Pre- and postsurgical medical therapy for endometriosis surgery

Review question

What are the effects of medical hormonal suppression therapies administered before or after (or both) surgical treatment of endometriosis compared to surgery alone or medical therapy before or after (or both) surgery?

Background

In endometriosis, tissue like the lining of the womb starts to grow in other places, such as the ovaries and fallopian tubes. It affects 10% to 15% of reproductive-age women, and may cause pain in the lower tummy (pelvic pain) or back (which usually worsen during a woman's periods), painful sexual intercourse, and difficulty becoming pregnant.

Treatment to lower the levels of reproductive hormones (called medical hormonal suppression therapy) is common to reduce the size of endometrial tissue along with surgery to cut it away. Medical therapy can reduce pain or its reappearance, reduce disease recurrence (the chance of it coming back), and improve pregnancy rate. Potential benefits of medication may depend on whether it is given before or after surgery for endometriosis, but evidence is not clear.

Study characteristics

We found 26 randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 3457 women who underwent surgery with or without medical therapy. We used the term "surgery alone" to refer to placebo or no medical therapy. The evidence is current to November 2019.

Key results

Medical therapy showed variable effects on pain, reappearance of pain or disease, and pregnancy rate when used before or after surgery for endometriosis. However, for outcomes disease recurrence and pregnancy, it may be most effective after surgery versus surgery alone compared to other comparisons reviewed.

Medical therapy before surgery compared with placebo or no medical therapy

Very weak evidence suggests that if pelvic pain recurrence at 12 months or less is 24% among women having surgery alone, the chance with medical therapy before surgery would be between 17% and 40%.

Very weak evidence suggests that if disease recurrence at 12 months or less is 85% among women having surgery alone, the chance with medical therapy before surgery would be 66% to 85%.

Very weak evidence suggests that if pregnancy rate is 64% among women having surgery alone, the chance with medical therapy before surgery would be between 64% and 87%.

Medical therapy after surgery compared with placebo or no medical therapy

Weak evidence suggests that if pain recurrence at 12 months or less is 25% among women having surgery alone, the chance with medical therapy after surgery would be 17% to 29%.

Weak evidence suggests that if disease recurrence at 12 months or less is 17% among women having surgery alone, the chance with medical therapy after surgery would be 3% to 9%.

Very weak evidence suggests that if disease recurrence at 12 months or less (different classification used) is 85% among women having surgery alone, the chance with medical therapy after surgery would be 59% to 77%.

Moderate-quality evidence suggests that if pregnancy rate is 37% among women having surgery alone, the chance with medical therapy after surgery would be 39% to 52%.

Medical therapy before surgery compared with medical therapy after surgery

Weak evidence suggests that if pelvic pain recurrence at 12 months or less is 20% among women having medical therapy after surgery, the chance with medical therapy before surgery would be 19% to 41%.

Very weak evidence suggests that if disease recurrence at 12 months or less is 68% among women having medical therapy after surgery, the chance with medical therapy before surgery would be 64% to 87%.

Very weak evidence suggests that if pregnancy rate is 71% among women having medical therapy after surgery, the chance with medical therapy before surgery would be 65% to 86%.

Quality of the evidence

The evidence was of very low to moderate quality.

Authors' conclusions: 

Our results indicate that the data about the efficacy of medical therapy for endometriosis are inconclusive, related to the timing of hormonal suppression therapy relative to surgery for endometriosis. In our various comparisons of the timing of hormonal suppression therapy, women who receive postsurgical medical therapy compared with no medical therapy or placebo may experience benefit in terms of disease recurrence and pregnancy. There is insufficient evidence regarding hormonal suppression therapy at other time points in relation to surgery for women with endometriosis.

Read the full abstract...
Background: 

Endometriosis is a common gynaecological condition affecting 10% to 15% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is combining surgery and medical therapy to reduce the recurrence of endometriosis. Though the combination of surgery and medical therapy appears to be beneficial, there is a lack of clarity about the appropriate timing of when medical therapy should be used in relation with surgery, that is, before, after, or both before and after surgery, to maximize treatment response.

Objectives: 

To determine the effectiveness of medical therapies for hormonal suppression before, after, or both before and after surgery for endometriosis for improving painful symptoms, reducing disease recurrence, and increasing pregnancy rates.

Search strategy: 

We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in November 2019 together with reference checking and contact with study authors and experts in the field to identify additional studies.

Selection criteria: 

We included randomized controlled trials (RCTs) which compared medical therapies for hormonal suppression before, after, or before and after, therapeutic surgery for endometriosis.

Data collection and analysis: 

Two review authors independently extracted data and assessed risk of bias. Where possible, we combined data using risk ratio (RR), standardized mean difference or mean difference (MD) and 95% confidence intervals (CI). Primary outcomes were: painful symptoms of endometriosis as measured by a visual analogue scale (VAS) of pain, other validated scales or dichotomous outcomes; and recurrence of disease as evidenced by EEC (Endoscopic Endometriosis Classification), rAFS (revised American Fertility Society), or rASRM (revised American Society for Reproductive Medicine) scores at second-look laparoscopy.

Main results: 

We included 26 trials with 3457 women with endometriosis. We used the term "surgery alone" to refer to placebo or no medical therapy.

Presurgical medical therapy compared with placebo or no medical therapy

Compared to surgery alone, we are uncertain if presurgical medical hormonal suppression reduces pain recurrence at 12 months or less (dichotomous) (RR 1.10, 95% CI 0.72 to 1.66; 1 RCT, n = 262; very low-quality evidence) or whether it reduces disease recurrence at 12 months – total (AFS score) (MD –9.6, 95% CI –11.42 to –7.78; 1 RCT, n = 80; very low-quality evidence).

We are uncertain if presurgical medical hormonal suppression decreases disease recurrence at 12 months or less (EEC stage) compared to surgery alone (RR 0.88, 95% CI 0.78 to 1.00; 1 RCT, n = 262; very low-quality evidence). We are uncertain if presurgical medical hormonal suppression improves pregnancy rates compared to surgery alone (RR 1.16, 95% CI 0.99 to 1.36; 1 RCT, n = 262; very low-quality evidence).

No trials reported pelvic pain at 12 months or less (continuous) or disease recurrence at 12 months or less.

Postsurgical medical therapy compared with placebo or no medical therapy

We are uncertain about the improvement observed in pelvic pain at 12 months or less (continuous) between postsurgical medical hormonal suppression and surgery alone (MD –0.48, 95% CI –0.64 to –0.31; 4 RCTs, n = 419; I2 = 94%; very low-quality evidence).

We are uncertain if there is a difference in pain recurrence at 12 months or less (dichotomous) between postsurgical medical hormonal suppression and surgery alone (RR 0.85, 95% CI 0.65 to 1.12; 5 RCTs, n = 634; I2 = 20%; low-quality evidence).

We are uncertain if postsurgical medical hormonal suppression improves disease recurrence at 12 months – total (AFS score) compared to surgery alone (MD –2.29, 95% CI –4.01 to –0.57; 1 RCT, n = 51; very low-quality evidence).

Disease recurrence at 12 months or less may be reduced with postsurgical medical hormonal suppression compared to surgery alone (RR 0.30, 95% CI 0.17 to 0.54; 4 RCTs, n = 433; I2 = 58%; low-quality evidence).

We are uncertain about the reduction observed in disease recurrence at 12 months or less (EEC stage) between postsurgical medical hormonal suppression and surgery alone (RR 0.80, 95% CI 0.70 to 0.91; 1 RCT, n = 285; very low-quality evidence).

Pregnancy rate is probably increased with postsurgical medical hormonal suppression compared to surgery alone (RR 1.22, 95% CI 1.06 to 1.39; 11 RCTs, n = 932; I2 = 24%; moderate-quality evidence).

Pre- and postsurgical medical therapy compared with surgery alone or surgery and placebo

There were no trials identified in the search for this comparison.

Presurgical medical therapy compared with postsurgical medical therapy

We are uncertain about the difference in pain recurrence at 12 months or less (dichotomous) between postsurgical and presurgical medical hormonal suppression therapy (RR 1.40, 95% CI 0.95 to 2.07; 2 RCTs, n = 326; I2 = 2%; low-quality evidence).

We are uncertain about the difference in disease recurrence at 12 months or less (EEC stage) between postsurgical and presurgical medical hormonal suppression therapy (RR 1.10, 95% CI 0.95 to 1.28; 1 RCT, n = 273; very low-quality evidence).

We are uncertain about the difference in pregnancy rate between postsurgical and presurgical medical hormonal suppression therapy (RR 1.05, 95% CI 0.91 to 1.21; 1 RCT, n = 273; very low-quality evidence).

No trials reported pelvic pain at 12 months or less (continuous), disease recurrence at 12 months – total (AFS score) or disease recurrence at 12 months or less (dichotomous).

Postsurgical medical therapy compared with pre- and postsurgical medical therapy

There were no trials identified in the search for this comparison.

Serious adverse effects for medical therapies reviewed

There was insufficient evidence to reach a conclusion regarding serious adverse effects, as no studies reported data suitable for analysis.

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