There is no evidence that any single agent or any particular dose is preferable to another. The effective doses of several progestins are summarized in Table 17.1. In most studies, the effect of treatment was evaluated after 3 to 6 months of therapy. Progestins appear to be an effective therapy for the painful symptoms associated with endometriosis (366).
Medroxyprogesterone Acetate MPA is the most studied agent. It is effective in relieving pain starting at a dose of 30 mg per day, increasing the dose based on the clinical response and bleeding patterns according to data from nonrandomized trials (367,368). A randomized placebo-controlled study reported a significant reduction in stages and scores of endometriosis in both the placebo group and the group treated with MPA 50 mg per day and placebo at laparoscopy within 3 months after cessation of therapy (369). These findings raise questions about the need for medical therapy with MPA in this dose.
Evidence suggests a possible role for depot MPA in the treatment of endometriosis. In a randomized controlled study, depot MPA (150 mg every 3 months) was more effective in the relief of dysmenorrhea than treatment with a cyclic 21-day oral contraceptive (ethinyl estradiol 20 μg plus desogestrel 0.15 mg) combined with very low-dose danazol (50 mg per day) (370). In another multicenter, randomized, evaluator-blinded, comparator-controlled trial, depot MPA (150 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months were equivalent in reducing endometriosis-associated pain during the study and the 12-month posttreatment follow-up period, with less impact on bone mineral density and fewer hypoestrogenic side effects but more bleeding being observed in the depot MPA treated group (371). Add-back therapy would prevent the negative effects on bone density and hypoestrogenic side effects associated with GnRH-agonist therapy. In a pilot study, pain relief, side effects, and treatment satisfaction were comparable during a 12-month treatment with etonogestrel implantate subcutaneous (68 mg) or depot medroxyprogesterone acetate 150 mg intramuscular depot MPA in 41 patients with dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia associated with histologically proven endometriosis (372). Although depot MPA treatment is effective for the treatment of pain associated with endometriosis, it is not indicated in infertile women because it induces profound amenorrhea and anovulation, and a varying length of time is required for ovulation to resume after discontinuation of therapy.
Dienogest In two randomized noninferiority trials, treatment during 6 months with dienogest 2 mg per day orally demonstrated equivalent efficacy to depot leuprolide acetate (3.75 mg, depot intramuscular injection, every 4 weeks) or intranasal buserelin acetate (900 μg per day, intranasally) in relieving the pain associated with endometriosis, offering a different safety and tolerability profile (less bone loss, fewer hot ﬂushes, more irregular genital bleeding) (373,374). Dienogest treatment was not compared to the recommended treatment of GnRH agonist combined with add-back (see discussion above) in these two trials.
Megestrol Acetate Megestrol acetate was administered in a dose of 40 mg per day with good results (370). Pain was reduced significantly during luteal phase treatment with 60 mg dydrogesterone, and this improvement was still evident at 12-month follow-up (316). Other treatment strategies included dydrogesterone (20 to 30 mg per day, either continuously or on days 5 to 21) and lynestrenol (10 mg per day).