Safety of testosterone replacement therapy

Safety of testosterone replacement therapy
Testosterone therapy is characterized by a wide margin of safety. Occasional adverse events for which there is evidence of association with testosterone administration include erythrocytosis (abnormally high numbers of red blood cells); acne and oily skin, particularly at the beginning of treatment and generally transient; reduced sperm production and fertility.1 Rarely, transient gynecomastia can occur at the beginning of treatment; in isolated cases frequent or sustained erections can occur. In these cases the dose must be reduced or the preparation withdrawn in order to prevent damage resulting from a sustained erection. Use of testosterone in high doses or over prolonged periods can result in clinically insignificant changes in lipid profiles. In predisposed men (e.g. marked obesity, chronic obstructive lung disease) induction or worsening of obstructive sleep apnea may rarely occur.1 The sleep apnea disappears when the testosterone therapy is discontinued.
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  • Contraindications and Precautions

    Contraindications and Precautions

    • Testosterone replacement therapy should only be administered if hypogonadism has been established and other etiology that may be responsible for the signs and symptoms has been excluded.1-7 For example, pituitary tumor; hypopituitarism; diabetes insipidus; Alzheimer’s disease, vascular dementia; hypothyroidism; partial deficiency of adrenocorticotropic hormone; acute infection, inflammatory disease.
    • Although there are no clear indications that androgens actually generate prostatic carcinoma, they can enhance the growth of any existing prostatic carcinoma. Therefore carcinoma of the prostate has to be excluded before starting therapy with testosterone preparations.1-7
    • Androgens must not be given to patients with the very rare male breast cancer. As androgens are aromatized to estrogens, androgen therapy can stimulate proliferation of an estrogen-receptor-positive breast carcinoma.1-7 Gynecomastia, which can occur as a result of hypogonadism, is not a contraindication and usually subsides on androgen therapy.
    • As testosterone replacement therapy can be associated with an increase in hematocrit it should be avoided in patients with erythrocytosis.1-7
    • Because testosterone replacement therapy impairs production of sperm, it should be used with caution in men with fertility concerns.1,6
    • Testosterone replacement therapy is not recommended for use in children. In adolescents, although testosterone therapy may be indicated (e.g. in delayed puberty or other forms of primary or secondary hypogonadism), not all currently available testosterone preparations are approved for use in adolescents. Regulations relevant to your country of practice should be consulted.
    • Other conditions that can potentially be made worse by testosterone therapy include severe lower urinary tract symptoms associated with benign prostatic hypertrophy, severe congestive heart failure, and liver or renal disease.1-7
    • Abuse or overuse of testosterone treatment can be dangerous. For example, using higher than replacement doses to increase muscle bulk can cause acne, decreased testicular size, impotence, liver disease, heart attack, and stroke.4 Physicians should be aware of the signs and symptoms of anabolic abuse.


1 Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.

2 Qoubaitary A, Swerdloff RS, Wang C. Advances in male hormone substitution therapy. Expert Opin Pharmacother 2005; 6(9): 1493-506

3 Seftel A. Testosterone replacement therapy for male hypogonadism: part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents. Int J Impot Res 2007; 19(1): 2-24

4 Sharma V, Perros P. The management of hypogonadism in aging male patients. Postgrad Med 2009; 121(1): 113-21

5 Tung DS, Cunningham GR. Androgen deficiency in men. The Endocrinologist 2007; 17(2): 101-115

6 Zitzmann M, Nieschlag E. Testosterone substitution: current modalities and perspectives. J Reproduktionsmed Endokrinol 2006; 3(2): 109-116

7 ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Aging Male. 2009 Mar;12(1):5-12.
Last updated: 2017