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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, over sixty 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 including women of reproductive age.

The BioCycle Study has also contributed substantially to the field of nutritional, environmental, and social epidemiology. We have thoroughly assessed varying dietary patterns (e.g., Mediterranean Diet), food/beverage intake (e.g., whole grains, fiber, and sweetened soda), macro/micronutrients (e.g., fiber, folate, carotenoids, isoflavones, and fructose), 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. Overall, these papers have been influential in describing not only the short-term impact of a healthy diet and lifestyle on hormonal function and markers of menstrual cycle dysfunction (e.g., anovulation, luteal phase deficiency, and abnormal menses) but 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. Planned analyses will evaluate additional diet, lifestyle, environmental, and psychosocial factors, focusing on their interplay with endocrine function and biomarkers of chronic disease.

Principal Investigator

DIPHR Collaborators

Selected Publications

  • 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(1), 71-82. PMID: 24042431

  • Gaskins AJ, Mumford SL, Zhang C, Wactawski-Wende J, Hovey MS, Whitcomb BW, Howards PP, Perkins NJ, Yeung E, Schisterman EF. (2009) Effect of daily fiber intake on reproductive function: the BioCycle Study.  American Journal of Clinical Nutrition, 90(4),1061-9. PMID:19692496

  • Mumford SL, Schisterman EF, Siega-Riz AM, Gaskins AJ, Wactawski-Wende J, VanderWeele TJ.  (2011) Effect of dietary fiber intake on lipoprotein cholesterol levels independent of estradiol in healthy premenopausal women. American Journal of Epidemiology, 173(2), 145-56. PMID: 21148240

  • Kissell KA, Danaher MR, Schisterman EF, Wactawski-Wende J, Ahrens KA, Schliep KC, Perkins NJ, Sjaarda L, 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

  • 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? Journal of Clinical Endocrinology and Metabolism, 99(6):2208-16. PMID:24606085

  • Ahrens K, Mumford SL, Schliep KC, Kissell KA, Perkins NJ, Wactawski-Wende J, Schisterman EF. (2014) Serum leptin levels and reproductive function during the menstrual cycle. American Journal of Obstetrics and Gynecology, 210(3):248.e1-9. PMID: 24215851

  • 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 among premenopausal women in the BioCycle Study. Epidemiology. 26(2):177-84. PMID: 25643098
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Last Updated Date: 08/27/2015
Last Reviewed Date: 08/27/2015

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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