Levonorgestrel, Pharmacokinetics, Efficacy and Safety 55compared with the LNG group [128]. Another study of 80 healthy women
randomized into groups of 3 mg of drospirenone combined with a 30-, 20-, or
15 - μg dose of EE found that systolic blood pressure at 6 months fell by a range
of 1 to 4 mm Hg across the groups, compared with an elevation of blood
pressure of 4 mm Hg in the control group of LNG/ [129]. Additionally, there
was a weight loss of 0.8 to 1.7 kg in the groups receiving the drospirenone
compared with an increase in weight in the LNG/EE group by 0.7 kg.
Glucose Tolerance and Diabetes Mellitus: Contraceptive hormones can
also impact glucose tolerance and diabetes mellitus. Oelkers et al. [129]
studied glucose levels in 80 healthy women assigned to 4 equal groups who
received 3 mg of drospirenone combined with 30-, 20-, and 15-μg doses of EE
or LNG/30-μg EE. Each woman performed oral glucose tolerance tests at the
pre-treatment and at the end of the 6-month OCP cycle. On treatment, fasting
glucose was unchanged for all groups, but the area under the curve for the
glucose tolerance increased for all formulations. Although not statistically
significant between groups, the drospirenone/30-μg EE group had a 19%
worsening of glucose tolerance [129]. No worsening of diabetes has been
demonstrated with the earlier generation OCPs [130, 131].
Contraceptive use in the past in younger and perimenopausal women has
not shown any increased risk of cardiovascular disease. The Nurses' Health
Study, an 8-year self-report prospective study did not find increased risk of
cardiovascular diseases among past users of OCPs compared with those who
had never used OCPs [132]. Among current OCP users, however, there was a
2.5 relative increased risk of adverse cardiovascular events [132]. The increase
in cardiovascular deaths and nonfatal MI and stroke in current users but not
with past use was believed to be associated with the prothrombotic effects.
Stopping OCPs was associated with a declined risk of adverse cardiovascular
events, with an RR of 0.95 (95% CI: 0.81 to 1.11) among past users,
suggestive of a reversal of the OCP prothrombotic effects with cessation of
use. Two separate case-control studies evaluated the association between OCP
use and MI, based on the second- and third-generation preparations with
differing progestins and reached varying conclusions [133, 134].
In a meta-analysis which included 24 studies oral contraceptive pill users
were not found to be at increased at increased risk of myocardial infarction or
ischemic stroke compared with non-users (OR 1.0, 95% CI 0.9 to 1.0). The
risk did not vary according to the generation of progestagen or type of the
progestagen type. The risk of myocardial infarction or ischemic stroke
appeared to increase with the usage of higher doses of estrogen. The risk of
myocardial infarction or ischemic stroke was only increased in women taking