title: 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.
abstract: Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements.
  
  
  
  We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race.
  
  
  
  Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation.
  
  
  
  The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race.
  
  
  
  Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; Department of Family and Preventive Medicine, University of Utah Health Sciences Center, Salt Lake City, UT;
authors.forename: Karen C
authors.identifier: 0000-0003-1771-3157
authors.initials: KC
authors.lastname: Schliep
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Enrique F
authors.initials: EF
authors.lastname: Schisterman
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY; and.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Perkins
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Rose G
authors.initials: RG
authors.lastname: Radin
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.
authors.forename: Shvetha M
authors.initials: SM
authors.lastname: Zarek
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mitchell
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Sjaarda
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; mumfords@mail.nih.gov.
authors.forename: Sunni L
authors.initials: SL
authors.lastname: Mumford
mesh_terms: D000328:Adult; D044466:Asian People; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D003069:Coffee; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation; D034445:Ovulation Inhibition / Q000187:drug effects* / Q000208:ethnology; D044469:Racial Groups; D012307:Risk Factors; D013739:Testosterone / Q000097:blood*; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D003069:Coffee; D002110:Caffeine; D013739:Testosterone; D013806:Theophylline; C021183:1,7-dimethylxanthine
keywords: 1,7-dimethylxanthine; anovulation; biological markers; caffeine; menstrual cycle