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Effects of antiinflammatory and immunosuppressive drugs on gonadal function and teratogenicity in men with rheumatic diseases

Bonnie L Bermas, MD
Section Editors
Peter H Schur, MD
Alvin M Matsumoto, MD
Deputy Editors
Paul L Romain, MD
Kathryn A Martin, MD


A number of antiinflammatory and immunosuppressive drugs have advanced the treatment of rheumatoid arthritis (RA), spondyloarthritis, systemic lupus erythematosus, and other rheumatic disorders; however, information regarding the effects of these agents on reproductive function has been limited, especially in men. While much of the available data have focused on the effects of antiinflammatory and immunosuppressive drugs on pregnancy, little attention has been paid to the impact of these drugs on male gonadal function, particularly spermatogenesis and risk of teratogenicity in offspring.

The effects of drugs used to treat rheumatic disease on male gonadal function and the risk of teratogenicity will be reviewed here. The impact of these agents on female fertility, pregnancy, and lactation and the effects of cytotoxic agents on gonadal function in adult men are discussed in detail elsewhere. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation" and "Fertility, pregnancy, and nursing in inflammatory bowel disease" and "Effects of cytotoxic agents on gonadal function in adult men".)


Drug-induced infertility in men, such as that seen with alkylating agents, results from the toxic or suppressive effects of the medications on the testes. The testes contain two anatomical units: the seminiferous tubules, composed of germ cells and Sertoli cells, and the interstitium, containing Leydig cells that produce testosterone. Spermatogenesis is much more likely to be disrupted than testosterone production, because the actively proliferating germinal epithelium of the testes is more sensitive to damage from cytotoxic drugs than are the Leydig cells. The magnitude of the effect on sperm production is drug-specific, dose-dependent, and duration-dependent. Additional factors that may influence gonadal function in patients receiving these medications include effects of the underlying disease (eg, chronic kidney or pulmonary disease). (See "Effects of cytotoxic agents on gonadal function in adult men", section on 'Mechanism of drug-induced infertility'.)

When a drug has adverse effects on sperm production and function, there is concern that the exposure could also affect fetal outcome. However, unlike teratogenic agents affecting pregnant women, in the male, these agents do not seem to directly interfere with normal fetal development. (See 'Teratogenic concerns' below.)


The chemotherapeutic agents with the most deleterious effect on male fertility are the alkylating agents, which can induce irreversible or prolonged oligozoospermia or azoospermia, compromising fertility. The risk of alkylating agent-related infertility is dose- and age-dependent. These drugs all have cumulative dose ranges above which most patients will be rendered permanently infertile. (See "Effects of cytotoxic agents on gonadal function in adult men".)

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Literature review current through: Sep 2017. | This topic last updated: Oct 09, 2017.
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