11th April 2024

Gynaecomastia

Background 

Gynaecomastia is a benign proliferation of the glandular breast tissue, as opposed to pseudo-gynaecomastia, that is due to fat deposition. It occurs in 35% of men and is most common in men between 50 – 69, although it is also common in adolescence and infancy.

It is caused by an imbalance between circulating oestrogen and androgen. Androgens have an apoptotic and anti-proliferative effect on glandular breast tissues, whereas oestrogen promotes proliferation. Any increase in free circulating oestrogen or decrease in testosterone can therefore lead to gynaecomastia. The four main mechanisms through which this can occur are shown in Fig. 1.

Image source: Authors’ Own Image

The cause is often multi-factorial and will vary depending on patient age. For instance, older males experience a decrease in testosterone production and an increase in adipose tissue, which increases the aromatisation of androgens into estrone (E1) and oestradiol (E2). Drugs are a common cause and act through suppression of androgen production, promotion of oestrogens or an increase in prolactin, resulting in hypogonadism.

The main causes are as follows:

Table 2. Causes of gynaecomastia

Investigations

Initial blood tests should include morning testosterone, LFTs, TFTs and U&Es. If testosterone is low, then it should be repeated alongside FSH, prolactin, oestradiol and SHBG. If the history or examination is suggestive of testicular malignancy, then β-hCG, AFP and LDH should be performed alongside testicular ultrasound.

Management

All men with pathological gynaecomastia should be referred for specialist advice. Adolescents should not be treated unless symptoms have been present for at least 2 years, as in most cases, gynaecomastia is transient in this age group. Men whose gynaecomastia is likely secondary to drugs should be offered alternative treatment.

Medical management has a high success rate but is ineffective once breast fibrosis is established. Danazol is a synthetic steroid with anti-gonadotrophic and anti-estrogenic effects that is licensed to treat gynaecomastia. However, it is also associated with weight gain, which can exacerbate symptoms. Common off-licence medications include tamoxifen (a selective oestrogen receptor modulator) and aromatase inhibitors (e.g. letrozole, anastrozole). Tamoxifen should be avoided in patients with a history of venous thromboembolism.

Surgical intervention should be considered for men with fibrotic gynaecomastia.

References

• National Institute for Health and Care Excellence (UK). Clinical Knowledge Summaries (CKS). Last revised May 2023. Available at https://cks.nice.org.uk/.
• Thiruchelvam P, Walker J N, Rose K, Lewis J, Al-Mufti R. Gynaecomastia BMJ 2016; 354 :i4833 doi:10.1136/bmj.i4833.
• UpToDate. Clinical features, diagnosis and evaluation of gynaecomastia in adults. Last revised April 2023. Available at https://www.uptodate.com/contents/clinical-features-diagnosis-and-evaluation-of-gynecomastia-in-adults?search=gynecomastia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1