"Sunday start" multiphasic oral contraception: Ovulation prevention and delayed follicular atresia in primates

Utilization of the "sunday start" method for oral contraceptive therapy can result in the initiation of oral contraceptive administration as late as day 6 of the ovarian/menstrual cycle. Potentially, "breakthrough" ovulations could occur due to rapid follicular progression, especially if the dominant follicle is overtly established prior to the onset of estrogen-progestin administration. Here, we examined the efficacy of two new oral contraceptive regimens on potential "breakthrough" ovulations in the first cycle of treatment begun on cycle days 1 or 6 in cynomolgus monkeys having normal menstrual cycles. Our endocrine findings show that follicular recruitment, and probably selection of the dominant follicle, had occurred by day 6 of the follicular phase. Both oral contraceptive treatments (Loestrin 5/7/9^R, LoDose 5/7/9^R, Parke-Davis) were effective in blocking preovulatory-like gonadotropin and estradiol surges as well as luteal phase progesterone elevations, whether treatment was begun on day 1 or day 6 of the menstrual cycle. Despite hormonal evidence of significant maturational progression, oral contraceptive administration successfully blocked the completion of follicular maturation, thereby sustaining contraceptive reliability, even in the initial cycle of treatment using a "sunday start" regimen. Under these conditions, dissolution of the failed dominant follicle within ovarian stroma may be characterized by delayed follicular atresia. This research was supported in part by the CONRAD Program (a cooperating agency of the U.S. Agency for International Development) and Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan, 48105.