Oral contraceptives (OC) are among the most frequently used drugs in the world with approximately 100 million women worldwide taking OC. In contrast to the active controversy surrounding hormone replacement therapy, little attention has been focused on OC, a drug therapy taken by far more women for far longer time periods. We describe the population effects of current and long-term OC exposure on a prognostically well validated marker of arterial stiffness: carotid-femoral pulse wave velocity (PWV). The Asklepios study is a representative sample (2524 apparently healthy M/F volunteers, aged 35–55 years, 1301 women) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened (biochemistry, lifestyle, cardiac and vascular echography, arterial tonometry). PWV was measured from flow patterns registered by Doppler echography in the femoral and carotid arteries. Of 1301 women (median age 45.7 y), 27.4% were actively taking OC. In contrast past use of OC is far more prevalent with 81% of women having taken OC for at least 1 year. The median duration of exposition in these women was 13 years. Age-adjusted PWV was higher in women currently taking OC: 6.75 versus 6.55 m/s (difference 0.19 ± 0.09 m/s; p = 0.034). However, current OC users also had higher blood pressures (BP): systolic BP (+4.4 ± 0.9 mmHg; p < 0.001), diastolic BP (+2.3 ± 0.6 mmHg; p < 0.001). After adjustement for BP, the difference in PWV between current OC users and non-users became non-significant: 6.60 versus 6.62 m/s (difference 0.02 ± 0.09 m/s; p = 0.814). In contrast, duration of OC use is a significant determinant of PWV, even after adjustement for age, BP, lipid levels, body size, heart rate, drug therapy (lipid-lowering, antihypertensive), glycemic status and smoking: F = 6.1; p = 0.013. Per 10 years of OC exposure PWV increased by 0.1 m/s (0.02– 0.18; p = 0.013). Use of OC is associated with increased vascular stiffness in women. Current use is associated with increased PWV because OC’s increase blood pressure, long-term use (probably through structural remodelling of the vessels) is an independent determinant of PWV, increasing PWV by 0.10 m/s per 10 years exposure.
oral contraceptives arterial stiffness long-term cardiovascular risk, pulse wave velocity oral contraceptive use women, long-term oral contraceptive use vascular remodeling stiffness, OC exposure carotid-femoral pulse wave velocity population study, oral contraceptive blood pressure arterial stiffness independent risk, Asklepios study oral contraceptive cardiovascular effects, Rietzschel oral contraceptive arterial stiffness Belgian population, hormonal contraception vascular stiffness dose duration, oral contraceptive independent predictor PWV adjusted analysis, long-term OC use structural vascular changes women
DOI 10.1161/circ.118.suppl_18.S_803-d 10.1161/circ.118.suppl_18.S_803-d
Cite this article
Rietzschel, E., De Buyzere, M., Segers, P., Bekaert, S., De Bacquer, D., De Backer, G., & Gillebert, T. (2008). Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening. Circulation, 118(suppl_18). https://doi.org/10.1161/circ.118.suppl_18.S_803-d
Rietzschel E, De Buyzere M, Segers P, Bekaert S, De Bacquer D, De Backer G, et al. Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening. Circulation. 2008;118(suppl_18). doi:10.1161/circ.118.suppl_18.S_803-d
Rietzschel, E., et al. "Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening." Circulation, vol. 118, no. suppl_18, 2008.
Over 100 million women currently use oral contraceptive pills (OCPs) worldwide. However, little is known about the effects of OCPs on arterial stiffness and hemodynamics. Furthermore, whether arterial stiffness and hemodynamics vary throughout the natural menstrual cycle remains controversial. Herein, we estimated the effect of the natural menstrual cycle and OCP use on arterial stiffness and hemodynamics. Healthy, nonsmoking women, aged 18-30 years, were recruited if they had regular menstrual cycles and never used OCPs (OCP nonuser group), or were using low-dose OCPs for at least 6 months (OCP user group). Using applanation tonometry, three assessments of arterial stiffness and central and peripheral hemodynamics were performed during the early follicular (days 3-6), late follicular (days 14-16), and luteal (days 22-26) phases. Within group and between group comparisons were performed using general linear models. Sixty women (21.7 ± 2.8 years) were recruited. Compared with OCP nonusers, OCP users had significantly increased aortic and peripheral SBPs during the active OCP use, but not during the inert tablet phase. No differences in arterial stiffness were noted. OCP use was associated with significant increases in aortic and peripheral blood pressures, but not with increased arterial stiffness. Given the widespread OCP use, future longitudinal studies are needed to confirm our findings and assess the long-term effect of OCPs on arterial stiffness and hemodynamics.
EndometriosisInflammatory MarkersStaging and TypologyCytokine Profiling
Endometriosis, affecting 11% of reproductive-aged persons, is characterized by ectopic endometrial tissue and chronic inflammation. Prior research suggests those with endometriosis have higher cardiovascular disease risk, but mechanisms remain elusive. The objective of this study is to assess whether endometriosis diagnosis, staging, and typology (superficial endometriosis (SE), ovarian endometriomas (OE), and deep infiltrating endometriosis (DE)) are associated with serum interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-) concentrations. The study analyzed data from 395 premenopausal persons in Utah undergoing gynecologic laparoscopy who participated in the NICHD ENDO study (2007–2009). Post-operative reports determined endometriosis typology (SE, OE, DE) and staging (minimal, mild, moderate, severe) using Revised American Society for Reproductive Medicine classification. Elevated serum cytokine concentrations were defined as IL-6 ≥2pg/mL, IL-8 ≥3pg/mL, and TNF- ≥7.5pg/mL. Generalized linear models generated adjusted prevalence ratios (aPR) 95% CI controlling for age, BMI, marital status, race/ethnicity, and serum cotinine. Participants were on average 32 years (SD=7) at time of gynecologic laparoscopy/laparotomy, non-Hispanic white (79%), married (71%), mean BMI 28 (SD=8) and non-smokers (83% serum cotinine <10ng/mL). Forty-two percent (n=166) were diagnosed with incident endometriosis. We found no differences among those with, compared to without, endometriosis and elevated IL-6, 12% vs 10%, 1.01 (0.97, 1.10), IL-8, 5% vs 8%, 0.99 (0.94, 1.04); and TNF, 16% vs 13%, 1.00 (0.96, 1.04). While there were no statistically significant associations between endometriosis staging or typology and cytokines, those with moderate to severe endometriosis had nonsignificant lower IL-6 and IL-8 (aPR: 0.61 [0.15, 2.52] 0.74 [0.17, 3.20]) but higher TNF- (aPR: 1.27 [0.56, 2.84]), compared to no endometriosis. Individuals with OE and DE had nonsignificant trends of IL-6 and Il-8 (aPR: 0.86 [0.11, 2.52] 0.93 [0.14, 6.43]) but higher TNF- (aPR: 1.93 [0.77, 4.84]). In summary, this study found no clear correlation between endometriosis diagnosis, staging, typology and inflammatory markers IL-6, IL-8, and TNF-. Whether endometriosis severity or typology is associated with TNFshould be explored in future studies with adequate power and more representative samples.
EndometriosisCardiovascular RiskStaging and TypologyLipid Biomarkers
Individuals with endometriosis, a gynecologic condition affecting approximately 11% of people with a uterus, may have an elevated risk for developing cardiovascular disease (CVD) later in life. However, the mechanisms underlying this association are not well understood. We investigated the association between incident endometriosis diagnosis, staging, and typology and lipid biomarkers measured at time of diagnostic surgery among women participating in the NICHD ENDO study (n=395). Endometriosis was categorized using the American Society for Reproductive Medicine staging (I−IV). Endometriosis typology was defined by lesion depth and location and categorized as superficial endometriosis (SE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DE). With no endometriosis as our reference, we evaluated the associations between endometriosis diagnosis, stage (I/II vs III/IV), and typology (SE, OE, DE, OE+DE) and dyslipidemia using standard clinical thresholds (total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, Apolipoprotein A-1 (APO-A1) <125 mg/dL, Apolipoprotein B (APOB) ≥120 mg/dL; APOB/APO-A1 ratio >0.78). We calculated adjusted prevalence ratios (aPR) and 95% CIs via generalized linear models, controlling for age, race/ethnicity, marital status, BMI, income (poverty level), and serum cotinine as a marker of smoking. At the time of gynecologic surgery, individuals were mean 32 years (SD: 7 years), non-Hispanic white (79%), married (71%), and mean BMI 28 (SD=8). While we found no differences in endometriosis diagnosis or endometriosis staging and dyslipidemia (
Figure 1; Table 1
), a pattern emerged regarding endometriosis typology (
Table 2
). Women with OE+DE, compared to no endometriosis, had increased total cholesterol >200 1.87 (0.99, 3.57); >
175 2.48 (1.34, 4.57); VLDL ≥30 2.08 (1.28, 3.38); and APOB mg/dL ≥120: 2.86 (1.22, 6.66). OE appeared to be driving this association. SE was not associated with dyslipidemia. The association between endometriosis, especially of more severe typology, and subsequent CVD may be through dyslipidemia, which may be detectable at the time of endometriosis diagnosis. Further research in larger, more representative samples is needed before definitive conclusions can be made.
Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.