Long-term profile of a new progestin

Abstract

Major complications attributable to oral contraceptives (OCs) may occur in the circulatory system. The inherent risk factors, such as race and family history, are unchangeable. Others may be altered by patient counseling and subsequent adjustment of certain behaviors. Hypercoagulability is estrogen dose related. Older, high-dose-estrogen OC users were at 40% increased risk of mortality from thromboembolic phenomena. Reduction in estrogen content has unmasked the androgenic effects of some synthetic progestogens. These effects may include progression of atherogenesis, effected through changes in cholesterol and lipoproteins; reduction in sex hormone binding globulin (SHBG), which enhances the androgenic effect; and changes in carbohydrate metabolism. This review of clinical findings is based on four studies; three had prospective cohort designs, and one was a prospective randomized comparison of a norgestimate-containing OC with a norgestrel-containing one. Numbers of subjects ranged from 20 to 59,701; the largest evaluated 343,348 cycles of treatment. Study intervals were from 4 to 24 months. The findings reported here are from the individual studies. 1. The normal value for cholesterol is less than 200 mg/dL. Of 2,197 women who met this cut-off point, 95% remained below it after 6 months of treatment. Of 756 who initially exceeded this value, 25% were below after 6 months and 75% remained above it. All studies to date have demonstrated that norgestimate produces consistent and significant elevations in high-density lipoprotein levels and variable change in low-density lipoproteins. A similar effect was noted on serum triglyceride values.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: 4 studies involving a combined oral contraceptive devised with norgestimate as the progestin and low-dose ethinyl estradiol as the estrogen, designed to have virtually no androgenic effects, are reviewed. A study of lipid metabolism found that cholesterol rose above desirable limits of 200 mg/dl in only 5% of women and fell within these limits in 25% who surpassed it. Similarly, triglycerides rose above 150 mg/dl in 5% with normal levels and fell in 28% who initially had high levels. 2 other studies documented increases in HDL and decreases in LDL, improving the HDL/LDL ratio. Coagulation factors were followed in a small series: no adverse effects on fibrinopeptide A, antithrombin III, protein C, Fibrinogen, factor VII, or factor VIII were seen in 6 months. No significant changes in mean levels of fasting glucose, insulin, hemoglobin A1C, or glucose tolerance were found. 2% of 2738 women developed abnormal fasting glucose levels after 6 months, while 35% lowered their initially abnormal glucose levels into the normal range after 6 months on the combined pill. Androgenicity was assessed by sex hormone binding globulin (SHBG) and free testosterone levels. The norgestimate pill elevated SHBG about 3-fold, lowering free testosterone. The prevalence of acne in norgestimate pill users is 2%. No change was noted in average blood pressure or weight. Similar results have been reported in studies on a triphasic norgestimate formulation. These results are optimistic for beneficial effects on major risk factors for cardiovascular disease, but large longterm epidemiological studies will have to be done to confirm them.