title: Reproductive status is associated with the severity of fibrosis in women with hepatitis C.
abstract: BACKGROUND
  Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men.
  
  
  METHODS
  A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis.
  
  
  RESULTS
  Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001).
  
  
  CONCLUSIONS
  The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the inflammatory process leading to fibrosis.
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy. erica.villa@unimore.it
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
authors.forename: Ranka
authors.initials: R
authors.lastname: Vukotic
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Stefano
authors.initials: S
authors.lastname: Gitto
authors.forename: Elena
authors.initials: E
authors.lastname: Turola
authors.forename: Aimilia
authors.initials: A
authors.lastname: Karampatou
authors.forename: Luisa
authors.initials: L
authors.lastname: Losi
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernabucci
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cenci
authors.forename: Simonetta
authors.initials: S
authors.lastname: Tagliavini
authors.forename: Enrica
authors.initials: E
authors.lastname: Baraldi
authors.forename: Nicola
authors.initials: N
authors.lastname: De Maria
authors.forename: Roberta
authors.initials: R
authors.lastname: Gelmini
authors.forename: Elena
authors.initials: E
authors.lastname: Bertolini
authors.forename: Maria
authors.initials: M
authors.lastname: Rendina
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006526:Hepatitis C / Q000503:physiopathology*; D006801:Humans; D007247:Infertility, Female / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D012189:Retrospective Studies; D012720:Severity of Illness Index