Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

Serum Müllerian inhibiting substance levels are lower in premenopausal women with breast precancer and cancer

<p>Abstract</p> <p>Background</p> <p>In preclinical studies, müllerian inhibiting substance (MIS) has a protective affect against breast cancer. Our objective was to determine whether serum MIS concentrations were associated with cancerous or precancerous lesions. Blood from 30 premenopausal women was collected and serum extracted prior to their undergoing breast biopsy to assess a suspicious lesion found on imaging or physical examination. Based on biopsy results, the serum specimens were grouped as cancer (invasive or ductal carcinoma <it>in situ</it>), precancer (atypical hyperplasia or lobular carcinoma <it>in situ</it>), or benign.</p> <p>Findings</p> <p>Serum from women with cancer and precancer (p = .0009) had lower MIS levels than serum from women with benign disease.</p> <p>Conclusion</p> <p>Our findings provide preliminary evidence for MIS being associated with current breast cancer risk, which should be validated in a larger population.</p

The challenge of measuring circulating estradiol at low concentrations

Demand for measuring estradiol at low concentrations is increasing, and the widely used 'direct' radioimmunoassays that do not require a preliminary organic purification step may be inadequate in patient care because of their limited accuracy. In observational epidemiology, however, the main concern is to obtain a correct ranking of individuals' hormone concentration relative to the true level (as determined through a 'gold standard'). Despite differences in the absolute scale of measured and true concentrations, correct ranking will permit calculation of unbiased estimates of hormone–disease associations. In prospective studies, the major concerns are the limited volume of often irreplaceable specimens and the need to perform a large number of assays within a reasonable period of time. Organic purification is often not feasible because of sample volume requirements and logistic difficulties, and so the development of accurate, rapid and inexpensive methods to measure sex steroids at low concentrations would represent a valuable new research tool for both clinicians and epidemiologists

Childhood meat eating and inflammatory markers: The Guangzhou Biobank Cohort Study

<p>Abstract</p> <p>Background</p> <p>We hypothesized that socio-economic development could, via nutritionally driven levels of pubertal sex-steroids, promote a pro-inflammatory state among men but not women in developing countries. We tested this hypothesis, using recalled childhood meat eating as a proxy for childhood nutrition, in southern China.</p> <p>Methods</p> <p>We used multivariable linear regression in the Guangzhou Biobank Cohort Study phase 3 (2006-8) to examine the adjusted associations of recalled childhood meat eating, <1/week (n = 5,023), about once per week (n = 3,592) and almost daily (n = 1,252), with white blood cell count and its differentials among older (≥50 years) men (n = 2,498) and women (n = 7,369).</p> <p>Results</p> <p>Adjusted for age, childhood socio-economic position, education and smoking, childhood meat eating had sex-specific associations with white blood cell count and lymphocyte count, but not granulocyte count. Men with childhood meat eating almost daily compared to <1/week had higher white blood cell count (0.33 10⁹/L, 95% confidence interval (CI) 0.10 to 0.56) and higher lymphocyte count (0.16 10⁹/L, 95% CI 0.07 to 0.25). Adjustment for obesity slightly attenuated these associations.</p> <p>Conclusion</p> <p>If confirmed, this hypothesis implies that economic development and the associated improvements in nutrition at puberty may be less beneficial among men than women; consistent with the widening sex differentials in life expectancy with economic development.</p

Lifetime physical activity and risk of breast cancer

We conducted a case–control study of 394 women with breast cancer and 788 control women (91% response) to investigate the association of lifetime physical activity with mainly menopausal breast cancer risk. After controlling for potential confounders, the odds ratios (95% confidence intervals) for increasing quartiles of lifetime physical activity were 1.00 (referent), 0.91 (0.60–1.37), 0.91 (0.60–1.39), and 1.10 (0.73–1.67), respectively;P, trend = 0.47. We also separately examined physical activity at ages 12–18, 19–34, 35–49 and ≥50 years; no significant trends were observed in any age group. These data do not support a role of physical activity in preventing breast cancer. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies

This paper presents a quantitative review of the data from eight prospective epidemiological studies, comparing mean serum concentrations of sex hormones in men who subsequently developed prostate cancer with those in men who remained cancer free. The hormones reviewed have been postulated to be involved in the aetiology of prostate cancer: androgens and their metabolites testosterone (T), non-SHBG-bound testosterone (non-SHBG-bound T), di-hydrotestosterone (DHT), androstanediol glucuronide (A-diol-g), androstenedione (A-dione), dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), the oestrogens, oestrone and oestradiol, luteinizing hormone (LH) and prolactin. The ratio of the mean hormone concentration in prostate cancer cases to that of controls (and its 95% confidence interval (CI)) was calculated for each study, and the results summarized by calculating the weighted average of the log ratios. No differences in the average concentrations of the hormones were found between prostate cancer cases and controls, with the possible exception of A-diol-g which exhibited a 5% higher mean serum concentration among cases relative to controls (ratio 1.05, 95% CI 1.00-1.11), based on 644 cases and 1048 controls. These data suggest that there are no large differences in circulating hormones between men who subsequently go on to develop prostate cancer and those who remain free of the disease. Further research is needed to substantiate the small difference found in A-diol-g concentrations between prostate cancer cases and controls