Impact of HCV infection on male reproductive hormones; a systematic review and meta-analysis.

Abstract

Previous research has suggested a correlation between hepatitis C infection and male reproductive hormones. This study systematically reviewed the literature and determined the pooled effect of hepatitis C infection on male reproductive hormones. PubMed, Scopus, and Web of Science were searched on 1 October 2024. Studies were included if they compared reproductive hormone levels between hepatitis C-positive and hepatitis C-negative men. Excluded were animal studies, reviews, editorials, preprints, and studies lacking hormone data or hepatitis C status differentiation. The effect measures were weighted mean differences. Heterogeneity was measured with I² index. Risk of bias was assessed using the Newcastle-Ottawa Scale, and evidence certainty was evaluated with the GRADE approach. PROSPERO Registration number=CRD42024596571. The initial search yielded 569 documents. After screening, 10 documents were eligible for meta-analysis, each showing high methodological quality (NOS score≥7). Hepatitis C infection was associated with a decrease of 22.62 pmol/L free testosterone (95%CI: -28.65, -16.60; p-value < 0.01; I² = 21.96%), an increase of 1.98 ng/ml prolactin (95%CI: 0.76, 3.19; p-value < 0.01; I² = 75.28%), and an elevation of 37.66 nmol/L sex hormone binding globulin (95%CI: 21.81, 53.51; p-value < 0.01; I² = 95.42%). No publication bias was detected for free testosterone, prolactin, or sex hormone binding globulin, whereas publication bias was observed for total testosterone and estradiol. After publication bias adjustment, hepatitis C infection was associated with 4.16 nmol/L lower total testosterone (95%CI: -4.74, -3.57) and 7.06 pg/ml higher estradiol (95%CI: 6.11, 8.02). Subgroup analysis showed stronger hepatitis C infection effects on free testosterone, prolactin, and estradiol in studies with an average participant age under 40 than in those over 40. In conclusion, hepatitis C infection has been associated with alterations in male reproductive hormones; however, as the certainty of evidence is low to very low (GRADE), these findings should be interpreted cautiously and require confirmation in well-designed studies before clinical implications can be established.