Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time. Incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention. Environ Health Perspect 104(Suppl 4): 741-803 (1996)

Background-Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis.We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD). Methods and Results-We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group. Conclusions-Individuals

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time. Incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention. Environ Health Perspect 104(Suppl 4): 741-803 (1996)

No abstract

The predictive value of sperm motility parameters obtained by computer-assisted semen analysis (CASA) was evaluated for the fertility of men from general population. In a prospective study with couples stopping use of contraception in order to try to conceive, CASA was performed on semen samples from 358 men. A recently developed CASA system, Copenhagen Rigshospitalet Image house sperm Motility Analysis System (CRISMAS) was used for assessment of motility parameters. This system has an editing function which allows correction of tracks made by the computer. Probably due to this function, the concentration assessment made by CRISMAS was very close to that made by the technician (median difference <5%) in all concentration ranges. Correlation between CASA parameters and fertility of normal couples (measured as probability of achieving pregnancy) was examined by the Cox regression model. In univariate models ln(sperm concentration) [beta = 0.331, risk ratio (RR) = 1.392, P = 0.0001], ln(total sperm count) (beta = 0.252, RR = 1.286, P = 0.0007) and percentage motile spermatozoa (beta = 0.014, RR = 1.014, P = 0.0004) were most significant predictors for fertility. In a multivariate analysis ln(sperm concentration) (beta = 0.268, RR = 1.307, P = 0.0016) and percentage motile spermatozoa (beta = 0.010, RR = 1.010, P = 0.011) but even more significantly the combined parameter, ln(concentration of motile spermatozoa) (beta = 0.329, RR = 1.389, P = 0.0001), were the only parameters of predictive value for fertility of men in the general population. In conclusion, these parameters obtained by CASA measurements can be used for prediction of fertility potential in normal men. This appears to be the first study showing the value of CASA in prediction of fertility in the general male population.

Two recent epidemiological studies (PROS and NHANES III) from the USA noted earlier sexual maturation in girls, leading to increased attention internationally to the age at onset of puberty. We studied the timing of puberty in a large cohort of healthy Danish children in order to evaluate differences between USA and Denmark, as well as to look for possible secular trends in pubertal development. Healthy Caucasian children from public schools in Denmark participated in the study which was carried out in 1991-1993. A total number of 826 boys and 1,100 girls (aged 6.0-19.9 years) were included, and pubertal stages were assessed by clinical examination according to methods of Tanner. In boys testicular volume was determined using an orchidometer. We found that age at breast development 2 (B2) was 10.88 years, and mean menarcheal age was 13.42 years. Girls with body mass index (BMI) above the median had significantly earlier puberty (age at B2 10.42 years) compared with girls with BMI below the median (age at B2 11.24 years, p < 0.0001). Similarly, menarcheal age was significantly lower in girls with BMI above the median compared with girls with BMI below the median (13.12 vs. 13.70 years, p = 0.0012). In Danish boys we found that age at genital stage 2 (G2) was 11.83 years. Both sexes were significantly taller compared with data from 1964, but timing of pubertal maturation seemed unaltered. Finally, puberty occurred much later in Denmark compared with recent data from USA. We could not detect any downwards secular trend in the timing of puberty in Denmark between 1964 and 1991-1993 as seen in the US. Obesity certainly plays a role in the timing of puberty, but the marked differences between Denmark and USA cannot be attributed exclusively to differences in BMI. A possible role of other factors like genetic polymorphisms, nutrition, physical activity or endocrine disrupting chemicals must therefore also be considered. Therefore, we believe it is crucial to monitor the pubertal development closely in Denmark in the coming decades.

Biologic fertility can be measured using time to pregnancy (TTP). Retrospective designs, although lacking detailed timed information about behavior and exposure, are useful since they have a well-defined target population, often have good response rates, and are simpler and less expensive to conduct than prospective studies. This paper reviews retrospective TTP studies from a methodological viewpoint and shows how methodological problems can be avoided or minimized by appropriate study design, conduct, and analysis. Sensitivity analyses using data from four European retrospective TTP studies are presented to explore the issues. Although the identified biases tend to have small impacts, the effects are not systematic across studies, and sensitivity analyses are recommended routinely. Planning bias can be checked by comparing propensity to report contraceptive failures in different exposure groups. Medical intervention bias can be avoided by censoring and inclusion of unsuccessful pregnancy attempts. Truncation bias can be a serious problem if unrecognized, but it is avoidable with appropriate study design and/or analysis. Behavior change bias can be minimized by assessing the covariates at the beginning of unprotected intercourse. More complete inference is possible if the study design covers the whole population, not just those who achieve a pregnancy. data collection; fertility; infertility; questionnaires; reproduction Abbreviation: TTP, time to pregnancy.Time to pregnancy (TTP) measures how long a couple takes to conceive. The TTP distribution in a population describes its degree of fertility. It is a functional measure, the final common path of a large number of biologic mechanisms in both sexes (1); its use is complementary to more mechanistic research on the biologic processes necessary for fertility and studies of specific medical conditions. Information about TTP is easy to obtain, and it has proven useful in descriptive epidemiology, for example, to identify time trends (2) and spatial variation (3) and to identify risk factors (4-7). Since the unit of study is the couple, covariates relating to both partners are required.TTP can be studied by use of either a prospective or retrospective design. Each has its strengths and weaknesses, and their roles are complementary. Prospective studies (the detailed discussion of which is beyond the scope of this paper) recruit couples at the start of their attempt, that is, couples who are prepared to undertake regular testing and to be followed up. These studies are therefore able to obtain detailed, timed information on key biologic events, including ovulation, implantation, and exposures, and on certain covariates, such as the frequency/timing of intercourse (8). They are becoming more sophisticated, and their feasibility has been demonstrated (8-11). The drawbacks are lack of a clear sampling frame (except in occupational studies) (12) and need for highly motivated participants, which might cause response bias and planning bias (see below). These drawbacks may ad...

The data suggest that oxidative damage to sperm DNA influences fecundity and the level of damage is relatively constant within an individual and not influenced by smoking.