Functional Hypothalamic Amenorrhea Linked to Higher Coronary Heart Disease Risk: Study
Functional hypothalamic amenorrhea in mid-adulthood was associated with an increased risk of coronary heart disease, independent of traditional cardiovascular risk factors, according to a prospective cohort study published in the Journal of Clinical Endocrinology & Metabolism. The findings suggest that a history of functional hypothalamic amenorrhea may be an important marker of long-term cardiovascular risk. The study was conducted by Chrisandra L. and colleagues.
To investigate the influence of the FHA phenotype on incident cardiovascular disease and metabolic risk factors, prospective data of 52,655 premenopausal women participating in the Nurses’ Health Study II, without history of cardiovascular disease in 1993, were examined. Biennial follow-up was conducted for participants up until 2019. The FHA phenotype was clearly identified as irregular or absence of menstrual cycles without clinical features of PCOS, low body mass index (BMI), and/or high physical activity.
Primary endpoint outcomes were the incidence of composite cardiovascular disease consisting of coronary heart disease (myocardial infarction or coronary revascularization) and ischemic stroke, as well as incidence of cardiometabolic risk factors, namely hypercholesterolemia, systemic hypertension, and type 2 diabetes mellitus.
Key findings:
- A total of 1,007 incident cardiovascular outcomes were recorded within up to 26 years of longitudinal follow-up with a median time to first event of 17.0 years (IQR, 11.3–21.0) amongst affected women.
- FHA phenotype during mid-adulthood was associated with statistically significant increase in the risk of developing cardiovascular diseases with a hazard ratio (HR) of 62% (HR = 1.62; 95% confidence interval (CI): 1.01–2.59).
- Mid-adulthood FHA was linked to nearly twofold increased risk of developing coronary heart disease (HR = 1.91; 95% CI: 1.11–3.27) when compared with women having regular cycles.
- Mid-adulthood FHA was also found to be associated with significantly higher risk of developing type 2 diabetes mellitus (HR = 1.86; 95% CI: 1.41–2.47); however, it was not linked with any risk of development of hypertension and high cholesterol levels.
- Non-FHA menstrual irregularities were associated with high cholesterol, hypertension, and type 2 diabetes mellitus but not with incident cardiovascular outcomes.
In summary, prospective data accumulated over almost three decades have shown that hypothalamic amenorrhea during middle adulthood increases the risk of coronary heart disease and type 2 diabetes independently. It is clear from the conclusions of the study that reproductive history plays an important role as an early biomarker of cardiovascular risk.
Reference:
Chrisandra L Shufelt, Jennifer J Stuart, Jana Karam, Xiaoyu Che, JoAnn E Manson, Karen K Miller, Kathy Rexrode, Stephanie Faubion, Sarah Berga, C Noel Bairey Merz, Janet W Rich-Edwards, Functional Hypothalamic Amenorrhea Phenotype and Cardiovascular Disease Risk, The Journal of Clinical Endocrinology & Metabolism, 2026;, dgag405, https://doi.org/10.1210/clinem/dgag405
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