The silent spermatozoon: are man-made endocrine disruptors killing male fertility?

Abstract

In 1992, a Danish group led by Skakkebaek reported in a meta-analysis that global mean sperm counts were falling and that testicular cancer, hypospadias and cryptorchidism were increasing. They hypothesized that environmental factors were the cause. Their meta-analysis was criticized subsequently for many methodological flaws. However, their controversial meta-analysis and hypothesis spurred public and scientific interest in the study of male reproductive function and stimulated more rigorous scientific work in the area. Subsequent research has not convincingly supported their hypothesis. However, it is crucial to continue high quality studies of the effects of drugs and man-made pollutants on male reproductive function. In 1962, Rachel Carson published her work ‘A Silent Spring'.1 The thesis of the book was that widespread use of pesticides was jeopardizing the health of animals, including humans. Although some of its conclusions have been disproven, the book is often credited with sparking the modern environmental movement. The title of the book was inspired by the last line in the John Keats poem ‘La Belle Dame sans Merci': ‘The sedge is wither'd from the lake, And no birds sing.' Thirty years after the publication of ‘A Silent Spring', a Danish group led by Skakkebaek2 reported in a meta-analysis that the mean sperm counts had declined by nearly 50% worldwide during the previous five decades. They also reported an increase in testicular cancer, hypospadias and cryptorchidism and hypothesized that environmental factors were affecting male gonadal function worldwide. In a follow-up article in 1993, Sharpe and Skakkebaek3 argued that increased exposure to estrogens via prescription drugs, dietary phytoestrogens and man-made estrogenic chemical pollutants (including pesticides) was the cause of falling global average sperm counts in men. They hypothesized that excessive exposure to these estrogens early in life was disrupting prepubertal Sertoli cell multiplication and resulting in a smaller number of Sertoli cells in adulthood. Because of the stoichiometric relationship between the Sertoli cells necessary to maintain germ cell development, a smaller number of Sertoli cells results in decreased spermatogenesis. Similar to Carson's ‘A Silent Spring', these articles created quite a sensation. Since their publication, there has been considerable controversy about whether global spermatogenesis and therefore male fertility is declining. The Carlsen meta-analysis has been criticized for inappropriate statistical methods, skewed data and failure to control for key variables,4,5,6,7,8 but the controversy generated enthusiasm and resources for a number of important studies investigating the possibility that male fertility was in jeopardy from environmental estrogens. The controversies include the following: 1. Is there really a secular decline in human sperm counts? 2. Is the sperm count a meaningful marker for male fertility? 3. Is there a meaningful decline in male fertility? 4. Do man-made chemicals with estrogenic properties represent a danger to the health of men?