Changes in semen and the testis

Infertility currently affects at least one man in 20, but we are unable to assess whether it is becoming more prevalent because we have extremely poor past records. Male reproduction has been given little attention scientifically and in medical practice. However, our recent meta-analysis in the BMJ of 61 papers on semen quality, which clearly pointed to a decrease over the past 50 years,1 has been repeatedly quoted in the BMJ,2 3 4 Science,5 and the popular media.

We have already responded to the various technical criticisms, several of which concerned the known limitations of meta-analysis.*RF6-8* Though the data for 1970-90 were compatible with a decrease as well as with no change or an increase in semen quality, the cautious general conclusion is that a real decline in semen quality did occur over the full period 1940-90. Three recent reports have found that semen quality has declined among candidates semen donors during the past 20 years.9 10 11 Two of these studies not only included data on sperm count but also showed that important measures of quality - morphology of sperm heads and motility - had also deteriorated.9 10

These changes are all the more worrying since the quality of “normal” human semen is already very poor when compared with that of other mammalian species - more than half of our sperm usually have one or more morphological abnormalities compared with less than 5% in some other species - and several studies have shown a relation between abnormal sperm heads and infertility.12 Whether the prevalence of abnormalities in human sperm has always been so high is not known; some recent reports indicate that a change might have occurred.^9,10 The relatively high number of abnormal sperm may explain in part our low fecundity compared with that of most mammals.

The evidence of a decline in the quality of semen is not the only indicator that the human testis is at risk. For a generation or more, cancer of the testis has been becoming more common.13 This is a disorder of young men and is associated with a high rate of other abnormalities of the testis, including undescended testis and poor semen quality. One quarter of men with unilateral cancer of the testis have severe impairment of the contralateral testis, including the “Sertoli cell only” pattern and spermatogenic arrest. Furthermore, the incidence of both hypospadias and undescended testes has been reported to be rising in the general population. The evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders in men.12

We believe, then, that there are grounds for concern about the function of the testes. Cancer of the testis is clearly associated with undescended testis and dysgenetic testis, but we do not know its cause. Nor do we know that of undescended testis, and the causes of poor semen quality are in most cases obscure.

What possible explanations have been put forward? Many years ago oestrogens were suggested as playing a part in cancer of the testis,14 and epidemiological data show that administration of stilboestrol during pregnancy may lead to an increase in cancer of the testis and other abnormalities, including undescended testis and a low sperm count. Clearly only a few men were exposed to stilboestrol in utero, and neither it nor drugs can be blamed for the general trends, but many manmade toxins in the environment may act as oestrogens,^15,16 and these pose a theoretical risk to the male fetus if ingested by the mother before of during pregnancy.

This “oestrogen hypothesis,”17 which has received wide coverage in the media, is just that - a hypothesis - but progress in science must be based on refutable ideas. Much more basic and clinical research work is needed. When research in male reproduction is compared with that in many other branches of medicine our understanding of disorders of the testis is seen to be extremely limited.12 Much more work is needed on the environmental toxins that are potentially oestrogenic.18 How are they absorbed and metabolised? Are they bioaccumulative? Several chemicals, including isomers of dicophane (DDT), polychlorinated biphenyl compounds, and certain surfactants, have been shown to be oestrogenic, and the list of such chemicals is still growing. We still do not know what concentrations and mixtures of these chemicals might be hazardous to male reproductive function.

In the meantime we should, perhaps, try to obtain better prospective data on the function and health of the testes of men in the general population.