Sex hormone levels by presence and severity of cirrhosis in women with chronic hepatitis C virus infection

Abstract

Summary Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive‐aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post‐menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child‐Turcotte‐Pugh (CTP) class. Results: There were n = 18 cirrhotic and n = 21 noncirrhotic women with a median age of 57 years (interquartile range [IQR] 53‐62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0 pg/mL, P = 0.05) and oestrone levels (32.0 vs 8.0 ng/mL, P < 0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6 nmol/L, P = 0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P < 0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio‐metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV‐infected women warrants investigation.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women

“…Studies of HCV-infected individuals reported that SHBG levels were positively associated with severity of liver disease in men, (37) but this association was not observed in women. (38) However, it has been hypothesized that SHBG may be a marker of liver damage. The mechanism underlying this correlation between SHBG and liver damage has been suggested to be through insulin-like growth factor 1 (IGF-1), which down-regulates SHBG production.…”

An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia

“…Since testosterone directly modulates osteoblasts and osteocytes via the androgen receptor to stimulate trabecular bone formation and prevent its loss, low testosterone level owing to hypogonadism in male enhances osteoclast function and induces bone turnover [ 53 , 90 ]. Though estrogen levels are increased in patient with liver cirrhosis due to increased peripheral conversion of androgen to estrogen, altered estrogen metabolism in liver cirrhosis contributes to a decrease in degradation of estrogen metabolites [ 91 ]. Because the bone protective effect of these estrogens is weak, it is not enough to overcome post-menopausal osteoporosis in women and liver-disease related osteoporosis in men [ 92 , 93 ].…”

Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases

“…( 13‐15 ) Produced in the liver, SHBG synthesis is stimulated by estrogens, although with further progression from compensated to decompensated cirrhosis, SHBG levels ultimately decline. ( 16,17 ) Estrogen levels are also elevated in the setting of portosystemic shunting, ( 10,18 ) and increased circulating levels suppress the hypothalamic‐pituitary axis, ( 19 ) contributing to erectile dysfunction, oligospermia, testicular atrophy, and feminization. ( 20 )…”