Early effects of continuous low-dosage all-norgestrel administered alone or with estrogen

Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either (i) dl-norgestrel alone (0.075 mg/day) continuously for two cycles, (ii) estradiol-17 beta alone (1 mg on 25 of 28 days) for two cycles, or (iii) the combined hormones for six cycles. A placebo control cycle followed each hormonal treatment. Plasma triglycerides decreased by an average 22% during treatment with either dl-norgestrel alone (123 +/- 11 vs. 160 +/- 10 mg/dl, n = 25, P < 0.005) or combination therapy (126 +/- 11 vs. 162 +/- 11, n = 25, P < 0.005) as compared with control. Plasma total cholesterol fell by 5% during two cycles of treatment with either dl-norgestrel alone (229 +/- 11 vs. 242 +/- 10 mg/dl, n = 25, P < 0.02) or combination therapy (233 +/- 11 vs. 246 +/- 10, n = 25, P < 0.05) versus placebo. During the fifth and sixth cycles of combination therapy 94% of cycles were free of flushing (vs. 31% for control, P < 0.01), 64% of cycles were free of spotting not requiring protection (control 75%), 96% of cycles were free of vaginal bleeding (control 100%), endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied, fasting blood pyruvate decreased by 20% (P < 0.05) and diastolic blood pressure fell by 4% compared with control (P < 0.05), whereas glucose tolerance was unchanged. There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy.