Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development

Abstract

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.

Selective Progesterone Receptor Modulators in Early-Stage Breast Cancer: A Randomized, Placebo-Controlled Phase II Window-of-Opportunity Trial Using Telapristone Acetate

“…Our data also document the suppression of menstruation and of serum progesterone levels in premenopausal women, which points to the possibility that some of the effects of telapristone acetate on tumor cell proliferation may be indirect. It is also consistent with the present interest in the long-term contraceptive potential of these drugs (30) and NCT03296098. The effects of ulipristal acetate on breast epithelial proliferation are currently being assessed in NCT02922127; and those of mifepristone on the breast epithelium of in BRCA 1/2 mutation carriers is under study in NCT01898312.…”

Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double‐Blind, Placebo‐Controlled Phase II Trial

“…Because TPA is known to suppress ovulation in premenopausal women, 27,29 we measured serum concentrations of estradiol, progesterone, and FSH prior to and following intervention. The median concentration of each hormone is summarized in Table 4.…”

Clinical Pharmacology at the Intersection of Women's Health and Regulation: Drug Development Considerations for Uterine Fibroids

“…Although SPRMs are approved for emergency contraception and are being developed as regular HCs for prolonged use, 66 when concomitantly used with HCs or their use is followed by HCs, they may have PD‐mediated drug‐drug interaction (DDI) potential with the progestin component of HCs because of competitive binding to progesterone receptors. Consequently this interaction potential may affect the contraceptive effectiveness of both drugs as contraceptives.…”