A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Environmental Research |
Volume | 160 |
Pages (from-to) | 121-131 |
Number of pages | 11 |
ISSN | 0013-9351 |
DOIs | |
Publication status | Published - 2018 |
- Adult, Anti-Inflammatory Agents, Non-Steroidal/administration & dosage, Cross-Over Studies, Dibutyl Phthalate/adverse effects, Endocrine Glands/drug effects, Gonadal Hormones/blood, Gonadotropins, Pituitary/blood, Humans, Male, Mesalamine/administration & dosage, Plasticizers/adverse effects, Prospective Studies
Research areas
ID: 213964948