feb. 18 at the annual meeting of the American Association for the Advancement of Science in Denver.

"Our studies have shown that although pain is influenced by both genetics and brain chemistry, it is clear that gender and hormones also play a role in our individual response to pain," says Dr. Jon-Kar Zubieta, lead researcher and a University of Michigan neuroscientist.

The key to pain response in women, Zubieta says, may be the hormone estrogen.

"When estrogen levels are high, the brain's natural pain chemicals -- endorphins or enkephalins -- are much more potent. The response is much greater than when estrogen levels are low," Zubieta says.

Pregnancy, he adds, is a good example of this brain chemistry in motion: One of the reasons women can tolerate the pain of childbirth is that just before they deliver, estrogen levels are soaring.

According to his new research, this hormone activity increases the number of receptor sites in the brain where such natural pain-relieving chemicals as endorphins can "dock."

The more "ports" available to receive the endorphins, the greater the ability of the brain to control the pain response, and ultimately, the less pain a woman feels, Zubieta says.

For pain management expert Allen Lebovits, the research makes good sense and it may help open the door for better and more efficient use of anesthesia, particularly in women.

"We don't routinely question women about where they are in their menstrual cycle when we are prescribing pain medications or even anesthesia. But if these studies prove right, then perhaps that should be something that doctors should consider when prescribing certain medications for women," says Lebovits, co-director of the pain management program at New York University Medical Center.

Zubieta and his colleagues spent several years using positron-emission topography (PET) scans to document brain changes linked to hormone activity. Rather than rely on just the images of brain chemistry in motion, they used the scans to document actual changes in the levels of brain chemicals under varying conditions.

In their first study, published in the July 2001 issue of Science , researchers injected the jaws of volunteers with a harmless solution designed to initiate a painful muscle spasm. Using the PET scan they documented how, within 20 minutes, the pain response activated endorphins, the brain's natural pain-mediating chemicals. Not surprisingly, Zubieta says, the rise in endorphin activity correlated with a reduction in the volunteers' perception of pain.

In the latest study, they used the same techniques to document how a woman responds to pain during high and low phases of estrogen production.

In the first part of the study, jaw pain was induced during the early follicular phase of the menstrual cycle -- a time when estrogen levels are low. In the second part, the women were given an estrogen patch to wear for one week, and the jaw pain experiment was repeated. In both instances, researchers recorded the women's reactions to the pain, while the PET documented brain activity.

The result: Under high estrogen conditions, the number of brain receptors available to receive endorphins increased dramatically, compared to the low estrogen conditions. During high estrogen times, the women also showed what researchers called a "remarkable" ability to release endorphins and activate the receptor sites.

The women reported less pain when estrogen levels were high, even though the level of pain inflicted was the same as it was during their low estrogen cycle, Zubieta says.

The data, now being confirmed in larger studies, hints at the powerful effects of female hormones on the pain and stress response, he adds.

More information

  • To learn more about the effects of estrogen on brain chemistry, visit Southern Illinois University Carbondale
  • For more on how the brain controls pain, visit The National Institute of Neurological Disorders and Stroke

SOURCES: Jon-Kar Zubieta, M.D., Ph.D, neuroscientist and director, psychiatry division, University of Michigan Depression Center, Ann Arbor; Allen Lebovits, Ph.D., associate professor, clinical anesthesiology and psychiatry, and co-director, pain management, New York University Medical Center, New York City; Feb. 18, 2003, presentation, American Association of The Advancement of Science, Denver

Colette Bouchez is an award winning medical journalist with more than twenty years experience. She is the former medical writer for the New York Daily News, and the top selling author of The V Zone, co-author of Getting Pregnant, Your Perfectly Pampered Pregnancy and upcoming book, Your Perfectly Pampered Menopause. Currently a daily medical correspondent for HealthDay News Service/The New York Times Syndicate, and WebMD, her popular consumer health articles appear daily online, as well as in newspapers nationwide and in Europe and Japan. She is a regular contributor to,, and more than two dozen radio and television news stations nationwide. She lives in New York City.

All content copyrighted © Colette Bouchez. Permission to republish granted to, LLC.