The effect of norethisterone (500 mcg) and ethinyl estradiol (35 mcg) capsules on the pituitary-ovarian axis.

PIP: 12 normal female volunteers were recruited to examine the effects of capsules containing 35 mcg ethinyl estradiol (EE) and 500 mcg norethisterone (NET) and suspended in an oily medium of polyethylene glycol 400 surrounded by a soft gelatin capsule on the pituitary-ovarian axis. These women were studied for 2 cycles; in the 1st cycle no capsules were taken and daily blood samples were drawn from days 5-21. FSH, LH, estradiol, and progesterone were assayed. In the next cycle, 35 mcg EE and 500 mcg NET were taken on days 5-21 with daily blood samples drawn. Capsules were taken 2 hours before blood sampling and FSH, LH, estradiol, and progesterone as well as EE and NET were assayed. Hormone profiles are displayed in Figures 1 and 2. 10 of 12 volunteers showed a control cycle suggestive of ovulation (serum progesterone levels greater than 30 nmol/1 and a significant midcycle LH surge). During the pill cycle, these same 10 patients experienced suppression of ovulation as demonstrated by low progesterone levels in the second 1/2 of the cycle. NET and EE levels varied to the extent that they indicate a resonably physiologic variation. Results indicate that ovulation was suppressed in 11 of 12 subjects and cervical mucus studies showed that the local sperm blocking mechanism of the progestogen was operating whenever this parameter was assessed. This capsule formulation did suppress pituitary-ovarian function satisfactorily and the capsule is mainly acting by suppressing the positive feedback of estradiol on LH and not as strongly by suppressing follicular activity. Increased bioavailability may help in devising future formulations with a lesser amount of progestogen while still maintaining similar efficacy. Research is presently in process to examine the possibility of using a progestogen-only formulation which has increased bioavailability and which could be used cyclically.^ieng