Rozati, R, PP Reddy, P Reddanna and R Mujtaba. 2002. Role of environmental estrogens in the deterioration of male factor fertility. Fertility and Sterility 78:1187-1194. [note]

Commentary in Epidemiology about this paper

This intriguing but limited study suggests that PCBs and phthalate esters are linked to infertility in men. They report that a series of sperm parameters were significantly lower in a group of infertile men than in a control group, and that the infertile men also had higher levels of contaminants. Unfortunately, the sample sizes are extremely small and the chemical analysis technique used is vulnerable to contamination. No firm conclusions can be drawn from this study. But it surely points toward important areas of research.

What did they do? Rozati et al. measured sperm parameters and contamination levels in 21 infertile men, whose infertility was established but for which there was no overt and obvious reason. They compared these measurements to those of 32 control men.

The 21 infertile men came from an original pool of 557 infertile couples, screened at a fertility assistance center in Andhra Pradesh, India. Men from these infertile couples were put through a complete clinical and case history evaluation, which included semen analysis. These analyses identified 300 cases in the pool of 557 infertile couples in which infertility could be attributed to male problems or combined male/female problems, based on sperm characteristics (e.g., sperm count < 20 million per ml).

Further analysis of the 300 cases of male factor infertility revealed 52 men for which no obvious causes of the poor sperm quality were identified by medical analysis (e.g., hormon disorders, infections, genetic abnormalities, immunological problems). Also excluded from this final group were men with a history of systemic diseases, a family history of infertility/delayed conception, occupational exposure to reproductive toxicants, tobacco/alcohol consumption, iatrogenic problems associated with medical treatment... anything that could be anticipated, a priori, as having possible adverse effects on fertility.

Details on the selection process for the control men are not provided, although the criteria used are. They include: previous evidence of fertility, no history of tobacco or alcohol consumption, no history of occupational exposure to reproductive toxicants, no history of medication or surgery, etc., i.e., the same criteria used above for the infertile men, except for the history of fertility.

What did they find? The sperm of men coming to the fertility center for assistance was of lower quality than the matched controls. Ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity and chromatin characteristics were all lower.

Among the infertile men, PCB and phthalate ester levels in semen were highest in urban fish eaters, followed by: rural fish eaters, urban vegetarians, rural vegetarians. Fish eaters had higher levels than non-fish eaters, independent of place of dwelling, and urban living men had higher levels than rural living men, controlling for diet.

PCBs were detected in the semen of the infertile men, but not in that of the controls.

Rozati et al. found significant inverse correlations between PCB levels and ejaculate volume (p < 0.001), motility (p < 0.05), vitality (p < 0.001) and osmoregulatory capacity ( p < 0.001). Higher PCBs were associated with sperm damage ( p < 0.05). There was no correlation between PCB level and sperm count.

Phthalates were significantly higher in the infertile men. Abnormal sperm were more likely at higher phthalate levels (p < 0.001), as was sperm DNA damage (p < 0.001).

Total mobile sperm counts were inversely related to both PCB and phthalate concentrations.

What does it mean? This study must be interpreted cautiously because of the small sample size and, for phthalates, the analytical chemistry method.

Phthalates are widespread contaminants in virtually every setting. Hence separating real exposures from laboratory contamination has been problematic. In 2000 the US CDC published a methodological breakthrough, measuring the urinary metabolites of phthalates instead of the parent compound. This allowed them to be certain they were measuring a compound that had been in a human body, instead of a contaminant picked up, say, because a plastic had volatilized phthalates in the lab.

Rozati et al. measured phthalate esters directly, instead of metabolites. Some portion of their measured phthalate levels may therefore be a result of laboratory contamination, and hence it is not certain what absolute levels of phthalates were actually in the men. Relative comparisons between the infertile men and the controls, however, should still be possible, as long as there was no reason for the infertile samples to be at greater risk to contamination than the control samples.

While the sample size is small, the statistical tests are not marginally significant. This argues that Rotazi et al. are seeing real associations between impaired semen quality and elevated contamination levels.

They observe:

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