Medications known as non-steroidal anti-inflammatory drugs, or NSAIDs (EN-seds), already used to treat symptoms of endometriosis, may be effective as treatment for the disease itself, claim doctors in Boston who studied the drugs in mice.1
What is Endometriosis?
Endometriosis is a common and often painful disorder characterized by the abnormal growth of tissues that normally line the inside of the uterus in areas outside the uterus. This tissue is most commonly found on the fallopian tubes, the ovaries, or the tissue that lines the pelvis. When this happens, uterine tissue continues to act as if it still lines the uterus. It thickens then later breaks down and bleeds as part of a woman's monthly cycle. But because there's nowhere for blood to escape in this case, it becomes trapped, and surrounding tissues become inflamed and irritated.2
Current therapy for endometriosis includes prescribing supplemental hormones, conservative surgery to remove the endometriotic growths that build up, and hysterectomy. Prescribing pain relievers like NSAIDs is common to treat symptoms.2 But, to this point, these medications haven't been thought of as a treatment for the disease.
Additionally, the treatment options that are available are "limited", write Maria Rupnick, MD, PhD, in the Vascular Biology Program at Children's Hospital in Boston, and her colleagues. Surgery "provides only temporary pain relief, and estrogen removal results in adverse effects on bone integrity, lipid profiles, and vasomotor control [function of blood vessels]."
The Possible NSAID Connection
Why did Rupnick's group hypothesize that NSAIDs might be an efficacious alternative? There were two key theories. Endometriosis is closely related to inflammation and NSAIDs are used as therapy for inflammation. Further, like some cancers, endometriosis possesses angiogenic properties, and NSAIDs have been shown to reduce angiogenesis. (Angiogenesis is a process by which new blood vessels are grown near the endometriotic lesions that form, which those lesions then use as a new supply of nutrients, helping them grow further.)
"NSAIDs are used as first-line agents to control the pain associated with the disease," Rupnick told Priority Healthcare. "However, they are prescribed indiscriminately based on cost, availability, patient preference, etc. We reasoned that if NSAIDs were selected based on their anti-angiogenic efficacy, the patient may not only receive pain relief, but their disease burden may also be reduced."
Most of the medical literature has focused on prescribing NSAIDs to treat the symptoms of endometriosis, and not even case studies have been reported suggesting that the drugs might be effective against the disease, mostly because of the difficulty in making that determination in a clinical setting, Rupnick explained. Even though NSAIDs may effectively treat pain associated with endometriosis, treating the symptoms does not always mean the disease has been effectively treated at the same time.
Evaluating NSAID's Role Against Endometriosis
To answer their questions, Rupnick's team surgically induced endometriosis in a group of mice, then divided them into 2 groups: one, receiving treatment with an NSAID, and the second receiving no therapy. The initial study lasted 4 weeks. Some of the animals received the medication orally and some by injection. The scientists then monitored the animals once per day during the study.
The types of NSAIDs used included aspirin, celecoxib, indomethacin, naproxen, rofecoxib, and sulindac.
At the end of the 4-week study, Rupnick and her team checked for endometrial growths in both the mice that received treatment and in those that didn't.
The researchers found numerous lesions in the animals. But they also discovered that the NSAIDs celecoxib and indomethacin had significantly reduced the growths compared with animals who hadn't been treated, and compared to the other NSAIDs tested. Only aspirin had the least effect.
"Because celecoxib and indomethacin demonstrated the greatest efficacy and celecoxib is better tolerated in humans, the remainder of the study focused on this NSAID," wrote Rupnick's group.
Established Lesions Weren't Affected
While celecoxib was effective during treatment, the effect wasn't maintained afterwards. The scientists found that while the drug had significantly reduced lesions immediately after it was discontinued, the number and size of lesions was similar between treatment and non-treatment groups 4 weeks after therapy was stopped, they wrote.
In addition, the investigators learned that while this drug inhibited the growth of newly formed lesions, it had little effect on established endometrial growths. Thus, any future treatment plan would have to take this into account, Rupnick said, adding that "it is too early to be definitive." But since this study suggests that certain NSAIDs could be effective against newly formed lesions, and since endometriosis is cyclic in nature, "well-timed administration of NSAIDs around the time of potential [lesion] implantation may reduce the disease burden," she said.
Estrogen Levels Can Be Maintained During Therapy
In conclusion, the researchers wrote that that certain NSAIDs may be effective against endometriosis, even without the need to block estrogen levels, as was tested in this study. In theory, a medication that blocked estrogen production could cause unwanted side effects like osteoporosis, hot flashes, and infertility, they wrote. (Endometriosis relies on estrogen for its growth and development).
While it's not yet known how NSAIDs may reduce endometriotic lesions, the drugs' anti-inflammatory nature may not be the key link since aspirin had no effect in this study. As such, there could be many factors involved, Rupnick's team speculated.
"The preclinical evidence that these drugs can impact the disease process is certainly mounting, and would support pursuing clinical confirmation," said Rupnick.
"Since NSAIDs are already prescribed to endometriosis patients, including anti-angiogenic efficacy in the criteria used to select the specific agent would be a reasonable clinical approach to consider," she said.
1. Etstathiou JA, Sampson DA, Levine Z et al. Nonsteroidal anti-inflammatory drugs differentially suppress endometriosis in a murine model. Fertil Steril 2005 Jan;83(1):171-81.
2. Endometriosis. Mayo Foundation for Medical Education and Research. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00289. Accessed February 8, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
