Effects of tyrosine kinase inhibitors on spermatogenesis and pituitary gonadal axis in males with chronic myeloid leukemia
Journal Title: Journal of Cancer Research & Therapy - Year 2014, Vol 2, Issue 8
Abstract
Objective: The introduction of several classes of targeted therapeutics for the treatment of chronic myelogenous leukemia (CML) raises the question of whether male fertility is affected and the degree of this affection, if any, among the different generations of tyrosine kinase inhibitors (TKIs). Additionally, when two drugs are equally effective, the drug with less toxic effect on fertility is favourable. Our aims were to evaluate semen parameters and pituitary gonadal function before and four months after starting TKIs namely, dasatinib, nilotinib, and imatinib in patients with CML. Design: Prospective study. Setting, patients and interventions: We studied the effect of TKIs' first generation (imatinib) and second generation (dasatinib and nilotinib) on semen parameters and endocrine functions in 20 eugonadal male patients with CML, aged between 35 to 51 years. They were receiving imatinib (400 mg) once daily, dasatinib (100 mg) once daily or nilotinib (300 mg) twice daily as upfront therapy. We assessed the serum gonadotropins (LH and FSH) and testosterone (T) secretion and sperm parameters before and after four months of using these TKIs. Results: Four months after starting TKIs, serum testosterone, LH and FSH concentrations decreased significantly. The total sperm count (SC), total and rapid progressive sperm motility, and % sperms with normal morphology decreased significantly versus pre-treatment. After 4 months of therapy, dasatinib had comparatively the least deleterious effects on SC, ejaculate volume (SV), sperm motility and % of sperms with normal morphology (%NM) compared to imatinib and nilotinib. Significant correlations were found between serum T concentrations and semen parameters before and after TKIs therapy including SC (r = 0.658 and r = 0.73 respectively, p < 0.001), rapid progressive motility (r = 0.675 and r = 0.758, respectively; p < 0.001), and the % NM (r = 0.752 and r = 0.834, respectively; p < 0.001). After TKIs therapy, LH were correlated significantly with T concentrations, SV and SC (r = 0.434, 0.439 and 0.376, respectively; < p: 0.01). Conclusions: Our study showed that CML patients treated with TKIs have significant decrease of sperm parameters and decreased serum concentrations of serum T, LH and FSH. These potentially toxic effects on spermatogenesis are less prominent in patients treated with dasatinib compared to imatinib and nilotinib. The mechanisms and pathways for these effects need further human and/or experimental studies.
Authors and Affiliations
Yassin MA, Soliman AT, Sanctis VD
Keywords
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- EP ID EP547957
- DOI 10.14312/2052-4994.2014-18
- Views 69
- Downloads 0
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