• August 23, 2012 – 11:06

    Identifying Men for Active Surveillance in Prostate Cancer

    Since the PSA assay hit the mainstream for prostate cancer screening in the late 1980's, detection of prostate cancer has allowed for various levels of stratification for treatment, including active surveillance.  This modality for prostate cancer treatment has not been widely adopted based upon the imprecision of the risk status based upon TRUS-guided prostate biopsy. 

    A recent trial examined 124 men with favorable risk prostate cancer who were assigned to active surveillance.  The trial sought to describe the extent to which repeat TRUS biopsy can detect and rule out clinically relevant prostate cancer in men with favorable risk cancer.

    In this trial, repeat TRUS biopsy failed to detect 80% of clinically relevant cancers, with a negative predictive value of 23-60%.  The authors state that from this unique study, their data will allow clinicians to discuss conservative approaches for presumed favorable risk prostate cancer.  Importantly, the imprecision of testing and biopsy may be directly related to the choice of active surveillance. 

    The authors conclude that in patients to be considered for active surveillance, they should undergo template guided perineal prostate biopsies, since this modality is more likely to detect cancer than TRUS biopsies.  Ultimately, there may be a selection bias for diagnosis of higher volume disease if a larger number of biopsies overlap and sample the cancerous lesion more than once, which would provide a false-positive result.

    Reference: Barzell WE, Melamed MR, Cathcart P, et al.  Identifying candidates for active surveillance: an evaluation of the repeat biopsy strategy for men with favorable risk prostate cancer.  Journal of Urology 2012;188:762-768.

  • August 21, 2012 – 11:01

    Sweet Orange Aroma and Treatment of Anxiety

    While anxiety disorders remain one of the most prevalent psychological conditions in the general public worldwide, treatment options that do not promote dependence still provide a substantial challenge.  Aromatherapy has shown great promise with respect to an integrative approach to management of psychological conditions rather than treatment with more conventional (standard pharmacotherapeutic) options.

    Forty Brazilian men between ages of 18 and 30 completed the State-Trait Anxiety Inventory, then were randomized to treatment with inhalation of sweet orange essential oil; tea tree essential oil; or water (non-aromatic control), then completed a video-monitored Stroop Color-Word Test, which served as an anxiety provocation.  Measurements of psychological stress included heart rate and an electromyogram of the gastrocnemius muscle.

    Men who were exposed to test aromas did not exhibit significant alterations in anxiety, subjective tension or agitation.  Tranquility levels were increased in men who received sweet orange aromatherapy, which offers some scientific support for its use as an anxiolytic.  The higher dose of 10 drops compared to 2.5 drops provided a decrease in anxiety symptoms.  One limitation of this study was that it included a small number of graduate students under 30 years of age.  While larger and more rigorous trials are needed to prove a greater degree of efficacy, this study provides some promise for additional therapeutic options for the treatment of anxiety.

    Reference: Goes TC, Antunes FD, Alves PB, Teixeria-Silva F.  Effect of sweet orange aroma on experimental anxiety in humans.  Journal of Alternative and Complimentary Medicine 2012;18(8):798-804.

  • August 21, 2012 – 11:00

    2012 Updated ACCF/AHA Guidelines for Unstable Angina and Non-ST-Elevation Myocardial Infarction

    Recent guideline updates for unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) recommend the following:

    • Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely to patients who do not have contraindications
    • A loading dose followed by daily maintenance dose of either clopidogrel, prasurgel, or ticagrelor should be administered to UA/NSTEMI patients who are unable to take aspirin
    • After cardiovascular stress testing, the patient is classified as:
      • Not at low risk, diagnostic angiography should be performed
      • At low risk, continue aspirin indefinitely, continue clopidogrel or ticagrelor for up to 12 months, continue unfractionated heparin for 48 hours
      • For UA/NSTEMI patients in who coronary artery bypass grafting (CABG) is selected as a postangiography management strategy, continue aspirin and unfractionated heparin
      • Diagnostic angiography with intent to perform revascularization is indicated in initially stabilized UA/NSTEMI patients without serious comorbities who have an elevated risk for clinical events
      • It is reasonable to choose an early invasive strategy (within 12 to 24 hours of admission) over a delayed invasive strategy for initially stabilized high-risk patients with UA/NSTEMI
      • For UA/NSTEMI patients treated with a stent, aspirin should be continued indefinitely with clopidogrel 75mg daily, prasurgel 10mg daily or ticagrelor 90mg twice daily for at least 12 months in patients receiving a drug-eluting stent
      • Medical treatment in acute phase of UA/NSTEMI and decisions on whether to perform stress testing, angiography, and revascularization should be similar in patients with or without diabetes
      • Creatinine clearance should be estimated in patients with UA/NSTEMI and the doses of renally-cleared medications should be adjusted according to the pharmacokinetics of specific medications

    Reference: Jneid H, Anderson JL, Wright RS, et al.  2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update).  Circulation 2012;126:875-910.

  • July 30, 2012 – 12:47

    Potentially Permanent Sexual Side Effects of Finasteride

    Finasteride has been implicated in the development of sexual side effects including decreased libido, decreased incidence and volume of orgasm, and erectile dysfunction.  Previous trials have reported that while the incidence of these effects is generally low, they resolve over time and discontinuation of the medication. A cohort of 54 men who reported persistent sexual side effects associated with finasteride were reassessed 9-16 months after drug discontinuation.  The Arizona Sexual Experience Scale (ASEX) was used to assess severity and incidence of symptoms, and 89% of male respondents met criteria for sexual dysfunction.  The author reported that neither length of finasteride use nor duration of sexual side effects correlated to scores in sexual dysfunction. The blockage of conversion to dihydrotestosterone has been implicated in erectile dysfunction.  Animal studies on dutasteride have shown increased collagen deposition and altered expression of neuronal and inducible nitric oxide synthase, whereas trials using finasteride have concluded a 26% weight reduction in the weight of the corpora cavernosa.  To date, treatment with phosphodiesterase type-5 inhibitors and testosterone have not sufficiently restored sexual dysfunction in men treated with finasteride, as men who take finasteride do not typically have suppressed testosterone levels. 

    While selection bias in this trial may provide a significant limitation to its conclusions, the results may not apply to men with less severe side effects on the ASEX scale; men with more significant sexual side effects are more likely to participate in such a study.  Additional research is needed to understand the potential underlying mechanisms of causation, as well as to understand strategies for treatment of these adverse effects.

    Reference: Irwig MS.  Persistent sexual side effects of finasteride: could they be permanent?  J Sex Med 2012 (published online ahead of print)

  • July 25, 2012 – 09:04

    Testosterone and Mortality in Hypogonadal Men

    Low serum testosterone levels in men has been associated with an increased risk of diabetes mellitus, obesity, metabolic syndrome, osteoporosis, cardiovascular events, and all-cause mortality.  Numerous studies evaluating testosterone supplementation have described beneficial effects including increased strength and muscle mass, libido, bone mineral density, and insulin sensitivity.

    An observational, retrospective cohort study of multiple Veterans Administration (VA) centers in the Northwest US identified 1031 hypogonadal men with serum testosterone < 250ng/dl and age greater than 40 years with no history of prostate cancer.  Testosterone supplementation was given to 398 men (39%).  The mortality rate in men treated with testosterone was 10.3% compared to 20.7% in untreated men with a mortality rate of 3.4 deaths per 100 person-years for men treated with testosterone and 5.7 deaths per 100 person-years in untreated men (hazard ratio – 0.61).

    The authors conclude that testosterone supplementation was associated with decreased mortality compared to no treatment, the first trial to specifically examine this relationship.  One limitation of the study is that the men had an average of 7 pharmacologically-treated medical conditions, as 21% had coronary heart disease and 38% had diabetes.  The authors acknowledge that larger-scale randomized trials are needed to gain an improved understanding of the relationship between improvement in mortality outcomes and low serum testosterone in hypogonadal older men.

    Reference: Shores MM, Smith NL, Forsberg CW, et al.  Testosterone treatment and mortality in men with low testosterone levels.  J Clin Endocrinol Metab 2012;97:2050-2058.

  • July 23, 2012 – 19:10

    Vitamin D and Development of Metabolic Syndrome

    To date, the relationship between serum 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome has not been clearly validated, with respect to a prospective and predictive model.  Several small retrospective trials have demonstrated a link between the 2 conditions, with an estimate that low baseline 25(OH)D was inversely associated with 10-year risk of future development of metabolic syndrome when adjusted for age, gender, smoking status, seasonal variation, and body habitus.

    This trial evaluated 6,537 adults aged 25 years or older (42% men).  The authors of this study concluded that after a 5-year follow-up, low serum 25(OH)D concentrations were associated with an increased risk of development of metabolic syndrome, increased abdominal waist circumference, serum triglycerides, fasting glucose, and insulin resistance.  The incidence of metabolic syndrome was highest in subjects with the lowest quintiles of 25(OH)D (<18-23 ng/ml); odds ratio [OR] 1.41-1.74).  For each 10-ng/ml decrease in 25(OH)D, the risk of developing metabolic syndrome at 5 years increased by 23% (OR – 1.22). 

    Interestingly, this study found an association between baseline serum 25(OH)D and the risk of developing metabolic syndrome persisted after adjusting for body mass index in overweight or obese people but disappeared after taking into account baseline insulin resistance.  One limitation of this trial was that it did not evaluate serum parathyroid hormone levels, a potentially important cofactor in vitamin D metabolism. 

    Reference: Gagnon C, Lu ZX, Magliano DJ, et al.  Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab).  J Clin Endocrinol Metab 2012;97:1953-1961.

  • July 18, 2012 – 07:09

    New Male Osteoporosis Guidelines

    The US Endocrine Society's Clinical Guidelines Subcommittee published the first guidelines specific to men and osteoporosis in June 2012.  Key recommendations are as follows:

    • Screen men at increased risk for osteoporosis by measurement of bone mineral density (BMD) via dual-energy x-ray absorptiometry (DEXA) at age 70; men ages 50-69 should be tested if additional risk factors are present (e.g. low body weight, prior fracture as an adult, smoking)
    • Screen men ages 50-69 for osteoporosis if they have delayed puberty, hypogonadism, hyperparathyroidism, hyperthyroidism, chronic obstructive pulmonary disease, use chronic glucocorticoids or GnRH agonists, or have a history of smoking and/or alcohol abuse
    • If history and physical examination do not suggest a specific cause of osteoporosis, further testing should include bioavailable testosterone, sex hormone binding globulin, serum and urine protein electrophoresis, tissue transglutaminase antibodies, thyroid function tests, and parathyroid hormone levels
    • Men should take 1000-1200mg calcium daily ideally from dietary sources, supplemented if necessary
    • Men with vitamin D levels < 30ng/ml should receive supplementation
    • Men at risk of fracture who are receiving testosterone supplementation should take agents proven to reduce fracture risk (e.g. bisphosphonate or teriparatide)
    • Hypogonadal men with serum testosterone levels < 200ng/dl should receive testosterone replacement therapy unless contraindicated (e.g. prostate cancer)
    • Clinicians should monitor (BMD) via DEXA scan at the femoral neck and lumbar spine every 1-2 years to assess response to treatment
    • Men with osteoporosis should quit smoking, consume no more than 1 alcoholic beverage daily, and engage in weight-bearing exercise 30-40 minutes per session for 3-4 sessions per week

    Reference: Watts NB, Adler RA, Bilezikian JP, et al.  Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline.  J Clin Endocrinol Metab 2012;97:1802-1822.

  • July 15, 2012 – 07:07

    Survival Benefit of Radical Prostatectomy in Patients with Localized Prostate Cancer

    With the advent of new prostate cancer screening guidelines from the United States Preventive Services Task Force (USPSTF; http://www.uspreventiveservicestaskforce.org/prostatecancerscreening.htm) the debate continues with regard to active versus surveillance treatment for localized prostate cancer.  To date, only 1 randomized trial has compared radical prostatectomy to active surveillance.

    This trial reviewed the records of 44,694 patients treated with radical prostatectomy versus observation between 1992 and 2005 in the SEER (Surveillance, Epidemiology, and End Results)-Medicare database.  The number needed to treat to prevent a single adverse outcome ranged from 29 to 34 across the various Charlson comorbidity indices.  The 10-year cancer-specific mortality rate in men treated with radical prostatectomy versus observation was 5.2% compared to 12.8% for high risk prostate cancer, and 1.4% versus 3.8% for low to intermediate risk prostate cancer. 

    The authors of this trial conclude that men with high risk prostate cancer gain the largest survival benefit with radical prostatectomy, while the lowest benefit was observed in men with low to intermediate risk prostate cancer.  Given that this was observational data, the results may have been attributable to treatment bias.  Similar to previous trials, men who received active treatment longer than 6 months after diagnosis were placed in the observation group.  In most cases, prostate-specific antigen (PSA) values were not available, thus subjects could not be stratified by this measurement.

    Reference: Abdollah F, Sun M, Schmitges J, et al.  Survival benefit of radical prostatectomy in patients with localized prostate cancer: estimations of the number needed to treat according to tumor and patient characteristics.  J Urol 2012;188:73-83.

  • June 25, 2012 – 22:29

    SORRY, we do not have any news at the moment!