Mr X is a 33-year old HIV-positive male patient. He was initiated on antiretroviral therapy (stavudine, lamivudine and efavirenz) in June 2010. In November 2013, the patient developed bilateral gynaecomastia. His latest viral load was undetectable. Other medication history included atenolol, furosemide and minoxodil. How should the patient be managed?

ART-associated gynaecomastia

Gynaecomastia is defined as a benign proliferation of glandular breast tissue in males. The primary mechanism is an imbalance between oestrogens and androgens. Some underlying causes of gynaecomastia include:

• physiological factors - puberty and aging
• endocrine tumours
• endocrine dysfunctions - hypogonadism, hyperthyroidism, obesity
• non-endocrine factors - cirrhosis, renal failure, HIV
• drug-induced factors
• idiopathic factors[1]

ART-associated gynaecomastia occurs with an estimated frequency of 1.8 - 2.9%. [2-4] The antiretrovirals that have been implicated with gynaecomastia include stavudine and didanosine, but the most consistent association has been noted with efavirenz [2-3]. Gynaecomastia may either be unilateral or bilateral and may also be associated with pain. Onset of gynaecomastia is slow, occurring after several months on ART and is associated with immune suppression [5-6]. Resolution of gynaecomastia is slow and may take several months.

Since gynaecomastia is a cosmetic adverse drug reaction, its management is also dependent on the level of distress it causes to the patient. Some cases of gynaecomastia resolve spontaneously with no intervention. However, the general approach is to exclude hypogonadism by measuring serum testosterone. If low, appropriate investigations should be done to identify the cause and appropriate therapy administered. If testosterone is normal, efavirenz may be substituted.

Management of the case

Mr X had a free testosterone done. The level was normal. Efavirenz was implicated as the most likely cause of the gynaecomastia, after excluding other potential causes. The efavirenz was switched to nevirapine. The gynaecomastia resolved after 4 months post substitution. 

Summary of management of ART-associated gynaecomastia

• Take a detailed medication history to exclude other potential drug causes of gynaecomastia
• Exclude hypogonadism, by checking the free serum testosterone
• If free testosterone is low, keep patient on efavirenz and investigate other causes of low testosterone. If testosterone is normal, and the adverse drug reaction is distressing to the patient, substitute efavirenz.