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Safety aspects
7.2 Arterial disease
Epidemiological studies have suggested an association
between OCs and arterial disease. As the more androgenic
progestogens have been shown to have a greater adverse
effect on lipid metabolism (with a potential increase in the risk
of arterial diseases such as myocardial infarction and stroke;
Meade et al 1980; Kay 1982), new types of progestogens
were developed with a high level of progestogenic activity, but
substantially reduced androgenic properties.
Risk factors
Etiology
In the population at large, major recognized risk factors for
myocardial infarction (MI) have been identified: age, smoking,
diabetes, hypertension, hypercholesterolemia and a family
history of MI. Some studies, attempting to determine if
women with established risk factors for MI are especially at
risk of this disease while using OCs, have found an interaction
between current OC use and heavy smoking (Rosenberg et al
1990; Croft and Hannaford 1989), and between OC use and
older age (Mann and Inman 1975; Kreuger et al 1980).
The etiology of OC-associated venous thrombosis and
myocardial infarction may differ from each other in an
important aspect. Endothelial damage does not seem to be a
prerequisite for the formation of a venous thrombus (Godsland
and Crook 1996). In contrast, hemodynamic considerations
alone make it unlikely that an arterial thrombus will
accumulate on an entirely intact endothelium. An imbalance in
the normal cycle of arterial endothelial damage and repair, or
the endothelial and intimal lesions seen in OC users, could
result in platelet adhesion and activation and thrombus
accumulation in an apparently normal artery. This process will
be opposed by circulating factors which promote endothelial
integrity, and will be helped along by those factors which
disrupt endothelial function. There are three major candidates
for involvement in these processes: serum triglycerides, HDLcholesterol
and insulin (Godsland and Crook 1996).
Lipoprotein metabolism
Oral contraceptives have effects on a number of the serum
lipoproteins, but the most significant of these effects are
thought to be those on triglycerides and HDL-cholesterol.
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