Research Project
10289995
SUMMARY/ABSTRACT Hypothalamic amenorrhea (HA) occurs during reproductive years and results in ovulatory dysfunction, anovulation and infertility which can be prolonged from months to years. There are multiple HA phenotypes including varying combinations of psychosocial stress, anxiety, high levels of physical activity and/or weight loss. Large population studies, including the original Nurses? Health Study have related menstrual cycle irregularity/amenorrhea with cardiovascular disease (CVD) events. However, these analyses have not differentiated the HA phenotype from polycystic ovary syndrome (PCOS) and other lower prevalence menstrual disorders. Emerging data from our group indicates that one-third of women with HA (mean age 27 yrs) have preclinical CVD measured noninvasively as vascular dysfunction, and circulating cytokine patterns indicative of vascular inflammation compared to age-matched eumenorrheic controls not on hormone therapy. Our proposed research application responds to the funding opportunity announcement PA-20-281, ?Fertility Status as a Marker for Overall Health? and will study HA, a marker of fertility status, related to cardiovascular health. In Aim 1, we will use innovative remote patient monitoring and patient reported outcomes to investigate HA specific phenotype(s) related to preclinical CVD (Aim 1a) and vascular inflammation (Aim 1b). We will then expand our analysis in Aim 2 to the Nurses? Health Study II, a large prospective cohort study that can now phenotype women with HA in the premenopausal years and determine associations with subsequent 30 year incident CVD risk factors and clinical CVD events. Understanding the HA phenotype(s) related to CVD is a crucial next step to identify women at-risk in order to take preventive action and improve overall CVD health. Early identification of young at-risk women presents a unique opportunity to intervene earlier in life when CVD preventive approaches are most beneficial. Further, preclinical CVD is a multi-organ disease that left untreated can manifest in neurocognitive disorders, peripheral CVD, and chronic kidney disease that contribute to health disparities in women. The outcome of the proposed research will identify young women at risk of CVD using HA phenotyping to inform the design of next step intervention trials and, ultimately, to translate our findings to clinical care to address the CVD epidemic in younger women using existing and emerging cardiovascular preventive strategies.
