The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.
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 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone.


RESULTS
As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects.


CONCLUSIONS
The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.
Godsland
I F
IF
Wynn Institute for Metabolic Research, St. John's Wood, London, England.
Crook
D
D
Simpson
R
R
Proudler
T
T
Felton
C
C
Lees
B
B
Anyaoku
V
V
Devenport
M
M
Wynn
V
V
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D050260:Carbohydrate Metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D003279:Contraceptives, Oral, Sequential / Q000494:pharmacology; D017135:Desogestrel; D005040:Ethynodiol Diacetate / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D016912:Levonorgestrel; D050356:Lipid Metabolism; D008875:Middle Aged; D009640:Norethindrone / Q000494:pharmacology; D009644:Norgestrel / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003277:Contraceptives, Oral, Combined; D003279:Contraceptives, Oral, Sequential; D007328:Insulin; D009652:Norpregnenes; D045167:Progesterone Congeners; D014280:Triglycerides; D009644:Norgestrel; D016912:Levonorgestrel; D005040:Ethynodiol Diacetate; D017135:Desogestrel; D002784:Cholesterol; D009640:Norethindrone