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[Michael Scally MD]

Television Viewing And Health Risks

[Couch potatoes: Where the risks lie
TV’s health hazards may stem from more than just the time it takes away from healthy exercise
http://www.sciencenews.org/view/generic/id/331436/title/Couch_potatoes_Where_the_risks_lie ]


Television (TV) viewing is the most commonly reported daily activity apart from working and sleeping in many populations around the world. On average, 40% of daily free time is occupied by TV viewing within several European countries and 50% in Australia. This corresponds to a daily TV viewing time of about 3.5 to 4.0 hours. In the United States, the average number of daily hours of TV viewing has recently been reported to be 5 hours.

Beyond altering energy expenditure by displacing time spent on physical activities, TV viewing is associated with unhealthy eating (eg, higher intake of fried foods, processed meat, and sugar-sweetened beverages and lower intake of fruits, vegetables, and whole grains) in both children and adults. Furthermore, TV viewing may be associated with the intake of foods and beverages that are advertised on TV and could attract some individuals to begin smoking.

Physical inactivity, various dietary factors, and smoking are well-established independent risk factors of type 2 diabetes, cardiovascular disease, and all-cause mortality. Because TV viewing is the most prevalent and pervasive sedentary behavior, there is a great deal of interest in quantifying its independent association with health outcomes. However, a systematic and quantitative assessment of published studies is not available. Therefore, researchers conducted a meta-analysis to summarize all published prospective cohort studies to date on the incidence of type 2 diabetes, nonfatal or fatal cardiovascular disease, and all-cause mortality. Furthermore, they quantified the dose-response relationship of TV viewing with the risk of these health outcomes.

Their results from the meta-analysis of prospective cohort studies suggest that TV viewing is consistently associated with higher risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. They observed RRs of 1.20 for type 2 diabetes, 1.15 for cardiovascular disease, and 1.13 for all-cause mortality per every 2-hour increase in TV viewing per day. Based on incidence rates in the United States, they estimated that the absolute risk difference (cases per 100 000 individuals per year) per 2 hours of TV viewing per day was 176 for type 2 diabetes, 38 for fatal cardiovascular disease, and 104 for all-cause mortality.


Grontved A, Hu FB. Television Viewing and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality. JAMA: The Journal of the American Medical Association 2011;305(23):2448-55. Television Viewing and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality, June 15, 2011, Grøntved and Hu 305 (23): 2448 — JAMA

Context Prolonged television (TV) viewing is the most prevalent and pervasive sedentary behavior in industrialized countries and has been associated with morbidity and mortality. However, a systematic and quantitative assessment of published studies is not available.

Objective To perform a meta-analysis of all prospective cohort studies to determine the association between TV viewing and risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality.

Data Sources and Study Selection Relevant studies were identified by searches of the MEDLINE database from 1970 to March 2011 and the EMBASE database from 1974 to March 2011 without restrictions and by reviewing reference lists from retrieved articles. Cohort studies that reported relative risk estimates with 95% confidence intervals (CIs) for the associations of interest were included.

Data Extraction Data were extracted independently by each author and summary estimates of association were obtained using a random-effects model.

Data Synthesis Of the 8 studies included, 4 reported results on type 2 diabetes (175 938 individuals; 6428 incident cases during 1.1 million person-years of follow-up), 4 reported on fatal or nonfatal cardiovascular disease (34 253 individuals; 1052 incident cases), and 3 reported on all-cause mortality (26 509 individuals; 1879 deaths during 202 353 person-years of follow-up). The pooled relative risks per 2 hours of TV viewing per day were 1.20 (95% CI, 1.14-1.27) for type 2 diabetes, 1.15 (95% CI, 1.06-1.23) for fatal or nonfatal cardiovascular disease, and 1.13 (95% CI, 1.07-1.18) for all-cause mortality. While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day. The estimated absolute risk differences per every 2 hours of TV viewing per day were 176 cases of type 2 diabetes per 100 000 individuals per year, 38 cases of fatal cardiovascular disease per 100 000 individuals per year, and 104 deaths for all-cause mortality per 100 000 individuals per year.

Conclusion Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality.

 

[Michael Scally MD]

Association Of Lower Urinary Tract Symptoms And Erectile Dysfunction

In recent years, increasing attention has been given to the interaction and relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Both complaints are highly prevalent in the aging male and share common risk factors, such as hypertension, hypercholesterolemia and diabetes mellitus. Aside from these common denominators, an independent association has been elucidated in a number of large-scale international trials. There is a strong correlation between age and ED, with prevalence increasing steadily from 6.5% in men aged 20–39 years to 77.5% in those 75 years and older. A similar increase in the prevalence of LUTS in men has been observed from somewhat <1 in 10 in men aged 30–39 years to >1 in 3 in men aged 60–69 years. In total, as much as three in four men are likely to experience LUTS sometime during their lifespan. Both disorders have a major impact on quality of life (QoL) on individual patients, and further have a major socio-economic impact.

LUTS and ED are common disorders in aging men, which are independently associated to one another. The two disorders share certain pathophysiologic mechanisms and this association has many clinical implications. It is recommended that men presenting with LUTS should be evaluated for sexual dysfunction and ED in particular, and those presenting with sexual dysfunction should be evaluated for LUTS. Patients should further be screened for risk factors for underlying disorders. In treating LUTS, the presence or absence of sexual dysfunction may affect the choice of therapy, especially once patient preferences are considered. For this indication, the introduction of PDE-5 inhibitors is gaining acceptance. In patients with obstructive LUTS, the association of an ?-blocker may be of benefit. Ongoing research is further elucidating these complex interactions, and might hold promise for future therapy of men suffering from both LUTS and ED.


Orabi H, Albersen M, Lue TF. Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management. Int J Impot Res 2011;23(3):99-108. http://www.nature.com/ijir/journal/v23/n3/pdf/ijir201114a.pdf
International Journal of Impotence Research - Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

There is strong evidence from multiple epidemological studies that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are correlated, independent of age or comorbidities as diabetes or hypertension. Although a direct causal relationship is not established yet, four pathophysiological mechanisms can explain the relationship. These include alteration in nitric oxide bioavailability, ?1-adrenergic receptor hyperactivity, pelvic atherosclerosis and sex hormones.

This association has different clinical implications on the management of both disorders. Men seeking care for one condition should always be screened for complaints of the other condition. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment. There may be a potential therapeutic role for testosterone in LUTS treatment in cases of testosterone deficiency that needs to be investigated. Much further investigation is required, but it is evident that the association between LUTS and ED is fundamental for future therapies and possible preventative strategies.

 

[Michael Scally MD]

Association Of Body Mass Index With Future Site-Specific Cancer Mortality

A series of studies have examined the link between adiposity, measured in middle- and older-aged adults, and subsequent cancer development. Positive associations between body mass index (BMI), the most commonly used index of adiposity, and some site-specific malignancies—including colon, rectum, kidney, melanoma and pancreas—have been shown. Physiological mechanisms including metabolic disturbance have been posited as plausible explanations for these observed associations. However, despite the growing prevalence of obesity earlier in life, the long-term health consequences of obesity in early adulthood have not been well examined. This is due to a paucity of cohorts of young persons with BMI measurement who are then followed for several decades for the occurrence of cancer.

In the few studies relating body weight during early adulthood with future cancer risk, the number of events is low and statistical power is therefore sub-optimal. Other methodological constraints exist. Some studies suffer from an absence of covariate data to assess the effect of confounding, while in others, the potentially mediating role of adiposity in middle age has not been explored. This latter issue is particularly important since overweight young adults tend to remain overweight into middle age, such that the influence of excess weight during early adulthood on future cancer risk could simply be a result of perpetuated middle-aged adiposity.

The Harvard Alumni Health Study is a large prospective cohort with data collected across the entire adult life course. It therefore represents a rare opportunity to examine the associations of BMI during both early and middle adulthood with the risk of total and site-specific cancer mortality.


Gray L, Lee IM, Sesso HD, Batty GD. Association of body mass index in early adulthood and middle age with future site-specific cancer mortality: the Harvard Alumni Health Study. Annals of Oncology. Association of body mass index in early adulthood and middle age with future site-specific cancer mortality: the Harvard Alumni Health Study

Background: The association between adiposity in early adulthood and subsequent development of specific malignancies is unclear. Further, the potential for mediation by adiposity in middle age has not been well examined. In a rare study, we investigated the association of body mass index (BMI) in early adulthood with mortality from several site-specific cancers.

Design: In the Harvard Alumni Health Study cohort, 19 593 males had a physical examination at the university between 1914 and 1952 (mean age: 18.4 years) and returned a questionnaire in 1962 or 1966 (mean age = 45.1 years). BMI was computed using weight (kg)/height2 (m2) at both time points. Vital status follow up continued for a maximum of 82 years.

Results: Positive early adulthood cancer mortality gradients by BMI were found for all malignancies combined (adjusted hazard ratio

---

= 1.11; 95% confidence interval [CI]: 1.05–1.17 for a one standard deviation increase in early adulthood BMI), and for lung (HR = 1.24; 95% CI = 1.10–1.40) and skin (HR = 1.29; 95% CI = 0.96–1.75) cancers. There were also apparent associations for cancers of the oesophagus and urogenital sites. Mediation by BMI in middle age was found to be minimal.

Conclusion: Higher BMI in early adulthood appears to be a direct risk factor for selected malignancies several decades later.

 

[Michael Scally MD]

Identification Of Serum Biomarkers For Aging And Anabolic Response

In this study, researchers were interested in identifying age-associated biomarkers for healthy aging and evaluating whether biomarkers that differ between healthy young and older men at baseline, also differ in response to graded doses of testosterone. To achieve this, they used banked serum specimens from younger and older men to measure selected soluble cytokines and growth factors, based on predicted biomarkers from previous studies by us and others. Herein, they report results from this pilot analysis to identify biomarkers that change either in association with age and/or testosterone dosage.


Banerjee C, Ulloor J, Dillon E, et al. Identification of serum biomarkers for aging and anabolic response. Immunity & Ageing 2011;8(1):5. http://www.immunityageing.com/content/pdf/1742-4933-8-5.pdf

OBJECTIVE: With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.

METHODS: We measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens.

RESULTS: We identified nine serum biomarkers that differed between the young and older subjects. These age-associated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1beta (MIP-1beta), platelet derived growth factor beta (PDGFbeta) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA).

CONCLUSIONS: Results from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration.

 

[Michael Scally MD]

Crow's Feet Faceoff Yields Clear Winner

Crow's feet responded significantly better to treatment with abobotulinumtoxinA (Dysport) than with onabotulinumtoxinA (Botox), according to results of the first-ever randomized comparison of the two botulinum toxin compounds.


Comparison of the Efficacy of OnabotulinumtoxinA and AbobotulinumtoxinA

Botulinum toxin, a 149-kD protein produced by the bacterium Clostridium botulinum, is a potent neuromodulator, which works at the neuromuscular junction by inhibiting exocytosis of acetylcholine synaptic vesicles. The protein is composed of a heavy chain and a light chain, the latter a metalloproteinase responsible for cleaving a fusion protein responsible for vesicle docking and exocytosis. Although these proteins have been known as toxins, today they are better characterized as neuromodulators owing to their current widespread application in selective relaxation of muscles and muscle groups.

Seven naturally occurring serotypes of botulinum neuromodulator have been identified. However, only the A serotype has demonstrated sustained benefit and efficacy in clinical applications. The B serotype (Myobloc; Solstice Neurosciences, San Francisco, California) did offer favorable results in hyperfunctional frown lines. However, because of the pain associated with injection and short duration of action, clinical use has been limited.

In the 1970s and 1980s, Allen B. Scott, MD, of San Francisco, California, demonstrated relaxation of muscle groups in the treatment of strabismus. The US Food and Drug Administration (FDA) approved botulinum toxin type A for the treatment of strabismus and blepharospasm in 1989. Thus began clinical applications of the neuromodulator. This led to expanded clinical uses, including muscular relaxation in dystonias, hemifacial spasm, and rhytids.

Beginning in the 1990s and continuing through today, much investigation has been directed at the cosmetic applications of botulinum neuromodulator. In 1992, Carruthers and Carruthers3 in Canada were among the first to report on its use in the treatment of glabellar lines in the plastic surgery literature. Subsequently, in 2002, the FDA approved Botox Cosmetic (onabotulinumtoxinA) (Allergan Inc, Irvine, California) for the treatment of corrugator-mediated glabellar lines. Concurrently, another botulinum toxin type A product manufactured by Medicis Aesthetics (Scottsdale, Arizona), Dysport (abobotulinumtoxinA), had been used in other countries since 1991. It was approved for cosmetic use in Europe in 2001, before being approved by the FDA in April 2009 for the treatment of moderate-to-severe glabellar lines. Today, the cosmetic applications for onabotulinumtoxinA and abobotulinumtoxinA have expanded to the treatment of hyperfunctional lines related to the orbicularis oculi, frontalis, transverse nasalis, and depressor anguli oris, among other muscle groups.

While onabotulinumtoxinA and abobotulinumtoxinA have been used globally for 9 years and in the United States for nearly 2 years, to date, there have been no double-blind, internally controlled studies comparing the 2 products. Such an assessment could characterize and contrast their efficacy in clinical performance in the treatment of hyperfunctional lines and muscle relaxation. By using a split-face (internally controlled) paradigm, this would provide direct comparison of each product in the same patient. In an effort to minimize and/or eliminate any crossover effect or product diffusion (as would be seen in split-face forehead or glabellar studies), the lateral orbital rhytids (“crow's feet”) were chosen for study.

The data revealed that abobotulinumtoxinA offers superior efficacy in the treatment of lateral orbital rhytids compared with onabotulinumtoxinA, based on a 30-day assessment. While the greatest difference was seen in the investigator assessment of maximal contraction—the primary end point—a statistically significant difference was also seen in patient assessment of maximal contraction—a secondary end point. Two other secondary end points, investigator and patient assessments of resting lateral orbital rhytids, did not achieve statistical significance (P = .42 and P = .28, respectively). Nonetheless, live assessments of each patient and photographic documentation also suggest an advantage in resting lines with abobotulinumtoxinA.


Nettar KD, Yu KCY, Bapna S, Boscardin J, Maas CS. An Internally Controlled, Double-blind Comparison of the Efficacy of OnabotulinumtoxinA and AbobotulinumtoxinA. Archives of Facial Plastic Surgery. An Internally Controlled, Double-blind Comparison of the Efficacy of OnabotulinumtoxinA and AbobotulinumtoxinA -

Objective To compare 2 commercially available botulinum neuromodulators in a randomized, double-blind, split-face study.

Methods Ninety patients were treated with 10 U of onabotulinumtoxinA and 30 U of abobotulinumtoxinA for the treatment of lateral orbital rhytids. Patients were assessed live with a validated 5-point photographic scale prior to treatment and at 30 days. Patients were also photographed at each visit.

Results AbobotulinumtoxinA demonstrated a statistically significant advantage compared with onabotulinumtoxinA in the treatment of lateral orbital rhytids at maximal contraction, as evaluated independently by the investigator (P = .01) and patient (P = .03). AbobotulinumtoxinA was also favored by the patient over onabotulinumtoxinA 67% of the time. While abobotulinumtoxinA seemed to treat lateral orbital rhytids better at rest, as evidenced by the data and photographs, this difference was not statistically significant (P = .42).

Conclusions AbobotulinumtoxinA offers superior efficacy in the treatment of lateral orbital rhytids compared with onabotulinumtoxinA. Further studies are needed to compare the 2 products in different muscle groups and for other indications.

 

[Michael Scally MD]

Aromatase Inhibitors In Men - Effects And Therapeutic Options

Over the past 15 years, it has become evident that in men estradiol is responsible for a number of effects originally attributed to testosterone. Estradiol has an important role in gaining and maintaining bone mass, closing of the epiphyses, and the feedback on gonadotropin secretion. This fact became particularly evident in men with aromatase deficiency. Aromatase is the enzyme responsible for conversion of androgens to estrogens.

Men with estrogen deficiency caused by a mutation in the CYP19 gene suffer from low bone mineral density (BMD) and unfused epiphyses, and have high gonadotropin and testosterone levels. Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia, and low gonadotropin and testosterone levels. Lowering estrogen levels in men has emerged, consequently, as a potential treatment for a number of disorders including pubertas praecox, the andropause (also referred to as late-onset hypogonadism), and gynecomastia. Aromatase inhibitors were proven to be safe, convenient and effective for the treatment of hormone sensitive breast cancer in women although their use is associated with a modest increase in bone resorption. This review will discuss the potential targets and the evidence for the use of aromatase inhibitors in men.

Aromatase inhibitors, mostly combined with agonists of gonadotrophin-releasing hormone proved effective for the prevention of premature epiphysial closure in boys with pubertas praecox of various etiologies. There is also evidence that aromatase inhibitors can be used in boys with idiopathic short stature and boys with constitutional delay of puberty to increase adult height. Aromatase inhibitors are not effective for the treatment of gynecomastia in pubertal boys and have limited efficacy for the prevention of gynecomastia in bicalutamide-treated men with prostate cancer.

Although aromatase inhibitors increase FSH levels, there is no consistent evidence for a beneficial effect on spermatogenesis. In older men with so-called late onset hypogonadism, aromatase inhibitors may emerge as an attractive alternative for traditional testosterone supplementation to improve testosterone levels. The long-term benefits of higher testosterone levels in older men remain controversial, however. Moreover, it is questionable whether aromatase inhibitors are able to stimulate testosterone production sufficiently in men with truly low testosterone levels for whom testosterone treatment is currently recommended. Although most of the recent studies with aromatase inhibitors in boys and adult men do not show major detrimental effects on bone long-term skeletal safety remains an issue of concern.


de Ronde W, de Jong FH. Aromatase inhibitors in men: effects and therapeutic options, Reproductive Biology and Endocrinology. 2011;9:93 (21 June 2011). http://www.rbej.com/content/pdf/1477-7827-9-93.pdf

Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.

 

[Michael Scally MD]

Reference Ranges for Testosterone In Men 19-40 Using Liquid Chromatography Tandem Mass Spectrometry

Androgen deficiency in men is a syndrome characterized by a constellation of symptoms and signs and low circulating testosterone levels. Thus, the diagnosis of androgen deficiency is predicated upon the determination of whether the circulating testosterone level is low or normal. Rigorously established reference ranges constitute the essential basis for identifying whether the circulating levels of an analyte, such as testosterone, are normal or low. The reference ranges for testosterone have been derived previously mostly from small convenience samples or from hospital or clinic-based patients; these approaches are limited by their inherent selection bias, because patients seeking medical care are more likely to have a disease than individuals in the general population.

Some recent efforts to generate reference ranges in community-dwelling men are notable; these studies included middle-aged and older men and used direct RIA, whose accuracy, particularly in the low range, has been questioned. In the absence of rigorously determined reference limits generated using reliable assays in community-based samples, the partitioning of total and free testosterone levels into normal or low values has been fraught with substantial risk of misclassification, relegating many healthy men to unnecessary risks of testosterone therapy and preventing others from receiving appropriate testosterone therapy because of a missed diagnosis.

Researchers generated reference limits for total and free testosterone concentrations in a community-based sample of healthy young men in the Framingham Heart Study (FHS) third generation (Gen 3) cohort. Total testosterone was measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), a method with high specificity, sensitivity, and accuracy. They applied these reference limits to three geographically distinct cohorts of community-dwelling men: FHS Gen 2 and 3, the European Male Aging Study (EMAS), and the Osteoporotic Fractures in Men Study (MrOS).

They determined whether men in these three cohorts, deemed to have low total and free testosterone levels by the proposed reference limits, had a higher prevalence of physical dysfunction, sexual symptoms, and diabetes mellitus (DM), the three categories of conditions that have been associated most consistently with low testosterone levels. They used thresholds based on a healthy young reference sample (T-score approach) because in exploratory analyses, the T-score approach and age-adjusted thresholds (Z-score approach) yielded concordant results for most outcomes. Also, the spline plots of testosterone levels against outcomes in the FHS sample did not reveal clear inflection points at which the relationship between testosterone levels and outcomes changed abruptly. The T-score approach based on limits derived in a healthy young population has been favored historically for analytes that exhibit clinically meaningful age-related trends, such as estradiol and bone mineral density.

They demonstrated that values below the proposed lower reference limits were associated with increased risk of conditions that have been associated previously with androgen deficiency in three geographically distinct populations. Thus, men deemed to have low total or free testosterone levels had increased prevalence of sexual symptoms, physical dysfunction, and DM in one or more cohorts.


Bhasin S, Pencina M, Jasuja GK, et al. Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts. Journal of Clinical Endocrinology & Metabolism. http://jcem.endojournals.org/content/early/2011/06/16/jc.2010-3012.abstract

Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men.

Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study.

Results: In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes.

Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

 

[Michael Scally MD]

Hormones and Human Sexual Orientation

Because male and female embryos are exposed to a different hormonal milieu during specific phases of their intrauterine life, male and female newborns are substantially different on the day of birth. Balthazart summarizes here the main principles that govern sexual differentiation identified by experimental studies in animals. Then he discusses to what extent these principles could also determine sexual differentiation of brain and behavior in humans and finally reviews evidence derived from epidemiological and clinical studies, suggesting that sexual orientation is a sexually differentiated behavioral feature that is most likely influenced, like other sexually differentiated features, by the prenatal hormonal environment. He does not mean to say that the postnatal social environment has no influence on sexual orientation, but based on currently available data, these social influences seem to play only a minor role, possibly via interaction with prenatal endocrine effects.

There is thus substantial evidence suggesting that sexual orientation is influenced before birth by a set of biological mechanisms. These mechanisms include genes that affect sexual orientation by currently unidentified mechanisms and hormonal actions classically mediating sexual differentiation. Our current understanding of these prenatal factors admittedly suffers many limitations.


Balthazart J. Minireview: Hormones and Human Sexual Orientation. Endocrinology. http://endo.endojournals.org/content/early/2011/06/15/en.2011-0277.abstract

Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa).

In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion.

First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development.

Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality.

It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined.

 

[Michael Scally MD]

Olive Oil Consumption, Plasma Oleic Acid, And Stroke Incidence

The assumption that high olive oil consumption may be associated with a reduced incidence of stroke independently of other dietary habits and stroke risk factors has never been explored. Researchers investigated the relationship between olive oil consumption, plasma oleic acid as a biological marker of oleic acid intake, and 6-year stroke incidence in older participants in the Three-City (3C) Study.

In the present population-based study, intensive olive oil use was prospectively associated with a lower stroke risk after controlling for numerous confounding factors, including lifestyle and nutritional factors, main stroke risk factors, and blood lipids.


Samieri C, Feart C, Proust-Lima C, et al. Olive oil consumption, plasma oleic acid, and stroke incidence. Neurology. http://www.neurology.org/content/early/2011/06/15/WNL.0b013e318220abeb.full.pdf

Objective: To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects.

Methods: Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee.

Results: In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41% (95% confidence interval 6%–63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10%–92%, p = 0.03) reduction of stroke risk.

Conclusions: These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.

 

[HeadDoc]

any data from Italy on the same?

Olive Oil Consumption, Plasma Oleic Acid, And Stroke Incidence

The assumption that high olive oil consumption may be associated with a reduced incidence of stroke independently of other dietary habits and stroke risk factors has never been explored. Researchers investigated the relationship between olive oil consumption, plasma oleic acid as a biological marker of oleic acid intake, and 6-year stroke incidence in older participants in the Three-City (3C) Study.

In the present population-based study, intensive olive oil use was prospectively associated with a lower stroke risk after controlling for numerous confounding factors, including lifestyle and nutritional factors, main stroke risk factors, and blood lipids.


Samieri C, Feart C, Proust-Lima C, et al. Olive oil consumption, plasma oleic acid, and stroke incidence. Neurology. http://www.neurology.org/content/early/2011/06/15/WNL.0b013e318220abeb.full.pdf

Objective: To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects.

Methods: Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee.

Results: In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41% (95% confidence interval 6%–63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10%–92%, p = 0.03) reduction of stroke risk.

Conclusions: These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.

 

[zkt]

This another confirmation of what we already know.
Cant have too many.

 

[Michael Scally MD]

Testosterone Replacement Therapy (TRT) In Opiate Induced Hypogonadism (OPIAD)

Opioid-induced hypogonadism in males (Opioid-Induced Androgen Deficiency, OPIAD) is usually ignored by pain physicians and rarely considered for treatment despite its high frequency (almost 100%) and persistence. The aim of the present study was to describe the time course/interactions between opioids and testosterone replacement therapy in a clinical sample of male chronic pain patients diagnosed with OPIAD and receiving morphine via the epidural route. This kind of patient was chosen to reduce variables due to the high numbers of opiates available, their dosage and combinations. Moreover, all these patients had been suffering from chronic pain for many years and their pain condition was considered severe and stable.

To obtain a broad picture of the effects induced by this treatment, researchers considered different aspects using a multidisciplinary approach. A team of experts, namely an andrologist, a psychologist, the project coordinator and a local pain therapist, met with each patient monthly for one year to check the clinical and laboratory outcomes. Testosterone was replaced via a gel formulation able to restore and maintain testosterone levels by virtue of the fact that its application on the skin prevents first liver clearance and allows steroids to be directly absorbed and stored in the stratum corneum. From this reservoir, testosterone or its metabolites (17-beta estradiol and DHT) are slowly released into the circulation over several hours. Testosterone and its related hormones (estradiol, DHT) were measured in the blood, together with cortisol as an index of adrenal activity. Pain intensity and its features were studied with the VAS, the Italian version of the McGill Questionnaire (QUID) and the Margolis method to determine the percentage of the body in pain. The andrological condition was studied with the dedicated questionnaire Ageing Males' Symptoms Scale (AMS), and different aspects of the psychological characteristics were evaluated through questionnaires able to study anxiety, depression and quality of life (POMS, CES-D and SF-36). The study was carried out for 12 months. The results suggest beneficial effects on the patients' quality of life.

Evidence from this study suggests that one year of testosterone replacement therapy in male patients suffering from a severe form of chronic pain and diagnosed with morphine-induced hypogonadism (OPIAD) is able to positively change hormonal and behavioural 'indicators' chosen to measure different aspects of their condition.


Aloisi AM, Ceccarelli I, Carlucci M, et al. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol 2011;9:26. RB&E | Full text | Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients

BACKGROUND: In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available.

METHODS: To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route), we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol), pain (VAS and other pain questionnaires), andrological (Ageing Males' Symptoms Scale-AMS) and psychological (POMS, CES-D and SF-36) parameters were evaluated at baseline (T0) and after 3, 6 and 12 months (T3, T6, T12 respectively).

RESULTS: The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID) progressively improved from T3 to T12 while the other pain parameters (VAS, Area%) remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time.

CONCLUSIONS: In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management.

 

[Michael Scally MD]

Hydrogen Sulfide And Erectile Function

In the past 10 years, hydrogen sulfide (H2S)—a third component of the human gaseous transmitter family (after NO and carbon monoxide)—has been identified as a physiological regulator in cardiovascular homeostasis. The finding that mammalian cells can produce H2S has garnered considerable interest in the biology and pharmacology of this molecule.

The gaseous transmitter, H2S, shares many features with NO but the finding that human corpus cavernosum relaxes in response to H2S in the absence of endothelium suggests that drugs that can stimulate this pathway selectively may be useful as a treatment in ED when PDE5 inhibitors fail. In addition, a better understanding of the crosstalk between the l arginine–NO and l cysteine–H2S pathways could lead to an improvement of current ED therapy.

d'Emmanuele di Villa Bianca R, Sorrentino R, Mirone V, Cirino G. Hydrogen sulfide and erectile function: a novel therapeutic target. Nat Rev Urol 2011;8(5):286-9. Hydrogen sulfide and erectile function: a novel th... [Nat Rev Urol. 2011] - PubMed result

Hydrogen sulfide (H(2)S) is a gaseous transmitter involved in the control of vascular homeostasis. H(2)S is formed endogenously from L-cysteine or L-methionine by two enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), and normally circulates in blood. Studies from the past few years have demonstrated the involvement of H(2)S in erectile mechanisms in animal and human tissues. Exogenous H(2)S relaxes human and animal tissues in vitro and increases intracavernous pressure in experimental animal models. Electrical field stimulation studies on animal and human tissues have demonstrated that endogenous H(2)S is involved in the physiological control of penile tone. In humans, both CBS and CSE are widely expressed on trabecular muscle, implying that the smooth muscle component is the major source of H(2)S. Thus, the L-cysteine-H(2)S pathway may represent a promising target for development of new therapeutics for erectile dysfunction.

 

[Michael Scally MD]

Finasteride-Induced Pseudoporphyria

Pseudoporphyria is a condition characterized by tense bullae, eroded plaques, and scarring, usually on the dorsal aspects of the hands and forearms. These cutaneous changes are also seen in porphyria cutanea tarda (PCT). Unlike PCT, a diagnosis of pseudoporphyria is made when blisters, erosions, and scars are present in sun-exposed areas of skin with no evidence of abnormal porphyrin excretion found on urine or serum analysis.


Domingo DS, Stevenson ML, Auerbach J, Lerman J. Finasteride-Induced Pseudoporphyria. Arch Dermatol 2011;147(6):747-8. Finasteride-induced pseudoporphyria. [Arch Dermatol. 2011] - PubMed result

 

[zkt]

Read more from the MESO-Rx Steroid Forum at: https://thinksteroids.com/community/threads/134301507

QUOTE
]Hydrogen sulfide (H(2)S) is a gaseous transmitter involved in the control of vascular homeostasis. H(2)S is formed endogenously from L-cysteine or L-methionine by two enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE).

Damn! Yet another player. It might be worth while to research the enzymes involved in H2S production. Or just pig out on rotten eggs.[)]

 

[Michael Scally MD]

F as in Fat: How Obesity Threatens America's Future 2011
F as in Fat: How Obesity Threatens America's Future 2011 - Trust for America's Health

Adult obesity rates increased in 16 states in the past year and did not decline in any state, according to F as in Fat: How Obesity Threatens America's Future 2011, a report from the Trust for America's Health (TFAH) and the Robert Wood Johnson Foundation (RWJF). Twelve states now have obesity rates above 30 percent. Four years ago, only one state was above 30 percent.

The obesity epidemic continues to be most dramatic in the South, which includes nine of the 10 states with the highest adult obesity rates. States in the Northeast and West tend to have lower rates. Mississippi maintained the highest adult obesity rate for the seventh year in a row, and Colorado has the lowest obesity rate and is the only state with a rate under 20 percent.

This year, for the first time, the report examined how the obesity epidemic has grown over the past two decades. Twenty years ago, no state had an obesity rate above 15 percent. Today, more than two out of three states, 38 total, have obesity rates over 25 percent, and just one has a rate lower than 20 percent. Since 1995, when data was available for every state, obesity rates have doubled in seven states and increased by at least 90 percent in 10 others. Obesity rates have grown fastest in Oklahoma, Alabama, and Tennessee, and slowest in Washington, D.C., Colorado, and Connecticut.

“Today, the state with the lowest obesity rate would have had the highest rate in 1995,” said Jeff Levi, Ph.D., executive director of TFAH. “There was a clear tipping point in our national weight gain over the last twenty years, and we can't afford to ignore the impact obesity has on our health and corresponding health care spending.”

 

[Michael Scally MD]

An Unhealthy Lifestyle Is Associated with Sexual Dysfunction

A new study published in The Journal of Sexual Medicine reveals that several unhealthy lifestyle factors, such as weight problems, physical inactivity, high alcohol consumption, tobacco smoking, and hard drugs are associated with sexual dysfunctions in men. Additionally, an unhealthy lifestyle is more common in persons who are sexually inactive.

Researchers used nationally representative survey data from 5,552 Danish men and women aged 16 – 97 years in 2005 to study the association of lifestyle factors with sexual inactivity and sexual dysfunction.

Results found that a number of unhealthy lifestyle factors are associated with increased risk of not having a partner-related sex life by up to 78% in men and up to 91% in women. Among those who had a sexual partner, risk of experiencing sexual dysfunction was greater in men who lead unhealthy lives by 71% in those with substantially increased waist circumference and more than 800% in men using hard drugs. Women who used hashish had almost 3 times increased risk of anorgasmia (difficulties or inability to reach climax during sexual activity with a partner) compared to non-users.

“Hopefully our findings can be used in future counseling of patients with unhealthy lifestyles,” Frisch concludes. “Knowing about possible negative consequences of an unhealthy lifestyle to one’s sexual health may help people quit smoking, consume less alcohol, exercise more, and lose weight.”

“There are many reasons for sexual dysfunction, including those over which you have no control, such as after cancer treatments, or following injuries,” explained Irwin Goldstein, Editor-in-Chief of The Journal of Sexual Medicine, “but lifestyle and recreational drug use are individual choices. Each person can modify lifestyle, especially diet and exercise and stop using recreational drugs that inhibit the sexual reflex, to be healthier thereby facilitating sexual function.”


Christensen BS, Grønbæk M, Pedersen BV, Graugaard C, Frisch M. Associations of Unhealthy Lifestyle Factors with Sexual Inactivity and Sexual Dysfunctions in Denmark. The Journal of Sexual Medicine. Associations of Unhealthy Lifestyle Factors with Sexual Inactivity and Sexual Dysfunctions in Denmark - Christensen - 2011 - The Journal of Sexual Medicine - Wiley Online Library

Introduction. Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting.

Aim. To examine associations between unhealthy lifestyle factors and sexual inactivity with a partner and four specific sexual dysfunctions in each sex.

Methods. We used nationally representative survey data from 5,552 Danish men and women aged 16–97 years in 2005. Cross-sectional associations of lifestyle factors with sexual inactivity and sexual dysfunctions were estimated by logistic regression-derived, confounder-adjusted odds ratios (ORs).

Main Outcome Measures. We calculated ORs for sexual inactivity with a partner and for sexual dysfunction and sexual difficulties overall in both sexes, for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, and for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women.

Results. Obesity (body mass index [BMI]?30 kg/m2) or a substantially increased waist circumference (men ?102 cm; women ?88 cm), physical inactivity, and, among women, tobacco smoking were each significantly associated with sexual inactivity in the last year. Among sexually active men, both underweight (BMI <20 kg/m2) and obesity, a substantially increased waist circumference, physical inactivity in leisure time, high alcohol consumption (>21 alcoholic beverages/week), tobacco smoking, and use of hard drugs were each significantly positively associated with one or more sexual dysfunctions (ORs between 1.71 and 22.0). Among sexually active women, the only significant positive association between an unhealthy lifestyle factor and sexual dysfunction was between hashish use and anorgasmia (OR 2.85).

Conclusion. In both sexes, several unhealthy lifestyle factors were associated with sexual inactivity with a partner in the last year. Additionally, among sexually active participants, men with unhealthy lifestyles were significantly more likely to experience sexual dysfunctions. Considering the importance of a good sex life, our findings may be useful in attempts to promote healthier lifestyles.

 

[Michael Scally MD]

Association Between Clomiphene Citrate (CC) And Visual Disturbances

The purpose of this article is to review the relationship between CC and central retinal vein occlusion (CRVO) in infertility patients, and secondly other related visual disturbances. Retinal vein occlusions are the second most common type of retinal vascular disorder after diabetic retinal disease, with an incidence of approximately 2 per 1,000 in the >40 years age group and 5.4 cases per 1,000 in the >64 years age group with equal gender distribution. Retinal vein occlusion is due to thrombosis of retinal veins (central, hemi or branch) and has been associated with cardiovascular risk factors. However, the pathogenesis and management of this disorder remains somewhat of an enigma. It is a complication not commonly seen by the gynecologists, but they should be aware of the condition in fertility patients undergoing ovulation induction with clomiphene citrate (CC).

CRVO is a common retinal vascular disorder and has been associated with various systemic and pathological conditions. The first endocrine event in response to a course of clomiphene therapy is an increase in the release of pituitary gonadotropins followed by an increase in thrombogenic estradiol. Therefore, CC may predispose to CRVO, especially in patients with underlying risk factors.

Patients should be instructed to inform the physician about any unusual visual symptoms such as blurring, spots or flashes. These visual symptoms generally disappear within a few days or weeks after CC is discontinued. Physicians should be aware of the potential risk of CC and if visual disturbances occur, therapy should be terminated and the patient referred for specialist ophthalmic care.


Viola MI, Meyer D, Kruger T. Association between clomiphene citrate and visual disturbances with special emphasis on central retinal vein occlusion: a review. Gynecol Obstet Invest 2011;71(2):73-6. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000319497

OBJECTIVES: To determine whether clomiphene citrate (CC) can be implicated as a cause for central retinal vein occlusion (CRVO) and other visual disturbances.

METHODS: For this systematic review, we performed a search of the following databases: PubMed (1976 to November 2009), Medline Plus 2009, Cochrane Library (1996 to November 2009), Google and Google Scholar (1996 to November 2009). Thirty-five relevant titles (25 full papers and 10 abstracts) were identified and read by authors. No review has been published in the literature. The publications included describe adverse effects with clomid and selective estrogen receptor modulators and in particular visual disturbances. The population consisted of infertility patients under ovulation induction with CC. The main outcome measures were loss of vision due to CRVO and other visual changes.

RESULTS: CC may predispose to CRVO, but further trials are clearly needed in this area.

CONCLUSION: Physicians should be aware of the potential risk of CC, especially in patients with associated risk factors for CRVO. If visual disturbances occur, therapy should be terminated and the patient referred for specialist ophthalmic care.

 

[Michael Scally MD]

Endogenous Testosterone And Cardiovascular Disease

Testosterone concentrations in men decline with ageing and obesity, although it is uncertain whether this hormonal decline itself results in increased risk for cardiovascular disease (CVD). Testosterone has been assumed to have an important impact on risk of CVD. This assumption was initially based on differences in CVD between men and women, though at present on differences in testosterone level and presence or absence of CVD in men. The speculations on the impact of testosterone on the cardiovascular system have resulted in various prospective studies for decades, though a definitive answer as to whether testosterone affects risk for CVD has yet to be provided.

One of the problems is that causal inference may be troublesome, that is, studies of patients with systolic chronic heart failure are difficult to interpret for the reason that heart failure as an illness affects sex steroid concentrations. Even straightforward intervention studies, for example, testosterone treatment in men with coronary heart disease, have been inconclusive. Yet, a better knowledge of the role of testosterone on the cardiovascular system is of importance in the light of potential reduction of CVD and the ongoing debate on testosterone supplementation in age- or obesity-related low serum testosterone.

So far, previous reviews on testosterone and CVD have been narrative in nature. Therefore, researchers performed a quantitative approach through a systematic review according to MOOSE guidelines. They performed a meta-analysis to estimate the predictive value of endogenous testosterone for CVD, and meta-regression analyses to identify study features that modify the relationship, that is, explain heterogeneity across studies. Study features hypothesised to be potential modifiers were study design, testosterone assay, type of outcome studied, number or type of confounders for which adjustment was made, age of study population, follow-up period, country of study and year of publication, as the last item might, for example, reflect improvement of technology.

The present systematic review does not confirm the ‘widespread idea’ that low endogenous testosterone increases the risk for CVD in middle-aged men, and somehow contrasts with previous narrative reviews. Yet, in elderly men, a negative association was revealed, which was particularly prominent in studies published after 1 January 2007.


Ruige JB, Mahmoud AM, De Bacquer D, Kaufman J-M. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 2011;97(11):870-5. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis -- Ruige et al. 97 (11): 870 -- Heart

Context The literature provides no clear answer as to whether low endogenous testosterone increases risk of cardiovascular disease (CVD) in healthy men.

Objective Our purpose was to estimate the predictive value of testosterone for CVD and to identify study features explaining conflicting results.

Data Sources Articles were identified by a Medline and Embase search and citation tracking.

Study Selection Eligible were prospective population-based cohort and nested case-control studies of testosterone and atherosclerosis, stroke, myocardial infarction, ischaemic heart disease, death from coronary heart disease or mortality.

Data extraction Two independent researchers re-expressed associations of testosterone and CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of testosterone for CVD.

Results and Conclusions 19 potentially eligible articles were identified. Overall, a weak independent association was found with an estimated summary RR of 0.89 for a change of one standard deviation in total testosterone level (95% CI 0.83 to 0.96). Age of study population and year of publication modified the relationship between testosterone and CVD. The estimated summary RR was 1.01 (0.95 to 1.08) for studies of men younger than 70 years of age, and 0.84 (0.76 to 0.92) for studies including men over 70 years of age. The latter studies showed a particular pronounced association if published after 1 January 2007. Results were largely confirmed by separate analyses of free- and bioavailable testosterone.

The systematic review displayed no association between endogenous testosterone and risk for CVD in middle-aged men. In elderly men, testosterone may weakly protect against CVD. Alternatively, low testosterone may indicate a poor general health.

 

[Michael Scally MD]

CT Scan Detects Silent CV Risk
Medical News: CT Scan Detects Silent CV Risk - in Cardiovascular, Atherosclerosis from MedPage Today

Coronary calcium buildup detected by coronary artery CT scan was associated with an increased risk of heart attack or stroke even in asymptomatic patients with low LDL cholesterol, researchers found.

Calcium in the coronaries predicted a 4.23-fold risk of heart disease events in such patients (95% CI 2.28 to 7.86), Khurram Nasir, MD, MPH, of Yale University, and colleagues reported.

Blankstein R, Budoff MJ, Shaw LJ, et al. Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2011;58(4):364-74. Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol: MESA (Multi-Ethnic Study of Atherosclerosis) -- Blankstein et al. 58 (4): 364 -- Journal of the American College of Cardiology

Objectives: Our aim was to identify risk factors for coronary heart disease (CHD) events among asymptomatic persons with low (</=130 mg/dl) low-density lipoprotein cholesterol (LDL-C).

Background: Even among persons with low LDL-C, some will still experience CHD events and may benefit from more aggressive pharmacologic and lifestyle therapies.

Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort of 6,814 participants free of clinical cardiovascular disease. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies, 3,714 (66%) had LDL-C </=130 mg/dl and were included in the present study. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors and biomarkers with CHD events. To determine if subclinical atherosclerosis markers provided additional information beyond traditional risk factors, coronary artery calcium (CAC) and carotid intima media thickness were each separately added to the multivariable model.

Results: During a median follow-up of 5.4 years, 120 (3.2%) CHD events were observed. In unadjusted analysis, age, male sex, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and subclinical atherosclerosis markers (CAC >0; carotid intima media thickness >/=1 mm) predicted CHD events. Independent predictors of CHD events included age, male sex, hypertension, diabetes, and low HDL-C. After accounting for all traditional risk factors, the predictive value of CAC was attenuated but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC.

Conclusions: Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for more aggressive therapies.