The treatment of hypogonadism in men of reproductive age

Testosterone therapy has a reversible suppression of spermatogenesis. Selective estrogen receptor modulators represent an alternative therapy for men who desire to maintain future potential fertility. Human chorionic gonadotropin therapy may be considered.

Edward D. Kim, M.D., Lindsey Crosnoe, B.S., Natan Bar-Chama, M.D., Mohit Khera, M.D., Larry I. Lipshultz, M.D.

Volume 99, Issue 3, Pages 718-724, 1 March 2013


To review the mechanisms of testosterone replacement therapy’s inhibition of spermatogenesis and current therapeutic approaches in reproductive aged men.

Review of published literature.

Pubmed search from 1990-2012.

Pubmed search from 1990-2012.

A literature review was performed.

Main Outcome Measure(s):
Semen analysis and pregnancy outcomes, time to recovery of spermatogenesis, serum and intratesticular testosterone levels.

Exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Therapies that protect the testis involve hCG therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data.

Exogenous testosterone supplementation decreases sperm production. Studies of hormonal contraception indicate that most men have a return of normal sperm production within 1 year after discontinuation. Clomiphene citrate is a safe and effective therapy for men who desire to maintain future potential fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment.

  • The general public should understand that some of these medications are off-label, non-FDA approved medications for males, and that the cost of long term use may be very expensive, since insurance companies are not going to cover these even though there is a real indication.

    We, as a community of Urologists treating Men’s Health and Hypogonadism, need to develop Best Practices Guidelines for these medications so that treatment protocols are consistent across practices. This will clear up a lot of the confusion that exists even within our own societies. When I look at the treatment algorithms in the male bodybuilding sites online, it seems like they have their act together better than we do even though there is no scientific data behind it… much to my chagrin.

  • disqus_ulbaZomf0n

    This article addresses a significant problem – the use of androgens of men in their reproductive years. With the increased variety of commercially available testosterone preparations, many of us that deal with male infertility are seeing increasing numbers of men on testosterone therapy. Often the men have no idea that this therapy affects spermatogenesis. It may be that the prescribing physicians are also unaware. This situation has become more that just a medical problem in that there is considerable controversy about what are the appropriate indications for testosterone replacement. For those of us who see these patients, we may find that the patients are not ‘hypogonadal” by traditional criteria. Often symptoms of overwork, obesity, poor lifestyle habits are being treated with androgens with no attention to the overall health issues that may underlie the symptoms. Those that deal with these patients need to be sure to determine if therapy is actually indicated rather than just adjust therapy to maintain spermatogenesis. This often involves multidisciplinary care with involvement by psychology and internal medicine to fully address multiple factors. When therapy is indicated, the knowledge presented in this article is invaluable for clinicians to understand.
    Mark Sigman
    Brown University

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