Cyclical progestogens for heavy menstrual bleeding

Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical pathology and so medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed in many western countries, although there is little objective evidence to support their use, especially in women with ovulatory menstruation. This review assesses the effectiveness of 2 different regimens of oral progestogens in reducing ovulatory HMB.

The primary objective of this review is to investigate the effectiveness of oral progestogen therapy taken either during the luteal phase or for a longer course of 21 days in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB).

Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted.

The inclusion criteria were randomised comparisons of oral progestogen therapy versus placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic causes for their heavy menstrual blood loss.

Seven randomised controlled trials (RCTs) were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data.

No RCTs comparing progestogen treatment with placebo were identified. Comparisons between oral progestogens and other medical therapies were assessed separately according to dosage regimen, progestogens given during the luteal phase of the menstrual cycle and progestogens given for 21 days between day 5 and 26. Progestogen therapy during the luteal phase was significantly less effective at reducing menstrual blood loss when compared with tranexamic acid, danazol and the progesterone releasing intrauterine system (IUS) and there was also a strong non-significant trend in favour of nonsteroidal anti-inflammatory drugs (NSAIDs). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter under danazol treatment. Compliance and acceptability of treatment where measured did not differ between treatments. Adverse events were significantly more likely under danazol when compared with progestogen treatment. Change in quality of life was not significantly different with progestogen and tranexamic acid therapy but there was a non-significant trend in favour of tranexamic acid for all three categories. Progestogen therapy administered from day 5 to 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the progestogen releasing intrauterine system (LNG IUS) although the reduction from baseline was significant for both groups. The odds of the menstrual period becoming "normal" (ie <80mls/cycle) were also less likely in patients treated with norethisterone (NET) (days 5 to 26) compared to patients treated with LNG IUS. A significantly higher proportion of NET patients found their treatment unacceptable compared to LNG IUS patients. However, the adverse events breast tenderness and intermenstrual bleeding were more likely in the patients with the IUS. (ABSTRACT TRUNCATED)