Current and future medical treatments for menometrorrhagia during the premenopause

Abstract

Excessive menstrual bleeding reflects aberrant angiogenesis, generally due to submucosal myomas and endometrial polyps, although it is also frequently observed with long-term progestin-only contraception, impaired haemostasis and hormonal disorders. Surgery (hysterectomy, endometrial ablation) is used too frequently. Uterine artery embolisation is also an option for myomas. Medical treatments include combined oral contraception, progestins and levonorgestrel-releasing Intrauterine System. Gonadotropin-releasing hormone agonists provide significant improvements in bleeding for myomas, but also decrease estrogen secretion (e.g. hot flushes, decreased bone mass). Progestins, although used widely, remain poorly effective as they promote myoma cell growth. Recently, Selective Progesterone Receptor Modulators (SPRMs) have been shown to induce amenorrhea whilst maintaining endogenous estrogen secretion. Phase II studies have also demonstrated decreased fibroid size in SPRM-treated women. Although the mechanism of amenorrhea observed after SPRM treatment is still poorly understood, they may control uterine bleeding via a direct effect on endometrial blood vessels. Suppression of bleeding in women with uterine fibroids receiving SPRMs is associated with moderate reductions in uterine artery blood flow, without major changes in angiogenic factors and extracellular matrix composition; a clear difference to modifications observed with progestins. These data suggest major progress in the treatment of excessive menstrual bleeding.

Keywords::

• Menometrorrhagia
• selective progesterone receptor modulators
• treatment
• ulipristal acetate

Declaration of interest: The author received an honorarium from Pierre Fabre for his participation in the symposium and producing the article. The author thanks David P. Figgitt PhD, Content Ed Net, for providing valuable editorial assistance in the preparation of the article; funding for this assistance was provided by Pierre Fabre. The author has received consulting fees, research funding and/or lecture fees from Schering Plough (Organon), Merck, P&G, Ferring, Nordic Pharma, Grünenthal, Besins Health Int, HRA Pharma, Wyeth, Pfizer, Preglem SA, Pierre Fabre, Repros, Takeda and Pantarhei Bioscience. In addition, the author has been a senior consultant for The Population Council, New York, USA, since 1986 and a consultant for HAS, EMEA, AFSSAPS and the WHO.