EB Research: The Biocycle Study

BiocycleThe primary goal of the BioCycle Study was to understand better the intricate relationship between reproductive hormone levels (e.g., estrogen and progesterone) and biomarkers of oxidative stress and antioxidants during the menstrual cycle.

Detectable oxidative stress in women may be affected by variations in hormone levels that occur as a part of normal menstrual function. Failure to address this underlying biological variability may impair study inference; however, this issue has received little attention.

Study Design and Progress

The BioCycle Study was a prospective longitudinal cohort study conducted at the University at Buffalo from 2005 to 2007. The study followed 259 women between 18 and 44 years of age for two menstrual cycles. Using biospecimens collected from participants, researchers measured multiple markers of:

  • Oxidative stress
  • Reproductive hormones
  • Inflammation
  • Metabolic biomarkers

Fertility monitors were utilized to schedule participants’ study visits to ensure appropriate timing of biospecimen collection. Researchers also collected information regarding diet, lifestyle, and physical measurements throughout the study via standardized questionnaires, anthropometric assessments, and daily diaries. Participants were highly adherent to the study protocol, with 94 percent of all women completing seven or eight visits per cycle.

Although data collection for the study is complete, researchers continue to analyze BioCycle Study data. To date, more than 80 papers have been published, and study data 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. Some key findings include the following:

  • Researchers evaluated physiologic and behavioral factors to determine any associations with reproductive hormones, menstrual cyclicity, and ovulatory function. In a recent report, EB investigators noted that circulating liver enzymes fluctuated during the normal menstrual cycle, possibly mediated by progesterone, and that the fluctuation varied with age and body mass index. These findings indicate that menstrual cycle phases should be accounted for when interpreting clinical liver enzyme measurements in menstruating women.
  • Analysis also showed that sleep patterns changed over the menstrual cycle, with the shortest sleep durations reported around ovulation. Estradiol and progesterone both increased with increasing sleep duration, but they were not associated with night/shift work or individual preference for when to sleep (chronotype), exposures strongly associated with sleep timing.
  • In addition, the researchers found that tampon use was associated with elevated mercury levels and oxidative stress biomarkers, suggesting tampons may be a potential, though largely ignored source of exposure to metals and chemicals.

Further research into the mechanisms that drive or mediate these associations is needed to understand the potential implications for women's health.

Overall, the BioCycle Study data has been influential in describing not only the short-term impacts of diet and lifestyle on hormonal function and markers of menstrual cycle dysfunction (e.g., anovulation, luteal phase deficiency, and abnormal menses), but also the potential long-term impacts on chronic disease risk as well. BioCycle researchers aim to build upon current findings to fill critical research gaps and answer important public health questions for women of reproductive age.

BioCycle Publications (PDF 271 KB)

Principal Investigator

Neil Perkins, Ph.D.

Need data? The Biocycle Study studies are now available in NICHD's Data and Specimen Hub (DASH).
Browse studies and request data for your research.

Selected Publications

Michels, K. A., Mendola, P., Schliep, K. C., Yeung, E. H., Ye, A., Dunietz, G. L., Wactawski-Wende, J., Kim, K., Freeman, J. R., Schisterman, E. F. & Mumford, S. L. (2020). The influences of sleep duration, chronotype, and nightwork on the ovarian cycle. Chronobiology International, 37(2), 260-271. PMID: 31778080. PMCID: PMC7054152 (available on 2021-02-01)

Singh, J., Mumford, S. L., Pollack, A. Z., Schisterman, E. F., Weisskopf, M. G., Navas-Acien, A., & Kioumourtzoglou, M. A. (2019). Tampon use, environmental chemicals and oxidative stress in the BioCycle study. Environmental Health, 18(1), 11. PMID: 30744632. PMCID: PMC6371574

Kim, K., Wactawski-Wende, J., Michels, K. A., Plowden, T. C., Chaljub, E. N., Sjaarda, L. A., & Mumford, S. L. (2017). Dairy food intake is associated with reproductive hormones and sporadic anovulation among healthy premenopausal women. Journal of Nutrition, 147(2), 218-226. PMID: 27881593. PMCID: PMC5265695

Mumford, S. L., Chavarro, J. E., Zhang, C., Perkins, N. J., Sjaarda, L. A., Pollack, A. Z., Schliep, K. C., Michels, K. A., Zarek, S. M., Plowden, T. C., Radin, R. G., Messer, L. C., Frankel, R. A., & 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), 868-877. PMID: 26843151. PMCID: PMC4763493

Pollack, A. Z., Perkins, N. J., Sjaarda, L., Mumford, S. L., Kannan, K., Philippat, C., Wactawski-Wende, J., & Schisterman, E. F. (2016). Variability and exposure classification of urinary phenol and paraben metabolite concentrations in reproductive-aged women. Environmental Research, 151, 513-20. PMID: 27567355. PMCID: PMC5071150

Schliep, K. C., Schisterman, E. F., Wactawski-Wende, J., Perkins, N. J., Radin, R. G., Zarek, S. M., Mitchell, E. M., Sjaarda, L. A., & Mumford, S. L. (2016). Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study. American Journal of Clinical Nutrition, 104(1), 155-63. PMID: 27225433. PMCID: PMC4919523

Schliep, K. C., Mumford, S. L., Vladutiu, C. J., Ahrens, K. A., Perkins, N. J., Sjaarda, L. A., Kissell, K. A., Prasad, A., Wactawski-Wende, J., & Schisterman, E. F. (2015). Perceived stress, reproductive hormones, and ovulatory function: a prospective cohort study. Epidemiology, 26(2), 177-184. PMID: 25643098. PMCID: PMC4315337

Schisterman, E. F., Mumford, S. L., & Sjaarda, L. A. (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

Sjaarda, L. A., Mumford S. L., Kissell, K., Schliep, K. C., Hammoud, A. O., Perkins, N. J., Weck, J., Wactawski-Wende, J., & Schisterman, E. F. (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), 2208-2216. PMID: 24606085. PMCID: PMC4037725

Lynch, K. E., Mumford, S. L., Schliep, K. C., Whitcomb, B. W., Zarek, S. M., Pollack, A. Z., Bertone-Johnson, E. R., Danaher, M., Wactawski-Wende, J., Gaskins, A. J., & Schisterman, E. F. (2014). Assessment of anovulation in eumenorrheic women: comparison of ovulation detection algorithms. Fertility and Sterility, 102(2), 511-518.e2. PMID: 24875398. PMCID: PMC4119548

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