An Atlas of Lumps and Bumps, Part 35: Neonatal Breast Hypertrophy and Pubertal Gynecomastia
Neonatal Breast Hypertrophy
During pregnancy, the placenta transforms dehydroepiandrosterone and dehydroepiandrosterone sulfate to estrone and estradiol.1-3 Breast hypertrophy in newborn infants can be readily explained by the presence of high levels of maternal estrogens. The estrogens enter the infant via the placental-fetal circulation and stimulate breast glandular proliferation in the infant.1-5 Also, the falling estrogen levels in the maternal circulation towards the end of the pregnancy may trigger the secretion of prolactin from the neonate’s pituitary gland with resultant breast hypertrophy and sometimes galactorrhea.6-8 Neonatal breast hypertrophy is observed in approximately 70% of neonates (Figure 1) and is associated with galactorrhea in 5% of cases.6
Fig. 1 Neonatal breast hypertrophy is observed in approximately 70% of neonates.
The condition occurs in both male and female neonates.8,9 Neonatal breast hypertrophy is asymptomatic.8 The breast enlargement can be unilateral but more often bilateral.8 Neonatal breast hypertrophy is not usually evident at birth and often becomes apparent in the first week of life.10 The condition is transient and usually regresses spontaneously in 2 to 3 weeks in non-breastfed infants but may persist longer in breastfed infants.1-3 Neonatal breast hypertrophy usually subsides within the first year of life and in the majority of cases within 6 months.1-3,8
Pubertal gynecomastia is a physiologic enlargement of the male glandular breast tissue (Figure 2) that often develops in adolescent boys between 10 and 12 years of age, with a peak prevalence of 40% to 65% between 13 and 14 years of age.1,3,9,11
Fig. 2 Pubertal gynecomastia is a physiologic enlargement of the male glandular breast tissue with a peak prevalence of 40 to 65% between 13 and 14 years of age.
This is followed by a decline in incidence in late teenage years.12 The breast development is most often Tanner stage 2 or 3 and is usually bilateral.9,11,12 Sometimes, the degree of breast development is so minor that it goes unrecognized unless intentionally searched for by palpation.1,3 Alternatively, adolescents with pubertal gynecomastia may complain of a lump behind the nipple.11 The lump may be tender for a few months, but the tenderness tends to gradually resolve as the glandular breast tissue undergoes fibrosis and the stretching of the breast tissue diminishes.11 The condition usually resolves over a period of months to 2 years in 85 to 90% of cases.9,11 In 5% to 15% of cases, the condition may persist beyond 17 years of age.9,11 Gynecomastia that persists after age 17 years is unlikely to spontaneously regress.2
The condition is usually idiopathic and is regarded as a part of normal development in adolescent boys.1,3,9 Transient development of breast tissue at the time of puberty is believed to result from a short-lived increase in plasma estrogens compared with plasma androgens.13 At puberty, both the adrenal glands and the testes are capable of producing androgens and estradiol and there is good evidence for increased peripheral conversion of testosterone to estradiol.1,3,9,13 In addition, insulin-like growth factor-1 (IGF-1) and leptin levels are significantly higher in boys with pubertal gynecomastia.9,14,15 Leptin is capable of activating estrogen receptors as well as increasing aromatase enzyme activity in breast tissue, with resultant gynecomastia.15-17 IGF-1 also has a role in the pathogenesis of pubertal gynecomastia.9 In a recent study of 106 Danish adolescent boys, 52 (49%) had gynecomastia.18 Adolescent boys with physiological gynecomastia reached peak height velocity at a significantly younger age than boys who did not have gynecomastia.18 Boys with physiological gynecomastia had significantly higher serum levels of IGF-1, estradiol, free testosterone, and FSH.18 Pubertal gynecomastia is more common in adolescent boys with the GG genotype of rs3808350 and those with the AA genotype of rs3808351.19 Zinc deficiency and vitamin D deficiency may contribute to the development of pubertal gynecomastia.20,21
Leung AKC, Barankin B, Lam JM, Leong KF. An Atlas of Lumps and Bumps, Part 35: Neonatal Breast Hypertrophy and Pubertal Gynecomastia. Consultant. 2023;63(11):e6. doi:10.25270/con.2023.11.000002
Alexander K. C. Leung, MD, #200, 233 16th Ave NW, Calgary, AB T2M 0H5, Canada (email@example.com)
This article is part of a series describing and differentiating dermatologic lumps and bumps. To access previously published articles in the series, visit: https://www.consultant360.com/resource-center/atlas-lumps-and-bumps.
Leung AK. Gynecomastia. Am Fam Phys. 1989;39:215-222.
Leung AK, Pacaud D. Diagnosis and management of galactorrhea. Am Fam Phys. 2004;70:543-550.
Leung AKC, Leung AA. Gynecomastia in infants, children, and adolescents. Recent Pat Endocr Metab Immune Drug Discov. 2017;10:127-137. doi: 10.2174/1872214811666170301124033.
Einav-Bachar R, Phillip M, Aurbach-Klipper Y, Lazar L. Prepubertal gynaecomastia: aetiology, course and outcome. Clin Endocrinol (Oxf). 2004;61:55-60. doi: 10.1111/j.1365-2265.2004.02059.x.
Haibach H, Rosenholtz MJ. Prepubertal gynecomastia with lobules and acini: a case report and review of the literature. Am J Clin Pathol. 1983;80:252-255. doi: 10.1093/ajcp/80.2.252.
Amer A, Fischer H. Images in clinical medicine. Neonatal breast enlargement. N Engl J Med. 2009;360:1445. doi: 10.1056/NEJMicm0707832.
Hung W. Marked neonatal breast hypertrophy in a male with transient hyperprolactinemia. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1996;37(4):286-288.
Jawahar A, Vade A. Sonographic features of physiologic neonatal breast enlargement. J Clin Neonatol. 2014;3:106-108. doi: 10.4103/2249-4847.134701.
Taylor SA. Gynecomastia in children and adolescents. In: Post TW, ed. UpToDate. Waltham, MA. Accessed November 10, 2023.
Kaufman J, Messazos B, Sharples-Blissland N, Cameron F. Extreme physiological gynaecomastia in the neonate: Observation not intervention. J Paediatr Child Health. 2015;51(10):1030-1032. doi: 10.1111/jpc.12903.
Paris F, Gaspari L, Mbou F, Philibert P, Audran F, Morel Y, et al. Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia. Andrology. 2016;4:263-269. doi: 10.1111/andr.12145.
Soliman AT, De Sanctis V, Yassin M. Management of adolescent gynecomastia: An update. Acta Biomed. 2017;88:204-213. doi: 10.23750/abm.v88i2.6665.
Lawrence SE, Faught KA, Vethamuthu J, Lawson ML. Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia. J Pediatr. 2004;145:71-76. doi: 10.1016/j.jpeds.2004.03.057.
Dundar B, Dundar N, Erci T. Leptin levels in boys with pubertal gynecomastia. J Pediatr Endocrinol Metab.2005;18:929-934. doi: 10.1515/jpem.2005.18.10.929.
Nordt CA, DiVasta AD. Gynecomastia in adolescents. Curr Opin Pediatr. 2008;20:375-382. doi: 10.1097/MOP.0b013e328306a07c.
Eren E, Edgunlu T, Korkmaz HA, Cakir ED, Demir K, Cetin ES, et al. Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent. Gene. 2014;541:101-106. doi: 10.1016/j.gene.2014.03.013.
Lazala C, Saenger P. Pubertal gynecomastia. J Pediatr Endocrinol Metab. 2002;15:553-560. doi: 10.1515/jpem.2002.15.5.553.
Mieritz MG, Rakêt LL, Hagen CP, Nielsen JE, Talman ML, Petersen JH, et al. A longitudinal study of growth, sex steroids, and IGF-1 in boys with physiological gynecomastia. J Clin Endocrinol Metab. 2015;100:3752-3759. doi: 10.1210/jc.2015-2836.
Korkmaz HA, Edgünlü T, Eren E, Demir K, Çakir ED, Çelik SK, et al. GPR30 gene polymorphisms are associated with gynecomastia risk in adolescents. Horm Res Paediatr. 2015;83:177-182. doi: 10.1159/000369013.
Erkekoglu P, Durmaz E, Kızılgün M, Özmert EN, Derman O, Yurdakök K, et al. Low zinc levels may contribute to gynecomastia in puberty. J Trace Elem Med Biol. 2017;44:274-278. doi: 10.1016/j.jtemb.2017.09.001.
Kızılkan MP, Akgül S, Akbıyık F, Derman O, Kanbur N. Evaluation of serum vitamin D levels in adolescents with pubertal gynecomastia. Breast Care (Basel). 2016;11:333-337. doi: 10.1159/000451074.