In a recent double-blind, randomized, placebo-controlled trial, patients with suspected or surgically proven endometriosis were randomly assigned to receive either monophasic OC (ethinylestradiol plus norethisterone) or placebo during four cycles (360). Total dysmenorrhea scores assessed by verbal rating scale were significantly decreased at the end of treatment in both groups. From the first cycle through the end of treatment, dysmenorrhea in the OC group was significantly milder than in the placebo group. The volume of ovarian endometrioma was significantly decreased in the OC group but not in the placebo group (360).
The treatment of endometriosis with continuous low-dose monophasic oral contraceptives (one pill per day for 6 to 12 months) was originally used to induce pseudopregnancy caused by the resultant amenorrhea and decidualization of endometrial tissue (279). The concept was to induce an adynamic endometrium through elimination of the normal cyclic hormonal changes characteristic of the menstrual cycle (361). This induction of a pseudopregnancy state with combination oral contraceptive pills is effective in reducing dysmenorrhea and pelvic pain. The subsequent amenorrhea induced by oral contraceptives could decrease the risk for disease progression by preventing or reducing (retrograde) menstruation. Pathologically, oral contraceptive use is associated with decidualization of endometrial tissue, necrobiosis, and possibly absorption of the endometrial tissue (362). There is no convincing evidence that medical therapy with oral contraceptives offers definitive therapy. Instead, the endometrial implants survive the induced atrophy and, in most patients, reactivate after termination of treatment.
Any low-dose OC containing 30 to 35 μgof ethinyl estradiol used continuously can be used for the management of endometriosis. The objective of the treatment is the induction of amenorrhea, which should be continued for 6 to 12 months. Continuous or extended cyclic use of oral contraceptives is well tolerated when compared to the cyclic use of OCs for contraceptive purposes (363). In a randomized controlled trial of women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis, continuous treatment with oral ethinyl E2, 0.01 mg plus cyproterone acetate, 3 mg per day, or norethindrone acetate, 2.5 mg per day during 12 months resulted in substantially reduced dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores without major between-group differences in patient satisfaction rates (62% and 73%, respectively) (364).
In a patient preference cohort study to evaluate the efficacy and tolerability of a contraceptive vaginal ring (supplying 15 μgof ethinyl E and 120 μg per day of etonogestrel) and transdermal patch (delivering 20 μgof ethinyl E and 150 μg per day norelgestromin) in the treatment of women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis and endometriosis-associated pain, patients who preferred the ring were significantly more likely to be satisfied and to comply with treatment than those who chose the patch (282). Both systems were associated with poor bleeding control when used continuously.
Progestins may exert an antiendometriotic effect by causing initial decidualization of endometrial tissue followed by atrophy. They can be considered as the first choice for the treatment of endometriosis because they are as effective as danazol or GnRH analogues and have a lower cost and possibly a lower incidence of side effects than these agents (365).
Table 17.1 Medical Treatment of Endometriosis-Associated Pain: Effective Regimens (Usual Duration: 6 Months)
PO, oral; SC, subcutaneous; IM, intramuscular; IN, intranasal.