Are Problems With Male Reproductive Health Caused by Endocrine Disruption?

ore than 20 years ago, it was suggested that the normal reproductive development of the male embryo may be aVected by exposure to oestrogens, the focus initially being on the mother's endogenous oestrogen.In 1993, Sharpe and Skakkebaek proposed the hypothesis that increased oestrogen exposure in early life increases the risk of the two genital malformations hypospadias and cryptorchidism, and of testis cancer in adult life, as well as restricting the achievable sperm concentration (also called density, or more loosely, sperm count). 1 In recent years, the focus has shifted to concern about exogenous (xenobiotic) substances.This has become generalised beyond oestrogens to encompass eVects relating to other types of hormone, leading to the concept of an endocrine disrupter: " . ..an exogenous substance that causes adverse health eVects in an intact organism, or its progeny, consequent on changes in endocrine function".w1 Some prefer the term "endocrine modulator", as some eVects may be neutral or beneficial.It has been suggested that this type of mechanism has caused a deteriorating trend in male reproductive health-involving the same four end points of hypospadias, cryptorchidism, testicular cancer, and sperm density-throughout the world in recent decades, w1-4 although it is generally agreed that direct evidence is lacking.Juxtaposition of the fragmentary human evidence with that on fish, reptiles, and other wildlife has fuelled concern in the media, and has led to a large research eVort.It is important to separate the two main questions-the possible existence of a generalised deterioration in male reproductive health, and the hypothesis that endocrine disruption can cause these eVects.There are other possible mechanisms: the most potent known testicular toxin in adult life is the nematocide dibromochloropropane (DBCP), an alkylating agent (like many pesticides).w5 Germ line genetic damage to either parent before conception could theoretically aVect male reproductive health, but this possibility has received little attention.The purposes of this paper are: (a) to summarise the descriptive epidemiology; and (b) to review critically the plausibility of the endocrine disruption hypothesis as a possible explanation.Evidence from toxicology and endocrinology and from studies on wildlife are not directly considered, although they inform the discussion.Prostatic cancer is excluded, as age distribution and other features indicate that it is epidemiologically distinct from these four end points.Other human health end points are not reviewed, such as thyroid function, female reproduction, and breast cancer, which have also been linked with endocrine disruption.