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EB Research - Reproductive Epidemiology

The BioCycle Study: A Longitudinal Study of the Estrogen and Progesterone Effects on Biomarkers of Oxidative Stress and Antioxidant Status During the Menstrual Cycle

Study Design

The BioCycle Study is a prospective cohort study completed at the University at Buffalo and offers a unique and comprehensive assessment of menstrual cycle function. The primary goal of the BioCycle Study was to better understand the intricate relationship between reproductive hormone levels and oxidative stress during the menstrual cycle. Multiple markers of oxidative stress, reproductive hormones, inflammation, and metabolic biomarkers were measured in a cohort of 259 women of reproductive age over the course of two menstrual cycles. Fertility monitors were utilized to time the subjects' visits to ensure appropriate timing of biospecimen collection. Additional information regarding diet, lifestyle, and physical measurements was obtained throughout the study via standardized questionnaires, anthropometric assessments, and daily diaries. Participants were highly adherent to the study protocol, with 94% of all women completing seven or eight visits per cycle.

Important Research Findings

Since completion of the study, much progress has been made in the analysis of the BioCycle Study data. To date, more than 70 papers have been published. We have shown that metabolic markers such as markers of oxidative stress, lipoprotein cholesterol, inflammatory and glucose metabolism markers, and uric acid vary significantly across the menstrual cycle among healthy, regularly cycling women. These findings have implications for clinical practice (i.e., certain doctor visits should be timed to menstrual cycle phase), and for study designs that include women of reproductive age.

The BioCycle Study has contributed substantially to the fields of nutritional, environmental, and social epidemiology, offering valuable insights into various factors associated with premenopausal women’s reproductive and cardio-metabolic health. We have thoroughly assessed varying dietary patterns (e.g., Mediterranean Diet), food/beverage intake (e.g., dairy intake, fat intake, whole grains, fiber, and sweetened soda), macro/micronutrients (e.g., fiber, folate, carotenoids, isoflavones, caffeine, fructose, serum antioxidants), environmental factors (e.g., blood cadmium, lead, and mercury levels), and psychosocial stress and depression in relation to premenopausal women's reproductive and cardio-metabolic health. Further research evaluating potential environmental factors, including urinary phenol and paraben metabolites, found that these markers were variable across two months in healthy women, highlighting that additional biospecimens may be needed to characterize exposure for certain compounds.

Overall, this body of work has been influential in describing not only the short-term impact of diet and lifestyle on hormonal function and markers of menstrual cycle dysfunction (e.g., anovulation, luteal phase deficiency, and abnormal menses), but also their potential long-term impact on chronic disease risk. The team intends to build upon its current findings from the BioCycle Study to fill critical research gaps in its quest to answer important public health questions for women of reproductive age.

Principal Investigator

DIPHR Collaborators

Selected Publications

  • Mumford SL, Chavarro JE, Zhang C, Perkins NJ, Sjaarda LA, Pollack AZ, Schliep KC, Michels KA, Zarek SM, Plowden TC, Radin RG, Messer LC, Frankel RA, Wactawski-Wende J. (2016) Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women. The American Journal of Clinical Nutrition. 103(3): 868-77. PMID: 26843151. PMCID: PMC4763493.
  • Schliep KC, Mumford SL, Vladutiu CJ, Ahrens KA, Perkins NJ, Sjaarda LA, Kissell KA, Prasad A, Wactawski-Wende J, Schisterman EF. (2015) Perceived stress, reproductive hormones, and ovulatory function: a prospective cohort study. Epidemiology. 26(2): 177-84. PMID: 25643098. PMCID: PMC4315337
  • Matyas RA, Mumford SL, Schliep KC, Ahrens KA, Sjaarda LA, Perkins NJ, Filiberto AC, Mattison D, Zarek SM, Wactawski-Wende J, Schisterman EF. (2015) Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women. Human Reproduction. 30(7): 1714-23. PMCID: PMC4472321. PMID: 25954035
  • Schisterman EF, Mumford SL, Sjaarda LA. (2014) Failure to consider the menstrual cycle phase may cause misinterpretation of clinical and research findings of cardiometabolic biomarkers in premenopausal women. Epidemiologic Reviews. 36: 71-82. PMID: 24042431. PMCID: PMC3873842
  • Kissell KA, Danaher MR, Schisterman EF, Wactawski-Wende J, Ahrens KA, Schliep K, Perkins NJ, Sjaarda L, Weck J, Mumford SL. (2014) Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheric women. Human Reproduction. 29(8): 1764-72. PMID: 24925522. PMCID: PMC4093994
  • Sjaarda LA, Mumford SL, Kissell K, Schliep KC, Hammoud AO, Perkins NJ, Weck J, Wactawski-Wende J, Schisterman EF. (2014) Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype? The Journal of Clinical Endocrinology and Metabolism. 99(6): 2208-16. PMID: 24606085. PMCID: PMC4037725
  • Lynch KE, Mumford SL, Schliep KC, Whitcomb BW, Zarek SM, Pollack AZ, Bertone-Johnson ER, Danaher M, Wactawski-Wende J, Gaskins AJ, Schisterman EF. (2014) Assessment of Anovulation in Eumenorrheic Women: Comparison of Ovulation Detection Algorithms. Fertility and Sterility. 102(2): 511-518.e2. PMID: 24875398. PMCID: PMC4119548
  • Gaskins AJ, Mumford SL, Zhang C, Wactawski-Wende J, Hovey KM, Whitcomb BW, Howards PP, Perkins NJ, Yeung E, Schisterman EF. (2009) Effect of daily fiber intake on reproductive function: the BioCycle Study. The American Journal of Clinical Nutrition. 90(4): 1061-9. PMID: 19692496. PMCID: PMC2744625

Contact Information

Name: Dr Enrique Fabian Schisterman
Chief and Senior Investigator
Epidemiology Branch
Phone: 301-435-6893
Fax: 301-402-2084
E-mail: schistee@mail.nih.gov

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