On label and off label drugs used in the treatment of male infertility

Capsule:
Male factor infertility is the cause of infertility in 50% of infertile couples. This manuscript reviews the commonly used off-label medications used to treat idiopathic male factor infertility: clomiphene citrate, letrozole/anastrozole, exogenous androgens, and pentoxifylline.

Authors:
Mahmoud Chehab, M.D., Alosh Madala, M.D., J.C. Trussell, M.D.

Volume 103, Issue 3, Pages 595-604

Abstract:

Infertility affects 6.1 million U.S. couples—representing 10% of reproductive-age adults and 15% of all couples trying to conceive. Half of the time, infertility is the result of an abnormal semen analysis or other male factors, with 40%–50% of these infertile men diagnosed with idiopathic or nonclassifiable infertility. While the role of hormone therapy for men with an identified abnormality is well defined, the literature remains inconclusive and controversial regarding hormone manipulation using empirical (off-label) medical therapies for men with idiopathic infertility. This manuscript reviews the commonly used off-label medications used to treat idiopathic male factor infertility: clomiphene citrate, letrozole/anastrozole, exogenous androgens, and pentoxifylline.

  • J.C. Trussell

    Treating male infertility is challenging–especially for those men without a clear diagnosis (idiopathic). Having a diagnosis (Klinefelters, Y-microdeletion, testis failure with elevated FSH, etc) only allows for a more focused (albeit, not easier) discussion with the client.

    With normal LH/FSH levels and low T, I do use clomiphene citrate quite a bit. Moreover, I consider adding Letrozole if the T:Estradiol ratio is worse than 10:1 (with an elevated Estradiol level).

    When discussing such treatment options with patients, I mention they are off-label and, if improved semen parameters are realized, translation into improved full-term pregnancy rates may not happen.

    I certainly look forward to prospective studies to help clarify how to best care for the (idiopathic) infertile male.

  • jimdupree4

    The author team has done an outstanding job summarizing the pertinent information about medications available for treating men with infertility in a concise and usable format. I would like to ask the authors how they define idiopathic and if clomiphene, likely the most commonly used medication in these men, is FDA approved for ‘non-idiopathic’ indications like hypogonadism? Also, what recommendations do the authors have for using information from this manuscript with patients? Is there a standard discussion that the author believe we should have when using off-label medications?

  • “Idiopathic” male infertility remains an enigma to me. The authors nicely summarize the treatments for male infertility, focusing on the treatment of idiopathic male infertility with empiric medical therapy (EMT). Just to clarify: in the section on gonadotropins, a lot of the discussion focuses on hypogonadism. It would appear to me that hypogonadal patients are not included in the “idiopathic” group (correct me if I am wrong). Are gonadotropins FDA-approved specifically for hypogonadal patients or also for idiopathic infertility? Also, what is the difference between “recombinant FSH” and “recombinant-human FSH (r-h FSH)”?

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