asoprisnil and telapristone-acetate

Uterine fibroids are common in women of reproductive age and can have a significant impact on quality of life and fertility. Although a number of international obstetrics/gynecology societies have issued evidence-based clinical practice guidelines for the management of symptomatic uterine fibroids, many of these guidelines do not yet reflect the most recent clinical evidence and approved indication for one of the key medical management options: the selective progesterone receptor modulator class. This article aims to share the clinical experience gained with selective progesterone receptor modulators in Europe and Canada by reviewing the historical development of selective progesterone receptor modulators, current best practices for selective progesterone receptor modulator use based on available data, and potential future uses for selective progesterone receptor modulators in uterine fibroids and other gynecologic conditions.

Topics: Contraceptive Agents, Female; Disease Management; Estrenes; Female; Forecasting; Humans; Leiomyoma; Mifepristone; Norpregnadienes; Oximes; Population Growth; Receptors, Progesterone; Steroids; Uterine Neoplasms

Fibroids are the most common tumor of the female reproductive tract, but approved medical treatments are limited. Patients demand uterine-sparing treatments which preserve fertility and avoid surgery. We systematically reviewed PubMed and Cochrane databases from January 1985 to November 2015 for evidence-based medical therapies for fibroids in the context of disease prevention, treatment of early disease, treatment of symptomatic disease, and preoperative management. We identified 2182 studies, of which 52 studies met inclusion and exclusion criteria. Published data affirm the efficacy of multiple agents, which are promising avenues for the development of medical alternatives to surgery.

Topics: Androgens; Aromatase Inhibitors; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Curcumin; Delayed-Action Preparations; Drugs, Chinese Herbal; Estradiol; Estrenes; Estrogen Receptor Antagonists; Evidence-Based Medicine; Female; Fulvestrant; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Intrauterine Devices, Medicated; Leiomyoma; Levonorgestrel; Medroxyprogesterone Acetate; Mifepristone; Neoadjuvant Therapy; Norpregnadienes; Oximes; Plant Extracts; Receptors, Progesterone; Selective Estrogen Receptor Modulators; Tea; Uterine Myomectomy; Uterine Neoplasms; Vitamin D; Vitamins

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.

Topics: Endometrium; Estrenes; Female; Hormone Antagonists; Humans; Hyperplasia; Intrauterine Devices, Medicated; Leiomyoma; Levonorgestrel; Mifepristone; Norpregnadienes; Oximes; Receptors, Progesterone

In view of the spate of recent publications related to mifepristone and some second generation progesterone receptor modulators (PRMs), this appears to be an opportune time to view the clinical status of these compounds.. Randomized double-blind placebo-controlled trials have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914, Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment of uterine fibroids where they are associated with a reduction in pain, bleeding and improvement in quality of life and decrease in fibroid size. CDB-4124 is also efficacious in endometriosis. Long-term treatment with PRMs may be associated with endometrial thickening on ultrasound and there have been reports of endometrial hyperplasia. Several reassuring recent publications have done much to explain the mechanism underlying these endometrial changes. The most common histological finding is cystic glandular dilatation often associated with both admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histology has not been previously encountered in clinical practice and should not be confused with endometrial hyperplasia. The endometrial thickness is related to this cystic glandular dilatation.. At this stage of development, PRMs cannot be administered for longer than 3 or 4 months. Even over this time, there is improvement of symptoms associated with fibroids and endometriosis. Clinicians and pathologists need to be aware that the endometrial thickening and histological appearance do not represent endometrial hyperplasia.

Topics: Drug Administration Schedule; Endometriosis; Endometrium; Estrenes; Female; Hormone Antagonists; Humans; Leiomyoma; Mifepristone; Norpregnadienes; Oximes; Randomized Controlled Trials as Topic; Receptors, Progesterone; Time Factors; Uterine Neoplasms