The risk of adverse outcomes in association with use of testosterone products: a cohort study using the UK-based general practice research database

Authors


Dr Susan S Jick DSc, Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, 11 Muzzey Street, Lexington, MA 02421, USA. Tel.: +1 781 862 6660, Fax: +1 781 862 1680, E-mail: sjick@bu.edu

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Testosterone products are indicated for primary or secondary hypogonadism and can be delivered through various routes including oral and intramuscular injection.

• While many clinical trials have evaluated the effectiveness of testosterone therapy, there is little information on safety particularly in different formulations.

• Hypertension, polycythemia and prostatic abnormalities (prostatism, benign prostatic hypertrophy or prostate cancer) have been identified as potential adverse effects of testosterone replacement therapy, but data are limited.

WHAT THIS STUDY ADDS

• Risks of prostate cancer and prostatism were similar in users of the oral and injectable testosterone preparations, but risks were higher for hypertension and polycythemia in the injectable compared with the oral testosterone users.

• Risk of benign prostatic hypertrophy was slightly higher in the oral users, but the difference was small and could have been due to bias.

AIMS To study the relative safety of the intramuscular injection formulation of testosterone with oral testosterone undecanoate in relation to the risks for hypertension, polycythemia, prostate cancer, benign prostatic hypertrophy (BPH) and prostatism.

METHODS We conducted a cohort study of men in the UK based General Practice Research Database who were users of the oral undecanoate and injectable forms of testosterone and calculated rates and relative risks of hypertension, polycythemia and prostate conditions (cancer, BPH and prostatism).

RESULTS We identified 5841 men who received at least one study testosterone preparation. There were 202 cases of hypertension (crude incidence rates (IRs) for oral and injectable testosterone respectively 12.3/1000 person-years (PY) and 14.4/1000 PY). There were 146 cases of polycythemia (IRs 1.2/1000 PY and 10.1/1000 PY), 46 cases of prostate cancer (IRs 2.5/1000 PY and 1.8/1000 PY), 106 cases of BPH (IRs 4.1 /1000 PY and 2.1/1000 PY), and 251 cases of prostatism (IRs 8.4/1000 PY and 6.1/1000 PY respectively). Adjusted relative risks for oral compared with injectable testosterone were 0.8 (95% CI 0.6, 1.2) for hypertension, 0.13 (0.05, 0.35) for polycythemia, 1.1 (0.7, 1.7) for prostate cancer, 1.5 (1.1, 2.2) for BPH and 1.1 (0.8, 1.4) for prostatism.

CONCLUSIONS Risks of prostate cancer and prostatism were similar in users of the two preparations, but risks were higher for hypertension and polycythemia in the injectable compared with the oral testosterone users. Risk of BPH was slightly higher in the oral users, but the difference was small and could have been due to bias.

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