Estradiol, SHBG and leptin interplay with food craving and intake across the menstrual cycle

Highlights

• Leptin is associated with reduced sweet food intake in normal weight healthy adult women.

• Women that crave more sweet tasting foods (“high-cravers”) had higher estradiol, estradiol/leptin ratio and SHBG.

• Healthy adult women experience cravings differently based on circulating ovarian hormones and leptin concentrations.

Abstract

Objective

To understand the association between ovarian hormones, non-acute satiety hormones and craving calorie dense foods in the luteal phase.

Methods

17 premenopausal women, mean age 23.2 y, mean BMI 22.4 kg/m² with regular menstrual cycles were studied during late follicular (FP) and luteal phases (LP). Estradiol, progesterone, DHEAS, SHBG, insulin and leptin, were measured in fasting samples. The validated Food Craving Inventory was used to record the types of foods volunteers habitually ate – rich in fat, carbohydrate or sweet taste, as well as craved during the LP of their menstrual cycle.

Results

Estradiol was inversely associated with leptin in FP (r = − 0.62, p = 0.01). Leptin was inversely associated with habitual intake of sweet foods, in both phases (FP: r = − 0.64, p = 0.01; LP: r = − 0.63, p = 0.01). SHBG in LP was positively associated with craving sweet and carbohydrate rich foods. Hierarchical cluster analysis revealed two groups of women, one with high estradiol, high estradiol/leptin ratio, high sweet and carbohydrate cravings (p < 0.05); the other group had lower estradiol, lower estradiol/leptin ratio, and reported less craving.

Conclusions

The estradiol-leptin axis may be a determinant of luteal phase craving and habitual food intake in menstruating women.

Clinical Trial Registration Number: NCT01407692

Introduction

Appetite regulation and energy intake fluctuate with phases of the menstrual cycle [1], and it is recommended that the cycle phases be considered for dietary intervention studies [2]. Positive energy balance in the luteal phase, compared to a more negative or energy balance during the follicular phase has been reported in lean women [3], [4]. In addition, food cravings for sweet tasting, carbohydrate- and fat-rich foods have been linked to the luteal phase of the menstrual cycle [5], [6]. These food cravings may be associated with increased energy intake [6]. Since food cravings may be crucial to managing obesity and its treatment [7], it is highly relevant to understand if food cravings are associated with menstrual cycle hormones [8].

Estradiol and progesterone influence food intake behaviors in animals [9]. Estradiol reduces food intake in rats [10], [11] via activation of estrogen receptor α [12]. The effect of progesterone has been unclear; some evidence suggests it enhances [9], while other evidence suggests it antagonizes the anorexigenic effect of estradiol [13]. Estradiol has also shown to increase sucrose taste threshold in rats [14]. The satiety hormone leptin has been shown to reduce sweet taste sensitivity in rats, thereby affecting palatability, and subsequent behavioral responses [15]. Limited human studies yield conflicting results; leptin appears to be positively associated with stress-induced sweet-craving in one study [16], while in another study higher leptin is associated with preference for lower sugar intake in obese women [17]. Interestingly, leptin has been shown to increase at peak follicular and luteal phase, alongside estradiol and progesterone, in young women (18 – 30y age) [18]. Researchers speculate that estradiol likely increases leptin secretion in humans [19], and animal studies suggest a similar role [20]. While estradiol is necessary for leptin action in the hypothalamus [21], the anorexigenic effect of estradiol is independent of estradiol's modulation of leptin [22]. A study looking at food intake, body weight and preference for sweet tasting food across the menstrual cycle noted that there was increase in both food intake and body weight in the luteal phase, compared to the follicular phase, but that the sweet preference was significantly lower in the luteal than the follicular phase [23]. The luteal phase increase in body weight could be due to increased blood volume, but the reduced preference for sweet seems contrary to the reported increase in food intake. However, this study did not measure leptin concentrations, nor did it report other factors that can influence satiety measures, such as insulin.

Based on animal literature, estradiol reduces food intake, and it is unclear whether progesterone enhances or antagonizes this. While estradiol and leptin have a positive association with each other, and can be viewed as anorexigenic hormones, their impact on eating and craving behaviors in humans is unclear. It is possible to speculate that estradiol in the unopposed state (follicular phase) reduces food intake, but when opposed by progesterone (luteal phase), estradiol has diminished impact. However, this needs to be tested and established.

Given that high sweet/fat/carbohydrate craving and food intake appear to increase during the luteal phase of the menstrual cycle, the consideration that both estradiol and progesterone may be anorexigenic is probably unlikely. While several studies have looked at craving and binge eating behaviors in women with eating disorders or pre-menstrual dysphoric disorder (PMDD), the association between ovarian hormones and craving in healthy women is not well established. Further, as pointed out by Davidsen et al. no menstrual cycle study has examined food intake and cravings to associate these behaviors with estradiol and leptin [24]. The current study addressed the following questions: Does circulating leptin concentration alter craving of sweet-tasting and carbohydrate-rich foods in the luteal phase? Are cravings associated with circulating estradiol and progesterone? The follicular phase of the study is associated with low estradiol and progesterone concentrations (i.e. conducive to metabolic testing), while the luteal phase is marked by higher circulating ovarian steroid hormones [25]. Since the physiological and behavioral impacts of the phases are a function of their circulating ovarian hormones, we decided to choose the time to test women based on their peak concentrations, hence, we chose to study estradiol at its peak (i.e. late follicular phase, close to ovulation), and estradiol and progesterone at their peak in the luteal phase (mid-late luteal phase). We hypothesized that leptin would be associated with reduced cravings as well as reduced intake of sweet-tasting and carbohydrate rich foods. Moreover, we also hypothesized that we could determine whether women are “high cravers” or “low cravers” based on their ovarian and leptin hormone concentrations.