An official website of the United States government
The Missing Middle: Perimenopause as an Understudied Life Stage
When beginning your next investigator-initiated application, consider the following NIH highlighted topic. The area of science described below is of interest to the listed NIH Institutes, Centers, and Offices (ICOs). This is not a notice of funding opportunity (NOFO).
Apply through an appropriate NIH Parent Funding Announcement or another broad NIH opportunity available on Grants.gov. Learn how to interpret and use Highlighted Topics.
Topic Description
Post Date: October 19, 2026
Expiration Date: October 19, 2028
Background
Perimenopause, or the menopausal transition, is a near-universal midlife event in women, yet it remains a systematic blind spot in research. Studies tend to enroll women who are clearly premenopausal or clearly postmenopausal and skip the variable, symptomatic window in between, leaving the transition itself poorly characterized. For perimenopause, its basic biology, its wide heterogeneity in onset, duration, and symptom burden, and the tools used to stage it are all underdeveloped. This heterogeneity includes populations of special interest in which the transition occurs earlier or is accelerated, such as people with Down syndrome and other intellectual and developmental disabilities. Compounding this, care during the transition is guided largely by age-based conventions and expert opinion rather than robust evidence.
Perimenopause is also not a single-system event. The hormonal shifts that define the transition to menopause have consequences across reproductive, skeletal, cardiometabolic, cognitive, and mental health domains, and several of these changes, including bone loss, begin during the transition rather than after menopause. Yet, because the window is so often skipped in studies, the transition-specific evidence base for conditions otherwise well-studied in younger or postmenopausal women is sparse. Understanding perimenopause as a life stage on its own terms and distinguishing the effects of the transition from those of chronological aging is essential to improving health and function in the decades that follow.
Purpose
This topic encourages investigator-initiated research that treats perimenopause as a distinct life stage warranting its own evidence base. Applications may address any area in which a transition-focused framing advances the science, and there is no expectation that a project will span multiple systems. Areas of interest include:
- The basic biology and heterogeneity of the menopausal transition, including its mechanisms, trajectories, and determinants of variation between women
- Improved approaches to stage and characterize the transition, including cases where standard cycle- and hormone-based assessment may be unreliable
- Transition-specific presentation, mechanisms, and management of conditions across affected systems
- How the timing and management of the transition relate to longer-term health and aging outcomes
- Decision-making, counseling, communication, and disparities in care across the transition
Investigators are encouraged to contact scientific staff early to discuss alignment and appropriate parent funding opportunities.
It aligns with:
- New Approach Methodologies (NAMs) : The expanded use of NAMs can enable earlier, more predictive insights into chronic disease mechanisms using human-relevant models such as organoids, computational simulations, and real-world data integration. This improves prevention, diagnosis, and personalized treatment strategies while reducing reliance on animal studies that often fail to replicate complex human conditions. The Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and NIH have all committed to using NAMs moving forward, when appropriate.
- Repurposed Drugs : The NIH and FDA will jointly investigate opportunities to strengthen the use of repurposed drugs for the treatment of chronic disease, while harmonizing authorization processes through collaborative clinical trial designs to achieve FDA approval.
- Longitudinal Research for Chronic Disease Prevention : The NIH will leverage its extensive portfolio of longitudinal birth cohort data, including the Adolescent Brain Cognitive Development Study, Healthy Brain and Child Development Study, All of Us Research Program, and Environmental Influences on Child Health Outcomes Program to deepen our understanding of chronic disease at various stages of life by elucidating root causes, identifying modifiable risk factors, and uncovering effective prevention strategies. Examples of new research initiatives will include the importance of sleep and nutrition, health impacts of insulin resistance, potential health benefits of select high-quality supplements, and using fitness as a vital sign.
- Artificial Intelligence : HHS, NIH, and the Office of Science and Technology Policy will develop an evidenced-based and AI-driven approach to harnessing the data and technology available to transform research and clinical trials on pediatric cancer. This can be a model for future research in other critical areas.
Participating ICOs
NICHD supports research on the gynecologic and reproductive dimensions of perimenopause. NICHD is particularly interested in:
- Predicting the timing and duration of the transition, including predictive algorithms and biomarkers
- Determining menopausal status when hormonal contraception confounds cycle-based assessment; contraceptive method choice and transitions during perimenopause
- Perimenopause-specific presentation and management of gynecologic and other conditions including infections like HIV
- Hormonal therapy during the transition, including management of abnormal uterine bleeding, vasomotor and other symptoms, and endometrial protection
- Individualizing the shift from contraception to menopausal hormone therapy, including counseling and disparities in care
- Ovarian aging and its mechanisms, including premature or accelerated aging and Primary Ovarian Insufficiency, and dysfunction such as with Polyendocrine Metabolic Ovarian Syndrome/Polycystic Ovary Syndrome
- Implementation studies
NICHD Gynecologic Health and Disease Branch
[email protected]
ODP interests:
- Identify modifiable risk and protective factors associated with the menopausal transition, and evaluate how interventions that reduce risks and strengthen protective factors influence the onset, progression, and long‑term consequences of chronic diseases and other adverse health outcomes
- Develop and rigorously evaluate preventive interventions using experimental, quasi-experimental, pragmatic, or other appropriate study designs to determine the optimal timing and effectiveness of strategies to prevent adverse health outcomes, preserve functioning, and improve quality of life during the menopausal transition and beyond.
- Advance the translation of effective preventive interventions into practice by examining their implementation, acceptability, scalability, sustainability, and impact in clinical, community, and other real-world settings, including approaches to improve access to evidence-based preventive care and enhance health outcomes during the menopausal transition.
Keisha Shropshire
[email protected]
ORWH is interested in:
- Development and validation of biomarkers to accurately stage the menopause transition and predict symptoms and health outcomes.
- Evaluation of short- and long-term effects of menopause hormone therapies, including formulation, route, and timing, on health and chronic disease risk.
- Standardized screening and risk assessment protocols for cardiovascular, metabolic, musculoskeletal, mental, and urogenital health during perimenopause.
- Solution-oriented health disparities research and models of care that improve outcomes across all populations.
- Standardized Common Data Elements (CDEs), computable phenotypes, and harmonized outcome measures for perimenopause staging, symptoms, and outcomes to support reproducible research.
- Evidence-based workforce education, training, and competency standards for perimenopause care.
Annina Burns, Ph.D., RD.
[email protected]
For technical issues E-mail OER Webmaster