Three formulations of dl-norgestrel were administered daily to groups of three women for five consecutive days. The serum levels of d-norgestrel were related to the dosage of dl-norgestrel ingested. Peak concentrations in the circulation of synthetic gestagen were attained a half hour to three hours after oral administration, followed by a rapid and sharp decline in levels until the next dose. Three women received 500 micrograms of dl-norgestrel and 50 micrograms of ethinyl estradiol for 21 days followed by six to seven days of no medication for two consecutive cycles. The gonadotropins remained suppressed for four to six days when therapy was discontinued. The daily concentrations of estradiol varied from less than 5 to 81 pg. per milliliter, and there was no difference in estrogen values during the nontreatment and treatment days. Due to the long half life of norgestrel, the one-week pill-free interval is not long enough for the complete recovery of the reproductive axis from the inhibition of oral contraceptives.
PIP: 3 formulations of dl-norgestrel were administered daily to 4 groups of 3 women each for 5 consecutive days in order to determine the profile and absolute levels of circulating d-norgestrel, the biologically active enantiomer, following ingestion of the drug. In addition, serum d-norgestrel levels were measured in women during and after daily ingestion of .5 mg dl-norgestrel and .05 mg ehtinyl estradiol for 2 21 day periods interrupted by a 6-7 day pill-free interval. Serum d-norgestrel levels were correlated with circulating luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone levels. The serum levels of d-norgestrel were related to the dose of dl-norgestrel ingested. Peak concentrations of d-norgestrel occurred 1/2-3 hours after ingestion, followed by a rapid and sharp decline until the next dose. Patients receiving Ovral displayed suppressed gonadotropin levels for 4-6 days when therapy was discontinued. Daily concentrations of estradiol varied from less than 5 to 81 pg/ml. During the 2nd treatment cycle, serum estradiol concentrations were even lower than during the 1st cycle. Serum progesterone levels were consistently below 1 ng/ml. Norgestrel has a long half-life and a 1-week interval between cycles is insufficient for the complete recovery of the reproductive axis.