Treatment of abnormal uterine bleeding with micronized flavonoids

Menorrhagia during the reproductive years may be caused by an imbalance in the metabolism of local endometrial prostaglandins [1]. A micronized purified flavonoid fraction (MPFF; Daflon 500, Serdia, India) containing 90% of diosmin and 10% of flavonoids expressed as hesperidin has been shown to suppress prostaglandins E2, F2α, thromboxane A2, and prostacycline; reduce capillary hyperfragility; and increase lymphatic drainage [2]. This study examines the efficacy of MPFF in preventing ovulatory menorrhagia and dysmenorrhoea due to dysfunctional uterine bleeding. In the absence of an institutional review board, the authors approved the study protocol. Consecutive outpatients aged between 20 and 45 years who had a history of untreated menorrhagia over the three previous cycles were identified. Following a detailed examination that included transvaginal ultrasonography, hysteroscopy, and endometrial biopsy, those with ovulatory cycles but no evidence of pregnancy, pelvic pathology, coagulation disorder, hypothyroidism, or hepatic or renal disease, and who were not taking steroids or using an intrauterine contraceptive device, were selected for the study. After obtaining informed consent, MPFF was prescribed at a dose of 1000 mg/day (2 tablets of 500 mg) 5 days prior to the expected onset of menstruation (preventive phase) and up to the end of bleeding (treatment phase) for three consecutive cycles. The women were trained to use a pictorial blood assessment chart (PBAC) [3] and were followed up for three cycles. The 36 patients studied had a mean (S.D.) age of 33.3 (7.1) years, with a clinical history of menorrhagia for 11.7 (14.4) months. The effect of treatment on the variables studied is shown as mean change from baseline in Table 1 and as the proportion of patients showing improvement on an intention-to-treat basis in Fig. 1. Three patients reported adverse effects (one experienced headache, one experienced epigastric discomfort, and one experienced loss of appetite). Compliance with medication was 96.1%. Frequency of patients with dysfunctional uterine bleeding manifesting as menorrhagia showing improvement after MPFF treatment for three consecutive menstrual cycles (with confidence intervals). PBAC indicates pictorial blood assessment chart [3]. The small number of patients, the lack of a double-blind cross-over design, and the subjective assessment of menstrual flow at baseline were study limitations. However, treatment 5 days prior to and during menstruation reduced PBAC-assessed menstrual blood flow by one half and duration by one third in about 70% of patients, in whom a significant rise in hemoglobin was noted. There was a 50% improvement in associated dysmenorrhoea in about three of every four women. By comparison, cyclo-oxygenase inhibitors given during menstruation to suppress prostaglandins reduce menstrual blood flow by about 20%, with no effect on the duration of bleeding or dysmenorrhoea [4]. The results of this preliminary study suggest that since endometrial prostaglandin imbalance may precede and initiate menorrhagia in women with dysfunctional uterine bleeding during their reproductive years [1], preventive suppression of endometrial prostaglandins with MPFF may be a safe and more effective alternative to the conventional treatment and therefore warrants further study.