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Contraceptive hormone use and cardiovascular disease.

ABSTRACT: Contraceptive hormones, most commonly prescribed as oral contraceptives (OCs), are a widely utilized method to prevent ovulation, implantation, and, therefore, pregnancy. The Women's Health Initiative demonstrated cardiovascular risk linked to menopausal hormone therapy among women without pre-existing cardiovascular disease, prompting a review of the safety, efficacy, and side effects of other forms of hormone therapy. A variety of basic science, animal, and human data suggests that contraceptive hormones have antiatheromatous effects; however, relatively less is known regarding the impact on atherosclerosis, thrombosis, vasomotion, and arrhythmogenesis. Newer generation OC formulations in use indicate no increased myocardial infarction risk for current users, but a persistent increased risk of venous thromboembolism. There are no cardiovascular data available for the newest generation contraceptive hormone formulations, including those that contain newer progestins that lower blood pressure, as well as the nonoral routes (transdermal and vaginal). Current guidelines indicate that, as with all medication, contraceptive hormones should be selected and initiated by weighing risks and benefits for the individual patient. Women 35 years and older should be assessed for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other vascular diseases, including migraines, prior to use. Existing data are mixed with regard to possible protection from OCs for atherosclerosis and cardiovascular events; longer-term cardiovascular follow-up of menopausal women with regard to prior OC use, including subgroup information regarding adequacy of ovulatory cycling, the presence of hyperandrogenic conditions, and the presence of prothrombotic genetic disorders is needed to address this important issue.

SUBMITTER: Shufelt CL

PROVIDER: S-EPMC2660203 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Contraceptive hormone use and cardiovascular disease.

Shufelt Chrisandra L CL Bairey Merz C Noel CN

Journal of the American College of Cardiology 20090101 3

Contraceptive hormones, most commonly prescribed as oral contraceptives (OCs), are a widely utilized method to prevent ovulation, implantation, and, therefore, pregnancy. The Women's Health Initiative demonstrated cardiovascular risk linked to menopausal hormone therapy among women without pre-existing cardiovascular disease, prompting a review of the safety, efficacy, and side effects of other forms of hormone therapy. A variety of basic science, animal, and human data suggests that contracepti ...[more]

PMID: 19147038

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Project description:OBJECTIVE:Researchers traditionally rely on participant self-report for contraceptive use. We hypothesized that self-reported contraceptive use by clinical research participants may disagree with objectively measured hormonal status. STUDY DESIGN:We enrolled women in Harare, Zimbabwe, aged 18-34, who by self-report had not used hormonal or intrauterine contraception for >30 days, or depot medroxyprogesterone acetate for >10 months, into a study designed to assess biologic changes with contraceptive initiation and use. Blood samples obtained at enrollment and each follow-up visit (N=1630 from 447 participants) were evaluated by mass spectrometry for exogenous hormones. We individually interviewed a subset of participants (n=20) with discrepant self-reported and measured serum hormones to better understand nondisclosure of contraceptive use. RESULTS:Discrepant with self-reported nonuse of hormonal contraception, synthetic progestogens were detectable in 120/447 (27%, 95% confidence interval 23%-31%) enrolled women. Measured exogenous hormones consistent with use of contraceptive pills (n=102), injectables (n=20) and implants (n=3) were detected at enrollment, with 7 women likely using >1 contraceptive. In-depth interviews revealed that participants understood the requirement to be hormone free at enrollment (100%). Most (85%) cited partner noncooperation with condoms/withdrawal and/or pregnancy concerns as major reasons for nondisclosed contraceptive use. All interviewed women (100%) cited access to health care as a primary motivation for study participation. Of participants who accurately reported nonuse of hormonal contraception at enrollment, 41/327 (12.5%) had objective evidence of nonstudy progestin use at follow-up that disagreed with self-reported nonuse. CONCLUSIONS:Women joining contraceptive research studies may misrepresent their use of nonstudy contraceptive hormones at baseline and follow-up. Objective measures of hormone use are needed to ensure that study population exposures are accurately categorized. IMPLICATIONS STATEMENT:Among Zimbabwean women participating in a contraceptive research study, 27% had objective evidence of use of nonstudy contraceptives at enrollment that disagreed with self-report. Studies that rely on self-report to identify contraceptive hormone exposure could suffer from significant misclassification.

Project description:Epidemiological studies have shown that cardiovascular disease (CVD) is less common in pre-menopausal women (Pre-MW) compared to men of the same age or post-menopausal women (Post-MW), suggesting cardiovascular benefits of estrogen. Estrogen receptors (ERs) have been identified in the vasculature, and experimental studies have demonstrated vasodilator effects of estrogen/ER on the endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several natural and synthetic estrogenic preparations have been developed for relief of menopausal vasomotor symptoms. However, whether menopausal hormone therapy (MHT) is beneficial in postmenopausal CVD remains controversial. Despite reports of vascular benefits of MHT from observational and experimental studies, randomized clinical trials (RCTs), such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women's Health Initiative (WHI), have suggested that, contrary to expectations, MHT may increase the risk of CVD. These discrepancies could be due to agerelated changes in sex hormone synthesis and metabolism, which would influence the effective dose of MHT and the sex hormone environment in Post-MW. Age-related changes in the vascular ER subtype, structure, expression, distribution, and post-ER signaling pathways in the endothelium and VSM, along with factors related to the design of RCTs, preexisting CVD condition, and structural changes in the blood vessels architecture have also been suggested as possible causes of MHT failure in CVD. Careful examination of these factors should help in identifying the causes of the changes in the vascular effects of estrogen with age. The sex hormone metabolic pathways, the active versus inactive estrogen metabolites, and their effects on vascular function, the mitochondria, the inflammatory process and angiogenesis should be further examined. Also, the genomic and non-genomic effects of estrogenic compounds should be viewed as integrated rather than discrete responses. The complex interactions between these factors highlight the importance of careful design of MHT RCTs, and the need of a more customized approach for each individual patient in order to enhance the vascular benefits of MHT in postmenopausal CVD.

Project description:Background and objectivesIn patients with CKD, elevated plasma parathyroid hormone (PTH) levels are associated with greater cardiovascular morbidity and mortality. However, the reference method for PTH measurement is disputed. It has been argued that measurement of nonoxidized PTH better reflects biologically active PTH than measurements with conventional assays.Design, setting, participants, & measurementsPTH and nonoxidized PTH levels were measured at study baseline in 535 patients with CKD with an eGFR range between 89 and 15 ml/min per 1.73 m2. Patients were followed over 5.1 years for the occurrence of acute heart failure, atherosclerotic events, CKD progression (doubling of serum creatinine or initiation of RRT), or all-cause death.ResultsAtherosclerotic events, acute heart failure, CKD progression, and deaths from any cause occurred in 116, 58, 73, and 85 patients, respectively. In Kaplan-Meier analyses, patients at the highest PTH and nonoxidized-PTH tertile (79-543 and 12-172 pg/ml, respectively) showed a higher rate of atherosclerotic events, acute heart failure, CKD progression, and death from any cause. After adjustment for eGFR and albuminuria, nonoxidized PTH was no longer associated with atherosclerotic events (hazard ratio third versus first tertile, 1.04 [95% confidence intervals, 0.62-1.75]), acute heart failure (hazard ratio third versus first tertile, 1.24 [95% confidence intervals, 0.59-2.62]), CKD progression (hazard ratio third versus first tertile, 0.93 [95% confidence intervals, 0.46-1.90]), and death from any cause (hazard ratio third versus first tertile, 1.23 [95% confidence intervals, 0.66-2.31]), and PTH lost its association with atherosclerotic events (hazard ratio third versus first tertile, 0.80 [95% confidence intervals, 0.46-1.38]) and CKD progression (hazard ratio third versus first tertile, 0.99 [95% confidence intervals, 0.46-2.10]), although it remained associated with acute heart failure (hazard ratio third versus first tertile, 2.76 [95% confidence intervals, 1.11-6.89]) and all-cause death (hazard ratio third versus first tertile, 2.35 [95% confidence intervals, 1.13-4.89]). After further adjustment for cardiovascular and kidney risk factors, PTH remained associated with all-cause death (hazard ratio third versus first tertile, 2.79 [95% confidence intervals, 1.32-5.89]), but with no other end point.ConclusionsIn a cohort of patients with CKD, PTH was associated with all-cause mortality; there was no association of nonoxidized PTH with any of the clinical outcomes examined.

Project description:Rationale & objectiveAlthough end-stage kidney disease (ESKD) adversely affects fertility, pregnancies can occur among women receiving dialysis. ESKD increases the risk for adverse pregnancy outcomes and little is known about contraceptive use in women undergoing dialysis.Study designRetrospective cohort study.Setting & participantsUsing the US Renal Data System covering January 1, 2005, through December 31, 2014, we evaluated for each calendar year women who for the entire year were aged 15 to 44 years, receiving dialysis, and with Medicare as the primary payer.PredictorsAge, race/ethnicity, and calendar year of prevalent ESKD.OutcomeContraceptive use.Analytic approachWe determined rates of contraceptive use and used multivariable logistic regression to identify factors associated with contraceptive use.ResultsThe study cohort included 35,732 women and represented 115,713 person-years. The rate of contraceptive use was 5.30% of person-years (95% CI, 5.17%-5.42%). Overall, contraceptive use increased from 2005 to 2014 (4.21%; 95% CI, 3.84%-4.59% vs 6.54%, 95% CI, 6.10%-6.99%). Compared with women aged 25 to 29 years, contraceptive use was higher in women aged 15 to 24 years (OR, 1.30; 95% CI, 1.18-1.43) and lower in women aged 30 to 34 years (OR, 0.74; 95% CI, 0.68-0.81), 35 to 39 years (OR, 0.46; 95% CI, 0.42-0.50), and 40 to 44 years (OR, 0.30; 95% CI, 0.27-0.34). Compared with White women, contraceptive use was higher in Black (OR, 1.12; 95% CI, 1.02-1.24) and Native American women (OR, 1.60; 95% CI, 1.25-2.05). Women with ESKD due to glomerulonephritis had a higher likelihood of contraceptive use than women with ESKD due to diabetes (OR, 1.22; 95% CI, 1.06-1.42). Women receiving peritoneal dialysis had a lower likelihood of contraceptive use than women receiving hemodialysis (OR, 0.85; 95% CI, 0.78-0.93). Compared with women without predialysis nephrology care, contraceptive use was higher in women who received predialysis nephrology care for 12 or fewer months (OR, 1.22; 95% CI, 1.09-1.37) and more than 12 months (OR, 1.33; 95% CI, 1.20-1.47).LimitationsRetrospective design and use of administrative data.ConclusionsAmong women with ESKD undergoing dialysis, contraceptive use remains low at 5.30%. Younger age, Native American and Black race/ethnicity, ESKD due to glomerulonephritis, hemodialysis, and predialysis nephrology care are associated with a higher likelihood of contraceptive use. The study highlights the importance of prepregnancy counseling for contraceptive use in women receiving dialysis.

Project description:Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD.We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-related surgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs).We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) for past users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (Ptrend = .036) and higher prescribed daily dose (Ptrend = .016). Specifically, for women with more than 3 years of OC use, the MV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients who have not taken OCs (all Pcomparisons > .20).In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD.

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Contraceptive hormone use and cardiovascular disease.

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Contraceptive hormone use and cardiovascular disease.

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