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, which makes medical therapy, with the avoidance of possibly unnecessary surgery, an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed. This review assesses the effectiveness of two different regimens of oral progestogens in reducing ovulatory HMB.

The primary objective of this review was 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).

We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2007), MEDLINE (1966 to April 2007) and EMBASE (1985 to April 2007). 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. The review authors extracted the data independently. 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.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). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter with danazol treatment. Adverse events were significantly more likely with danazol when compared with progestogen treatment. Progestogen therapy from day 5 to day 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the IUS. A significantly higher proportion of norethisterone (NET) patients taking progestogens found their treatment unacceptable compared to IUS patients. However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the IUS.

Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia.