Environmental endocrine modulators and human health: an assessment of the biological evidence, 1998
It is biologically plausible that in utero exposure to estrogen can affect sperm counts.
In studies with mice, in utero exposure to DES is associated with decreased sperm production and abnormal sperm morphology in adult offspring.
There are also numerous studies of adult male humans prenatally exposed to DES, however, with respect to decreased sperm counts, the results of these studies are mixed.
- Decreased sperm count (115 million/ml in 87 controls vs. 91 million/ml in 134 DES exposed) and abnormal Eliasson scores in 18% of 134 DES-exposed men compared with 8% in 87 placebo-exposed controls have been reported. This study was conducted on a cohort of men exposed in utero to DES according to the dosing protocol in use at the University of Chicago where mean total maternal DES dosages were, on average, 11,603 mg.
- Another small study reported lower average sperm counts in 20 DES-exposed men and pathologic Eliasson scores in 18 DES-exposed men, but no unexposed comparison group was used and maternal DES dosages were unknown.
- In contrast, in a cohort of men from the Mayo Clinic exposed in utero to DES in which total mean maternal DES doses were approximately 1.4 g there were no differences between 110 DES-exposed men and unexposed men in sperm count, motility, or abnormal Eliasson scores.
While clinical data suggest that in utero exposure to DES at some maternal dose level can result in decreased sperm counts, the data also suggest the existence of an apparent maternal dose threshold for such effects.
Even at the dose levels of DES that produced adverse effects on sperm following in utero exposure, the magnitude of such effects is not large with average sperm counts reduced from 115 million/ml in men not exposed to DES to 91 million /ml in DES exposed men. While this shows a DES effect, it also demonstrates that an estrogen as potent as DES does not produce a decrease in mean sperm counts approaching the levels at which fertility might be affected. Despite the small sample size the failure of the maternal DES dosages used at the Mayo Clinic to cause any effects on sperm count or morphology underscores this point. As noted later in this review, fertility in the high dose cohort of men (University of Chicago cohort) was not adversely affected, even after in utero exposure to DES at maternal doses sufficient to produce adverse effects on sperm counts and morphology.
This raises the question of whether in utero exposure to environmental estrogens, which are significantly less potent than DES, could cause a decline in sperm counts.
- Environmental endocrine modulators and human health: an assessment of the biological evidence, Critical reviews in toxicology, NCBI PubMed, PMID: 9557209, 1998.
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