Tamoxifen Treatment for Idiopathically Reduced Semen Quality: A Single‐Center Experience

Introduction Idiopathic male infertility poses a challenge in andrology due to limited treatment options. Tamoxifen, a selective estrogen receptor modulator (SERM), has been proposed to improve semen quality, although evidence remains limited. This study aims to address the uncertainty surrounding tamoxifen treatment outcomes. Methods We retrospectively assessed male subjects with idiopathically reduced semen quality marked by density, progressive motility, or normal morphology rates below reference values. As an individual attempt to improve semen quality, all patients had received tamoxifen (20 mg/day) for 3 months. Statistical analysis included comparison of semen quality parameters pre‐ and post‐treatment alongside an analysis of follicle‐stimulating hormone (FSH) as an outcome predictor alongside age, body mass index (BMI), and the frequency of adverse events. Results 120 subjects were included in the analysis. Tamoxifen treatment resulted in a small but significant increase in sperm density (median + 1.2 x 10 6 /mL, interquartile range (IQR): 0.7–6.3; p < 0.001). Analysis of progressive motility and morphology revealed differences that were likely statistical artifacts, potentially influenced by regression to the mean, while only higher pretreatment BMI was linked to an increase in sperm density. Adverse events (AEs) were mild and infrequent. Discussion We present a comprehensive analysis of semen quality changes associated with a 3‐month tamoxifen intake, with results indicating a slight improvement in sperm density of questionable clinical relevance. Further research to understand the underlying mechanisms and biomarker development to overcome the large inter‐individual outcome variation is warranted.