Hydroxyurea discontinuation improves spermatogenesis in patients with sickle cell anemia

A systematic review by Simone Cilio and team found the impact of a common cytoreductive agent the hydroxyurea (HU) which is used in treating sickle cell anemia/disease (SCD), essential thrombocythemia (ET) and polycythaemia vera (PV) on male fertility. The key findings of the study were published in The World Journal of Men’s Health.

Hydroxyurea stands as a standard treatment option for various hematological disorders by showcasing an overall good safety profile so far. Concerns arose regarding its effects on spermatogenesis despite the established safety record, particularly in relatively young patients. This study explored its potential impact on spermatogenesis, specially in younger patients.

The systematic review combed through PubMed, EMBASE, and Cochrane databases with the keyword search that included “hydroxyurea,” “fertility,” “male,” “sperm,” and specific disorders. Data until 15th november 2022 were utilized and 48 articles were identified in total, of which 8 studies involving 161 patients met the eligibility criteria.

The results revealed that spermatogonia in seminiferous tubules decreased in SCD patients compared to healthy males, with HU treatment exacerbating this decline that can lead even to azoospermia. Also, discontinuation of HU showed promise in PV and ET cases where semen parameters improved with a trend toward normalization. This effect was less pronounced in SCD cases. In two paradigmatic cases of PV and ET, HU discontinuation correlated with a significant improvement in spermatogenesis that resulted in successful spontaneous pregnancies.

This findings highlight the complex relationship between HU and male fertility by emphasizing that spermatogenesis normalization after HU discontinuation is inconsistent in SCD cases. But, a clear trend toward improvement in semen parameters upon HU cessation was observed in PV and ET cases.

Reference:

Cilio, S., Fallara, G., Stanghellini, M. T. L., Ciceri, F., Montorsi, F., Lunghi, F., & Salonia, A. (2024). Impact of Hydroxyurea to Treat Haematological Disorders on Male Fertility: Two Case Reports and a Systematic Review. In The World Journal of Men’s Health (Vol. 42). XMLink. https://doi.org/10.5534/wjmh.230069