Apple data: Irregular menstrual cycles may predict cardiometabolic risk

Key takeaways:

• Irregular menstrual cycles with or without polycystic ovary syndrome are associated with increased cardiometabolic risk.
• Data suggest menses history is a vital sign for health.

Women reporting irregular menstrual cycles with or without diagnosed polycystic ovary syndrome are more likely to have cardiometabolic conditions such as diabetes and hypertension, according to new data from the Apple Women’s Health Study.

In an analysis of more than 60,000 women who reported menstrual cycle and other hormone-related data via the Apple research app, researchers also found that longer time to menstrual cycle regularity since menarche was associated with a higher prevalence of several cardiometabolic conditions. Women with longer time to cycle regularity also tended to be younger at diagnosis of cardiometabolic conditions.

“These data show that just having a persistently irregular cycle — for whatever reason — is enough to have a manifestation of cardiometabolic risk,” Shruthi Mahalingaiah, MD, MS, FACOG, assistant professor of environmental, reproductive and women’s health at the Harvard T.H. Chan School of Public Health, told Healio. “The flavors are a little different depending on the condition, but persistently irregular cycles need additional attention during the clinical encounter to assess and address risk for cardiovascular disease. The goal is to be sensitive to the menstrual cycle as a vital sign and discuss very basic risk reduction options, which need to be individualized. Clinically, we also need to understand and treat what might be contributing to women’s irregular cycles.”

Collecting menstrual data with smartphones

Shruthi Mahalingaiah

As Healio previously reported, Apple partnered with the Harvard T.H. Chan School of Public Health and the NIH’s National Institute of Environmental Health Sciences to create the first long-term study on a large scale focused on menstrual cycles and gynecologic conditions. The Apple Women’s Health Study, using the capabilities of the Apple Watch, will inform screening and risk assessment of women’s health conditions, such as PCOS, infertility, osteoporosis, pregnancy and menopausal transition.

For the cross-sectional study, researchers analyzed data from 60,789 U.S. women enrolled in the Apple Women’s Health Study from November 2019 to December 2022. The mean age of participants was 34.5 years. Participants completed a demographic survey and at least one of four other surveys assessing medical and reproductive history, hormonal symptoms and general health and lifestyle. PCOS status was based on self-reported physician diagnosis at enrollment. Researchers assessed prolonged time to menstrual regularity with the question, “After your first menstrual cycle, how long did it take for your cycle to become regular?” and defined “prolonged” as more than 5 years, after using hormones or reporting continued cycle irregularity.

“This is a comprehensive look at irregular cycles and ovulatory disorders, as much as we could phenotype in this cohort,” Mahalingaiah said during an interview. “It was mostly focused on PCOS because we have a specific question on it, but also looking at other ovulatory disorders that can sometimes get mixed in. One is hypothalamic amenorrhea and another premature ovarian insufficiency. Those are much harder to determine in a large cohort without clinic appointments and a blood test.”

The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and type 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, myocardial infarction, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis and pulmonary embolism.

The findings were published in JAMA Network Open.

‘Menstrual cycles should be addressed, discussed’

Within the cohort, 12.3% of participants had diagnosed PCOS and 26.3% reported prolonged time to menstrual regularity. Among a subset of 25,399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles.

Researchers found that diagnosed PCOS was associated with a higher prevalence of all metabolic and several CV conditions, including arrhythmia (OR = 1.37; 95% CI, 1.2-1.55), coronary artery disease (OR = 2.92; 95% CI, 1.95-4.29), myocardial infarction (OR = 1.79; 95% CI, 1.23-2.54), and stroke (OR = 1.66; 95% CI, 1.21-2.24).

Among the 37,707 participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (OR = 1.24; 95% CI, 1.05-1.46), hypertension (OR = 1.09; 95% CI, 1.01-1.19), arrhythmia (OR = 1.2; 95% CI, 1.06-1.35), and TIA (OR = 1.33; 95% CI, 1.01-1.73). Similarly, women without PCOS but reporting irregular cycles were more likely to have type 2 diabetes (OR = 1.36; 95% CI, 1.08-1.69), high cholesterol (OR = 1.17; 95% CI, 1.05-1.3), arrhythmia (OR = 1.21; 95% CI, 1.02-1.43), and TIA (OR = 1.56; 95% CI, 1.06-2.26).

“Our goal was to share that taking a look at menstrual cycle patterns within the context of PCOS, but also more broadly looking at any irregular menstrual cycles, should be addressed, discussed and perhaps evaluated further with an eye toward long-term health,” Mahalingaiah told Healio. “Historically, the menstrual cycle was not something to discuss outside of the OB/GYN visit. This research shows menses is a very important vital sign for half the population. There are major cardiometabolic implications. Some may need cardiologist intervention or support. Unfortunately, by that time, we have missed our opportunity for prevention.”

Mahalingaiah said enrollment continues to be open for the Apple Women’s Health Study and more analyses are ongoing.

Reference:

Apple Women’s Health Study. Available at: https://www.hsph.harvard.edu/applewomenshealthstudy/. Accessed May 13, 2024.

For more information:

Shruthi Mahalingaiah, MD, MS, FACOG, can be reached at shruthi@hshp.harvard.edu.