Jørgensen, N, E Carlsen, I Nermoen, M Punab, J Suominen, A-G Andersen, A-M Andersson, TB Haugen, A Horte, TK Jensen, Ø Magnus, JH Petersen, M Vierula, J Toppari and NE Skakkebæk. 2002. East–West gradient in semen quality in the Nordic–Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Human Reproduction 17: 2199-2208.

Skakkebæk et al. proposed in 2001 that four adverse conditions in male reproductive health—poor sperm quality, cryptorchidism, hypospadias and testicular cancer—are all part of a single pattern, testicular dysgenesis syndrome (TDS).

Previous observations had established an east-west gradient in the Nordic-Baltic area of testicular cancer. Denmark and Norway have high incidence rates while Finland and Estonia have low rates. In this paper, Jørgensen et al. used this previous observation as an opportunity to test the TDS hypothesis. If these male reproductive tract anomalies are part of a common syndrome, then sperm quality should follow the same gradient as testicular cancer.

Indeed, Jørgensen et al. confirm the prediction. Finnish and Estonian men have higher sperm concentrations and sperm counts, as well as higher percentages of normal sperm, than do men from Denmark and Norway. Thus the best semen quality is located in areas with the lowest risk of testicular cancer. This adds weight to the TDS hypothesis, and heightens focus on identifying factors contributing causally to the syndrome. According to Skakkebæk et al., endocrine disrupting contaminants are a prime suspect.

What did they do? With cooperation from military authorities, Jørgensen et al. obtained sperm samples during compulsory medical examinations required of young men living in four cities in Finland, Estonia, Denmark and Norway (Turku, Tartu, Copenhagen and Oslo, respectively) to assess their fitness for military service. Samples were taken irrespective of whether the examination found the individual fit for military service. This means the sample is broadly representative of the population and not biased by self-selection problems that are typical of most sperm studies.

All participants were instructed to abstain from ejaculation for at least 48 hrs prior to the examination. Information about relevant confounding variables (abstinence time, age, fertility history, etc.) was obtained via questionnaire. During the physical exam, a blood sample was obtained to allow characterization of serum hormone levels.

Sperm parameters were then measured using standardized techniques carefully applied to minimize inter-laboratory differences. The participating labs also conducted a quality-control study to identify inter-lab differences. When this study revealed significant differences between labs, statistical methods were used in the final analysis to correct for them.

What did they find? Increasing time of abstinence had a very large effect on sperm volume, sperm density and total sperm count as revealed by regression analysis. This effect was then factored into subsequent analyses statistically using a multiple regression.

Sperm volumes did not differ among men in the four cities sampled. Sperm concentration, however, varied markedly, both before the inter-lab differences were taken into account, and after correcting for them.

Median adjusted sperm concentrations observed in the four cities varied from a high in Estonia of 63 million sperm per milliliter to a low of 42 million per milliliter in Norway. These data are from the subgroup of the sample of men not currently taking any medicine nor with any known history of andrological disease, including impairment. The total sample demonstrated a similar (but not identical) pattern.

The statistical analysis revealed two groups: Estonia and Finland, and Denmark and Norway. Estonian and Finnish men from the cities sampled had similar sperm counts to one another, but men these differed from men in Denmark and Norway. Danish and Norwegian men were not different from one another.

The Estonian and Finnish men also had higher percentages of normal sperm. Because of the relatively subjectivity of methods to determine the percentage of motile sperm, reliable statistical comparisons of motility were prevented.

What does it mean? Jørgensen et al. interpret their results as consistent with the prediction based on geographic patterns in testicular cancer. Men in areas with higher risk of testicular cancer have lower sperm quality and quantity. This adds credibility to the proposal by Skakkebæk et al. that testicular cancer and sperm quality, along with hypospadias and cryptorchidism, are elements of a single syndrome, testicular dysgenesis syndrome. Confirmation of this proposal, however, is likely to wait until detailed information becomes available about the actual common mechanisms underlying the syndrome. These results should further encourage studies of those mechanisms.

Jørgensen et al.also express concern about the low sperm concentration reported in Denmark and Norway. The Denmark results corroborate an earlier study finding low concentrations in that country. In both countries, almost half the men sampled had sperm concentrations sufficiently low to contribute to fertility impairment via increased time to pregnancy. The authors also observe that the Finnish results are the lowest sperm concentrations yet reported for that country.