Ovulation inhibition with nafarelin acetate nasal administration for six months

Abstract

A group of 24 women with normal menstrual cycles were treated with nafarelin acetate administered in doses of either 125 ug or 250 ug daily intranasally for 6 months. Each subject was studied for one ovulatory control cycle, six treatment cycles, and post-treatment until the return of ovulation was documented. Once a week progesterone, estradiol, follicle stimulating hormone, and luteinizing hormone were measured in the serum. Acute hormone responses to nafarelin acetate were determined on-day 1, day 98 and day 186 of treatment. Two subjects failed to complete the treatment phase. One subject using the 250 ug daily dose of nafarelin acetate discontinued treatment on the sixth day because of heavy uterine bleeding. One subject using the 125 ug daily dose of the study drug terminated treatment on day 126 because of a 21-pound weight gain. There were significantly less presumed ovulatory cycles at the higher dose (2 out of 60 cycles) than at the lower dose (10 out of 54 cycles) (p<0.01). On the average menstrual cycles were reestablished 28.5 ± 8.3 (S.D.) days after discontinuing the 125 ug daily dose and 33.7 ± 17.9 (S.D.) days after terminating the 250 ug daily dose. With the higher dose of nafarelin acetate there were significantly fewer bleeding episodes, less number of days of bleeding, and longer cycles. During the treatment phase the area under the LH curve was significantly less and the acute response of LH in the last week of treatment was significantly less with the higher dose of drug. With both doses of nafarelin acotate the acute responses of LH, FSH and estradiol were significantly greater on day 1 than on either day 98 or day 186. Side effects observed during this study included galactorrhea (2 subjects) and vasomotor symptoms (7 subjects).