Phthalates Linked to Testosterone Reductions in Both Genders

Nancy A. Melville

August 19, 2014

Increased urinary levels of endocrine-disrupting phthalates, found in flexible plastic and some personal-care products, are associated with significant declines in testosterone levels not just in men, but in women and children as well, according to research published online August 14 in the Journal of Clinical Endocrinology & Metabolism.

"We found associations between markers of phthalate exposure and testosterone levels among multiple age groups and in both sexes, including children — 6- to 12-year-old boys and girls, and girls ages 12 to 20," lead author John D. Meeker, ScD, CIH, told Medscape Medical News.

The findings add to mounting evidence on reproductive risks linked to exposure to the endocrine-disrupting chemicals; however, many questions have remained regarding which chemicals are disruptive and who is most at risk. Dr. Meeker admits that while their findings expand the body of research in this field, the clinical implications remain unclear.

Asked to comment, Andrea C. Gore, PhD, the Gustavus & Louise Pfeiffer Professor of pharmacology and toxicology at the University of Texas at Austin, said this new work "really has taken the research up a step in terms of drawing stronger conclusions." This is primarily because of the study's relatively large sample size and its use of a more accurate methodology than is typically used, she told Medscape Medical News.

First Work in a Large and General Population

While previous studies have identified phthalates, particularly di-2-ethylhexyl phthalate (DEHP), to be antiandrogenic in rats and associated with decreased testosterone levels, most studies looking at their effect on testosterone have been small or involved unique subpopulations.
In seeking to investigate the relationship in a larger, more general population, Dr. Meeker and colleagues evaluated new data on 13 urinary phthalate metabolites and serum testosterone levels in 2208 participants in the National Health and Nutrition Examination Survey (NHANES) in 2011–2012.

Serum testosterone was measured in the study using isotope dilution-liquid chromatography tandem mass spectrometry.

Whereas multiple phthalates were associated with significant reductions in testosterone in both sexes and various age groups, the strongest association among females was in the 40- to 60-year age group, among whom testosterone levels were reduced by as much as 24% with exposure particularly to mono-benzyl phthalate (MBzP; P = .001).

Urinary increases in DEHP were also associated with a 20.1% decrease in testosterone, in general, and in the subgroup of boys ages 6 to 12, increases in DEHP were associated with as much as a 29% reduction in testosterone (P = .018).

Among those showing increases in all phthalate metabolites, with the exception of mono-(carboxynonyl) phthalate (MCNP) and mono-(carboxyoctyl) phthalate (MCOP), serum testosterone concentrations were 10.8% to 24.0% lower than in those without the phthalate concentrations.

Interestingly, the associations were not as strong in adult men, with the only significant associations between phthalates and testosterone observed among men involving higher levels of DEHP and dibutyl phthalate in men ages 40 to 60.

Some of First Research Examining Effects of Phthalates on Testosterone in Women

"It was surprising that we did not observe significant associations among men ages 20 to 40, which is an age group for which previous research has reported a relationship," Dr. Meeker said. "We were also surprised that associations among women ages 40 to 60 were among the strongest for most types of phthalates studied."

The possible mechanisms explaining the associations remain uncertain, Dr. Meeker noted.

"We still don't know how this may be happening in males or females at different life stages in humans, and it is possible that the different specific phthalate chemicals may be acting through differing or multiple mechanisms simultaneously."

The authors underscore that previous research evaluating the effects of phthalates on testosterone in women is especially scarce, despite the importance of testosterone for women as well as men.

"The novel findings presented here for reduced testosterone among women may be of high public-health significance, because androgen deficiency among women may impair sexual function, libido, energy, cognitive functions, bone density, cardiovascular function, and overall well-being," they write.

Dr. Meeker said it is not easy to fully understand the clinical implications of the work, however. "Because our study was conducted on the population level, it is difficult to interpret how our findings might affect the individual, and some individuals may be more susceptible than others," he said.

"Things are also complicated by the fact that most products that contain phthalates aren't labeled as such, making it very difficult for clinicians to be able to make sound recommendations for patients to avoid or reduce exposure."

Study Still Highly Valuable

The study is nevertheless highly valuable in improving the understanding of endocrine-disrupting chemicals, said Dr. Gore.

"Most research on the effects of endocrine-disruptive chemicals on humans have relied on other types of hormone measures, and there have not been many that have measured it the way they did here, with isotope dilution-liquid chromatography tandem mass spectrometry," she told Medscape Medical News.

The more accurate assessment is critical because some hormone assays either grossly under- or overestimate hormone levels, especially when looking at the kinds of very low levels that are typical seen in women, Dr. Gore explained.

"Because of the low levels, if you don't use a very sensitive and well-validated method for measuring the hormones, you will really not get reliable data."

As reported by Medscape Medical News, the Endocrine Society published recommendations in 2012 to better define and improve screening of endocrine disruptors, and the UN's Environment Programme and the World Health Organization followed suit with a global assessment of the chemicals .

The authors and Dr. Gore have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online August 14, 2014. Abstract

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