| Summary: | Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (<i>n</i> = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (<i>n</i> = 13) and a group with other histological types (non-GCT) (<i>n</i> = 458). Results: The GCT group had significantly lower serum LH and FSH (<i>p</i> = 0.03 and <i>p</i> < 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (<i>p</i> < 0.001, <i>p</i> < 0.001, and <i>p</i> = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026–0.22, <i>p</i> = 0.004; estradiol, OR = 0.98, 95% CI = 0.96–0.998, <i>p</i> = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors.
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