Germaine M. Buck Louis

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

OBJECTIVE: To assess measures of puberty-presence of pubic hair, breast development, and menarche-for 3 racial/ethnic groups of girls in the United States. METHODS: Using data from the Third National Health and Nutrition Examination Survey, this study sample was restricted to 1623 girls aged 8 to 16 years (466 non-Hispanic white, 589 non-Hispanic black, and 568 Mexican American) for whom information was available on Tanner stages of pubic hair and breast development. Subsequently, the sample was restricted to 1168 girls aged 10 to 16 years (330 non-Hispanic white, 419 non-Hispanic black, and 419 Mexican American) for whom menarche data were available. Tanner stage II or higher was used to define pubic hair and breast development; menarche status was self-reported. The percentage of girls who had pubic hair and breast development and had achieved menarche was computed by age and race/ethnicity. Probit and failure time models were applied to estimate mean ages at onset of pubic hair, breast development, and menarche. The racial/ethnic differences also were examined after adjustment for social and economic variables and current body mass index. RESULTS: Black and Mexican American girls had pubic hair and breast development and had achieved menarche at younger ages than white girls. For example, 49.4% of black girls aged 9 years had breast development compared with 24.5% of Mexican American girls and 15.8% of white girls. The mean age at onset of pubic hair, breast development, and menarche was 9.5, 9.5, and 12.1 year for black girls; 10.3, 9.8, and 12.2 years for Mexican American girls; and 10.5, 10.3, and 12.7 years for white girls. These ethnic differences remained even after adjustment for current body mass index and several social and economic variables. CONCLUSION: Black girls on average enter puberty first, followed by Mexican American and then white girls.

The literature on exposure to lipophilic agents such as polychlorinated biphenyls (PCBs) is conflicting, posing challenges for the interpretation of potential human health risks. Laboratory variation in quantifying PCBs may account for some of the conflicting study results. For example, for quantification purposes, blood is often used as a proxy for adipose tissue, which makes it necessary to model serum lipids when assessing health risks of PCBs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of PCB exposure, serum lipids, and health outcome risk (breast cancer). We applied eight candidate true causal scenarios, depicted by directed acyclic graphs, to illustrate the ramifications of misspecification of underlying assumptions when interpreting results. Statistical models that deviated from underlying causal assumptions generated biased results. Lipid standardization, or the division of serum concentrations by serum lipids, was observed to be highly prone to bias. We conclude that investigators must consider biology, biologic medium (e.g., nonfasting blood samples), laboratory measurement, and other underlying modeling assumptions when devising a statistical plan for assessing health outcomes in relation to environmental exposures.