Risk factors for gynaecomastia include hepatitis C, fat loss, and low testosterone

Low levels of testosterone have been identified as a risk factor for the development of gynaecomastia (breast enlargement) in HIV-positive men taking highly active antiretroviral therapy (HAART) in a Spanish study published in the November 15^th edition of Clinical Infectious Diseases. The investigators from Barcelona also found that gynaecomastia was rare, and that coinfection with hepatitis C virus and lipoatrophy were independent risk factors for the development of the condition.

Gynaecomastia affects less than 1% of HIV-negative adult males. Although cases have been reported in HIV-positive men taking HAART, studies have been limited to small case series which often lacked data on participants’ hormonal levels.

Accordingly, investigators in Barcelona conducted a case-control study of the prevalence, risk factors and potential hormonal abnormalities associated with the condition. Data were gathered in early 2003 from a total of 2275 adult male HIV-positive patients. Gynaecomastia was diagnosed by physical examination and ultrasound, and case-controls were randomly selected.

In total, 44 cases of breast enlargement were detected and forty of these were confirmed as gynaecomastia using ultrasound examination. This provided an overall prevalence of gynaecomastia in the clinic population of 1.8%.

Compared to controls, individuals were significantly more likely to be coinfected with hepatitis C virus (p = 0.02), and to have fat loss (lipoatrophy; p = 0.03). Patients with gynaecomastia were also significantly more likely to currently be taking d4T (stavudine, Zerit; p = 0.004), efavirenz (Sustiva; p = 0.04), and AZT (zidovudine, Retrovir; p = 0.008). However, total exposure to these drugs did not differ significantly between individuals with gynaecomastia and control patients.

In multivariate logistic regression analysis, co-infection with hepatitis C virus (p = 0.003), lipoatrophy (p = 0.005), and current use of d4T (p = 0.05) and efavirenz (p = 0.008) remained independently associated with gynaecomastia.

When the investigators looked at levels of hormones in both patients with gynaecomastia and controls, they found that 67% of patients with breast enlargement had hypogonadism (low levels of testosterone) compared to 38% of controls (p = 0.008).

The investigators then included hypogonadism as a variable in their multivariate logistic regression model and found that hypogonadism (p = 0.003), hepatitis C virus coinfection (p = 0.003), and lipoatrophy (p = 0.005) were all significantly related to gynaecomastia.

“We found that 1.8% of HIV-infected men in our cohort had gynaecomastia”, write the investigators.

Regarding risk factors they note that “lipoatrophy and chronic hepatitis C were independently associated” with the side-effect. However, they add that gynaecomastia has been more commonly reported with fat gain than fat loss in the literature, and that none of the patients with hepatitis C had end-stage liver disease.

Although the investigators also found that hypogonadism was associated with gynaecomastia, it was also “not unusual among control subjects,” and they call for further study of this.

In many cases gynaecomastia improved or resolved in a significant number of patients without treatment, and testosterone patches and injections were safely used to treat the condition.