A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease

Abstract

Background 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. Objectives Taking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters. Methods 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). Results 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. Conclusions 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.

Male Sexual and Reproductive Health—Does the Urologist Have a Role in Addressing Gender Inequality in Life Expectancy?

“…Skakkebaek et al [82] has postulated the theory that the rising incidence of testicular cancer, cryptorchidism, hypospadias, and male infertility have all been linked to male in utero exposure to environmental endocrine disrupting chemicals (EDCs). Chemicals such as bisphenol A and phthalate, which are widespread in the environment and feature in many household items, have been shown to induce reproductive abnormalities in animal studies [83]; however, these have also been associated with abnormal semen parameters [84,85] and sexual dysfunction [86] in humans. Similarly, there is evidence that EDCs may play a role in the development of cancer [87] and MetS [88].…”

Temporal Trends of Urinary Phthalate Concentrations in Two Populations: Effects of REACH Authorization after Five Years

“…Phthalates having a smaller molecular structure and lower molecular weight are more soluble in water and are therefore used as industrial solvents, in the composition of cosmetics and pharmaceuticals, or as insecticides; this is the case, for example, of diethyl phthalate (DEP) and di- n -butyl phthalate (DnBP) [ 2 , 3 ]. In particular, DEP is the phthalate of choice used in the cosmetic and personal hygiene products industry, both for adults and for children/infants [ 4 ], while DnBP is usually used as excipient in pharmaceuticals products [ 5 , 6 ], and it was present in cosmetics, particularly nail care products for adults [ 7 ]; in Europe this last use is forbidden by the EU cosmetics directive, Dir. 76/768/EEC, where other forbidden phthalates were also listed: di(2-ethylhexyl)-phthalate (DEHP), benzylbutylphthalate (BBP), bis2-methoxyethylphthalate, n -pentylisopentyl-phthalate, di- n -pentylphthalate, diisopentylphthalate and di ( n -butyl) phthalate (DnBP).…”

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study

“…Studies have shown significant impacts on laboratory animals but due to inadequate data, the human health impacts from low dose exposure are difficult to determine [ 6 ]. Nevertheless, some studies have shown that phthalate exposure adversely affects human male reproductive development [ 7 ] and sperm quality [ 8 , 9 ], and is also associated with risk factors for cancer, asthma and allergies [ 10 ]. Phthalates have been associated with obesity [ 11 ] but their impact on overall cardiovascular health is unclear [ 12 ].…”