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A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men

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  • Feiby L Nassan
  • Brent A Coull
  • Niels E Skakkebaek
  • Anna-Maria Andersson
  • Michelle A Williams
  • Lidia Mínguez-Alarcón
  • Stephen A Krawetz
  • Janet E Hall
  • Elizabeth J Hait
  • Joshua R Korzenik
  • Jennifer B Ford
  • Alan C Moss
  • Russ Hauser
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BACKGROUND: Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD).

OBJECTIVES: Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones.

METHODS: Men (N=73) with IBD participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background) at baseline crossed-over for 4 months to DBP-mesalamine (high) and then crossed-back for 4 months to non-DBP mesalamine (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). We divided H1BH2-arm at the median (H1<3yrs or H1≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models.

RESULTS: When B1HB2-arm (26 men,134 samples) crossed-over, luteinizing hormone decreased 13.9% (95% confidence interval(CI): -23.6,-3.0) and testosterone, inhibin-B, and follicle-stimulating hormone (FSH) marginally decreased; after crossback all increased 8-14%. H1BH2-arm, H1≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H1BH2-arm,H1<3yrs (22 men,100 samples) after crossover, inhibin-B increased 13.2% (CI: 4.2,22.9), FSH decreased 9.9% (CI: -17.9,-1.1) and after crossback, inhibin-B further increased 11.3%, and FSH marginally increased.

CONCLUSIONS: High-DBP exposure may disrupt pituitary-gonadal hormones that largely reversed after exposure removal, but only in men with no or short previous high-exposure history. Paradoxically, men with longer duration of high-DBP exposure, exposure removal did not change hormone levels, suggesting that long-term high-DBP exposure may alter the pituitary-gonadal axis and make it insensitive to exposure changes.

Original languageEnglish
JournalEnvironmental Research
Volume160
Pages (from-to)121-131
Number of pages11
ISSN0013-9351
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

ID: 52004681