More than 20 years ago, it was suggested that the normal reproductive development of the male embryo may be affected 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 effects relating to other types of hormone, leading to the concept of an endocrine disrupter: “ . . .an exogenous substance that causes adverse health effects in an intact organism, or its progeny, consequent on changes in endocrine function”.^w1 Some prefer the term “endocrine modulator”, as some effects 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,^w1–4although 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 effort.

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 effects. 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 affect …