Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids

University of London, Londinium, England, United Kingdom
European journal of obstetrics, gynecology, and reproductive biology (Impact Factor: 1.7). 08/2012; 165(2). DOI: 10.1016/j.ejogrb.2012.07.023
Source: PubMed


The majority of symptomatic uterine fibroids are currently treated by surgical interventions (myomectomy or hysterectomy) or radiological treatments (uterine artery embolisation or focussed ultrasound surgery). None of these treatments is a panacea, and what is conspicuous is the lack of an effective long-term medical therapy for a disorder so common among women of reproductive age. It has been known for some time that progesterone and its receptors enhance proliferative activity in fibroids and this has raised the possibility that anti-progestins and (PRMs) could be useful in the medical management of fibroids. Some of the compounds which have produced promising results in recent clinical trials or research studies include mifepristone, CDB-4124 (telapristone), CP-8947, J-867 (asoprisnil) and CDB-2914 (ulipristal acetate or UA). UA has recently completed Phase III clinical trials with very encouraging results, and has now acquired a licence for clinical use in Europe. While considerable research has yet to be done on the long-term safety and efficacy of UA there is nevertheless good reason for optimism on the emergence of effective medical therapy in the form of UA and possibly other PRMs.

Download full-text


Available from: Vikram Sinai Talaulikar
  • Source
    • "Additionally, UPA increases the expression of matrix metalloproteinases (MMPs) and decreases the expression of tissue inhibitor of metalloproteinases (TIMPs) and collagens in cultured fibroid cells. Thus, UPA may impair fibroid tissue integrity by reducing the deposition of collagen in the extracellular spaces.21 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids. However, the US Food and Drug Administration recently authorized ulipristal acetate (UPA), an oral selective progesterone-receptor modulator, for the same indication. UPA is a new, effective, and well-tolerated option for the preoperative treatment of moderate and severe symptoms of uterine fibroids in women of reproductive age. According to clinical data, UPA shows several advantages: it is faster than leuprolide in reducing the fibroid-associated bleeding, it significantly improves hemoglobin and hematocrit levels in anemic patients, and it grants a significant reduction in the size of fibroids, which lasts for at least 6 months after the end of the treatment. Furthermore, UPA displays a better tolerability profile when compared to leuprolide; in fact, it keeps estradiol levels at mid follicular phase range, thereby reducing the incidence of hot flushes and exerting no impact on bone turnover. On the grounds of this evidence, the administration of 5 mg/day ulipristal acetate for 3 months is suggested for different patient categories and allows for planning a treatment strategy tailored to meet an individual patient's needs.
    Full-text · Article · Feb 2014 · Drug Design, Development and Therapy
  • Source
    • "Most existing studies have described the endometrial changes over short periods (months) of follow-up, but atypical hyperplasia and possibly malignant change take years to develop. Long-term studies are therefore necessary to evaluate such outcomes.94 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Uterine fibroids are a major cause of morbidity in women of a reproductive age (and sometimes even after menopause). There are several factors that are attributed to underlie the development and incidence of these common tumors, but this further corroborates their relatively unknown etiology. The most likely presentation of fibroids is by their effect on the woman's menstrual cycle or pelvic pressure symptoms. Leiomyosarcoma is a very rare entity that should be suspected in postmenopausal women with fibroid growth (and no concurrent hormone replacement therapy). The gold standard diagnostic modality for uterine fibroids appears to be gray-scale ultrasonography, with magnetic resonance imaging being a close second option in complex clinical circumstances. The management of uterine fibroids can be approached medically, surgically, and even by minimal access techniques. The recent introduction of selective progesterone receptor modulators (SPRMs) and aromatase inhibitors has added more armamentarium to the medical options of treatment. Uterine artery embolization (UAE) has now been well-recognized as a uterine-sparing (fertility-preserving) method of treating fibroids. More recently, the introduction of ultrasound waves (MRgFUS) or radiofrequency (VizAblate™ and Acessa™) for uterine fibroid ablation has added to the options of minimal access treatment. More definite surgery in the form of myomectomy or hysterectomy can be performed via the minimal access or open route methods. Our article seeks to review the already established information on uterine fibroids with added emphasis on contemporary knowledge.
    Full-text · Article · Jan 2014 · International Journal of Women's Health
  • [Show abstract] [Hide abstract]
    ABSTRACT: Uterine leiomyomata (fibroids) are very common, mostly benign tumors in women of reproductive age. Symptomatic fibroids cause significant morbidity and are characterized by heavy prolonged menstrual bleeding, by pain and pelvic pressure and, in some cases, they may lead to reproductive dysfunctions. Up to date, surgical procedures (hysterectomy or myomectomy) have been the dominant managements but recently uterine artery embolization and focused ultrasound surgery have also been taken into consideration. Hysterectomy is curative but for women of reproductive age the need for uterus-sparing medical therapy is evident. There are convincing data that progesterone and its receptors increase the proliferation activity of the cells in uterine leiomyomata, hence treatment with antiprogestins and progesterone receptor modulators seems to be reasonable. Results of a successfully completed phase III clinical trials with the application of ulipristal acetate (UPA) (first-in-class selective progesterone receptor modulator--SPRM) have been published at the beginning of this year Administration of 5 mg or 10 mg UPA daily has been shown to rapidly stop (within a week) excessive uterine bleeding, reduce the volume of the three largest fibroids by -44.8% and -54.8% for UPA 5 mg and 10 mg, respectively The effect on fibroid volume has been observed for up to 6 months after treatment cessation. It is also important that UPA restores patient Quality of Life scores to the level of healthy women and in the majority of patients resumes menstruation and ovulation within one month after treatment cessation. When compared with the Gn-RH agonist (leuprolide acetate), UPA has controlled uterine bleeding faster and more consistently (7 days vs. 30 days), fibroid reduction for up to 6 months has been smaller for Gn-RH a (-16.5%) and UPA has shown a superior safety profile as estradiol levels are maintained in the mid-follicular range. The UPA has caused temporary changes in endometrial morphology but 6 month after the treatment the endometrium returned to normal histology in the majority of cases. The presented results on the application UPA in the medical treatment of symptomatic uterine fibroids are very promising and gynecologists are given a new treatment option.
    No preview · Article · Mar 2013 · Ginekologia polska
Show more