Resumption of Spermatogenesis and Fertility Post Withdrawal of Hydroxyurea Treatment

Hydroxyurea (HU), a drug for treating cancers of the blood and the management of sickle cell anemia, induces hypogonadism in males. However, the impact of HU on testicular architecture and function, as well as its effects on the resumption of male fertility following treatment withdrawal, remain poorly understood. We used adult male mice to determine whether HU-induced hypogonadism is reversible. Fertility indices of mice treated with HU daily for similar to 1 sperm cycle (2 months) were compared with those of their control counterparts. All indices of fertility were significantly reduced among mice treated with HU compared to controls. Interestingly, significant improvements in fertility indices were apparent after a 4-month withdrawal from HU treatment (testis weight: month 1 post-HU withdrawal (M1): HU, 0.09 +/- 0.01 vs. control, 0.33 +/- 0.03; M4: HU, 0.26 +/- 0.03 vs. control, 0.37 +/- 0.04 g); sperm motility (M1: HU,12 vs. 59; M4: HU, 45 vs. control, 61%; sperm density (M1: HU, 1.3 +/- 0.3 vs. control, 15.7 +/- 0.9; M4: HU, 8.1 +/- 2.5 vs. control, 16.8 +/- 1.9 million). Further, circulating testosterone increased in the 4th month following HU withdrawal and was comparable to that of controls. When a mating experiment was conducted, recovering males sired viable offspring with untreated females albeit at a lower rate than control males (p < 0.05); therefore, qualifying HU as a potential candidate for male contraception.

Automated summary

Hydroxyurea (HU), a drug for cancer treatment and sickle cell anemia management, reduces male fertility. This study aimed to investigate the reversibility of HU-induced hypogonadism using adult male mice. After 2 months of HU treatment, fertility indices were significantly reduced. However, a 4-month withdrawal from HU resulted in improvements in fertility indices, including testis weight, sperm motility, and sperm density, as well as an increase in circulating testosterone level. Mating experiments showed that recovering males could produce viable offspring, qualifying HU as a potential male contraceptive.