Abstract
Imatinib side effects related to testicular function have been reported in male patients with chronic myeloid leukemia. These include decreased testosterone levels, gynecomastia and impaired spermatogenesis. To further investigate testicular function in relation to imatinib treatment, a longitudinal study on reproductive hormone profiles was conducted in 17 male patients with chronic myeloid leukemia. Blood samples were taken before and at one or more time points during imatinib therapy. Serum samples were analyzed for the hormones testosterone, estradiol, and luteinizing hormone (LH) to reflect testicular Leydig cell function. Sex hormone-binding globulin (SHBG) serum levels were measured to evaluate free testosterone, and serum levels of inhibin B and follicle stimulating hormone were measured to reflect spermatogenesis. Out of the 17 patients included in the study, one patient developed gynecomastia after 7-10 months of therapy. Testosterone levels were generally low in the patients both before and during the study, and did not change in response to imatinib therapy. Conversely, SHBG levels decreased transiently at 3 and 6-9 months of therapy (p=0.002 and p=0.008, respectively). Estradiol levels decreased at 12-15 months of therapy (p=0.048). LH and hormones reflecting spermatogenesis were unchanged. In conclusion, our longitudinal study of men with chronic myeloid leukemia showed a significant, but largely transient, decrease in SHBG levels in response to imatinib therapy. Testosterone levels were low in the men both before and during imatinib therapy.
Highlights
Imatinib mesylate is a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL1, and a targeted therapeutic agent in the treatment of chronic myeloid leukemia (CML)
Fourteen patients were excluded from analysis due to missing pre-treatment samples or because no samples were taken after onset of imatinib therapy
A significant, but transient, decrease in Sex hormone-binding globulin (SHBG) levels was observed after 3-9 months of imatinib therapy
Summary
Imatinib mesylate is a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL1, and a targeted therapeutic agent in the treatment of chronic myeloid leukemia (CML). The small molecule inhibits tyrosine kinases associated with cKIT and platelet derived growth factor (PDGF) receptors [1]. Though the drug is generally well tolerated [2], impaired testosterone production after imatinib therapy has been reported [3,4]. Amongst other symptoms, result in gynecomastia, which has been reported as a side effect of tyrosine kinase inhibitor therapy [3,5,6,7,8]. Inhibition of cKIT and PDGF receptors is thought to be involved in these unintended testicular effects, in that both play crucial roles in Leydig and Sertoli cell development and function and in germ cell differentiation [11,12,13]
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