|Year : 2017 | Volume
| Issue : 3 | Page : 182-184
Gynaecomastia in AIDS patient: An association with zidovudine treatment
Himanshu Bhusan Sahoo1, Prasanna Kar2, Bandana Rath1
1 Department of Pharmacology, MKCG Medical College and Hospital, Berhampur, Odisha, India
2 Art Center, MKCG Medical College and Hospital, Berhampur, Odisha, India
|Date of Web Publication||27-Oct-2017|
Himanshu Bhusan Sahoo
Department of Pharmacology, MKCG Medical College and Hospital, Berhampur - 760 001, Odisha
Source of Support: None, Conflict of Interest: None
Adverse drug reactions (ADRs) occupy a significant role in the etiology of gynecomastia. Gynecomastia is an ADR, rarely formed due to some antiretroviral drugs. Zidovudine is a first-line drug of choice in AIDS patients, but consumption of this drug has not been reported yet for gynecomastia as an adverse effect. Here, we present the case of a 36-year-old male, who developed bilateral gynecomastia following zidovudine use and was completely regressed after discontinuation. Discontinuation of the zidovudine is quite efficient approach without any pharmacological or surgical treatment.
Keywords: Adverse drug reaction, antiretroviral drugs, gynecomastia, zidovudine
|How to cite this article:|
Sahoo HB, Kar P, Rath B. Gynaecomastia in AIDS patient: An association with zidovudine treatment. Apollo Med 2017;14:182-4
| Introduction|| |
Gynecomastia is characterized by enlargement of the male breast, caused by glandular proliferation and fat deposition. It occurs due to the physiological changes (i.e., puberty and older ages), systemic diseases, tumors, and certain medication. It can be unilateral or bilateral, symmetrical or asymmetrical, and painless or tender mass from the acute nonspecific stretching of tissues. Today, certain medications were a big issue for gynecomastia. Such as, the introduction of highly active antiretroviral therapy (HAART) was used for the treatment of HIV-infected individuals, with reductions in morbidity and mortality. A number of cases of gynecomastia associated with HAART have been reported in HIV-infected men. The incidence of gynecomastia in AIDS patient was 0.8% per year with a prevalence of 2.8% in those treated longer than 2 years. HAART includes stavudine, didanosine, efavirenz, nevirapine, and protease inhibitors has been reported gynecomastia in HIV-infected men. Zidovudine is belonged to nucleoside reverse transcriptase inhibitors (NRTIs) used as a first line of drug in HAART. However, the frequency of zidovudine-associated gynecomastia in HIV-infected men has not ever been reported yet.
| Case Report|| |
A 36-year-old male patient, who had neither smoker nor alcoholic habit, was prescribed antiretroviral therapy (ART) of zidovudine 300 mg, lamivudine 150 mg, and nevirapine 200 mg OD for AIDS. However, the patient presented with a complaint of bilateral breast swelling and pain after 16 months of the above ART medication [Figure 1]. Bilateral nodular gynecomastia and swollen glandular tissue in the retroareolar region were detected by mammography and breast ultrasonography. The patient was referred to the Endocrinology and General Surgery Departments and diagnosed with Grade II gynecomastia. The patient was interrogated for any drug or herbal preparation use, except ART regimen. Testicular and abdominal ultrasonography and computed tomography of adrenal glands were unremarkable. His blood pressure and fasting glucose levels were in the normal range during his follow-up. The hepatic, renal, and thyroid function tests and sex hormone levels were all within the normal range. Luteinizing hormone (6.7 mIU/mL), follicle-stimulating hormone (5.4 mIU/mL), testosterone (6.7 ng/dL), thyroid-stimulating hormone (2.3 μIU/mL), prolactin (4.3 ng/mL), and progesterone (0.48 ng/mL) were all in the normal range. Gynecomastia was thought to be induced by zidovudine, and hence it was discontinued. Abacavir (600 mg) was prescribed as zidovudine substitute along with lamivudine and nevirapine. After 3 months of initiation of new ART regimen, the gynecomastia had completely regressed, and there was no swelling or pain anymore. A casualty assessment of probable was made according to the Naranjo adverse drug reaction probability scale.
|Figure 1: Zidovudine induced Gynaecomastia in AIDS Patient (a) front view and (b) side view|
Click here to view
| Discussion|| |
Gynecomastia is mainly characterized by improvement of the male breast; sometimes developed due to body physiology, i.e., particularly in the neonatal period, puberty, and older ages. However, in this case study, the patient is a 36 years old, who does not belong to any of above periods. Liver cirrhosis, chronic kidney failure, hyperthyroidism, and testicular or adrenal tumors are also prime causes of gynecomastia. None of these illnesses were found in our patient. Another mechanism of gynecomastia is mostly established due to imbalance between the androgen and estrogen. Such hormonal imbalance was not also found in our patient.
Drug-induced gynecomastia comprises approximately 10%–20% of all types of gynecomastias. These drug-induced gynecomastias generally regress after medication discontinuation, as have happened in our case. Certain antiretroviral drugs such as stavudine, didanosine, efavirenz, nevirapine, and protease inhibitors have been reported to induce gynecomastia. Among above antiretroviral drugs, efavirenz has shown more prominently to cause bilateral or unilateral gynecomastias.,, However, there is a lack of reports found on zidovudine associated with gynecomastia. The previous scientific literature claims that zidovudine has gynecomastia potential.,,
Zidovudine is frequently used NRTIs that is prescribed as a first-line treatment to AIDS patients. In our case study, the patient was taken zidovudine along with lamivudine and nevirapine, all of which may also have potential to cause gynecomastia as a rare side effect. It is not easy to specify which drug causes gynecomastia when many of the above-stated drugs are used. After 3 months of withdrawal of zidovudine, the gynecomastia was automatically regressed. No medical or surgical treatment was required to recover from gynecomastia. Therefore, we suspected that zidovudine was the suspected agent which is responsible for the gynecomastia.
Benign breast disorders comprise infections and changes in the breast stroma including pseudoangiomatous stromal hyperplasia, lipomastia, and true gynecomastia. Lipomastia occurred due to deposition of adipose tissue in the setting of a lipodystrophy syndrome, whereas true gynecomastia arises due to an enlargement of the male breast by glandular proliferation. There is evidence that an increase in estrogen levels and a decrease in testosterone levels can lead to gynecomastia. These hormonal imbalances may be due to testicular neoplasia, renal or hepatic diseases, certain drugs, and primary/secondary hypogonadism. Hypoandrogenism was also a primary cause of gynecomastia in HIV-infected men. In most of the gynecomastia cases, there was an imbalance between estrogenic and androgenic activity over breast. Estrogens stimulate breast tissue growth whereas androgens antagonize breast tissue growth. Another cause of gynecomastia is the elevation of serum prolactin levels. Elevated prolactin levels may suppress gonadotropin release, producing secondary hypogonadism, which contributes to the development of gynecomastia., Moreover, not all patients with hyperprolactinemia have caused gynecomastia. In our case study, the patient had found a normal hormonal level at the time of gynecomastia.
The frequency of specific antiretroviral drug and its relationship with gynecomastia need to be clarified. The specific goals were to assess the frequency of gynecomastia in HIV-infected men receiving HAART and determine its association with antiretroviral drugs and hormone abnormalities. It is important to educate health-care professionals about the gynecomastia and lipodystrophy on physical examination. This distinction is important to avoid incorrect substitution of drugs as lipodystrophy is usually caused by NRTIs. In our case study, the substitution of abacavir for zidovudine is considered safe and maintains virologic suppression in most of the patients.
| Conclusion|| |
Zidovudine may induce gynecomastia in HIV-infected patients on ART with complete resolution after withdrawal of zidovudine. Early recognition and differentiation from lipodystrophy are important to timely and correctly manage this adverse effect to improve health, sustain adherence to ART, and to reduce psychosocial stigma.
The authors would like to thanks to Dr C.S. Maharana (Professor in Pharmacology) and Dr R.M.V. Rao (SMO, ART center) for their valuable guidance and suggestion.
Financial support and sponsorship
NCC-PvPI, Indian Pharmacopoeia Commission, Ghaziabad, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Carlson HE. Gynecomastia. N
Engl J Med 1980;303:795-9.
Narula HS, Carlson HE. Gynecomastia. Endocrinol Metab Clin North Am 2007;36:497-519.
Paech V, Lorenzen T, von Krosigk A, Graefe K, Stoehr A, Plettenberg A, et al.
Gynaecomastia in HIV-infected men: Association with effects of antiretroviral therapy. AIDS 2002;16:1193-5.
Piroth L, Grappin M, Petit JM, Buisson M, Duong M, Chavanet P, et al.
Incidence of gynecomastia in men infected with HIV and treated with highly active antiretroviral therapy. Scand J Infect Dis 2001;33:559-60.
Mira JA, Lozano F, Santos J, Ramayo E, Terrón A, Palacios R, et al.
Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: Association with efavirenz and didanosine treatment. Antivir Ther 2004;9:511-7.
Köklü E, Arslan Ş, Yüksel İÖ, Bayar N, Demirci D. Nebivolol-induced gynecomastia. J Pharmacol Pharmacother 2015;6:166-8.
Braunstein GD. Gynecomastia. N
Engl J Med 1993;328:490-5.
Catherine O. Antiretroviral adverse drug reactions and their management. CME 2011;29:234-7.
Kumarasamy N, Patel A, Pujari S. Antiretroviral therapy in Indian setting: When & what to start with, when & what to switch to? Indian J Med Res 2011;134:787-800.
] [Full text]
Jover F, Cuadrado JM, Roig P, Rodríguez M, Andreu L, Merino J, et al.
Efavirenz-associated gynecomastia: Report of five cases and review of the literature. Breast J 2004;10:244-6.
Giuseppe R, Mauro M, Chiara B. Drug-induced gynecomastia. Focus Farmacovigilanza 2013;77:2.
Ismail AA, Barth JH. Endocrinology of gynaecomastia. Ann Clin Biochem 2001;38:596-607.
Pantanowitz L, Connolly JL. Pathology of the breast associated with HIV/AIDS. Breast J 2002;8:234-43.
Andò S, De Amicis F, Rago V, Carpino A, Maggiolini M, Panno ML, et al.
Breast cancer: From estrogen to androgen receptor. Mol Cell Endocrinol 2002;193:121-8.
Turkington RW. Serum prolactin levels in patients with gynecomastia. J Clin Endocrinol Metab 1972;34:62-6.
Shirley AB, Harold EC. Gynecomastia: Its features and when and how to treat it. Cleve Clin J Med 2004;71:511-7.
van Ramshorst MS, Kekana M, Struthers HE, McIntyre JA, Peters RP. Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: A case report. BMC Pediatr 2013;13:120.