Selektive Progesteronrezeptormodulatoren

und Methoden Anhand der vorliegenden Literatur wird der Wissensstand zu den Wirkmechanismen der SPRM zusammengefasst. Zudem werden die möglichen Indikationen diskutiert. Ergebnisse Die Effekte von Progesteron werden durch den Progesteronrezeptor (PR) vermittelt. SPRM wirken agonistisch und/oder antagonistisch an den Isoformen des PR. Die Isoformen funktionieren primär als ligandenaktivierte Transkriptionsfaktoren. Mögliche Indikationen der SPRM-Gabe sind die Kontrazeption, Notfallkontrazeption, Endometriosetherapie und Behandlung von Uterusmyomen. Klinisch zugelassen sind derzeit Ulipristalacetat (UPA) und Mifepriston (MFP). MFP und UPA können als effektives Notfallkontrazeptivum verschrieben werden, wobei der genaue Wirkmechanismus noch nicht abschließend geklärt ist. UPA ist zudem eine Therapieoption für prämenopausale Frauen mit symptomatischen Uterusmyomen. Relativ wenige Fortschritte gibt es in der Entwicklung von SPRM zur Kontrazeption. Bisher liegen nur wenige Daten für die Indikation im Sinne der Langzeitkontrazeption vor. Schlussfolgerungen Haupteinsatzgebiete der SPRM sind die Notfallkontrazeption und die präoperative Behandlung von Uterusmyomen. Forschungsbemühungen bezüglich des Einsatzes von SPRM sind derzeit auf die Langzeitkontrazeption gerichtet. Hier ist insbesondere der UPA-freisetzende Vaginalring ein möglicher Ansatz.

Background Selective progesterone receptor modulators (SPRM) are a group of substances with a multitude of potential applications in the field of gynecological endocrinology.

The state of knowledge on the mechanisms of action of SPRMs is summarized based on the currently available literature. In addition, the possible indications are discussed.

The effects of progesterone are mediated by progesterone receptors (PR) and SPRMs have agonistic as well as antagonistic effects on the isoforms of PR. The isoforms primarily function as ligand-activated transcription factors. Possible indications are contraception, postcoital contraception, endometriosis therapy and treatment of uterine leiomyomas. Currently approved for clinical use are ulipristal acetate (UPA) and mifepristone (MFP), which can be prescribed as an effective postcoital contraceptive but the exact mechanism of action is not yet fully clarified. Additionally, UPA is a therapy option for premenopausal women with symptomatic uterine leiomyomas. There has been relatively little progress in the development of SPRMs for contraception. So far the amount of data currently available on the indications in the sense of long-term contraception are scarce.

The main fields of application of SPRMs are postcoital contraception and preoperative treatment of uterine leiomyomas. Future research efforts concerning the use of SPRMs are currently centered on the field of long-term contraception. Of particular interest is the vaginal ring delivery of UPA. Literatur Giangrande PH, McDonnell DP (1999) The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. Recent Prog Horm Res 54:291–313. (Diskussion 313–314) Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S (2015) Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update 21:155–173 Glasier A (2013) Emergency contraception: clinical outcomes. Contraception 87:309–313 Koyama A, Hagopian L, Linden J (2013) Emerging options for emergency contraception. Clin Med Insights Reprod Heal 7:23–35 Taneepanichskul S (2009) Emergency contraception with mifepristone 10 mg in Thai women. J Med Assoc Thai 92:999–1002 Cheng L, Che Y, Gülmezoglu AM (2012) Interventions for emergency contraception. Cochrane Database Syst Rev 8:CD001324 Carbonell JL, Garcia R, Gonzalez A, Breto A, Sanchez C (2015) Mifepristone 5 mg versus 10 mg for emergency contraception: double-blind randomized clinical trial. Int J Womens Health 7:95–102 Mozzanega B, Gizzo S, Di Gangi S, Cosmi E, Nardelli GB (2014) Ulipristal acetate: critical review about endometrial and ovulatory effects in emergency contraception. Reprod Sci 21:678–685 Fine P, Mathé H, Ginde S, Cullins V, Morfesis J, Gainer E (2010) Ulipristal acetate taken 48–120 hours after intercourse for emergency contraception. Obstet Gynecol 115:257–263 Brache V, Cochon L, Jesam C et al (2010) Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 25:2256–2263 Brache V, Cochon L, Deniaud M, Croxatto HB (2013) Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens. Contraception 88:611–618 Horak P, Mara M, Dundr P et al (2012) Effect of a selective progesterone receptor modulator on induction of apoptosis in uterine fibroids in vivo. Int J Endocrinol 2012:436174 Donnez J, Vázquez F, Tomaszewski J et al (2014) Long-term treatment of uterine fibroids with ulipristal acetate ☆. Fertil Steril 101:1565–1573.e1–18 Melis GB, Piras B, Marotto MF et al (2012) Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment. Expert Opin Drug Metab Toxicol 8:901–908 Hoellen F, Griesinger G, Bohlmann MK (2013) Therapeutic drugs in the treatment of symptomatic uterine fibroids. Expert Opin Pharmacother 14:2079–2085 Talaulikar VS, Manyonda I (2012) Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids. Eur J Obstet Gynecol Reprod Biol 165:135–140 Jensen JT (2013) Vaginal ring delivery of selective progesterone receptor modulators for contraception. Contraception 87:314–318 Spitz IM (2010) Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century. Contraception 82:442–452 Spitz IM (2009) Clinical utility of progesterone receptor modulators and their effect on the endometrium. Curr Opin Obstet Gynecol 21:318–324 Williams ARW, Critchley HOD, Osei J et al (2007) The effects of the selective progesterone receptor modulator asoprisnil on the morphology of uterine tissues after 3 months treatment in patients with symptomatic uterine leiomyomata. Hum Reprod 22:1696–1704 Cleve A, Fritzemeier KH, Haendler B, Heinrich N, Möller C, Schwede W, Wintermantel T (2013) Pharmacology and clinical use of sex steroid hormone receptor modulators. Handb Exp Pharmacol 214:543–587. (Buch: Sex and Gender Differences in Pharmacology; doi des Buchs:10.1007/978-3-642-30726-3; doi des Kapitels:10.1007/978-3-642-30726-3_24) Author information Authors and Affiliations Corresponding author Ethics declarations Interessenkonflikt C. Selgrad und O. Ortmann geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren. Additional information Redaktion M. Birkhäuser, Basel A.O. Mueck, Tübingen O. Ortmann, Regensburg Rights and permissions About this article Cite this article Selgrad, C., Ortmann, O. Selektive Progesteronrezeptormodulatoren. Gynäkologische Endokrinologie 14, 44–48 (2016). https://doi.org/10.1007/s10304-015-0050-2 Published: Issue date: DOI: https://doi.org/10.1007/s10304-015-0050-2