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Oncotarget. 2018 Apr 10;9(27):19415-19426. doi: 10.18632/oncotarget.24767. eCollection 2018 Apr 10.

Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review.

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University of Foggia, Department of Clinical and Experimental Medicine, Foggia, Italy.
University of Catania, Department of Medical, Surgical and Advanced Technologies, "G.F. Ingrassia", Catania, Italy.
University of Campania "L. Vanvitelli", Department of Experimental Medicine, Naples, Italy.
Università degli Studi di Roma "La Sapienza", Department of Public Health, Roma, Italy.
University of Catania, Department of Surgery, Catania, Italy.
University of Campania "L. Vanvitelli", CEINGE Biotecnologie Avanzate S.C. a r.l., Naples, Italy.


Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor. AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via IGF-1. This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation. AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage.


abuse; anabolic-androgenic steroids (AAS); carcinogenicity; insulin-like growth factor 1 (IGF-1); molecular mechanisms

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no conflict of interests, financial or otherwise, regarding the publication of this paper.

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