Efavirenz-Associated Gynecomastia: Report of Five Cases and Review of the Literature

Jover, Federico Blanco; Cuadrado, J.M.; Roig, P; Rodríguez, Marta; Andreu, L; Merino, J.

doi:10.1111/j.1075-122x.2004.21392.x

Cited by 36 publications

(34 citation statements)

References 11 publications

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“…In contrast, previous case series do not report any cases of gynaecomastia in adolescents [6, 7, 12, 15, 17–19]. Cross-sectional data from the general population has shown that gynaecomastia occurs in 4% of adolescent boys aged 10–19 years [20].…”

Section: Discussionmentioning

confidence: 90%

“…The proposed mechanism from in vitro data is that efavirenz mimics the effects of oestrogen on breast tissue [14]. Two other hypothesized mechanisms have been suggested for ART-associated gynaecomastia: immune restoration may increase breast tissue oestrogen availability, and efavirenz has been shown to increase the area under the curve of ethinyl oestradiol by at least 37%, thereby elevating the oestrogen–androgen ratio [15]. …”

Section: Discussionmentioning

confidence: 99%

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Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

et al. 2016

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BackgroundGynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa.MethodsWe identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes.ResultsWe received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%).ConclusionsGynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

et al. 2016

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“…Upon a change of regimen, resolution was seen in all cases after several months. 9 In vitro experiments have suggested that efavirenz activates oestrogen receptors in breast tissue, 10 although subsequent experiments to confirm this finding have not yet been conducted. A systematic review concluded that the quality of the evidence of the association between gynaecomastia and antiretroviral drugs was moderate in general, being most convincing with efavirenz.…”

Section: Discussionmentioning

confidence: 99%

Breast enlargement in Malawian males on the standard first line antiretroviral therapy regimen: Case reports and review of the literature

Kwekwesa¹,

Kandionamaso²,

Winata³

et al. 2015

Mal. Med. J

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1. A 35-year-old man was referred to Zomba Central Hospital in June 2014 from a health center with a presenting complaint of enlarged breasts. This had started gradually, approximately six months prior. He did not experience any pain or discharge from his nipples. He had no other complaints and felt generally healthy. In early 2013 he had been concomitantly diagnosed with pulmonary tuberculosis and HIV infection and was started on cotrimoxazole prophylaxis and antiretroviral therapy (ART) with tenofovir, lamivudine, and efavirenz, which is the standard first-line adult ART regimen, known in Malawi as regimen 5A. At that point, he had WHO clinical stage III HIV disease; a CD4 count was not done. There was no further relevant past medical history. He looked healthy and had normal vital signs. The rest of the physical examination was normal except for bilateral, symmetrical, elastic, and concentric swelling of the breasts, without discrete nodules, skin changes, or lymphadenopathy in the axillae and neck. There were no features of lipodystrophy and no stigmata of chronic liver disease. The genital examination was normal, without palpable abnormalities of the normal-sized testes. Upon laboratory investigation, his CD4 count was 130 cells/µL and a full blood count was normal apart from the presence of macrocytosis. Liver enzymes were unremarkable.2. In October 2014, we saw a 56-year-old male who presented with development of painless bilateral breast enlargement. This had started in May 2014, followed by spontaneous regression and then subsequent worsening from August 2014. The left breast was more conspicuously affected. He also mentioned experiencing weight loss but had no other symptoms. He was diagnosed with HIV infection in 2005 and started on ART in 2008 due to a low CD4 count of 83 cells/µL. While on his first ART regimen-stavudine, lamivudine, and nevirapine-he experienced progressive peripheral neuropathy and was eventually switched to a regimen of zidovudine, lamivudine, and nevirapine, after which his CD4 count was 409 cells/µL and plasma HIV-1 RNA was undetectable. Six months later, in January 2010, he developed severe anaemia, secondary to zidovudine, and his ART regimen was changed again, this time to tenofovir, lamivudine, and efavirenz (regimen 5A). He had no other significant past medical history and the only medications he used were cotrimoxazole prophylaxis and tenofovir, lamivudine, and efavirenz. Bilateral breast enlargement (left more than right, see Figure 1) was the only abnormality found on physical examination, with the same pertinent negative findings as in the first case presented in this report.

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“…Large prospective studies have documented an association between gynaecomastia and EFV and didanosine. 10 EFV is known to induce gynaecomastia by direct oestrogen receptor modulation, 2 an effect that varies with ethnicity and weight. 11 Mutations in CYP2B6 have been reported throughout Africa, 12 as well as in Germany, 13 resulting in impaired hepatic metabolism of EFV.…”

Section: Respiratorymentioning

confidence: 99%

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis

Kratz¹,

El-Shazly²,

Mambuque³

et al. 2017

Mal. Med. J

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Efavirenz-Associated Gynecomastia: Report of Five Cases and Review of the Literature

Cited by 36 publications

References 11 publications

Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

Breast enlargement in Malawian males on the standard first line antiretroviral therapy regimen: Case reports and review of the literature

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis

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