Researchers aim to Alleviate Endometriosis Pain in Women

Endometriosis affects millions of women in the United States, a medical disorder that can lead to infertility and severe pelvic discomfort, particularly during menstruation.

The endometrium, a mucous layer that aids embryo implantation, lines the uterus of a woman. The endometrial lining is lost during the menstrual cycle in the absence of implantation of a fertilized egg. Endometriosis is a condition in which endometrial tissue grows outside of the uterus in places such as the fallopian tubes, ovaries, peritoneal wall, stomach, or intestines. These tissues combine to produce cysts, which can cause inflammation and scarring.

The fundamental etiology of endometriosis is uncertain, but one popular theory involves the immune system.

“Normally, the immune system removes any endometrial tissue that doesn’t belong in this area, but for some women the immune response is inadequate, and the tissue grows,” said Edita Navratilova, PhD, member of the University of Arizona Health Sciences Comprehensive Pain and Addiction Center and associate professor of pharmacology at the UArizona College of Medicine – Tucson.

More study is needed to determine the cause of endometriosis and develop a treatment. At the same time, there is an urgent need to create improved methods of controlling the condition’s pain.

“Treatments for endometriosis usually rely on pain medications, surgery or hormonal therapies, such as those used for birth control,” said Frank Porreca, PhD, associate department head and professor in the Department of Pharmacology at the College of Medicine – Tucson and Comprehensive Pain and Addiction Center member. “Surgery can clear the lesions, but the endometriosis and pain often comes back. Birth control can be effective, but that is not helpful for women who might be trying to conceive. We have found a hormone that might play a direct role in the pain of endometriosis and targeting it would not interfere with family planning.”

Navratilova and Porreca are investigating the function of prolactin in endometriosis-related pain, as well as how endometriosis may unintentionally predispose women to comorbidities such as migraine headache.

What role does prolactin play in pain?

Prolactin is a hormone that performs numerous physiological roles. It is best recognized for promoting mammary gland growth and boosting milk production, and it is found at higher levels in females than males.

Previous research by Navratilova and Porreca discovered that the interaction of prolactin with pain receptors may explain why specific pain syndromes are more common in women, such as migraine, fibromyalgia, and pelvic pain.

“Our research showed that prolactin changes the threshold for activation of pain receptors called nociceptors,” Porreca said. “Higher prolactin levels in female animal models lowered the threshold for triggering migraine pain, but interestingly, higher prolactin levels had no effect on males.”

“The answer to why women have more pain may be because female nociceptors have more receptors for prolactin and with high prolactin levels become more sensitive to painful stimuli,” Navratilova added

Endometriosis discomfort can be treated by targeting prolactin

If prolactin has such a high link with female-predominant pain problems, it stands to reason that female-specific illnesses like endometriosis may have a similar or even stronger relationship.

“Our previous research linking prolactin to several different conditions in several areas of the body suggest that there is a higher level of prolactin in the whole system,” Porreca said. “But endometriosis lesions have also been shown to produce prolactin locally.”

In their systematic review “Prolactin and Pain of Endometriosis,” Navratilova and Porreca looked at 18 peer-reviewed, published publications that looked at the association between prolactin levels and endometriosis. The studies compared patients with varied degrees of endometriosis, as well as fertility and reproductive concerns between those with and without endometriosis.

Prolactin levels were shown to be greater in women with endometriosis in all but one of the trials.

“This review gives us a clinical rationale for studying prolactin as a potential mechanism that promotes pain in the disease,” Navratilova said. “The goal is to eventually develop drugs that can lower prolactin levels or target prolactin receptors as a means of treating endometriosis pain.”

According to Navratilova, some dopamine agonists, or medications that activate dopamine receptors in the brain and have similar effects to the neurotransmitter dopamine, have been demonstrated to lower blood prolactin levels and help alleviate migraines. Dopamine agonists are already being utilized to treat neurological illnesses including Parkinson’s.

“We think these drugs might also help patients with the pain of endometriosis,” she said. “And they could possibly help decrease or eliminate endometriotic lesions as well.”

A step toward more comprehensive care

Navratilova and Porreca, along with postdoctoral research colleague Grace Lee, PhD, are currently looking at the comorbidity of endometriosis and migraine, or the likelihood of the two illnesses coexisting in the same patient. Their preliminary findings in animal models indicate that greater prolactin levels and stress appear to be common denominators when both conditions exist.

Recognizing that various illnesses may have overlapping mechanisms, they claim, is a step toward more holistic management.

“If you think about how our medical system works, when a woman has migraine, she goes to a neurologist. The neurologist may not ask about pelvic pain. When she has pelvic pain, she might go to a gynecologist. That individual may not ask about migraine,” Porreca said. “But these conditions are overlapping in the same woman and stressful, and stress increases prolactin, which can feed into other pain conditions. So, addressing prolactin could be a way of treating the whole person.”

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