Contraception with d-norgestrel silastic rods. Plasma levels of d-norgestrel and influence on the ovarian function
Weiner, E.; Johansson, E.D.
Contraception 14(5): 551-562
1976
ISSN/ISBN: 0010-7824 PMID: 987891 DOI: 10.1016/0010-7824(76)90006-8Document Number: 484959
Three silastic rods impregnated with d-norgestrel each containing 40 mg of the gestagen, were inserted s.c. in the left forearm of 4 women and left in place for 100-458 days. After about 300 days of treatment of daily oral dose of 50 .mu.g ethinylestradiol was given to 3 of the participants during 21 days, in order to increase the concentration of sex hormone binding globulin in plasma. The plasma levels of progesterone, estradiol and d-norgestrel were analyzed by radioimmunoassay. The study demonstrated fairly constant plasma levels of d-norgestrel during treatment. The concentrations observed were in the range found 4-6 h after intake of the mini-pill formulation of d-norgestrel (0.03 mg). When the sex hormone binding globulin levels were increased by oral ethinylestradiol treatment in the subjects with previous constant d-norgestrel levels in plasma, the d-norgestrel levels increased 2- to 6-fold, indicating that sex hormone binding globulin is the main carrier protein for d-norgestrel. The concentrations of d-norgestrel in plasma did not inhibit the baseline levels of estradiol in plasma, but ovulation was inhibited during the 1st yr of treatment. Ovulatory pattern of progesterone was restored within 20 days after removal of the rods. The amount of d-norgestrel lost from the rods during treatment suggest a contraceptive efficacy of at least 2 yr.