High oestradiol-to-testosterone ratio characterises true gynaecomastia

medwireNews: Pubertal boys with true gynaecomastia have a significantly higher oestradiol-to-testosterone ratio than those with pseudogynaecomastia or healthy controls, observational study data show.

The imbalance in the ratio was due to lower testosterone concentrations in boys with true gynaecomastia, suggesting that the condition may be attributed to a testosterone deficiency relative to oestradiol levels, Thomas Reinehr (University of Witten/Herdecke, Datteln, Germany) and colleagues report in The Journal of Clinical Endocrinology & Metabolism.

The study included 124 pubertal boys (mean age 14 years) who presented to an outpatient clinic with breast enlargement and 84 age-matched boys without breast enlargement. Boys with gynaecomastia due to causes such as Klinefelter syndrome, disorders of sexual development or medication use were excluded from the study.

Ultrasound analysis revealed that 86 of the participants with breast enlargement had true gynaecomastia, defined as benign glandular proliferation in the breast, and 38 had pseudogynaecomastia, defined as adipose tissue proliferation.

The boys with true gynaecomastia were significantly less likely to be obese than those with pseudogynaecomastia (42 vs 86%) and had a significantly smaller breast diameter (9.7 vs 14.9 cm in the left breast).

Liquid chromatography-tandem mass spectrometry showed that the median oestradiol-to-testosterone ratio was significantly higher in the boys with true gynaecomastia than in those with pseudogynaecomastia or in the healthy controls, at 22 versus 12 and 18, respectively.

The difference remained significant after adjustment for testicular volume, which was significantly lower in the boys with gynaecomastia relative to those with pseudogynaecomastia.

However, the researchers note that the oestradiol-to-testosterone ratio varied considerably in the boys with true gynaecomastia (interquartile range, 8–75), thus pointing “towards a multi-causal aetiology of gynecomastia,” they write. By comparison, the interquartile range was 5–21 in the boys with pseudogynaecomastia.

Reinehr and team also found that median testosterone concentrations were significantly lower in boys with gynaecomastia than in those with pseudogynaecomastia or healthy controls without breast enlargement (1.8 vs 4.3 and 3.1 nM/L, respectively), but the difference was less upon adjustment for testicular volume.

In addition, adjusted median levels of luteinising hormone (2.8 vs 3.5 mU/mL) and follicle-stimulating hormone (2.0 vs 2.9 mU/mL) were significantly lower in the boys with gynecomastia relative to those with pseudogynaecomastia, but the values in both groups “were in normal range for pubertal development,” the researchers note.

There was no difference between the groups, however, in the levels of progesterone, oestradiol, oestriol, oestrone, androstendione, dihydrotestosterone, prolactin, insulin-like growth factor 1 or insulin-like growth factor-binding protein-3.

Reinehr et al conclude: “Taken together, our findings suggest that a boy with gynecomastia has a lower activity of the pituitary-testes-axis with lower testosterone concentrations in the presence of a comparable estradiol at the same age.”

They add: “Future longitudinal studies are necessary also to prove that gynecomastia due to transient alteration in the [oestradiol-to-testosterone] ratio is reversible in contrast to pseudogynecomastia.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Endocrinol Metab 2020; doi:10.1210/clinem/dgaa044
Martin Savage
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