Format

Send to

Choose Destination
Environ Res. 2018 Jan;160:121-131. doi: 10.1016/j.envres.2017.09.025. Epub 2017 Oct 1.

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

Author information

1
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address: fen769@mail.harvard.edu.
2
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3
University Department of Growth and Reproduction, and EDMaRC, Rigshospitalet, Copenhagen, Denmark.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
5
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
6
Department of Obstetrics & Gynecology, Center for Molecular Medicine & Genetics, Wayne State University, Detroit, MI, USA.
7
Division of Intramural Research, NIH/NIEHS, NC, USA.
8
Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
9
Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
10
Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
11
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.

Abstract

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.

KEYWORDS:

Crossover study; Endocrine disruptor; Hormones; Men; Phthalate

PMID:
28978458
PMCID:
PMC5705343
[Available on 2019-01-01]
DOI:
10.1016/j.envres.2017.09.025
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center