Women on the Pill Have Comforting CVD Outcomes Years Down the Line

Reassuringly, a history of oral contraceptive use had no deleterious effects on cardiovascular disease (CVD) and survival over long-term follow-up, a U.K. Biobank study showed.

In a comparison between women who have used the pill and never-users, oral contraceptives were even linked to apparent reductions in CVD events and all-cause mortality over a median 11.8 years:

• All-cause mortality: 3.2% vs 5.9% (adjusted HR 0.92, 95% CI 0.86-0.99)

• Incident CVD: 5.8% vs 10.6% (adjusted HR 0.91, 95% CI 0.87-0.96)

• Coronary heart disease: 2.8% vs 5.1% (adjusted HR 0.88, 95% CI 0.81-0.95)

• Heart failure: 0.8% vs 2.0% (adjusted HR 0.87, 95% CI 0.76-0.99)

• Atrial fibrillation: 2.0% vs 4.3% (adjusted HR 0.92, 95% CI 0.84-0.99)

Prevention of these events was greater in people with more years of oral contraceptive use. On the other hand, there were no significant associations with CVD death, myocardial infarction, or stroke after adjusting for traditional risk factors, reported Huijie Zhang, MD, PhD, of Nanfang Hospital, Southern Medical University, in Guangdong, China, and colleagues.

“These findings provide significant public health insights and may facilitate a shift in public perception because OC [oral contraceptive] use is common in women of reproductive age, and previously negative publicity exists about the safety of OC use,” Zhang’s group wrote in the Journal of the American Heart Association.

The authors urged further investigation into dose-response associations between oral contraceptives and CVD outcomes, and the effects of specific formulations — both of which were not possible with their limited dataset. Prior studies assessing the link between oral contraceptives and cardiovascular events had yielded conflicting results, which may be related to the specific formulations.

C. Noel Bairey Merz, MD, of Cedars-Sinai Medical Center in Los Angeles, commented that the women in the study were likely using third- and fourth-generation oral contraceptives — the latter considered “not as ‘safe’ during active use with regard to thrombosis.”

Notably, Zhang’s team did not assess venous thromboembolic events, which have been more consistently tied to estrogen-based oral contraceptives, particularly among women who also smoke.

“It’s important to note that not all types of birth control pills are created equal and depending on the estrogen dose and type of progestin, may carry a slightly higher risk of clots compared with older formulations. Furthermore, cardiovascular risk when considering oral contraceptive pills remains individualized based on risk factors and lifestyle, and preference of contraceptive options,” said Chrisandra Shufelt, MD, MS, of Mayo Clinic in Jacksonville, Florida, who was not involved with the study.

Nevertheless, Shufelt told MedPage Today, the present study results are reassuring regarding the cardiovascular safety of contraceptive pills.

“I think this is really reassuring and that women who desire OC use, whether for conception or other health issues like polycystic ovary syndrome/endometriosis, can be reassured about the lack of signal for harm (and even a signal for benefit),” agreed Erin Michos, MD, MHS, of Johns Hopkins University School of Medicine in Baltimore, in an email comment.

Michos stressed that pregnancy is itself a high-risk condition, and “if pregnancy is not desired, women of reproductive age should have access to a full range of options for pregnancy avoidance and the safety data for contemporary OCs expands their indications to more women.”

The CDC estimates that 14% of women ages 15-49 are currently using oral contraceptives. These pills became more accessible in July 2023, when the FDA approved the first over-the-counter oral contraceptive: the norgestrel product Opill containing no estrogen.

For their cohort study, Zhang and colleagues identified 161,017 female U.K. Biobank participants (mean age 53.5 years, 93.2% of whom were white) who had no CVD when recruited in 2006-2010. Excluded were women on hormone replacement therapy.

Overall, 81.4% of the cohort self-reported ever using any oral contraceptive at baseline. Compared with never-users, this majority tended to be younger, had a lower body mass index, and were more likely to be current smokers and drinkers; they also had lower odds of hypertension and diabetes and tended to be taking less aspirin, antihypertensives, and lipid-lowering medication.

The study authors acknowledged the potential for residual confounding and reverse causality in the retrospective, observational analysis.

Michos suggested the possibility of confounding by indication, as women at higher risk for CVD might have been discouraged from using oral contraceptives.

“While this data found longer use may provide more protection, it is possible that those that benefit are women taking the pill for reproductive conditions that result in ovulatory dysfunction such as functional hypothalamic amenorrhea and polycystic ovarian syndrome,” Shufelt added. “Birth control pills in those conditions would therefore provide estrogen to a woman that would otherwise have disruptive and inconsistent levels.”

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