Estrogens and falling sperm counts

Abstract

Extravagant claims have been made repeatedly in recent years that human sperm counts are falling and that global exposure to environmental estrogens are responsible. The basis for these two distinct claims is reviewed. The claims of falling human sperm output, reviving an old debate, are prompted by a paper by Carlsen et al. (1992). This meta-analysis, however, is marred by numerous flaws that invalidate its claims. Major defects include severe heterogeneity of component studies, rendering them unsuitable for aggregation, and defective data analysis based on arithmetic mean rather than median, which showed no significant changes over time. This debate is likely to remain unresolved until valid, representative population-based studies of human sperm output can be achieved. None have been reported, or seem feasible in the near future, and so alternative strategies, based on surrogate variables for human male fertility not requiring sperm counts, need to be developed and validated. The plausible hypothesis that prenatal estrogen exposure might influence development of the human testis through effects on Sertoli cell replication and sperm carrying capacity has, however, been conclusively refuted by studies of boys born to women exposed to high doses of oral diethylstilbestrol during pregnancy. Neither fertility nor sperm output were adversely influenced by massive maternal estrogen exposure during pregnancy, although minor urogenital malformations did occur. The still wider claims of deteriorating male reproductive health, notably changes in prevalence or incidence of hypospadias or cryptorchidism, also lack convincing population-based evidence, although cancer registry data indicate a gradual increase in testis cancer in some countries. In summary, the available evidence does not support claims of falling sperm counts or any general deterioration in male reproductive health. Population-based studies of valid surrogate variables for male fertility not requiring semen analysis are needed. If population-based evidence regarding male fertility or sperm output could be generated, it is highly unlikely that prenatal estrogen exposure could be a valid explanation of any deterioration as massive maternal exposure to oral estrogen has negligible effects on male fertility or sperm output.