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

Karen C. Schliep, Enrique F. Schisterman, Jean Wactawski-Wende, Neil J. Perkins, Rose G. Radin, Shvetha M. Zarek, Emily M. Mitchell, Lindsey A. Sjaarda, Sunni L. Mumford

Research output: Contribution to journalArticle

Abstract

Background: 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. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: 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. Results: 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. Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Fingerprint

Anovulation
Beverages
Menstrual Cycle
Caffeine
Hormones
Testosterone
Serum
1,7-dimethylxanthine
Coffee
Adipose Tissue
Linear Models
Fasting
Biomarkers
Alcohols
Exercise
Depression

Keywords

  • 1,7-Dimethylxanthine
  • Anovulation
  • Biological markers
  • Caffeine
  • Menstrual cycle

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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. / Schliep, Karen C.; Schisterman, Enrique F.; Wactawski-Wende, Jean; Perkins, Neil J.; Radin, Rose G.; Zarek, Shvetha M.; Mitchell, Emily M.; Sjaarda, Lindsey A.; Mumford, Sunni L.

In: American Journal of Clinical Nutrition, Vol. 104, No. 1, 01.07.2016, p. 155-163.

Research output: Contribution to journalArticle

Schliep, Karen C. ; Schisterman, Enrique F. ; Wactawski-Wende, Jean ; Perkins, Neil J. ; Radin, Rose G. ; Zarek, Shvetha M. ; Mitchell, Emily M. ; Sjaarda, Lindsey A. ; Mumford, Sunni L. / 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. In: American Journal of Clinical Nutrition. 2016 ; Vol. 104, No. 1. pp. 155-163.
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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 = "Background: 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. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: 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. Results: 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. Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.",
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T2 - Correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study

AU - Schliep, Karen C.

AU - Schisterman, Enrique F.

AU - Wactawski-Wende, Jean

AU - Perkins, Neil J.

AU - Radin, Rose G.

AU - Zarek, Shvetha M.

AU - Mitchell, Emily M.

AU - Sjaarda, Lindsey A.

AU - Mumford, Sunni L.

PY - 2016/7/1

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N2 - Background: 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. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: 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. Results: 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. Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.

AB - Background: 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. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: 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. Results: 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. Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.

KW - 1,7-Dimethylxanthine

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KW - Biological markers

KW - Caffeine

KW - Menstrual cycle

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