Clinical Pain Medicine
ISSUE: OCTOBER 2015 | VOLUME: 13(10)
Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affected fertility in normally cycling women, in a new study. Researchers observed a dramatic decrease in progesterone, a hormone essential for ovulation, after only 10 days of treatment.
“This study confirms that the administration of diclofenac, naproxen and etoricoxib … can interfere with the ovulatory process [by] either inhibiting follicular rupture or delaying ovulation,” said study investigator Sami Salman, MD, professor in the Department of Rheumatology at the University of Baghdad. “These findings may serve as a warning against the harmful effects of these drugs on female fertility, and should be taken into consideration by women planning to have a child.”
As Dr. Salman explained to Pain Medicine News, NSAIDs are among the most commonly used drugs in the world, taken by millions of people every day for the treatment of pain, inflammation and fever.
“These drugs are dirt cheap,” he said, “and they’re available over the counter. Because many users are women of childbearing age, it’s important to investigate the effects on ovulation and progesterone levels.”
Participants in the double-blind, placebo-controlled trial were visitors of the rheumatology consultation clinic at Baghdad Teaching Hospital who had been diagnosed with minor aches and pains. Before beginning treatment, researchers performed ultrasonography to assess the mean diameter of the dominant follicle, endometrial thickness and ovarian size of each patient. A blood sample was also taken for hormonal analysis (i.e., progesterone level).
Over a 10-day period (approximately 10 days after the onset of their menstrual cycle), patients were treated with one of three test drugs or placebo. After treatment, ultrasonography was repeated and an additional blood test taken.
Of the 97 women initially chosen to participate, 49 continued until the end of the study. Treatment was divided as follows: 16 patients received diclofenac 100 mg per day; 12 patients received naproxen 500 mg twice daily; 11 patients received etoricoxib 90 mg per day; and 10 patients received placebo.
According to Dr. Salman, the study presented several new findings.
“We observed a significant delay in ovulation, between 73% and 94%, in patients treated withdiclofenac, naproxen and etoricoxib,” he reported, “with diclofenac being the highest inhibitor of ovulation. Compared to the control group, there was also a significant decrease in progesterone level in all three groups.”
Of the women receiving NSAIDs, only 6.3% (diclofenac), 25% (naproxen) and 27.3% (etoricoxib) ovulated, compared with 100% of the control group. Functional cysts were also observed in one-third of patients by the end of the treatment period.
Although Dr. Salman expected to see some harmful effects on ovulation, he called the extent of impairment “alarming.” “I was not expecting such a dramatic effect,” he said. “To be honest, I was very, very worried when I saw the results.”
Despite these negative effects, Dr. Salman stressed that researchers found no evidence of a prolonged effect on ovulation. “I have to emphasize that this is a temporary effect,” he said. “When patients were tested during their follow-up, they had normal ovulation.”
“That being said,” he concluded, “this information needs to be revealed to doctors and patients so that people can be aware of all the risks. If you are a woman who is trying to get pregnant during the critical time for conception, you should not take these drugs.”
Asked to comment on this study, Charles E. Argoff, MD, professor of neurology at Albany Medical College and director of the comprehensive pain center at Albany Medical Center, in New York, issued the following caution:
“The results of this pilot study are provocative,” said Dr. Argoff, “adding further concerns to the widespread use of NSAIDs. If the results of this study are confirmed by independent investigations, [it] will undoubtedly change the way we view and use these agents for pain management.”
The study results were presented at the recent European League Against Rheumatism Annual Congress, held in Rome.