, Volume 64, Issue 17, pp 1861–1891 | Cite as

Androgen Replacement Therapy

Present and Future
  • Louis J. G. Gooren
  • Mathijs C. M. Bunck
Review Article


The major goal of androgen substitution is to replace testosterone at levels as close to physiological levels as is possible. For some androgen-dependent functions testosterone is a pro-hormone, peripherally converted to 5α-dihydrotestosterone (DHT) and 17β-estradiol (E2), of which the levels preferably should be within normal physiological ranges. Furthermore, androgens should have a good safety profile without adverse effects on the prostate, serum lipids, liver or respiratory function, and they must be convenient to use and patient-friendly, with a relative independence from medical services.

Natural testosterone is viewed as the best androgen for substitution in hypogonadal men. The reason behind the selection is that testosterone can be converted to DHT and E2, thus developing the full spectrum of testosterone activities in long-term substitution.

The mainstays of testosterone substitution are parenteral testosterone esters (testosterone enantate and testosterone cipionate) administered every 2–3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone, which are not in the physiological range at least 50% of the time. Also, the generated plasma E2 is usually supraphysiological. A major improvement is parenteral testosterone undecanoate producing normal plasma levels of testosterone for 12 weeks, with normal plasma levels of DHT and E2 also. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3–6 months. However, their use is not widespread. Oral testosterone undecanoate dissolved in castor oil bypasses the liver via its lymphatic absorption. At a dosage of 80mg twice daily, plasma testosterone levels are largely in the normal range, but plasma DHT tends to be elevated. For two decades transdermal testosterone preparations have been available and have an attractive pharmacokinetic profile. Scrotal testosterone patches generate supraphysiological plasma DHT levels, which is not the case with the nonscrotal testosterone patches. Transdermal testosterone gel produces fewer skin irritations than the patches and offers greater flexibility in dosage. Oromucosal testosterone preparations have recently become available.

Testosterone replacement is usually of long duration and so patient compliance is of utmost importance. Therefore, the patient must be involved in the selection of type of testosterone preparation.

Administration of testosterone to young individuals has almost no adverse effects. With increasing age the risk of adverse effects on the prostate, the cardiovascular system and erythropoiesis increases. Consequently, short-acting testosterone preparations are better suited for aging androgen-deficient men.


Testosterone Androgen Androgen Receptor Benign Prostate Hyperplasia Testosterone Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No funding was received to assist in the preparation of this manuscript. Louis Gooren has been a speaker at scientific meetings sponsored by Organon International, Oss, The Netherlands, manufacturer of oral testosterone undecanoate.


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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Endocrinology, Section of AndrologyVU University Medical CenterAmsterdamThe Netherlands

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