Danazol for heavy menstrual bleeding

Abstract

Background: Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women.

Objectives: To determine the effectiveness and tolerability of Danazol when used for heavy menstrual bleeding in women of reproductive years.

Search strategy: We searched the Menstrual Disorders and Subfertility Group's Specialised Register (April 2007). We also searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2007), MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007, CINAHL (1982 to April 2007). Attempts were also made to identify trials from citation lists of included trials and relevant review articles.

Selection criteria: Randomised controlled trials of Danazol versus placebo, any other medical (non-surgical) therapy or Danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded.

Data collection and analysis: Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format.

Main results: Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with Danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7 to 28.2) and progestogens (OR 4.05, 95% CI 1.6 to10.2). Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8 to -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3 to -4.8). There were no randomised trials comparing Danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system.

Authors' conclusions: Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified.

1.1. Analysis

Comparison 1 Danazol versus placebo, Outcome 1 Withdrawals due to side effects up to 3rd month.

1.2. Analysis

Comparison 1 Danazol versus placebo, Outcome 2 Weight after 3 months treatment.

2.2. Analysis

Comparison 2 Danazol versus progestagens, Outcome 2 Subjective efficacy of medication.

2.3. Analysis

Comparison 2 Danazol versus progestagens, Outcome 3 Number of women reporting adverse events.

2.4. Analysis

Comparison 2 Danazol versus progestagens, Outcome 4 Weight gain.

2.5. Analysis

Comparison 2 Danazol versus progestagens, Outcome 5 Duration of menses (days).

2.6. Analysis

Comparison 2 Danazol versus progestagens, Outcome 6 Mean MBL.

2.7. Analysis

Comparison 2 Danazol versus progestagens, Outcome 7 Mean weight gain.

2.8. Analysis

Comparison 2 Danazol versus progestagens, Outcome 8 Mean MBL (pictorial chart method) after 3 months follow up.

2.9. Analysis

Comparison 2 Danazol versus progestagens, Outcome 9 Withdrawal from treatment because of side effects.

2.12. Analysis

Comparison 2 Danazol versus progestagens, Outcome 12 Objective efficacy of intervention ( last MBL on treatment <80ml).

3.1. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 1 Mean MBL.

3.2. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 2 Subjective efficacy of medication rated as moderate to highly.

3.3. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 3 Number of women reporting adverse events.

3.4. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 4 Withdrawal from treatment due to adverse events.

3.5. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 5 Weight gain >2kg.

3.6. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 6 Duration of menses (days).

3.7. Analysis

Comparison 3 Danazol 200mg versus reducing dose danazol, Outcome 7 Objective efficacy of intervention (last MBL on treatment <80ml).

4.2. Analysis

Comparison 4 Danazol versus NSAID, Outcome 2 Duration of menses (days).

4.3. Analysis

Comparison 4 Danazol versus NSAID, Outcome 3 Improvement in dysmenorrhoea.

4.4. Analysis

Comparison 4 Danazol versus NSAID, Outcome 4 Side effects.

4.5. Analysis

Comparison 4 Danazol versus NSAID, Outcome 5 Acceptability of treatment (number unwilling to continue treatment).

4.6. Analysis

Comparison 4 Danazol versus NSAID, Outcome 6 Mean MBL.

6.2. Analysis

Comparison 6 Danazol versus progesterone releasing IUCD, Outcome 2 Duration of menses (days).

7.2. Analysis

Comparison 7 Danazol 200mg versus danazol 100mg, Outcome 2 Improvement in dysmenorrhoea.