Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.
BACKGROUND
As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma.


METHODS
This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs.


CONCLUSIONS
Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.
a Los Angeles BioMedical Research Institute, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology , 1457 3rd Street, Manhattan Beach, CA 90266, USA +1 310 937 7226 ; +1 310 937 1416 ; anitalnelson@earthlink.net.
Anita L
AL
Nelson
D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D009649:Norpregnadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors*
D003271:Contraceptive Agents, Female; D015507:Drugs, Investigational; D009649:Norpregnadienes; D011980:Receptors, Progesterone; D015735:Mifepristone; C555622:ulipristal acetate
contraception; mifepristone; selective progesterone receptor modulator; ulipristal acetate