Oral Contraceptives Increase C-Reactive Protein, An
Inflammatory Biomarker
New study results offer
potential explanation of complications from birth control pills
April 9, 2003 (San Diego, CA) – When women think
about birth control, estrogen, and cardiovascular risk, they often assume
that there are no answers. They would appear to be correct.
On the one hand, new pharmacological advancements have
provided combination oral contraceptive (OC) formulations with lower-dose
estrogen. These formulations have significantly less risk of cardiovascular
adverse events compared to the older combined formulations with higher
doses. They also provide excellent cycle control, a low incidence of
breakthrough bleeding and spotting, and increased patient satisfaction.
On the other hand, the current generation progestins
appear less safe than earlier formulations with respect to the risk of blood
clotting. Moreover, recent studies have associated current oral
contraceptive use with risks for ischemic stroke and myocardial infarction,
impaired blood anticoagulant pathways, and increased cardiovascular
reactivity. Thus, cardiovascular risk relating to consumption of oral
contraceptives still remains.
C-reactive protein (CRP) is
a protein in the body whose level increases when blood vessels become
inflamed. Measuring cardiovascular risk is thought to be possible by
assessing CRP levels. Previously published data has shown that blood levels
of CRP are elevated many years before a first heart attack or stroke occurs.
Accordingly, a team of researchers set out to investigate the
association between current low-dose oral contraceptives and levels of
plasma CRP.
A New Study
The authors of “Oral Contraceptive Use and Increased
Plasma Concentration of C-reactive Protein” are Darlene M Dreon, DrPH;
Joanne L Slavin, PhD; and Stephen D Phinney, MD, PhD, from Galileo
Pharmaceuticals, Inc, Santa Clara, CA and the University of Minnesota, St.
Paul, MN. They will present their findings at the American Physiological
Society’s upcoming conference, Experimental Biology 2003, being held
April 11-15, 2003, at the San Diego Convention Center, San Diego, CA.
Background
In a previously published study, investigators used an
insensitive, non-quantitative immunoprecipitation technique capable of
identifying CRP levels above the current normal range. That study reported
the presence of CRP in more than half of women using first generation
combined or sequential oral contraceptives of the 1960s. Among women using
the then “low dosage” progestin oral contraceptives, the study found no
difference in the prevalence of positive serum CRP between this class of OC
users versus nonusers.
Given the current availability of the high sensitivity
CRP test, it is possible to assess the effects of current low dose oral
contraceptives on this biomarker for cardiovascular disease risk. The
researcher team involved in the current study measured the levels of CRP in
otherwise healthy, young adult women according to the following methodology.
Methodology
CRP levels were measured
using stored samples from 30 healthy, premenopausal women who had
previously participated in a randomized, crossover study of the effects of
soy intake on sex hormone metabolism in women using OCs and non-users. The
study was sited at a university outpatient general clinical research
center.
Participants (women aged 18-40 years of age) consumed
their habitual diet or a soy-enriched diet for two menstrual cycles each.
(Soy consumption had no effect on sex hormone metabolism in OC or non-OC
users.) Non-OC users were trained in basal body temperature charting and
ovulation testing for verification of follicular and luteal phases. Serum
progesterone concentrations were used to confirm ovulation. Four fasting
blood samples and 24-hour urine (two mid-follicular and two mid-luteal) were
collected from each participant over two menstrual cycles and were stored at
–700C until laboratory analysis. OC users provided
fasting blood samples on days 8 and 22 after menses. Plasma samples were
later thawed and assayed for CRP by use of a high-sensitivity assay.
Results
There were no significant differences in baseline
demographic characteristics between oral contraceptive users and nonusers.
Plasma CRP levels were two times higher among OC users than among non-users
independent of diet assignment, diet treatment order, and phase of the
menstrual cycle. In a multivariate model, OC use predicted 32 percent of
the variance in CRP levels. As all CRP levels were within a previously
established normal range, further study is indicated to establish the
clinical significance of the observed elevated CRP levels in OC users.
Conclusions
The results from this research and past studies suggest
that estrogenic hormones significantly affect pro-inflammatory pathways.
Whether these changes have clinical significance remains to be determined.
The present data also showed that CRP levels are higher in the luteal, or
post-ovulatory phase, versus the follicular phase. This association was
more pronounced in OC users than non-users.
This cross-sectional survey demonstrates that CRP
levels are significantly increased among OC users versus non-users. The
possibility that these results are due to chance or confounding variables
cannot be excluded entirely, and the results need to be confirmed by larger
independent studies. The researchers suggest that the impact of OC use on
CRP and inflammatory parameters should be investigated in prospective
trials.
-end-
The American
Physiological Society (APS) is one of the world’s most prestigious
organizations for physiological scientists. These researchers specialize in
understanding the processes and functions underlying human health and
disease. Founded in 1887 the Bethesda, MD-based Society has more than
10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals
each year.
***
Editor’s
Note: For receive a copy of the abstract, or to schedule an interview with a
member of the research team, please contact Donna Krupa at 703.967.2751
(cell), 703.527.7357 (office) or at
djkrupa1@aol.com.
