. 2025 Sep 15;16:8221. doi: 10.1038/s41467-025-63469-0

Table 5.

Reproductive hormone levels in men with epilepsy or bipolar disorder, exposed and unexposed to valproate, after excluding those with key modifiable risk factors for infertility

Outcome	Cohort	Patient count before matching	Patient count after matching	Patients with sex hormone results	Mean ± SD	p-value
Total testosterone (ng/dL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	355	358 ± 268	0.609
Total testosterone (ng/dL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	354	367 ± 233	0.609
Free testosterone (pg/mL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	158	63 ± 66	0.258
Free testosterone (pg/mL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	199	70 ± 51	0.258
Luteinizing hormone (mIU/mL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	198	4 ± 4	0.355
Luteinizing hormone (mIU/mL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	157	5 ± 5	0.355
Follicle-stimulating hormone (mIU/mL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	202	6 ± 9	0.748
Follicle-stimulating hormone (mIU/mL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	152	6 ± 8	0.748
Prolactin (ng/mL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	551	39 ± 443	0.380
Prolactin (ng/mL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	446	20 ± 23	0.380
Estradiol (pg/mL)	Epilepsy or bipolar disorder exposed to valproate	32,885	27,946	36	31 ± 24	0.442
Estradiol (pg/mL)	Epilepsy or bipolar disorder not exposed to valproate	261,112	27,946	36	28 ± 12	0.442

Legend: Comparisons use two-sided t-test statistics (p < 0.05 cut-off). P-values are unadjusted for multiple comparisons. However, with Bonferroni correction applied across 6 comparisons, only p-values < 0.0083 would be considered statistically significant. SD = Standard deviation.