Our secondary objective was to determine whether caffeine and its associated beverages are associated with incident anovulation. The primary objective of this study was to determine whether caffeine and its associated beverages (coffee, tea, and soda) are related to serum concentrations of reproductive hormones in a cohort of 259 healthy premenopausal women and whether these associations differ by race. It is unknown whether differences in caffeine consumption and metabolism could partially explain these differences. Estrogen and caffeine metabolism and risk of breast and ovarian cancers have also been shown to differ between whites and Asians ( 28– 30). Polymorphisms of CYP1A2 have been linked to variability in caffeine clearance ( 24) and serum E2 concentrations ( 25) and have been shown to modify relations between caffeine intake and adverse health outcomes ( 26, 27). Both caffeine and E2 are metabolized by the hepatic enzyme CYP1A2 ( 22, 23). Studies in women have suggested that caffeine may have a positive ( 4), inverse ( 6), or null association with E2 4 ( 5), but has no effect on ovulatory function ( 16, 20, 21), although no studies to date have prospectively measured caffeine intake at multiple time points and directly measured ovulation. Animal models suggest that caffeine can inhibit oocyte maturation or enhance steroid production via inhibition of phosphodiesterase ( 4, 18) or, alternatively, may interfere with estrogen metabolism via inhibition of aromatase-the key enzyme responsible for converting androgens to estrogen ( 6, 19). Further understanding of these associations can inform the development of appropriate guidelines regarding consumption levels for women of reproductive age ( 17).Ī variety of pathophysiologic effects of caffeine and components of caffeinated beverages on sex hormones and ovulatory function exist. The association between caffeine and hormones is of interest, because persistent elevation or insufficiency of reproductive hormones during the premenopausal years may not only contribute in the long term to the etiology of certain diseases, such as breast, endometrial, and ovarian cancers ( 11– 14), but may also affect ovulatory function in the short term ( 15, 16). The inconsistent results may be due in part to interethnic variability in the endocrine dynamics of female reproductive hormones ( 7, 8) and caffeine metabolism ( 9, 10). Despite the prevalence of intake, research relating caffeine and reproductive hormone concentrations among premenopausal women is limited and inconclusive ( 3– 6). Approximately 89% of women aged 18–34 y consume an average of 166 mg caffeine/d (equivalent to 1.5–2 cups caffeinated coffee) from a variety of sources but mostly from caffeinated beverages ( 1, 2). Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race.Ĭaffeine intake by women of childbearing age is common in the United States. Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively.Ĭonclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Results: Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = −0.15 95% CI: −0.26, −0.05) and positively associated among Asian women (β = 0.61 95% CI: 0.31, 0.92). On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race.ĭesign: Participants ( n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood.
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