A two-year clinical study of the effects of two triphasic oral contraceptives on plasma lipids.
OBJECTIVE
Oral contraceptive formulations can alter plasma lipid and lipoprotein levels; however, lower-dose triphasic tablets show only minimal metabolic effects during 6 or 12 cycles of use. Involvement of lipids in chronic cardiovascular conditions, plus long-term use of oral contraceptive tablets, prompted this first 24-cycle study of the effect of triphasic formulations on young women.


METHODS
69 women assigned randomly to an ethinyl estradiol/levonorgestrel formulation (Triphasil) or an ethinyl estradiol/norethindrone formulation (Ortho 7/7/7) and 25 control women (no hormonal contraception) had blood sampled for lipids and lipoproteins pre-trial, and at 3- or 6-cycle intervals for 24 cycles.


RESULTS
At cycle 24, control women experienced no significant change from baseline in any variable except apolipoprotein B (apo B). Plasma apo B increased 42% (P < .01), reflecting the LDL apo B increase (42%, P < .01). Both combination formulations significantly increased apo B (plasma, VLDL, IDL and LDL); the increases ranged between 47% and 84%. Plasma apo A1 rose (15%, P < .001) in the Ortho 7/7/7 group only. Plasma and LDL triglycerides were increased significantly (P < .001) by the norethindrone product, 43% and 81%, respectively, and plasma and LDL cholesterol, 14% and 28%, respectively. Cholesterol decreased in all other subfractions, including HDL (11%, P < .01). HDL cholesterol decreased significantly in the Triphasil group (8%, P < .05); no other cholesterol subfractions changed significantly. All cycle-24 lipid and lipoprotein values remained well within respective normal ranges.


CONCLUSIONS
Although 2-year exposure to the triphasic oral contraceptive formulations changed the lipid risk factors for cardiovascular disease only within normal ranges, there remains potential for long-term health effects when compounded with other risk factors.
Kakis
G
G
Bay Centre for Birth Control, University of Toronto, Ontario, Canada.
Powell
M
M
Marshall
A
A
Woutersz
T B
TB
Steiner
G
G
D000293:Adolescent; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D019304:Ethinyl Estradiol-Norgestrel Combination; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000187:drug effects; D009640:Norethindrone / Q000494:pharmacology*; D009644:Norgestrel / Q000494:pharmacology*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D003280:Contraceptives, Oral, Synthetic; D004338:Drug Combinations; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C020416:norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; D009644:Norgestrel; D004997:Ethinyl Estradiol; D019304:Ethinyl Estradiol-Norgestrel Combination; D002784:Cholesterol; D009640:Norethindrone