Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones

Abstract

Background: We have shown previously that male and female adolescents differ in their responses to caffeine, but to date, the mechanisms underlying these gender differences are unknown.

Objective: The purpose of this study was to test the hypothesis that differences in circulating steroid hormones mediate gender differences in response to caffeine.

Methods: Subjective and physiological responses to caffeine were tested in adolescents using a double-blind, placebo controlled, crossover design. Participants were tested every 2 weeks for 8 weeks and received placebo and caffeine (2 mg/kg) twice each. Females were tested with placebo and caffeine in each phase of their menstrual cycle. Salivary concentrations of testosterone, estradiol, and progesterone were also measured.

Results: Males showed greater positive subjective effects than females. In females, higher levels of estradiol were associated with little or no subjective responses to caffeine, but lower levels of estradiol were associated with negative subjective responses to caffeine relative to placebo. There were gender differences in cardiovascular responses to caffeine, with males showing greater decreases in heart rate after caffeine administration than females, but females showing greater increases in diastolic blood pressure than males after caffeine administration. These gender differences may be related to steroid hormone concentrations. Blood pressure responses to caffeine were lower in males when estradiol was high, but higher in females when estradiol was high.

Conclusions: When taken together, these findings suggest that males and females differ in their responses to caffeine and that these differences may be mediated by changes in circulating steroid hormones.

FIG. 1.

Mean±SEM change from placebo in heart rate (beats/min) and diastolic blood pressure (DBP) and systolic blood pressure (SBP) (mmHg) after administration of 2 mg/kg of caffeine in males (black bars) and females (gray bars). There was a significant interaction between gender and caffeine administration on heart rate (p=0.005) and DBP (p=0.001), with males showing a greater response to caffeine than females for heart rate, but females showing a greater change in blood pressure after caffeine administration than males.

FIG. 2.

Mean±SEM change from placebo in (A) heart rate (beats/min) and (B) DBP and (C) SBP (mmHg) after administration of 2 mg/kg of caffeine in males (black bars) and females (gray bars) who were either low or high in estradiol. There was a significant interaction between gender, estradiol levels, and caffeine administration on DBP (p=0.008) and SBP (p = 0.001), with males showing a greater response to caffeine than females for heart rate, but females showing a greater change in blood pressure after caffeine administration than males. In the statistical analyses, estradiol was included as a continuous variable, but for the purposes of making graphs, a median split was performed for estradiol levels within each gender to determine who was “low” and who was “high.” *Significant difference within each gender as a function of estradiol level (p<0.01).

FIG. 3.

Mean±SEM change from placebo in responses on the drug effects questionnaire after administration of 2 mg/kg of caffeine in (A) (black bars, males; gray bars, females). There was a significant interaction between gender and caffeine administration on “feeling drug effects” (p=0.02), “liking drug effects” (p=0.04), and “wanting more of the drug” (p<0.0001). When these interactions were explored, males reported significantly great feeling of drug effect and liking of the drug effect than did females. (B) Mean±SEM change from placebo in responses on self-reported feelings of drug effects after administration of 2 mg/kg of caffeine in males (left) and females (right) with low levels of estradiol (black bars) or high levels of estradiol (gray bars). There was a significant interaction between gender, salivary estradiol levels, and caffeine administration on “feeling drug effects” (p<0.0001). When this interaction was explored, males showed no differences in subjective effects related to estradiol levels, but females had strong negative responses to the caffeine relative to placebo when estradiol was low.