SERUM NORETHINDRONE (NET) CONCENTRATIONS FOLLOWING INTRAMUSCULAR NET ENANTHATE INJECTION - EFFECT UPON SERUM LH, FSH, ESTRADIOL AND PROGESTERONE

Serum NET, FSH [follitroipin], LH [lutropin], estradiol (E2) and progesterone (P) concentrations were measured in 15 women twice weekly for 4-6 mo. following i.m. injection of 200 or 300 mg of norethindrone enanthate (NET-EN). Serum NET levels reached a peak of 12 to 17 ng/ml about 1 wk after injection. The serum NET levels were elevated for about 20 days after NET-EN injection and decreased thereafter, first precipitously, then gradually. Serum NET levels greater than 4 ng/ml persisted for 1-4 mo., suppressing gonadotropin secretion and ovarian follicle maturation. The first follicle maturation evidenced by preovulatory serum E2 levels was not followed by ovulation in 14of the 15 study subjects. Positive feedback inhibition of the midcycle LH peak occurred at serum NET levels ranging from 0.1 to 1.8 ng/ml. The first ovulation after NET-EN injection was observed after a median time interval of 98 days, the earliest being 45 days and the 2nd earliest 80 days after injection. Neither the dose difference of 300 vs. 200 mg of NET-EN nor the size of the vehicle (2 ml or 1 ml of oil) appeared to affect uterine bleeding patterns. Assuming a metabolic clearance rate of 551 l/day for serum NET, essentially all the NET-EN injected appears to be absorbed and converted to circulating NET. The 300 mg NET-EN dose does not present any contraceptive advantage: it results in unnecessarily high initial serum NET levels, but not not provide higher serum NET levels 3 weeks after NET-EN injection than the 200 mg dose. Alteration of the vehicle volume from 1 to 2 ml of oil does not have any noticeable effect on serum NET concentrations. The return of fertility seems to vary more because of apparent individual variation of the threshold of positive LH feedback inhibition than because of subject to subject differences in serum NET levels.