title: Seminal fluid ribavirin level and functional semen parameters in patients with chronic hepatitis C on antiviral combination therapy.
abstract: OBJECTIVE
  Due to the possible teratogenic effect of ribavirin, effective contraception is mandatory during antiviral therapy in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate seminal parameters and ribavirin and HCV-RNA concentrations in seminal fluid and serum prior to and during antiviral treatment.
  
  
  METHODS
  Fifteen male patients (age: 42+/-9 (years+/-SD)) with CHC treated with pegylated interferon-alpha-2a and ribavirin were investigated. Seminal fluid (sperm concentration, motility, and morphology) was analysed morphologically. HCV-RNA and ribavirin concentration were determined by quantitative PCR and HPLC, respectively. Examinations were carried out at baseline, week 4, and week 12.
  
  
  RESULTS
  Ribavirin concentration was higher in seminal fluid than in serum (week 4: 5.2+/-2.5 vs. 2.1+/-0.3; week 12: 4.4+/-1.8 vs. 2.0+/-0.3 (microg/ml, mean+/-SD; p<0.001)). Semen abnormalities were common at baseline (asthenoteratozoospermia: n=6; asthenozoospermia: n=3; teratozoospermia: n=3). Sperm density (BL: 67+/-33x10(6)/ml; week 4: 42+/-25 (p<0.05); week 12: 49+/-33 (n.s.)), percentage of sperm with progressive motility (BL: 40+/-26%; week 4: 27+/-25; week 12: 31+/-20 (n.s.)), and percentage of sperm with normal morphology (BL: 25+/-15; week 4: 20+/-11; week 12: 16+/-9; p<0.05 for both) further decreased during antiviral therapy. HCV-RNA was detectable in the seminal fluid of only two patients prior to antiviral therapy and was undetectable in all patients during combination therapy.
  
  
  CONCLUSIONS
  Semen abnormalities were common in CHC patients, with further impairment during antiviral therapy. Ribavirin concentration was elevated twofold in seminal fluid compared to serum levels, which reinforces the need for contraception during antiviral combination therapy.
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Waehringerguertel 18-20, Vienna, Austria. harald.hofer@meduniwien.ac.at
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.forename: Josef
authors.initials: J
authors.lastname: Donnerer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Sator
authors.forename: Katharina
authors.initials: K
authors.lastname: Staufer
authors.forename: Thomas-Matthias
authors.initials: TM
authors.lastname: Scherzer
authors.forename: Clemens
authors.initials: C
authors.lastname: Dejaco
authors.forename: Michael
authors.initials: M
authors.lastname: Sator
authors.forename: Harald
authors.initials: H
authors.lastname: Kessler
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D053627:Asthenozoospermia / Q000139:chemically induced* / Q000473:pathology; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000139:chemically induced / Q000473:pathology; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012661:Semen / Q000378:metabolism / Q000821:virology; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin