Reproductive Endocrinology Ovulation Physiology

Serum leptin levels and reproductive function during the menstrual cycle

Ahrens K, Mumford SL, Schliep KC, Kissell KA, Perkins NJ, Wactawski-Wende J, Schisterman EF

Published March 2014 American journal of obstetrics and gynecology, 210(3), 248.e1-248.e9
DOI 10.1016/j.ajog.2013.11.009 PMID 24215851 PMC PMC3943486

RRM Academy Synopsis

Leptin rises across the cycle and peaks at the LH surge

A study of 259 healthy women tracked leptin across up to two menstrual cycles. Leptin rose steadily and peaked near the LH surge. Higher leptin also tracked with higher estrogen, progesterone, and testosterone, and with lower FSH.

Key Findings

  • Leptin levels rose from menses to a mid-cycle peak at the LH surge and remained higher than menses levels through the late luteal phase (p < 0.01).
  • Each 10% rise in leptin across the cycle tracked with higher estradiol (2.2%; 95% CI, 1.5 to 3.0) and higher luteal progesterone (2.1%; CI, 0.5 to 3.7).
  • The same leptin rise tracked with lower FSH (-0.7%; CI, -1.1 to -0.4), alongside higher testosterone (0.6%; CI, 0.3 to 0.9) and higher ovulatory LH (1.2%; CI, 0.0 to 2.3).
  • At the expected LH surge, leptin showed a moderate inverse link to sporadic anovulation after adjustment (odds ratio, 0.58 per log increase in leptin; 95% CI, 0.28 to 1.22).
  • Leptin levels in just the first half of the cycle were not linked to anovulation odds (p > 0.31); anovulation occurred in 42 of 509 cycles (8.3%) overall.

Interpretation

This cohort study followed 259 healthy women ages 18 to 44 across up to two menstrual cycles; none used hormonal birth control. Leptin rose steadily across the cycle. Leptin tracked with the shifts in estradiol, progesterone, testosterone, and FSH that drive ovulation. The authors note these hormone relationships are likely bidirectional, forming a feedback loop. The findings support larger studies on leptin's role in timing ovulation.

RRM Context

Other research also links body fat, energy balance, and leptin to ovulation. Reproductive hormones shift together across the cycle, in a pattern that cycle charting tracks. Low energy intake and low body fat have also been linked to missed ovulation. Restorative reproductive medicine's cycle-charting approach is built to catch patterns like this.

Abstract

Objective

The purpose of this study was to investigate the role of leptin on reproductive hormones and ovulation.

Study Design

The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for ≤2 menstrual cycles (n = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone, and testosterone were measured ≤8 times per cycle. The association of time-varying leptin and reproductive hormones over the cycle was estimated with the use of linear mixed models that were adjusted for percent body fat and age with inverse probability weighting for time-varying physical activity, caloric intake, and other reproductive hormones. The odds ratio for sporadic anovulation (n = 42 cycles) was estimated with the use of generalized linear models that were adjusted for percent body fat and age.

Results

Geometric mean serum leptin levels increased from menses to the late luteal phase (16.7-20.4 ng/mL; P < .01), with a mid-cycle peak (21.7 ng/mL) at the time of the LH surge (P < .01). A 10% higher leptin level across the menstrual cycle was associated with higher estradiol levels (2.2%; 95% CI, 1.5-3.0), luteal progesterone levels (2.1%; 95% CI, 0.5-3.7), ovulatory LH levels (1.2%; 95% CI, 0-2.3), testosterone levels (0.6%; 95% CI, 0.3-0.9), and lower follicle-stimulating hormone levels (-0.7%; 95% CI, -1.1 to -0.4). Leptin at the time of the expected LH surge was moderately inversely associated with sporadic anovulation (per log increase in leptin; adjusted odds ratio, 0.58; 95% CI, 0.28-1.22).

Conclusion

The association that was observed between leptin level and reproductive function points to a possible relationship between serum leptin level and enhanced fertility.

Topics

By this author

Related research

Reproductive Endocrinology › Ovulation Physiology › Anovulation · Menstrual Cycle › Cycle Physiology › Hormonal Regulation
Katherine Ahrens, Sunni L Mumford, Karen C Schliep, Kerri A Kissell, Neil J Perkins, Jean Wactawski-Wende, Enrique F Schisterman
Kathy Ahrens, Kate Ahrens, Katie Ahrens, K Ahrens, S Mumford, K Schliep, K Kissell, N Perkins, J Wactawski-Wende, E Schisterman
PMID 24215851 24215851 DOI 10.1016/j.ajog.2013.11.009 10.1016/j.ajog.2013.11.009 Ahrens et al. 2014, Ahrens 2014