Hypothalamic Amenorrhea as a Fertility Status Marker for Cardiovascular Health

Hypothalamic amenorrhea (HA), occurring during reproductive years, leads to ovulatory dysfunction, anovulation, and prolonged infertility. Large population studies have linked menstrual cycle irregularity/amenorrhea with cardiovascular disease (CVD) events. Crucially, existing analyses often do not differentiate HA phenotypes from other menstrual disorders. Emerging data indicates that one-third of women with HA (mean age 27 yrs) show preclinical CVD, characterized by vascular dysfunction and circulating cytokine patterns indicative of vascular inflammation. 

This research will study HA as a marker for cardiovascular health through the use of innovative remote patient monitoring and patient-reported outcomes (PROs) to investigate HA-specific phenotype(s) related to preclinical CVD and vascular inflammation. Analysis will be further expanded to the Nurses’ Health Study II, a large prospective cohort, to determine associations with subsequent 30-year incident CVD risk factors and clinical CVD events.

Understanding HA phenotype(s) related to CVD is a critical step to identify at-risk women for early preventive action. Early identification in young women presents a unique opportunity for beneficial CVD prevention, as preclinical CVD can manifest in neurocognitive disorders, peripheral CVD, and chronic kidney disease, contributing to health disparities in women. The outcome will identify young women at risk of CVD using HA phenotyping, informing intervention trials and ultimately translating findings to clinical care to address the CVD epidemic in younger women.

Contact PI: Corey Arnold; Chrisandra Lee Shufelt (Mayo Clinic)

Funding Source:  NIH NICHD