Longitudinal Investigation of Pubertal Milestones and Hormones as a Function of Body Fat in Girls

J Clin Endocrinol Metab. 2021 May 13;106(6):1668-1683. doi: 10.1210/clinem/dgab092.


Context: Epidemiologic studies have demonstrated that overweight/obese girls (OW/OB) undergo thelarche and menarche earlier than normal weight girls (NW). There have been no longitudinal studies to specifically investigate how body weight/fat affects both clinical and biochemical pubertal markers in girls.

Objective: To investigate the effect of total body fat on reproductive hormones and on the maturation of estrogen-sensitive tissues during puberty in girls.

Methods: Ninety girls (36 OW/OB, 54 NW), aged 8.2 to 14.7 years, completed 2.8 ± 1.7 study visits over 4 years. Visits included dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and assessment of menarchal status. The effect of TBF on pubertal markers was determined using a mixed, multistate, or Cox proportional hazards model, controlling for baseline BMORPH.

Results: NW were older than OW/OB (11.3 vs 10.2 years, P < .01) at baseline and had more advanced BMORPH (P < .01). Luteinizing hormone, estradiol, and ovarian and uterine volumes increased with time with no effect of TBF. There was a time × TBF interaction for follicle-stimulating hormone, inhibin B, estrone, total and free testosterone, and androstenedione: Levels were initially similar, but after 1 year, levels increased in girls with higher TBF, plateaued in girls with midrange TBF, and decreased in girls with lower TBF. Girls with higher TBF progressed through BMORPH stage D more slowly but achieved menarche earlier than girls with lower TBF.

Conclusion: In late puberty, girls with higher TBF demonstrate differences in standard hormonal and clinical markers of puberty. Investigation of the underlying causes and clinical consequences of these differences in girls with higher TBF deserves further study.

Trial registration: ClinicalTrials.gov NCT02583646.

Keywords: adolescent; body fat; neuroendocrine; obesity; puberty.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue / physiology*
  • Adolescent
  • Adolescent Development / physiology
  • Body Composition / physiology*
  • Child
  • Female
  • Humans
  • Longitudinal Studies
  • Menarche / physiology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Overweight / metabolism
  • Overweight / physiopathology
  • Puberty / physiology*
  • United States / epidemiology

Associated data

  • ClinicalTrials.gov/NCT02583646