Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-07-01T04:47:06.085Z Has data issue: false hasContentIssue false

22 - Synthesis and pharmacological profiling of new orally active steroidal androgens

Published online by Cambridge University Press:  18 January 2010

E. Nieschlag
Affiliation:
Westfälische Wilhelms-Universität Münster, Germany
H. M. Behre
Affiliation:
Westfälische Wilhelms-Universität Münster, Germany
Get access

Summary

Introduction

There is a general need for new orally active androgens, to be used for androgen replacement therapy and male hormonal contraception. As a substitute for low levels of testosterone in hypogonadal men, therapy with the natural androgen testosterone is the first choice. However, testosterone is an androgen with a relatively low affinity for the androgen receptor. It is metabolically relatively unstable which results in poor oral bioavailability. In addition, testosterone is converted by 5α-reductase into the more potent androgen 5α-dihydrotestosterone (5α-DHT). Early attempts to prevent metabolic instability by 17α-alkylation of androgens (like introduction of 17 α-ethynyl in estrogens and progestagens) were not successful, due to liver toxicity or low androgenic activity (Vida 1969). Another approach to circumvent metabolic instability is esterification of the 17β-OH group of testosterone with long chain fatty acids. Testosterone undecanoate formulated in an oily solution (Andriol®/Andriol TestocapsTM, dissolved in oleic acid and a mixture of castor oil and polypropylene glycol laurate, respectively) is currently the only orally active testosterone derivative. This testosterone ester is hydrolysed by tissue (liver) esterases and testosterone is released (Bursi et al. 2001). However, due to the limited potency of testosterone and limited bioavailability of testosterone undecanoate, relative high doses of Andriol®/Andriol TestocapsTM are required twice a day for human androgen replacement (total dose 160–240 mg).

Although no side effects of testosterone replacement on the prostate have been reported, androgens which are not potentiated upon 5α-reduction in the prostate and skin, like 7α-methyl-19-nortestosterone (MENT) and 19-nortestosterone (nandrolone), are considered prostate-safe androgens (Kumar et al. 1992; Cummings et al. 1998).

Type
Chapter
Information
Testosterone
Action, Deficiency, Substitution
, pp. 665 - 684
Publisher: Cambridge University Press
Print publication year: 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×