contraceptives--postcoital and Uterine-Neoplasms

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women's health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.

Topics: Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Humans; Leiomyoma; Norpregnadienes; Receptors, Progesterone; Uterine Neoplasms

Several selective progesterone receptor modulators (SPRMs) show promise in several areas of medicine and this work has been summarized by us in 2008.. Since the publication of our reviews, several developments have taken place in the field of reproductive medicine. The first is emergency contraception (EC). Two SPRMs are clinically utilized today: mifepristone (MFP) and ulipristal acetate (UPA). MFP is available for EC in up to 120 h following unprotected intercourse. A dose of 10 mg is significantly more effective than levonorgestrel (LNG). In a metanalysis of the use of UPA versus LNG up to 72 h after unprotected intercourse, failure rates of 1.4 versus 2.2% were reported. The second is contraception. A daily dose of 2 mg MFP can block ovulation and several MFP regimens are being tested, including a vaginal ring releasing MFP. The third is the preoperative administration in women harboring leiomyomas, where clinical testing of several SPRM has shown that they can decrease uterine leiomyomas' size and substantially reduce uterine bleeding. SPRM can induce unusual, specific endometrial appearances. Many believe that these changes should not cause concern, but the issue remains controversial.. SPRMs are very effective in EC and for the preoperative treatment of uterine leiomyomas.

Topics: Adenomyosis; Animals; Clinical Trials as Topic; Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Endometriosis; Estrenes; Female; Hormone Antagonists; Humans; Leiomyoma; Levonorgestrel; Mifepristone; Norpregnadienes; Oximes; Receptors, Progesterone; Uterine Neoplasms

Review of recent data from clinical trials and descriptions of endometrial morphology with administration of selective progesterone receptor modulators (SPRMs).. Recent reports concerning administration of SPRMs, specifically the efficacy of ulipristal acetate in reducing fibroid size and rapid control of menstrual blood loss, have renewed clinical interest in this class of compound. Histological data from studies with SPRMs report that this class of drugs is associated with progesterone receptor modulator-associated endometrial changes. Data on mechanisms of action are lacking. The antagonistic progesterone effect of SPRMs has shown promising results in animal studies with endometriosis. Sex steroid receptor effects of PRMs outside the reproductive tract raise the potential for use in neurology and oncology, and although there are several randomized trials in these areas, there are limited small studies published to date.. The SPRM ulipristal acetate is an effective treatment for preoperative treatment of fibroids and a reliable emergency contraceptive. This class of compounds holds the potential for long-term effective medical management of fibroids and may have utility in the management of other sex steroid-dependent conditions.

Topics: Breast Neoplasms; Contraceptives, Postcoital; Endometriosis; Female; Hormone Antagonists; Humans; Leiomyoma; Menorrhagia; Norpregnadienes; Quality of Life; Receptors, Progesterone; Uterine Neoplasms

Since the discovery of the antiprogestin RU 486 (mifepristone), other compounds have been synthesised that function as pure progesterone antagonists or progesterone receptor modulators. The latter are mixed agonists-antagonists. Mifepristone is usually used to terminate pregnancy but these compounds have numerous other applications in female healthcare. Mifepristone is an excellent agent for emergency contraception. Many progesterone antagonists and progesterone receptor modulators display antiproliferative effects on the endometrium and thus have application in the treatment of endometriosis and uterine myoma without being associated with hypoestrogenism and bone loss. They also have contraceptive potential by suppressing follicular development, blocking the luteinising hormone surge and retarding endometrial maturation. Finally, they have clinical application in GeneSwitch system, a plasmid-based method enabling controlled expression of specific genes (e.g., erythropoietin) using a progesterone antagonist as the inducer.

Topics: Animals; Contraceptives, Postcoital; Drug Administration Schedule; Endometriosis; Endometrium; Female; Gene Transfer Techniques; Hormone Antagonists; Humans; Leiomyoma; Mifepristone; Progesterone; Receptors, Progesterone; Uterine Neoplasms

To discuss the mechanism of action of selective progesterone receptor modulators (SPRMs) and summarize the preclinical and clinical efficacy and safety data supporting the potential use of these compounds for gynecologic indications.. Relevant publications from 2005 onward were identified using a PubMed search. Additional relevant articles were identified from citations within these publications.. None.. Mifepristone was first developed as a progesterone receptor antagonist and licensed for pregnancy termination because of the unique property of this compound to terminate pregnancy when associated with prostaglandins. Then SPRMs were developed, and among those ulipristal acetate, an efficient emergency contraceptive. Because SPRMs effectively inhibit endometrial proliferation and reduce endometriotic lesions in animal models, this suggests a possible role in the treatment of endometriosis in humans. Finally, a number of double-blind, randomized, placebo-controlled trials have demonstrated the efficacy of asoprisnil, mifepristone, telapristone acetate, and ulipristal acetate in reducing leiomyoma and uterine volume, and suppressing bleeding in women with uterine fibroids.. Mifepristone in combination with prostaglandins has been licensed for pregnancy termination because of its unique ability is this area. Ulipristal acetate is available for emergency contraception. Several SPRMs hold further promise as an effective medical therapy for patients suffering from endometriosis and leiomyoma.

Topics: Abortifacient Agents; Abortion, Induced; Animals; Antineoplastic Agents, Hormonal; Contraception, Postcoital; Contraceptives, Postcoital; Endometriosis; Evidence-Based Medicine; Female; Hormone Antagonists; Humans; Leiomyoma; Pregnancy; Receptors, Progesterone; Reproduction; Treatment Outcome; Uterine Neoplasms

Topics: Breast Neoplasms; Cardiovascular Diseases; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital; Female; Humans; Liver Neoplasms; Uterine Neoplasms

Topics: Animals; Antimetabolites; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Postcoital; Decidua; Embryo Implantation; Endometrium; Estrogen Antagonists; Estrone; Female; Neoplasms, Experimental; Pregnancy; Progesterone; Rats; Sesame Oil; Uterine Neoplasms