Treatment of Endometriosis-Associated Pain Nonsteroidal Anti-inﬂammatory Drugs
Considering that endometriosis is a chronic inﬂammatory disease, anti-inﬂammatory drugs would appear to be effective for treatment of endometriosis-related dysmenorrhea. Although NSAIDs are used extensively and are often the first-line therapy for reduction of endometriosisrelated pain, the analgesic effect of NSAIDs was not studied extensively. Only one small, double-blind, placebo-controlled, four-period, crossover clinical study was published (353). This study claimed complete or substantial pain relief of endometriosis-related dysmenorrhea in 83% of cases treated with naproxen compared with 41% in cases treated with placebo. A different analysis of the data from the same study by the Cochrane Collaborative Network did not confirm a positive effect of naproxen on pain relief (OR 3.27; 95% CI. 0.61–17.69) in women with endometriosis (354). There was inconclusive evidence to indicate whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12; 95% CI, 0.01– 1.29) or to experience side effects (OR 0.46; 95% CI, 0.09–2.47) when compared to placebo (354).
Endometriosis-related pain is nociceptive, but persistent nociceptive input from endometriotic lesions leads to central sensitization manifested by somatic hyperalgesia and increased referred pain (355). The potential effectiveness of NSAIDs in the reduction of endometriosis-related pain may be explained by a local antinociceptive effect and a reduced central sensitization in addition to the anti-inﬂammatory effect. NSAIDs have significant side effects, including gastric ulceration and possible inhibition of ovulation. Prostaglandins are involved in the follicle rupture mechanism at ovulation, which is why women who wish to become pregnant should not take NSAIDs at the time of ovulation (356).
Effect of Hormonal Treatment on Pain Because estrogen is known to stimulate the growth of endometriosis, hormonal therapy is designed to suppress estrogen synthesis, thereby inducing atrophy of ectopic endometrial implants or interrupting the cycle of stimulation and bleeding (1). Implants of endometriosis react to gonadal steroid hormones in a manner similar, but not identical, to normally stimulated ectopic endometrium. Ectopic endometrial tissue displays histologic and biochemical differences from normal ectopic endometrium in characteristics such as glandular activity (proliferation, secretion), enzyme activity (17β-hydroxysteroid dehydrogenase), and steroid (estrogen, progestin, and androgen) hormone receptor levels. Withdrawal of estrogen stimulation causes cellular inactivation and degeneration of endometriotic implants but not their disappearance.
There is strong evidence that suppression of ovarian function for 6 months reduces pain associated with endometriosis. Combined oral contraceptives danazol, gestrinone, medroxyprogesterone acetate, and GnRH agonists are all equally effective but their side effects and cost profiles differ (1). Pain relief may be of short duration, presumably because endometriosis and endometriosis-associated pain recur after the cessation of medical treatment. The use of diethylstilbestrol, methyltestosterone, or other androgens is no longer advocated because they lack efficacy, have significant side effects, and pose risks to the fetus if pregnancy occurs during therapy. A new generation of aromatase inhibitors, estrogen receptor modulators, and progesterone antagonists may offer new hormonal treatment options.