The Menses Study: Menstrual blood as a novel target-tissue biomatrix for chemical exposures relevant to reproductive system disorders

PROJECT SUMMARY / ABSTRACT The long-term goal of this project is to transform women’s health by investigating the novel biological matrix of menstrual blood for measurement of environmental chemical exposure, advancing understanding of endocrine disrupting chemicals (EDCs) and reproductive system disorders. One such condition, endometriosis, is estrogen- driven, affects ~10% of people with uteruses, and can confer chronic, debilitating symptoms, including pelvic pain, menstrual pain, and heavy menstrual bleeding. EDCs may affect endometriosis through alteration of estrogen pathways, but studies have yielded inconsistent results. Unlike venous blood, menstrual blood contains endometrial tissue, allowing for the characterization of environmental chemical exposure in the target organ of the endometrium. A paucity of data exists on the chemicals present in menstrual blood, as well as sources of exposure (such as menstrual product use) and connection to reproductive health. To address this gap, this prospective study will measure EDCs in menstrual blood, including metals and perfluoroalkyl substances (PFAS), to which the US general population is ubiquitously exposed. The study will recruit 225 menstruating university students aged 18-49 in the Boulder, CO metro area (the ‘Menses Study’). This population will be followed for 3 menstrual cycles. Menstrual blood will be collected in cycles 2 and 3 using an established, successful collection protocol. A venous blood sample will also be collected during cycle 2, corresponding with menstrual blood collection. Daily menstrual blood samples will be collected in cycle 3. Data on menstrual product use and menstrual cycle characteristics, particularly symptoms of menstrual pain and heavy menstrual bleeding which are commonly reported with reproductive system disorders, will also be collected. The specific aims are: (Aim 1) Characterize exogenous chemical exposures in menstrual blood: (1a) Use standard targeted methods to quantify concentrations of 17 metals (As, Ba, Ca, Cd, Co, Cr, Cu, Hg, Pb, Mn, Ni, Sb, Se, Sr, Tl, V, and Zn) and 24 PFAS, (1b) Use a discovery-driven approach to elucidate novel exogenous compounds (non-targeted chemical analysis), (1c) Characterize variability of targeted and non-targeted chemicals within and between menstrual periods, (1d) Compare chemical concentrations in menstrual blood to those in venous blood collected concurrently. (Aim 2) Evaluate sources of exposure unique to menstruators, including use of tampons and other menstrual products, in relation to metals, PFAS and non-targeted compounds in menstrual blood. (Aim 3) Determine associations between metals, PFAS, non-targeted compounds and menstrual symptoms indicative of reproductive system disorders: menstrual bleeding severity and menstrual pain. This project aligns with the NIH crosscutting theme of advancing research on women’s health by kickstarting exposure assessment science in an understudied matrix indicative of uterine health: menstrual blood.