This application is responsive to PA-17-091: Fertility Status as a Marker for Overall Health
Across their reproductive years, many women experience substantial weight gain, declines in bone density and
muscle mass, and worsening cardiometabolic health, each predicting later life morbidity and mortality. Most
women have one or more pregnancies during this lifestage, and a large subset of women (up to 1/3), including
many who have successfully conceived and carried a previous pregnancy, experience subfertility or infertility.
Infertility, defined as the inability to conceive after 12 months of unprotected intercourse, is thus one of the
most common conditions among reproductive age adults. A growing body of evidence suggests that fertility-
related characteristics predict future health risks including excess weight gain, osteoporosis, cardiovascular
disease (CVD), and type 2 diabetes mellitus.
The overall goal of our proposed project is to test our hypothesis that women with evidence of impaired fertility
will have more adverse body composition, bone health, and cardiometabolic outcomes in perimenopause. We
propose a prospective longitudinal cohort study design as the optimal approach to address the proposed aims.
We will leverage data from Project Viva, a highly engaged existing cohort of over 1000 socio-demographically
diverse women from whom we have already collected detailed information on weight, diet, and other health
behaviors beginning at enrollment in 1999-2002, and updated continually since.
Exposures are assessed with validated self-reported, clinical, or research measures and will include several
time-updated markers of fertility: cycles to conception; gravidity and parity; infertility diagnoses and treatments;
diagnosis of polycystic ovary syndrome (PCOS) as well as measurement of testosterone, a defining
characteristic of PCOS; and levels of anti-Müllerian hormone (AMH), an objective marker of ovarian reserve.
Outcomes include markers of body composition (fat, lean, and bone mass), cardiovascular health, and
metabolic health and will be assessed using gold-standard measures at an in-person research visit. Since
study inception, we have also rigorously collected data on a wide set of behaviors, health measures,
environmental factors, and social and family experiences.
Results from the proposed series of investigations will inform clinical care for women from the reproductive
years through perimenopause, guidelines regarding screening and long-term follow-up, and future research
priorities. This proposal provides an exceptional opportunity to leverage outstanding existing data and
resources and include over 20 years of high quality prospective assessments within a 5-year project period.