Myocardial Infarction and Stroke It is now established that in addition to increasing the risk of venous thromboembolic disease, oral contraceptives increase the risks of myocardial infarction, thrombotic stroke, and hemorrhagic stroke.11 (Some recent data suggest that oral contraceptives may also increase the risk of other forms of cardiovascular disease,17 but the findings are inconclusive and are therefore not considered in this review.) Vital statistics and epidemiologic studies in Great Britain and the United States show that among nonpregnant women of reproductive age who are not using oral contraceptives, the risks of myocardial infarction and stroke (of both categories) increase . . .

Oral contraceptives and cardiovascular disease (first of two parts).

Background. Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. Methods. We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 μg), high (250 μg), and triphasic (50 to 125 μg) doses; norethindrone in low (500 μg), high (1000 μg), and triphasic (500 to 1000 μg) doses; and a new progestin, desogestrel, in one dose (150 μ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199011153232003

The Effects of Different Formulations of Oral Contraceptive Agents on Lipid and Carbohydrate Metabolism

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.

Effect of Estrogen/Progestin Potency on Lipid/Lipoprotein Cholesterol

Estrogen: a master regulator of bioenergetic systems in the brain and body.

Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions

Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism.

Analysis of high density lipoprotein subclasses by a precipitation procedure: comparison with preparative ultracentrifuge.

Clinical comparative research was carried out in order to determine the effects on carbohydrate and lipid metabolism of synthetic gonadal steroids administered alone and in various combinations. 496 premenopausal Caucasian women were studied before and during the use of OCs (oral contraceptives) so that each woman was her own control. They were divided into groups according to the OC preparation being taken. None of the observed changes in the metabolic parameters correlated with the duration of OC usage. Estrogen usage exerted significant metabolic effects but only in the fasting state. The effects of pregnane and nortestosterone derived (estrane and gonane) progestagens given alone were also limited to the fasting state. Estrogens lowered the fasting plasma glucose and elevated the fasting pyruvate and triglyceride levels; pregnane progestagen raised the fasting pyruvate levels; estrane-gonane progestagens lowered fasting pyruvate triglyceride and cholesterol levels. None of the preparations altered oral glucose tolerance or insulin responses. In combination preparations estrogenic effects were antagonized by estrane and gonane progestagens but not by a pregnane progestagen. The ideal OC should contain 30-35 mug estrogen combined with less than 1 mg of an estrane progestagen in order to reduce possible metabolic side effects.

R. Niththyananthan

Papers

Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism.

Analysis of high density lipoprotein subclasses by a precipitation procedure: comparison with preparative ultracentrifuge.

The influence on oral contraceptive formulation on carbohydrate and lipid metabolism.

High density lipoprotein subfraction cholesterol in hypertriglyceridaemia.