Sex Hormone Profile in Pubertal Boys With Gynecomastia and Pseudogynecomastia

J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgaa044. doi: 10.1210/clinem/dgaa044.


Content: Gynecomastia (defined by proliferation of glandular elements) and pseudogynecomastia (defined by adipose tissue) are frequent in pubertal boys. An association with sex hormones and the growth hormone axis has been discussed.

Objective: The objective of this work is to compare sex hormones, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) between boys with gynecomastia and pseudogynecomastia (separation by ultrasound).

Design: An observational study was performed.

Setting: The setting of this study was an outpatient clinic.

Participants: A total of 124 pubertal boys (mean age 14 ± 2 years) with breast enlargement and 84 healthy boys (mean age 14 ± 2 years) without breast enlargement participated in this study.

Interventions: No interventions were performed.

Main outcome measures: Measurements were taken for sex hormones (progesterone, estradiol [E2], estriol, estrone, androstendione, testosterone [T], dihydrotestosterone) measured by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1, and IGFBP-3.

Results: Eighty-six boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia, the E2/T ratio (median 22, interquartile range [IQR] 8-75) was significantly (P < .05) higher compared to boys with pseudogynecomastia (median 12, IQR 5-21) or healthy controls without breast enlargement (median 18, IQR 6-44) even after adjustment for testes volume. T concentrations were significantly (P < .05) lower in boys with gynecomastia (median 1.8, IQR 0.7-4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3, IQR 1.4-6.9 nM/L) or healthy controls without breast enlargement (median 3.1, IQR 0.6-7.6 nM/L). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to other sex hormones, prolactin, IGF-1, or IGFBP-3 concentrations.

Conclusions: True gynecomastia is characterized by a relative T deficiency to E2 concentrations in contrast to pseudogynecomastia.

Trial registration: NCT00435734.

Keywords: IGF-1; IGFBP-3; androgens; dihydrotestosterone; estradiol; estrogens; gynecomastia; prolactin; pseudogynecomastia; testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Diagnosis, Differential
  • Follow-Up Studies
  • Gonadal Steroid Hormones / metabolism*
  • Gonadotropins / metabolism
  • Gynecomastia / classification
  • Gynecomastia / metabolism
  • Gynecomastia / pathology*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Prognosis
  • Prolactin / metabolism
  • Puberty*


  • Biomarkers
  • Gonadal Steroid Hormones
  • Gonadotropins
  • IGF1 protein, human
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Prolactin

Associated data