Dihydrotestosterone: Hormone or Autocrine–Paracrine Signal?
Authors: Ronald S. Swerdloff, Christina Wang
Journal: Annals of Internal Medicine (2010)

Editorials16 November 2010Dihydrotestosterone: Hormone or Autocrine–Paracrine Signal?Ronald S. Swerdloff, MD and Christina Wang, MDRonald S. Swerdloff, MDFrom Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90502, and David Geffen School of Medicine at University of California, Los Angeles, CA 90509.Search for more papers by this author and Christina Wang, MDFrom Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90502, and David Geffen School of Medicine at University of California, Los Angeles, CA 90509.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-10-201011160-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The risk–benefit profile of testosterone replacement is a topic of ongoing debate. Men have a progressive decline in serum testosterone levels with age and may have symptoms of testosterone deficiency (andropause) (1–3). Studies of testosterone replacement therapy have suggested benefits of androgen-responsive outcomes, such as increased muscle strength, reduction of fat mass, improvement in bone mineral density (BMD), and improved libido (2). Yet, concerns remain about the potential adverse effects of testosterone replacement therapy on the prostate and the cardiovascular system.Because testosterone affects prostate growth, it has been postulated that androgens that are not 5α-reducible or that result in ...References1. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123-35. [PMID: 20554979] CrossrefMedlineGoogle Scholar2. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al; Task Force Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-59. [PMID: 20525905] CrossrefMedlineGoogle Scholar3. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159:507-14. [PMID: 18955511] CrossrefMedlineGoogle Scholar4. Swerdloff RS, Wang C. Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent. Baillieres Clin Endocrinol Metab. 1998;12:501-6. [PMID: 10332569] CrossrefMedlineGoogle Scholar5. Wang C, Swerdloff RS. Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? [Editorial]. J Clin Endocrinol Metab. 2002;87:1462-6. [PMID: 11932265] CrossrefMedlineGoogle Scholar6. de Lignieres B. Transdermal dihydrotestosterone treatment of ‘andropause’. Ann Med. 1993;25:235-41. [PMID: 7687444] CrossrefMedlineGoogle Scholar7. Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab. 2001;86:4078-88. [PMID: 11549629] CrossrefMedlineGoogle Scholar8. Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab. 2002;87:1467-72. [PMID: 11932266] CrossrefMedlineGoogle Scholar9. Idan A, Griffiths KA, Harwood DT, Seibel MJ, Turner L, Conway AJ, et al. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease. A randomized, placebo-controlled trial. Ann Intern Med. 2010;153:621-32. LinkGoogle Scholar10. Wang C, Iranmanesh A, Berman N, McDonald V, Steiner B, Ziel F, et al. Comparative pharmacokinetics of three doses of percutaneous dihydrotestosterone gel in healthy elderly men—a clinical research center study. J Clin Endocrinol Metab. 1998;83:2749-57. [PMID: 9709942] MedlineGoogle Scholar11. Thigpen AE, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin JE, et al. Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest. 1992;90:799-809. [PMID: 1522235] CrossrefMedlineGoogle Scholar12. Marks LS, Mazer , Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296:2351-61. [PMID: 17105798] CrossrefMedlineGoogle Scholar13. Page ST, Lin DW, Mostaghel EA, Marck B, Wright JL, Amory JK, et al. Exogenous dihydrotestosterone does not increase intraprostatic dihydrotestosterone concentrations in healthy men [Abstract]. Poster presented at ENDO 2010, the 92nd Annual Meeting and Expo, San Francisco, California, 19—22 June 2010. Poster P1-388. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90502, and David Geffen School of Medicine at University of California, Los Angeles, CA 90509.Disclosures: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2335.Corresponding Author: Ronald S. Swerdloff, MD, Harbor–University of California, Los Angeles, Medical Center, 1124 West Carson Street, Torrance, CA 90502.Current Author Addresses: Dr. Swerdloff: Harbor–University of California, Los Angeles, Medical Center, 1124 West Carson Street, Torrance, CA 90502.Dr. Wang: Harbor–University of California, Los Angeles, Medical Center, General Clinical Research Center, 1000 West Carson Street, Torrance, CA 90509. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLong-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease Amanda Idan , Kaye A. Griffiths , D. Tim Harwood , Markus J. Seibel , Leo Turner , Ann J. Conway , and David J. Handelsman Metrics Cited byMale hormonal contraception: Potential risks and benefits 16 November 2010Volume 153, Issue 10Page: 678-679KeywordsAndrogensAttentionEnzymesEstradiolFatsHormonesMusclesProstate diseasesTestosterone ePublished: 16 November 2010 Issue Published: 16 November 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...