A Cochrane review [Abstract] 1 included 13 studies evaluating progestagens in the treatment of painful symptoms of endometriosis, with a total of 1551 subjects. .The progestagen medroxyprogesterone acetate (MPA) (100 mg daily) was more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. However, there was more cases of acne and oedema in the MPA group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo, or between with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects. There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups. There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).
A systematic review 2 assessed efficacy of hormonal contraception for endometriosis. Combined hormonal contraception and progestin-only contraception (POC) were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in quality of life. There was no evidence that POC reduced the risk of disease recurrence.
An RCT 3 evaluated the clinical and cost-effectiveness of 150 mg depot medroxyprogesterone acetate or 52 mg LNG-IUS compared with the combined oral contraceptive pill (COC, 30 µg EE with 150 µg levonorgestrel) in preventing recurrence (n=405). In 3 years follow-up, pain scores improved in both groups (24 and 23 points on average) compared with preoperative values, there was no difference between the groups. The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the COC group (73 vs. 97; hazard ratio 0.67, 95% CI 0.44 to 1.00).
Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).
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