Friday, March 7, 2014
Estrogen and Androgen Receptor Activities of Hydraulic Fracturing Chemicals and Surface and Ground Water
Kassotis CD, Tillitt DE, Davis JW, Hormann AM, Nagel SC. Estrogen and androgen receptor activities of hydraulic fracturing chemicals and surface and ground water in a drilling-dense region. Endocrinology 2014;155(3):897-907. http://medicine.missouri.edu/news/docs/en.2013-1697.full.pdf
The rapid rise in natural gas extraction using hydraulic fracturing increases the potential for contamination of surface and ground water from chemicals used throughout the process. Hundreds of products containing more than 750 chemicals and components are potentially used throughout the extraction process, including more than 100 known or suspected endocrine-disrupting chemicals.
We hypothesized that a selected subset of chemicals used in natural gas drilling operations and also surface and ground water samples collected in a drilling-dense region of Garfield County, Colorado, would exhibit estrogen and androgen receptor activities. Water samples were collected, solid-phase extracted, and measured for estrogen and androgen receptor activities using reporter gene assays in human cell lines.
Of the 39 unique water samples, 89%, 41%, 12%, and 46% exhibited estrogenic, antiestrogenic, androgenic, and antiandrogenic activities, respectively. Testing of a subset of natural gas drilling chemicals revealed novel antiestrogenic, novel antiandrogenic, and limited estrogenic activities.
The Colorado River, the drainage basin for this region, exhibited moderate levels of estrogenic, antiestrogenic, and antiandrogenic activities, suggesting that higher localized activity at sites with known natural gas-related spills surrounding the river might be contributing to the multiple receptor activities observed in this water source.
The majority of water samples collected from sites in a drilling-dense region of Colorado exhibited more estrogenic, antiestrogenic, or antiandrogenic activities than reference sites with limited nearby drilling operations.
Our data suggest that natural gas drilling operations may result in elevated endocrine-disrupting chemical activity in surface and ground water.
Thursday, March 6, 2014
Prostatectomy is associated with lower prostate-cancer mortality than watchful waiting even after nearly 20 years of follow-up, according to long-term results from the Scandinavian Prostate Cancer Group Study Number 4.
Some 700 men with early prostate cancer were randomized to radical prostatectomy or watchful waiting. The cumulative incidence of disease-specific mortality at 18 years was reduced in the surgery group versus the observation group (18% vs. 29%).
The reduction was significant only for men younger than 65, in whom the number needed to treat to prevent one prostate cancer death was four.
Among men aged 65 and older, prostatectomy was associated with significantly lower risks for metastases and need for palliative therapy.
In terms of morbidity, the groups had similar rates of erectile dysfunction (roughly 80%), but the surgery group had a higher incidence of urinary leakage than the watchful-waiting group (41% vs. 11%).
Bill-Axelson A, Holmberg L, Garmo H, et al. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine 2014;370(10):932-42. http://www.nejm.org/doi/full/10.1056/NEJMoa1311593
BACKGROUND - Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.
METHODS - Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.
RESULTS - During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3).
The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).
CONCLUSIONS - Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment.
Wednesday, March 5, 2014
Nearly half a million elderly Americans likely died from Alzheimer's disease in 2010, a figure almost six times higher than previous estimates of annual deaths.
Current national estimates are based on death certificates, which tend to underestimate deaths from dementia. The Centers for Disease Control and Prevention has estimated that approximately 5 million people are living with Alzheimer's disease in the United States, and that 83,000 die from the condition each year.
Researchers analyzed data from two existing studies that followed people age 65 and older, starting at a time when they did not have Alzheimer's. The participants were tracked for an average of eight years, with annual checkups and brain donation in the case of death.
One study followed religious orders of nuns and priests and the other followed people in retirement communities and senior housing facilities. In all, the studies tracked 2,566 people. Over the course of the two studies, 559 participants developed Alzheimer's disease and 1,090 participants died.
People diagnosed with Alzheimer's were more than three times as likely to die as those without it. The risk was more than four times as high among participants aged 75 to 84.
Applying these figures to U.S. deaths in 2010, when the data in the two studies were collected, the authors estimate that about 500,000 people over age 75 died from Alzheimer's disease that year.
James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States. Neurology. http://www.neurology.org/content/early/2014/03/05/WNL.0000000000000240.abstract
Objective: To assess the burden of mortality attributable to Alzheimer disease (AD) dementia in the United States.
Methods: Data came from 2,566 persons aged 65 years and older (mean 78.1 years) without dementia at baseline from 2 cohort studies of aging with identical annual diagnostic assessments of dementia. Because both studies require organ donation, ascertainment of mortality was complete and dates of death accurate. Mortality hazard ratios (HRs) after incident AD dementia were estimated per 10-year age strata from proportional hazards models.
Population attributable risk percentage was derived to estimate excess mortality after a diagnosis of AD dementia. The number of excess deaths attributable to AD dementia in the United States was then estimated.
Results: Over an average of 8 years, 559 participants (21.8%) without dementia at baseline developed AD dementia and 1,090 (42.4%) died. Median time from AD dementia diagnosis to death was 3.8 years. The mortality HR for AD dementia was 4.30 (confidence interval = 3.33, 5.58) for ages 75–84 years and 2.77 (confidence interval = 2.37, 3.23) for ages 85 years and older (too few deaths after AD dementia in ages 65–74 were available to estimate HR).
Population attributable risk percentage was 37.0% for ages 75–84 and 35.8% for ages 85 and older. An estimated 503,400 deaths in Americans aged 75 years and older were attributable to AD dementia in 2010.
Conclusions: A larger number of deaths are attributable to AD dementia in the United States each year than the number (<84,000 in 2010) reported on death certificates.
Healy ML, Gibney J, Pentecost C, Wheeler MJ, Sonksen PH. Endocrine Profiles in 693 Elite Athletes in the Post-Competition Setting. Clinical Endocrinology. http://onlinelibrary.wiley.com/doi/10.1111/cen.12445/abstract
Objective To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focuses attention on what may be considered as normal in this unusual group.
Design Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a sub-set of 693.
Participants Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition.
Measurements Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes.
Results Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels while 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men – sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones.
Conclusions Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a ‘normal’ testosterone level is untenable.