Is the human testis still an organ at risk?

Regional differences in sperm counts and fertility may provide a clue

Although several lines of circumstantial evidence suggest that we may be seeing adverse changes in male reproductive health, it is the possibility that semen quality may have declined that has attracted most attention. In a meta-analysis Carlsen et al examined data from 61 papers published between 1938 and 1991 on the quality of semen in normal men.1 Using linear regression analysis, they identified statistically significant decreases over time in mean ejaculate volume and a fall in sperm concentration from 113x10⁶/ml in 1940 to 66x10⁶/ml in 1990. This report has aroused continuing debate.2 Subsequently, Auger et al published data on 1351 healthy fertile candidates for sperm donation who attended one centre between 1973 and 1992.3 Correcting for sexual abstinence, they observed a significant decline in sperm concentration, the percentage of motile spermatozoa, and the percentage of morphologically normal spermatozoa both as a function of year of birth and age at donation.

Several workers have since examined secular trends in semen quality, some apparently showing a trend downwards,4 5 while others have found no such trend.6 7 Most recently, two groups of workers from the United States have published data suggesting no changes in semen quality with time.8 9 Paulsen et al examined the semen quality of 510 men in Seattle, selected on the basis of endocrine and physical normality to participate in clinical research studies, and found no evidence of any change in semen quality with time.8 Fisch et al reported on 1283 men banking semen prior to vasectomy between 1970 and 1994 at three different sperm banks.9 Although they found no evidence of changes with time in semen quality, they did observe significant and unexplained differences in semen quality in the three locations—the average sperm concentration was 131.5x10⁶/ml in New York, 100.8x10⁶/ml in Minnesota, and 72.7x10⁶/ml in California.

These regional differences reflect similar differences observed in Europe, most notably between Finland and Denmark,6 10 and are at least as intriguing as the difficult and controversial issue of secular trends. Whether these regional differences are due to ethnic, environmental, or lifestyle factors remains to be explored.

The question of whether these apparent differences are relevant to fertility has recently been addressed by Joffe in a careful and thought provoking comparison of “time to pregnancy” in Finland and Britain.11 Couples in Finland conceived more quickly than their British counterparts, suggesting that semen in Finland is of higher quality.

If real, changes in semen quality are not happening in isolation. There is evidence that the incidence of testicular cancer is changing, with unexplained increases being observed in Europe12 and in the United States.13 In the west of Scotland, for example, the number of testicular germ cell tumours registered more than doubled between 1960 and 1990,14 while a recent study from Norway reported that the age standardised incidence for testis cancer increased from 2.7 per 100 000 in 1955 to 8.5 per 100 000 in 1992.15 It is of interest that there is also a substantial geographical variation in both the incidence of testis cancer and in the observed rate of increase.12 This geographical variation may be linked with that seen in semen quality—testis cancer is four times more common in Denmark, where some studies have revealed rather low sperm counts,12than in Finland, where semen quality is better.8

Rise in incidence of congenital malformations

It has also been suggested that the incidence of congenital malformations of the male genital tract is changing, with observed increases in the prevalence of cryptorchidism and hypospadias.16 Rates of cryptorchidism, for example, are reported to have increased by as much as 65%-77% over recent decades in Britain.17 Regional differences were also found, although these results are perhaps less robust. In a multicentre study of 8122 boys from seven malformation surveillance systems around the world, Kallen et al concluded that, even when differences in ascertainment were taken into account, true geographical differences existed in the prevalence of hypospadias at birth.18 Intriguingly, they also concluded that there seemed to be an inverse correlation between fertility in a population (estimated from mean parity in control women) and the prevalence of isolated hypospadias at birth.

The question of causation remains open. The provocative “oestrogen hypothesis”19 remains a hypothesis, albeit one which is gathering biological weight,20 21 and clinical data are scarce. Taken together, the available data on semen quality and other aspects of male reproductive health, at the very least, raise concerns that should be addressed by properly designed, coordinated, and funded research. Prospective multicentre studies with attention to possible confounding factors and appropriate quality control are required, together with more reliable methods of assessing semen quality. To paraphrase a recent BMJ editorial,22 delay may compromise the reproductive health of future generations.