# Hypothalamic Amenorrhea as a Fertility Status Marker for Cardiovascular Health

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2023 · $687,674

## Abstract

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.

## Key facts

- **NIH application ID:** 10669706
- **Project number:** 5R01HD106096-04
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Chrisandra Lee Shufelt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $687,674
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10669706

## Citation

> US National Institutes of Health, RePORTER application 10669706, Hypothalamic Amenorrhea as a Fertility Status Marker for Cardiovascular Health (5R01HD106096-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10669706. Licensed CC0.

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