title: A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease.
abstract: Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine formulations do not.
  
  
  
  Taking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters.
  
  
  
  73 men with IBD taking mesalamine participated in a crossover-crossback prospective study. Men taking non-DBP containing mesalamine at baseline i.e., background exposure, crossed-over for four months to high-DBP mesalamine and then crossed-back for four months to their non-DBP mesalamine (B1HB2-arm;Background1-High-Background2) and vice versa for men taking high-DBP mesalamine at baseline (H1BH2-arm;High1-Background-High2). Men provided up to six semen samples (2: baseline, 2: crossover and 2: crossback).
  
  
  
  We estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season and duration on high-DBP mesalamine at baseline. Semen parameters in B1HB2-arm (26 men, 133 samples) decreased after high-DBP mesalamine exposure (crossover versus baseline), especially motility parameters, and continued to decrease further even after crossback to non-DBP mesalamine (crossback versus crossover). The cumulative carryover effect of high-DBP (crossback versus baseline) was a decrease of % total sperm motility by 7.61(CI:-13.1, -2.15), % progressive sperm motility by 4.23(CI:-8.05, -0.4) and motile sperm count by 26.0% (CI:-46.2%, 1.7%). However, H1BH2-arm (47 men, 199 samples) had no significant change during crossover or crossback.
  
  
  
  Men newly exposed to high-DBP mesalamine for four months had a cumulative reduction in several semen parameters, primarily sperm motility, that was more pronounced and statistically significant even after exposure ended for four months.
authors: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address: fen769@mail.harvard.edu.
authors: Feiby L
authors: FL
authors: Nassan
authors: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors: Brent A
authors: BA
authors: Coull
authors: University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
authors: Niels E
authors: NE
authors: Skakkebaek
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors: Michelle A
authors: MA
authors: Williams
authors: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors: Ramace
authors: R
authors: Dadd
authors: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors: Lidia
authors: L
authors: Mínguez-Alarcón
authors: Department of Obstetrics & Gynecology, Center for Molecular Medicine & Genetics, Wayne State University, Detroit, MI, USA.
authors: Stephen A
authors: SA
authors: Krawetz
authors: Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors: Elizabeth J
authors: EJ
authors: Hait
authors: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Joshua R
authors: JR
authors: Korzenik
authors: Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Alan C
authors: AC
authors: Moss
authors: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors: Jennifer B
authors: JB
authors: Ford
authors: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Russ
authors: R
authors: Hauser
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage*; D008875:Middle Aged; D010795:Phthalic Acids; D011446:Prospective Studies; D012621:Seasons; D012661:Semen / Q000187:drug effects*; D055101:Semen Analysis; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010795:Phthalic Acids; D003993:Dibutyl Phthalate; D019804:Mesalamine; C032279:phthalic acid
keywords: Inflammatory bowel disease (IBD); Mesalamine; Phthalates; Semen quality