Hydroxyurea before puberty may not affect spermatogenesis in boys with sickle cell disease
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Toxicity on spermatogenesis may not be a major concern for boys with severe sickle cell disease who require hydroxyurea treatment before puberty, according to results of a study published in Blood.
The effect of hydroxyurea exposure on infants, however, remains unknown.
“In recent years, the very high likelihood of survival to adulthood has emphasized the importance of reproductive issues in patients with sickle cell disease,” Laure Joseph, MD, hematologist in the department of biotherapy at Assistance Publique-Hôpitaux de Paris in France, and colleagues wrote. “However, it has long been established that semen quality is significantly impaired in males with sickle cell disease.”
Nearly all these patients have impairment in at least one sperm parameter. About 40% have an abnormal sperm count. This is due to several causes, including hypogonadism, testicular ischemia, and repeated episodes of fever and hypoxia.
Sperm quality is further impacted by hydroxyurea and its cytotoxic effect.
Previous studies have shown that men experience significant, rapid and unpredictable impairment in spermatogenesis when using hydroxyurea. However, this is sometimes reversed when they stop taking the drug.
The effect of hydroxyurea on spermatogenesis among boys is a concern for parents and health care providers.
Joseph and colleagues compared parameters of 26 sperm samples from 15 patients (median age, 17 years; range, 16-23) treated with hydroxyurea during childhood with those of 46 samples from 23 hydroxyurea-naive patients (median age, 20 years; range, 16-24).
Median age of hydroxyurea initiation was 6 years (range, 1-14) with a median treatment duration of 4 years (range, 0.5-10). Mean dose was 22.4 mg/kg per day (standard deviation, ± 3.7).
At the time of semen analysis, all patients in the hydroxyurea group and 52% of the patients in the treatment-naive group were on transfusion therapy.
Researchers observed substantial quantitative and qualitative semen abnormalities in all patients. However, results showed no significant differences in semen volume, sperm concentration, total sperm count and spermatozoa motility, morphology and vitality between the groups.
The study’s small sample size served as a limitation.
“Our results show that an irreversible toxic effect on spermatogenesis may not be a major concern in boys with severe disease requiring hydroxyurea treatment before puberty [and that] the drug’s many beneficial effects largely outweigh its main negative effect in males,” Joseph and colleagues wrote. “The effect of hydroxyurea exposure on infants is still a relevant open question, given that a ‘mini-puberty’ characterized by the multiplication of spermatogonia cells occurs between the ages of 12 and 18 months and questions the true risk-benefit ratio of [hydroxyurea] initiation during this period in asymptomatic infants.”
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