Physiological Gynecomastia Common in Pubertal Boys

Miriam E Tucker

August 24, 2015

Physiological gynecomastia is common in pubertal boys and appears to be associated with increased levels of insulinlike growth factor-1 (IGF-1) and pubertal growth, but not with a shift in the balance between estrogen and testosterone, a new study suggests.

The findings were published online August 19 in the Journal of Clinical Endocrinology and Metabolism by Mikkel G Mieritz, MD, a PhD student working in the department of growth and reproduction, Rigshospitalet, University of Copenhagen, Denmark, and colleagues.

Physiological gynecomastia is generally thought to be related to an imbalance in the estrogen/testosterone ratio favoring estrogen because gynecomastia has been seen in conditions known to affect that balance, such as Klinefelter syndrome. However, sex steroid imbalances have rarely been detected in serum samples from boys with physiological gynecomastia, the authors note.

"The point of our research is to try to explain an extremely common phenomenon that is lacking a full physiological explanation. I believe we have come a lot closer to giving these boys an answer to why some of them develop breast tissue and others do not. Hopefully this will help the boys not to worry that much or feel less anxious going through puberty," Dr Mieritz told Medscape Medical News.

Hormonal Differences, but No Estrogen/Testosterone Imbalance

The 106 study subjects were participants in the longitudinal Copenhagen Puberty Study, in which healthy Danish boys were examined every 6 months from 2006 to 2014. The median age at first examination was 9 years.

Gynecomastia — the development of glandular tissue recognized by palpation at the level of the nipple — developed in 49% (52) of the boys during follow-up at a median age of 13 years and most frequently during pubertal stages G3 and G4 (mid-puberty).

Of those 52, 14 (27%) developed intermittent gynecomastia. Of those, six had two or three examinations without gynecomastia lasting a median of 2 years, while the other eight had just one intermittent exam without gynecomastia.

The median gynecomastia duration was 1.9 years (range, 1.1–2.6), and 19 of the boys still had breast development when the study ended.

Growth patterns differed significantly between those with and without gynecomastia, with peak height velocity occurring at 13.5 vs 13.9 years, respectively (P = .027). The boys who developed gynecomastia also had significantly more advanced pubic-hair development (P = .001 for a given adjusted age), although there was no difference in genital or testicular development.

Other measures such as weight, height, body mass index, and percentage body fat did not differ between groups.

Using both chronological and adjusted age (based on predicted height), the groups with and without gynecomastia had significantly different levels of IGF-1 (P = 0.000 for adjusted age), follicle-stimulating hormone (P = .03), testosterone (P = .006), free testosterone (P < .001), estradiol (P = .013), and follicle-stimulating-hormone/inhibin-B ratio (P = .01).

The group with gynecomastia had lower levels of serum anti-Müllerian hormone (P = .003 for adjusted age) and sex-hormone–binding globulin (P = .001), but no differences were found for luteinizing hormone, estradiol/testosterone ratio, or IGF-binding protein 3.

In their discussion, Mieritz and colleagues note that IGF-1 together with estrogen is essential for the growth of breast tissue, and it appears that the effect of growth hormone on breast growth is mediated through IGF-1. "The stimulatory effect of IGF-1 on breast formation was synergized by [estradiol], which was also elevated in boys with gynecomastia in our study. However, serum testosterone was similarly elevated, leaving the estradiol/testosterone ratio unaltered."

Clinically, Dr Mieritz told Medscape Medical News, "In general, there is no need to be concerned about gynecomastia in a pubertal boy. The main task in the clinic will be to reassure the boy and his family that the condition is usually benign; however, when dealing with breast development in boys/men I believe you should always keep the serious and treatable causes in mind."

He added, "The IGF-1 levels in these boys were not elevated beyond the normal limits, but if you have a kid with pathologically elevated IGF-1 levels this of course calls for further investigation."

Dr Mieritz and colleagues have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online August 19, 2015. Abstract