The Role of Leptin in the Etiology of Exercise-Associated Menstrual Disturbances

Open Access
- Author:
- Corr, Maggie
- Graduate Program:
- Kinesiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- April 02, 2010
- Committee Members:
- Nancy Williams, Thesis Advisor/Co-Advisor
Nancy Williams, Thesis Advisor/Co-Advisor - Keywords:
- leptin
amenorrhea
menstrual status
resumption of menses
body fat
sympathetic nervous activity - Abstract:
- Background: The exact etiology of functional hypothalamic amenorrhea (FHA) is still unknown, yet is often associated with a relative energy deficit. Low concentrations of the adipocyte-secreted hormone leptin are thought to be the peripheral signal whereby an energy deficit disrupts the hypothalamic-pituitary-gonadal (HPG) axis. Objectives: To further assess the role of leptin in the regulation of reproductive function, the first study was designed to identify the association between circulating leptin concentration and FHA, hypothesizing that suppression of the HPG axis results from either having low leptin per se or having a lower concentration of leptin than can be solely accounted for by adiposity. The second study assessed the role of leptin in the resumption of menses in exercising women with FHA. We hypothesized that an increase in leptin concentration would be associated with the resumption of menses in women with FHA. Lastly, the third study was designed to test the hypothesis that significant predictors of leptin concentration, after adjusting for adiposity, are different in women with and without FHA. A second aim was to explore whether changes in modulators of leptin production are found in association with changes in leptin concentration observed in women with FHA who resume menses. Design: Menstrual status, body composition, and fasting serum leptin concentration were assessed in fifty-two exercising, premenopausal women over the course of one baseline menstrual cycle for ovulatory women (OV; n=26) or for one 28-day monitoring period for amenorrheic women (Amen; n=24) (Study 1 and 3). Fourteen volunteers who were categorized as Amen at baseline completed a 6-month monitoring period, during which repeated measures of body composition, leptin concentration, and other metabolic and dietary parameters were assessed. These women were retrospectively categorized into 2 groups: 1) those who resumed menses between months one and six of the study (Amen-R; n=5), and 2) those who remained amenorrheic during the 6-month monitoring period (Amen-NR; n=7). Two women resumed menses within the first month and were thus excluded because the concentration of leptin with the resumption of menses could not be determined (Study 2 and 3). Results: Percentage body fat (21±1% vs. 27±0.7%; P<0.001) and leptin concentration (4.8±0.8ng/ml vs. 9.6±0.9ng/ml; P<0.001) were significantly lower in Amen vs. OV. However, the ranges observed in serum leptin concentration for Amen and for OV were similar (range for Amen: 2.61-7.24ng/ml; range for OV: 2.60-7.25ng/ml), and after adjusting for adiposity the difference in leptin concentration was no longer significant. Percentage body fat (17±2% vs. 24±2%; P =0.033), but not serum leptin concentration (2.3±0.7ng/ml vs. 6.5±2.8ng/ml; P=0.207), was significantly lower in Amen-NR vs. Amen-R at baseline. The increase in fasting serum leptin concentration, but not percentage body fat, from pre- to post-study was significantly greater in Amen-R vs. Amen-NR (Interaction Effect: P=0.002). A significant increase in resting respiratory exchange ratio was also observed in Amen-R vs. Amen-NR from pre- to post-study (Interaction Effect: P=0.006). The model that best predicted baseline serum leptin concentration in the OV women included percentage body fat only (r2=0.522), and in the Amen women included percentage body fat, serum insulin concentration, and serum glycerol concentration (r2=0.775). Conclusions: These date suggest that the reproductive system senses and responds to relative changes in leptin concentration rather than to a critical concentration of leptin. Changes in leptin concentration may not always reflect changes in adiposity and in such cases may be due to the influence of other modulators of leptin synthesis.