Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome

J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385.


Context: To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS.

Objective: To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI.

Design: Cross-sectional study.

Participants: Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33).

Outcome measures: Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis.

Results: All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing.

Conclusion: Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.

Trial registration: NCT02157974 NCT02585830.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Adolescent
  • Circadian Rhythm / physiology*
  • Cross-Sectional Studies
  • Fasting
  • Female
  • Humans
  • Insulin Resistance / physiology*
  • Melatonin / metabolism
  • Obesity / complications
  • Obesity / physiopathology*
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / physiopathology*
  • Saliva / chemistry
  • Sleep / physiology
  • Sleep Disorders, Circadian Rhythm / complications
  • Sleep Disorders, Circadian Rhythm / physiopathology*
  • Time Factors
  • Wakefulness / physiology


  • Melatonin

Associated data