Hydroxyurea therapy contributes to infertility in adult men with sickle cell disease: a review

Abstract

Hydroxyurea therapy, a chemotherapeutic agent, is the only US FDA approved therapy for the prevention of vaso-occlusive pain in sickle cell disease (SCD). The National Institutes of Health has sponsored two Phase III randomized, placebo-controlled trials, initially in adults, and subsequently in children with sickle cell anemia (SCA). Despite the overwhelming evidence that hydroxyurea therapy is beneficial to children and adults with SCA, individuals with SCA and their families express reservations about its use, in part because of the concerns about fertility, particularly in men. As adolescent boys with SCD are now expected to reach their reproductive years, a new concern is emerging about the role of hydroxyurea therapy as a barrier to their progeny. This review will systemically evaluate compromised fertility in men with SCD, and the evidence that hydroxyurea therapy is associated with further decreasing fertility in men with SCD.

Keywords::

• fertility
• hydroxyurea
• hypogonadism
• sickle cell disease
• spermatogenesis

Financial & competing interests disclosure

MR DeBaun was supported by the Burroughs Wellcome Fund and HRSA 5U38MC22220–04. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Limited research has been conducted on the fertility and fecundity rates of men with sickle cell anemia (SCA) with a partner who does not have SCA.

• Primary hypogonadism is the most common cause of infertility in men with SCA.

• In several case series of men with SCA, semen analysis revealed that only a small proportion of men will have semen that meet the WHO standard minimum criteria for fertility.

• Hydroxyurea therapy most likely decreases spermatogenesis in men with SCA, but better studies are need to determine, if so, under what circumstances and whether the effect is reversible.

• Preliminary evidence indicates that in men with SCA, the effects of hydroxyurea therapy on spermatogenesis and semen quality may only be partially reversed when stopped.

• Young men receiving hydroxyurea therapy should be aware of the predisposition for infertility as a result of the disease and the potential further compromise when started on hydroxyurea therapy.

• The area of reproductive epidemiology in SCA, but particularly men with SCA, is vastly understudied and requires future research.

Notes