Correlation between the serum norethindrone (NET) levels attained after insertion of a silastic implant releasing norethindrone acetate and the endogenous hormones particularly progesterone.

Six normally menstruating women were inserted each with a single silastic implant-D releasing norethindrone acetate (NETA). The levels of endogenous hormones, FSH, LH, E2 and progesterone, were estimated by radioimmunoassay (RIA) procedures in the control and treatment cycles. In addition, the levels of drug in the serum as norethindrone (NET) which is a major metabolite of NETA were also estimated by RIA procedures in the treatment cycles. In all, 12 treatment cycles were studied. In the initial treatment cycles (1st/2nd or 3rd), the serum NET levels were either 1 ng/ml or above. The LH and FSH showed either normal or suppressed mid-cycle peaks, but the progesterone levels were completely suppressed. In the sixth treatment cycles, the serum NET levels were either 0.5 ng/ml or below. The FSH and LH mid-cycle peaks were lower but distinct while the luteal progesterone levels were of normal ovulatory type. These studies lead us to the conclusion that a serum level of NET of the order of 1 ng/ml is required to bring about suppression of luteal progesterone, either as a result of direct action on the ovary or through suppression of pituitary gonadotropins. When the serum level falls to 0.5 ng/ml or below, the suppressive effect is removed and ovulatory pattern of progesterone returns.