Cross-Sectional Association of Coffee and Caffeine Consumption With Sex Hormone-Binding Globulin in Healthy Nondiabetic Women

Florence Pihan-Le Bars; Gaëlle Gusto; Marie-Christine Boutron Ruault; Guy Fagherazzi; Fabrice Bonnet


Clin Endocrinol. 2017;87(5):475-483. 

In This Article

Abstract and Introduction


Objective Low sex hormone-binding globulin (SHBG) is a consistent risk factor for type 2 diabetes, particularly in women. Coffee consumption has been associated with a lower risk of type 2 diabetes, but its effects on SHBG are less known.

Design and methods This was a cross-sectional study of 2377 nondiabetic pre- and postmenopausal women from the E3N cohort study whose baseline SHBG was measured. Information on diet (including coffee and caffeine consumption), lifestyle and medical conditions was collected through questionnaires. The relationship between coffee and caffeine consumption and SHBG was modelled, with adjustment for covariates and stratification by body mass index (BMI) categories (< or ≥25 kg/m2) and menopausal status.

Results The mean age was 57.2±6.4 years and 61% of the 2377 women were postmenopausal. High coffee (≥3 cups/day) and caffeine (≥265 mg/day) intakes were associated with a reduced risk of being in the 1st quartile of the SHBG level distribution (<46.3 nmol/L) in a multivariate adjusted model (OR: 0.72 [95% CI: 0.52–1.01] and OR: 0.71 [95% CI: 0.53–0.95], respectively). No association was found between tea consumption and SHBG levels. In multivariate models stratified on BMI categories and menopausal status, associations were restricted to women with a BMI ≥25 kg/m2 or being postmenopausal. The association with SHBG was consistently noted with consumption of both caffeinated coffee and caffeine, but not decaffeinated coffee.

Conclusions Consumption of high coffee and caffeine is associated with a reduced risk of low SHBG, an established risk marker for T2DM, which might contribute to the protective effects of coffee for type 2 diabetes.


Low sex hormone-binding globulin (SHBG) has been identified as a consistent risk factor for type 2 diabetes mellitus (T2DM), particularly in women and in the setting of a low metabolic risk at baseline.[1,2] In addition, Mendelian randomization studies showed that carriers of SHBG polymorphisms associated with low SHBG levels had an increased risk of T2DM, suggesting a causal relationship.[3–5]

In parallel, coffee consumption is one of the few dietary factors associated with reduced T2DM risk in several prospective studies, including the E3N/EPIC (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale/European Prospective Investigation into Cancer and Nutrition) cohort study in the setting of a low metabolic baseline risk.[6] Recent meta-analyses reviewed this relationship and showed a ~30% reduced risk of T2DM for the highest levels of coffee or caffeine intakes suggesting a potentially causal relationship.[7–9]

The mechanisms of a potential protective effect of coffee on the risk of T2DM have not been clearly identified. Some data suggest that SHBG could mediate the association between coffee and caffeine consumption and the risk of T2DM. Indeed, the inverse associations of caffeinated coffee and caffeine with T2DM risk disappeared after adjustment for plasma SHBG in a case-control study in postmenopausal women with or without T2DM.[10]

An inverse relationship between coffee and caffeine intake and SHBG has been observed in most studies conducted in postmenopausal women,[10–13] but studies which investigated the association in premenopausal women displayed conflicting and inconclusive results.[13–17]

Therefore, our objective was to investigate the relationship between both coffee and caffeine consumption and the risk of low plasma SHBG concentration in a large population of pre- and postmenopausal women.