Effects of different doses of norethisterone on ovarian function, serum sex hormone binding globulin and high density lipoprotein-cholesterol

Abstract

The ovarian effects of different doses of norethisterone (NET) were compared in 45 normally menstruating women in order to find the lowest effective dose of the Chinese NET "visiting pill". Subjects were randomly divided into 3 groups. Each subject in each group was taking 0.5, 1.5 or 3.0 mg per day from days 5 to day 18 of the cycle. Blood samples were taken on days 5, 8, 11, 14, 17, 20, 23, 26 and 29 of the cycle. Serum oestradiol (E2), progesterone (P), sex hormone binding globulin (SHBG), high density-lipoprotein cholesterol (HDL-C), and NET concentrations were measured. Ovulation, delayed ovulation, ovulation inhibition and follicular activity were classified by the analysis of the peripheral serum levels of sex hormones. Ovulation occurred in 7 women in the 0.5 mg group, in 2 women in the 1.5 mg group and in none of the 3.0 mg group. Mean serum SHBG levels were reduced progressively by 6.6% (Group 0.5), 15.5% (Group 1.5) and 23.4% (Group 3.0). There were no significant changes in HDL-C levels in any group. There was a significant correlation of mean serum NET concentrations with dose. The lack of complete inhibition of ovulation in most women in the 1.5 mg and 0.5 mg groups might suggest that the dose of NET required when used as a visiting pill could not be reduced below 3.0 mg.

PIP: In Shanghai, China, 45 25-35 year old women took a daily norethisterone (NET) "visiting pill" (vacation pills) on menstrual cycle days 5-18 as part of a clinical study comparing various doses of NET on ovarian function, sex hormone binding globulin (SHBG), and high density lipoprotein-cholesterol (HDL-C). The aim of the study was to determine the lowest effective dose of the NET visiting pill. Even though some ovarian activity occurred at all 3 doses (0.5, 1.5, and 3 mg), no woman experienced ovulation at 3 mg NET/day during days 5-18 of the cycle. It suppressed ovulation in 11 (73.3%) of the 15 women. Follicular activity occurred in the remaining 4 women. Ovulation occurred in 33% of women taking the 1.5 mg dose and in 66% of those taking the 0.5 mg dose. The higher the NET dose, the greater was the fall in mean serum SHBG levels from control levels (3 mg, 23.4%; 1.5 mg, 15.5%; and 0.5 mg, 6.6%). Both the regression equation and log dose regression equation showed a significant correlation between mean serum NET levels and dose (p .001). HDL-C levels remained basically the same as control levels. Since, at the 1.5 mg dose, ovulation occurred in 5 women and only 5 women experienced complete inhibition, a dose no lower than 3 mg should be used for the NET visiting pill.