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, Oct 07, 2015
213 Reads
  • 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.
    Drug Design, Development and Therapy 02/2014; 8:285-292. DOI:10.2147/DDDT.S54565 · 3.03 Impact Factor
  • 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.
    International Journal of Women's Health 01/2014; 6(1):95-114. DOI:10.2147/IJWH.S51083
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine the importance of self-reported family history of uterine leiomyoma (fibroids) as a marker of risk. Women, aged 35 to 49, were randomly selected from the membership of a large, urban health plan. Participants completed a self-administered questionnaire about family history of fibroids. Ultrasound screening for fibroids followed, regardless of whether participants had been previously diagnosed (660 black, 412 white). Data for each ethnic group were analyzed separately using Poisson regression. In both ethnic groups, women who reported a family history of fibroids had an elevated risk of fibroids compared with those without family history. However, no elevated risk was apparent for cases who did not know they had fibroids when they reported the family history information. Many women may first learn about their family history of fibroids when discussing their own clinical diagnosis with family members. Such bias would invalidate self-reported family history as a predictor of fibroid risk. As new pharmacologic treatments for fibroids are developed, women at high risk of fibroids would benefit from early screening and pharmacologic treatment to delay development of large fibroids and reduce the need for invasive treatments. Self-reported family history is not useful for identifying high-risk women.
    Annals of epidemiology 05/2013; 23(5):286-90. DOI:10.1016/j.annepidem.2013.03.003 · 2.00 Impact Factor
Show more