Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. It affects 8-13% of women worldwide and approximately 5 million women in the United States. PCOS was first described over 80 years ago as a gynecological disorder, characterized by irregular menses and high testosterone levels. Research conducted over the last few decades has made it clear that PCOS is a chronic, sometimes debilitating condition, associated with increased risk for heart disease, mental health disorders and uterine cancer. Although the diagnosis is usually established in adolescence and early adulthood, the different manifestations and complications—such as diabetes, high blood pressure, high cholesterol and obesity—need management throughout life. The personal and societal burden of PCOS is tremendous, and the annual economic burden was estimated at $8 billion US dollars in 2020. Unfortunately, there is significant dissatisfaction amongst patients regarding counselling about long-term complications, especially related to heart disease. Additionally, there is inadequate research that examines the risk of heart disease taking into consideration important factors such as common medications used to manage PCOS. The two most common medications are hormonal contraceptive pills used to regulate menstrual cycles and decrease testosterone levels, and metformin, a medication used to treat insulin resistance. These medications are commonly prescribed for long durations of time and there is no clear information about their impact on cardiovascular risk factors and more serious complications such as heart attack and stroke. Heart disease is the number one cause of death in women, and any interventions that impact heart disease are of great relevance to patients, providers, insurers and health systems.
The objectives of this study are to compare the risk of heart disease in women with PCOS prescribed oral contraceptive pills (OCPs), metformin, both or neither. Due to the significant costs and time required to recruit new patients and follow up for several years to assess heart disease, the project team will use novel methods to emulate the gold-standard clinical trial using readily available, real-world observational datasets that are large and diverse. All patients with PCOS worldwide and their providers can use the results of this study. Providers can use the results to determine which first-line treatment to prescribe for their patients and appropriately counsel them regarding impacts of these medications on heart health. In addition, medical and professional societies can use this data to develop guidelines, and health systems and insurers will value any interventions that can potentially decrease heart disease. The project team will identify adult women with PCOS in the IMRD dataset from the United Kingdom (>123,000) and Optum dataset from the United States (>400,000). Women with PCOS prescribed OCPs, metformin, both or no treatment will be identified, and comparisons performed between the four groups. The primary outcome of interest is a composite outcome of major cardiovascular events—angina, myocardial infarction, coronary artery disease, ischemic stroke, transient ischemic attacks, carotid artery disease, peripheral artery disease and heart disease related mortality—all-cause mortality and serious complications such as blood clots. The project team will also evaluate high blood pressure, high cholesterol and diabetes as mediators of the primary outcomes. They have data available over 20 years and outcomes will be evaluated from the diagnosis of PCOS or entry into the healthcare system. Experts in PCOS, heart health, pregnancy, epidemiology and biostatistics are included in the study team. Also included as key members of the study team are two patient investigators. The study team has created an advisory board that includes representatives from patient support groups in the United States and United Kingdom, leadership from medical societies (gynecology and preventive cardiology), allied health professionals (nutritionist) and a broad spectrum of providers (internist, pediatrician and psychiatrist) to ensure a patient-centered approach for this study. Answering these research questions will provide clinicians and patients evidence-based, PCOS-specific information on the impact of OCPs, metformin or both on ASCVD events and modifiable CVD risk factors.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.