R01HD106096

Hypothalamic Amenorrhea as a Fertility Status Marker for Cardiovascular Health - 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 years) 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.

Furthermore, preclinical CVD is a multi-organ disease that, if left untreated, can manifest in neurocognitive disorders, peripheral CVD, and chronic kidney disease, contributing 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.

Mayo Clinic Jacksonville (A Nonprofit Corporation)

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Florida United States

State-Wide

Fertility Status as a Marker for Overall Health (R01 Clinical Trial Optional) (PAR-20-281)

Amendment Since initial award the End Date has been extended from 07/31/25 to 07/31/26 and the total obligations have increased 371% from $766,614 to $3,607,770.