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Evidence summaries

Medical Therapy for Endometriosis Surgery

Post-operative oral contraceptive pill or GnRH agonist may reduce anatomical relapse of endometriosis and frequency/severity of recurrent dysmenorrhoea. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 25 studies with a total of 3 378 subjects. Medical therapy included nafarelin, goserelin, leuprolide, triptorelin, medroxyprogesterone acetate, oral contraceptives, danazol, or traditional Chinese medicine, gestrinone), which were analyzed as one group before or after surgery. Postsurgical medical therapy compared with no medical therapy or placebo reduced pain recurrence, disease recurrence, and increased pregnancy rate.

Another systematic review 2 included 7 studies (4 RCTs, 1 prospective self-controlled study, 1 cohort study, and 1 retrospective study) with a total of 1 158 subjects evaluating post-operative combined oral contraceptive pill (OCP) treatment on prevention of endometriosis recurrence. A low-dose monophasic oral contraceptive therapy was used in all the studies. Short-term therapy did not reduce recurrence (2 studies). A reduction in anatomical relapse rate was observed when OCP was administered for more than 1 year after conservative surgery; one cohort study (n=277) observed that at 36 months' follow-up, crude recurrence rate was 9% in the group of patients treated by post-operative OCP for the entire follow-up period and 56% in the untreated group (P < 0.001). Another study (RCT, n=217) observed at 24 months follow-up an endometrioma crude recurrence rate of 29% in untreated patients versus 14.7 and 8.2% in women treated with OCP in cyclic and continuous administration, respectively; the difference was significant between untreated versus women treated with OCP (P < 0.005). Long-term post-operative use of OCP was associated with a reduction in frequency and intensity of dysmenorrhoea recurrence. One RCT (n=271) observed a significant reduction in frequency and severity of recurrent dysmenorrhoea in patients receiving 24 months' OCP therapy compared with surgery alone. Benefits of oral contraceptives were evident since the first follow-up visit, at 6 months, for the patients in continuous treatment, and after 18 months of follow-up in the women treated in cyclic regimen (P < 0.0005). One self-controlled study (n=50) assessed the efficacy of continuous OCP administration in pain relief in women whom post-operative prophylaxis with cyclic OCP failed to prevent dysmenorrhea recurrence and reported a mean reduction in VAS score of 45.95% after 2 years of continuous OCP therapy (P < 0.001). No association was found between OCP therapy and dyspareunia prevention, although the effect of OCP on chronic pelvic pain was conflicting.

A meta-analysis 3 assessed continuous vs cyclic oral contraceptives after surgery for endometriosis. The primary outcomes were considered pain recurrence (evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain, and dyspareunia) and endometrioma recurrence evaluated at ultrasonography. 3 RCTs and 1 prospective controlled cohort study were included, for a total of 557 patients with endometriosis, 343 patients of whom had ovarian endometriomas completing the assigned treatment and follow-up. Lower recurrence rates for dysmenorrhea were obtained with a continuous schedule (RR 0.24; 95% CI, 0.06 to 0.91; P = .04). Nonsignificant differences were present for chronic pelvic pain and dyspareunia. A continuous oral contraceptive schedule was associated with a nonsignificant reduction of cyst recurrence rates compared with a cyclic schedule (RR 0.54; 95% CI, 0.28 to 1.05; P = .07).

Comment: The quality of evidence is downgraded by limitations in study quality (inadequate or unclear allocation concealment and lack of blinding) and by inconsistency (variability in results across studies).

    References

    • Chen I, Veth VB, Choudhry AJ et al. Pre- and postsurgical medical therapy for endometriosis surgery. Cochrane Database Syst Rev 2020;(11):CD003678. [PubMed]
    • Seracchioli R, Mabrouk M, Manuzzi L, Vicenzi C, Frascà C, Elmakky A, Venturoli S. Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis. Hum Reprod 2009 Nov;24(11):2729-35. [PubMed]
    • Muzii L, Di Tucci C, Achilli C et al. Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis. Am J Obstet Gynecol 2016;214(2):203-211. [PubMed]

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