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Drug Insight: testosterone preparations

Abstract

Testosterone has been used for substitution therapy in testicular and hypothalamopituitary diseases for almost six decades, with injectable testosterone esters and implanted testosterone pellets being the mainstay of treatment. Growing interest in the possible use of testosterone in nonclassical situations such as male contraception, aging (late-onset hypogonadism), muscle-wasting conditions like HIV, erectile dysfunction, and female hypoactive sexual disorder has stimulated research, leading to the development of several new modes of administration of testosterone. Transdermal patches, gels, mucoadhesive sustained-release buccal tablets and long-acting testosterone esters are designed to provide testosterone levels that approximate normal physiologic levels, to improve patient acceptability, and to further increase the number of treatment options available. In this Review, we briefly describe the chemistry, mechanism of action, and metabolism of testosterone. We then discuss the pharmacokinetics, advantages, and disadvantages of various formulations and summarize the various preparations currently available.

Key Points

  • Testosterone is an effective and safe form of physiologic hormone replacement for lifelong treatment of male hypogonadism

  • The choice of testosterone preparation is often a compromise between multiple considerations including perceived efficacy, convenience, adverse effects, cost, availability, and patient acceptance and preference

  • Testosterone pellets, surgically implanted, provide stable physiologic levels for 4–6 months, although they are not universally available

  • Shorter-acting parenteral testosterone esters are associated with supraphysiologic and subphysiologic fluctuations in circulating testosterone levels

  • Long-acting testosterone undecanoate injections and testosterone gel are more likely to provide stable physiologic levels than other preparations

  • Selective androgen-receptor modulators are promising novel nonsteroidal synthetic compounds, currently under clinical testing, that mimic the biological effects of testosterone with tissue-selective actions

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Figure 1: Esterification and alkylation of the testosterone molecule into various derivatives.
Figure 2: Overview of the metabolism of testosterone.
Figure 3: The mechanism of action of testosterone.
Figure 4: Multidose pharmacokinetic simulations (using single-dose pharmacokinetic parameters) of testosterone enanthate, 250 mg injection every 2 weeks (upper panel), every 3 weeks (middle panel), and every 4 weeks (lower panel).

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Acknowledgements

We are grateful to Mr Harry Heyes from the medical illustration department at Manchester Royal Infirmary for his assistance with the figures.

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Correspondence to Upendram Srinivas-Shankar.

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Competing interests

Dr U Srinivas-Shankar has received reimbursement for attending a conference from Schering AG, Berlin, Germany.

Professor FCW Wu has served as a paid consultant and received lecture fees and travel grants from Schering AG, Berlin, Germany; Organon BV Oss, The Netherlands; Pierre Fabre Medicaments, Castre, France; Ardana, Edinburgh, UK; and Proctor and Gamble, USA.

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Srinivas-Shankar, U., Wu, F. Drug Insight: testosterone preparations. Nat Rev Urol 3, 653–665 (2006). https://doi.org/10.1038/ncpuro0650

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