• May 13, 2013 – 22:38

    Latest Update on Prostate Cancer Screening at the AUA Meeting, May 2013

    At the American Urological Association Annual Meeting earlier this week, new guidelines from the AUA now recommend that men aged 55 to 69 who are considering prostate cancer screening discuss the benefits and potential harms of screening with their doctors, then to proceed based upon personal values and preferences.  This recommendation is based upon high-quality evidence that suggests the screening benefit over 2- to 4-year intervals would allow 1 man per 1,000 to avert death from prostate cancer over a decade, yet the benefit extrapolated over a man's lifetime may actually be greater. 

    The AUA guidelines state that screening for prostate cancer in men less than 40 years of age is not recommended, nor is routine screening in men 40 to 54 years of age at average risk.  To reduce harms of screening, a screening interval of 2 years may be preferable over annual screening in low-risk men who have engaged in shared-decision making with their physician.  Lastly, routine prostate cancer screening in men over 70, or in men with a less than 10- to 15-year life expectancy is not recommended.

    Reference: American Urological Association Annual Meeting, May 4-8, 2013, San Diego, California, USA

  • May 13, 2013 – 22:05

    Osteoporosis management program in patients with prostate cancer receiving androgen deprivation therapy

    Approximately one third of patients with prostate cancer receive androgen deprivation therapy (ADT). This treatment is associated with higher incidence of fractures and increased mortality of fractures. However, only a minority of patients receiving ADT has their bone mineral density (BMD) documented before or after initiation of ADT. Therefore, the aim of this study was to determine whether the implementation of a screening and treatment protocol reduced the rate of osteoporotic fractures in men with prostate cancer receiving ADT.

    This study included 1482 patients with prostate cancer receiving leuprolide identified in the electronic medical system of Kaiser Permanente Southern California. Of them, 1071 were included in the Healthy Bone Program (HBP) comprising BMD measurement by dual energy X-ray absorptiometry and treatment. The indications of anti-osteoporotic treatment were established using T-score corresponding to the number of standard deviations below the mean in young healthy adult men. Men with T-score ≥-2.5 were advised on smoking cessation, regular exercise, adequate calcium intake (1200 mg/d) and adequate vitamin D intake (400-800 IU/d). Men with T-score <-2.5 were also treated with pharmacological intervention (mainly bisphosphonates). The remaining 411 men received standard care. Strict exclusion criteria were used to reduce the selection bias.

    The men who were included in the HBP had much lower incidence of hip fracture (5 vs 18 fractures per 1000 person-years). After adjustment for confounders, patients who were not enrolled in the HBP had a fourfold higher risk of hip fracture compared with the HBP patients (hazard risk = 4.19, 95% confidence interval 1.92 – 9.13, p<0.001).

    In this study men with prostate cancer receiving ADT and enrolled in an active screening and treatment protocol experienced 72% lower rate of hip fracture compared with the nonscreened group. This difference may seem astonishingly high; however, two facts need to be remembered. Some older men have low BMD and high risk of fracture. ADT accelerates bone turnover leading to a rapid bone loss associated with a deterioration of bone microarchitecture and higher bone fragility. This rapid bone loss may be particularly dangerous in men with low BMD at baseline. ADT-induced hypogonadism may also result in rapid loss of muscle mass and strength leading to a higher risk of falling. Thus, the detection and treatment of men with low BMD may decrease markedly the risk of fracture. Moreover, the implementation if lifestyle changes may have a beneficial effect on bone and muscle.

    Some limitations of the study have to be recognized: retrospective identification of patients, observational design, potential imbalance in risk factors and medical care between two groups of men. However, despite these limitations, the paper and accompanying comment are important because they raise two major points. Firstly, ADT increases bone fragility. Thus, critical judgment of indications for ADT is necessary before its initiation in order to avoid the severe adverse effects. Secondly, the implementation of an osteoporosis management program in patients with prostate cancer receiving ADT may have a beneficial effect.

    Reference: Zhumkhawala AA, Gleason JM, Cheetham TC, Niu F, Loo RK, Dell RM, Jacobsen SJ, Chien GW. Osteoporosis management program decreases incidence of hip fracture in patients with prostate cancer receiving androgen deprivation therapy Urology. 2013 May; 81(5):1010-7.

  • May 1, 2013 – 14:08

    Naftopidil in the Management of BPH

    Naftopidil has affinity for both α1A- and α1D-adrenoreceptors for the treatment of benign prostatic obstruction and benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS).  It was originally developed as an α-adrenoceptor antagonistic anti-hypertensive drug.  It has been evaluated in both prazosin-controlled and double-blind-controlled trials in Japan that verified dose-dependent effects, and therefore has had an indication for treatment of BPH in Japan, China, and South Korea.  Several tamsulosin-controlled trials have suggested a potentially higher efficacy for alleviating storage symptoms with naftopidil.  The optimal dose is 50-75mg per day according to characteristics including baseline IPSS.  Well-designed randomized trials are warranted to confirm long-term outcomes regarding management of men with storage symptoms including nocturia, through comparisons of quality of life measures with other α-adrenergic blockers.

    Reference: Hara N, Mizusawa T, Obara K, Takahashi K.  The role of naftopidil in the management of benign prostatic hyperplasia.  Ther Adv Urol 2013;5(2)111-119.

  • May 1, 2013 – 14:03

    Udenafil in the Management of ED

    Udenafil is a novel PDE5-inhibitor approved for treatment of ED in Korea.  It has an onset of action of 1-1.5 hours and a half-life of 11-13 hours, suitable for both on-demand and daily use.  It has been tested across various levels of trials (through Phase III studies) in subjects with ED and concomitant diabetes mellitus, hypertension, and BPH.  It appears to be safe and well-tolerated, resulting in significant improvements in men with ED according to IIEF parameters.

    Commonly reported adverse effects include headache, facial flushing, and febrile sensation, and none were considered to be of moderate or severe intensity.  In a multiple-dose study, a color discrimination abnormality was reported that affected the blue-green region of the visual spectrum, yet this adverse effect spontaneously resolved upon successive testing defined as 1.5 hours after the fourth dose.  There were no clinically significant findings in routine laboratory parameters including platelet aggregation tests, bleeding time, or semen analysis.

    Udenafil appears to have a longer onset time compared with vardenafil and a shorter duration compared to tadalafil.  Larger cohort, multi-ethnic trials will be required to more accurately assess its efficacy for worldwide use.

    Reference: Kang SG, Kim JJ.  Udenafil: efficacy and tolerability in the management of erectile dysfunction.  Ther Adv Urol 2013;5(2):101-110.

  • May 1, 2013 – 14:01

    Personalized PSA Testing May Reduce Prostate Biopsies

    Recent studies have identified genetic variants associated with increased PSA levels and prostate cancer risk, raising the possibility of diagnostic bias.  By correcting for these variants, it has been postulated that a “personalized” cut-off for PSA levels could be determined which could help to better stratify patients for prostate biopsy to rule out cancer.  Genetic correction of PSA was performed by dividing a subject's PSA value by his combined genetic risk. 

    Four single nucleotide polymorphisms associated with PSA levels have been identified in healthy subjects without prostate cancer.  Genetic correlation of PSA results in 964 Caucasian men was associated with a significantly decreased percentage of men reaching biopsy thresholds, estimating a 15% to 20% relative reduction in biopsies using a threshold of 2.5ng/ml or greater or 4.0ng/ml or greater, respectively.  In addition, genetic correlation could results in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.

    Limitations of this study include a small cohort of only Caucasian men, suggesting the need for a larger study across various ethnicities.  The influence of genetic correction on clinical outcomes requires further prospective study in a large, independent cohort.  Lastly, the applicability of cost-effectiveness must be considered, since genetic testing may not be readily available across practices.

    Reference: Helfand BT, Loeb S, Hu Q, et al.  Personalized prostate specific antigen testing using genetic variants may reduce unnecessary prostate biopsies.  J Urol 2013;189:1697-1701.

  • April 18, 2013 – 18:30

    Effects of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction

    Testosterone is a major regulator of sexual desire, spontaneous sexual thoughts, motivation, attentiveness to erotic stimuli, and sexual activity in men. Experimental studies show that testosterone regulates penile nitric oxide synthase and blood flow. These data lead to speculation that, in men with erectile dysfunction (ED), normal testosterone level is necessary to achieve an optimum response to phosphodiesterase type 5 (PDE5) inhibitors.

    This randomized, parallel group trial was performed in 140 men aged 40 to 70 with ED and low levels of total or free testosterone levels (<330 ng/dl or <50 pg/ml, respectively). First, dose of sildenafil was optimized for 3 to 7 weeks (25-100 mg/d). Then, participants were randomized (1:1) to testosterone (Testim, Auxilium Pharmaceuticals, Malvern) or placebo gel. Men were treated for 14 weeks and testosterone was adjusted on the basis of testosterone measurements. During the treatment, erectile and sexual functions as well as ED-related quality of life were assessed using standardized and validated questionnaires.

    During the first phase, sildenafil administered alone increased testosterone levels by ~100 ng/dl. Later on, in the testosterone-treated group, testosterone levels increased further to the average level of 649 ng/dl. Sildenafil alone induced a substantial increase in all domains of the International Index of Erectile Function (IIEF) such as erectile function, sexual desire, orgasmic function, or intercourse satisfaction. Sildenafil alone also improved substantially all domains of the Sexual Encounter Profile (SEP), e.g. frequency of sexual encounters, vaginal penetration or ejaculation. Further, sildenafil also improved the ED-related quality of life. Importantly, there was no difference between men who did or did not take testosterone (in addition to sildenafil) as concerns the evaluated parameters of sexual function. The analysis limited to men who completed 14 weeks of treatment provided similar results. The effect of testosterone on ED did not vary by the testosterone levels, age or body mass index.

    Thus, sildenafil plus testosterone did not improve sexual function compared with sildenafil plus placebo. This may seem surprising in light of preclinical data. However, sildenafil may have increased testosterone levels higher than the upper limit of dose-response relationship of testosterone for erectile function. Testosterone and sildenafil may share common mechanistic pathways and the optimized dose of sildenafil may have maximally induced these pathways. The results are not related to methodological problems: this was a randomized, double-blind and placebo-controlled trial, dropout rate was low, patients responded robustly to sildenafil, duration of testosterone treatment was sufficient to induce a therapeutic response.

    Thus, in summary, these results do not support the routine addition of testosterone therapy for improving erectile response to selective PDE5 inhibitors in men with ED who have low testosterone levels.

    Reference: Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, Mazer NA, KNapp PE, Hanka S, Lakshman KM, Ulloor J, Zhang A, Orwoll K, Eder R, Collins L, Mohammed N, Rosen RC, DeRogatis L, Bhasin S. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012 157(10):681-91.

  • March 28, 2013 – 21:52

    Save the date: Men’s Health World Congress 2013; December 6-8, Washington DC

    The ISMH is please to announce that the 9th Men’s Health World Congress (MHWC) will be held for the first time in the USA on December 6 to 8, 2013.  The 2013 MHWC will be jointly conducted by our International Society of Men’s Health and the newly-launched American Society of Men’s Health. 

    This meeting will bring together all those interested in men’s health including multidisciplinary international groups of clinicians, academicians, researchers, key opinion leaders as well as professionals from the healthcare industry, medical education, health policy and others.  The 2013 MHWC will feature the latest science and progress in men’s health, new advances in early and late stages of prostate cancer, cardiovascular disease, hypogonadism, infertility, endocrinology, psychiatry and others.

    The meeting program will present lectures by top experts from around the globe, debates and interactive sessions on controversial clinical topics and much more!  In addition, specialized symposia will address contemporary important issues in men’s health.  The scientific program is designed by a multidisciplinary internationl committee of world-renouned experts and the 2013 MHWC is co-chaired by Alan Wein, Joel Heidelbaugh and Mikio Namiki. 

    SAVE THE DATE AND GO TO www.mhwc2013.org to receive further information !

  • February 20, 2013 – 18:10

    Erectile dysfunction is associated with higher cardiovascular risk and all cause mortality

    Cardiovascular (CV) disease and erectile dysfunction (ED) share common risk factors, whereas evidence-based studies have identified pathophysiological links as endothelial dysfunction and inflammation. Thus, identifying ED may be a useful predictor of future CV events.

    Vlachopoulos et al. (1) performed the meta-analysis of 14 studies including jointly 92757 men (various outcomes have not necessarily been studied in all men). Total CV events were defined as CV death, myocardial infarction, revascularization, cerebrovascular events (stroke, transient ischemic attacks, intracranial hemorrhage), peripheral vascular disease, angina, heart failure and arrhythmia. ED was associated with a significantly higher (by 44%) risk of total CV events. The risk was significantly increased in the intermediate-risk group (by 51%) and in the high-risk group (by 30%), but not in the low-risk group. In an analysis performed in the studies in which the analyses were adjusted for main CV confounders, the increase in the risk of total CV event associated with ED was similar to the overall combined estimated risk. It shows that the higher CV risk in men with ED was independent of their higher baseline CV risk. The increase in the CV risk associated with ED was higher in studies in which ED was diagnosed with a validated questionnaire (by 61%) compared with a single question (by 27%).

    ED was also associated with a significantly higher risk of myocardial infarction (by 62%) and of cerebrovascular event (by 39%). ED was associated with a significantly higher all-cause mortality (by 25%), mainly in men with known CV disease, but not with CV mortality. The findings of the meta-analyses were not related to the publication bias. Finally, meta-regression analyses showed that ED was predictive of CV events mainly in younger men, smokers as well as in men with higher total cholesterol and lower HDL-cholesterol levels.

    Thus, screening and diagnosing ED can be important for primary prevention in the clinical practice because ED assessment offers an easy, low-cost alternative for CV biomarkers. The risk conferred by ED on the CV events is of a magnitude similar to that of the risk conferred by established risk predictors such as hypertension or dyslipidemia. ED can describe the CV risk particularly in men belonging to the intermediate-risk category. This group requires further risk reclassification and ED may be an additional predictor permitting to better assess the individual CV risk. Furthermore, the use of a validated questionnaire improves the diagnosis of ED and provides a stronger association between ED and the CV risk.

    Overall these findings show that the assessment of ED using a validated method may help to estimate the CV risk in the clinical practice.

    Reference: Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013 6:99-109.

  • November 11, 2011 – 15:37

    ISMH launches TDS-Public Awarness Campaign “Let´s talk balls” in Sweden

    The ISMH is focusing on issues concerning gender specific medicine in general and men’s health in particular. Hypogonadism caused by low levels of testosterone is a common problem that is often undiagnosed and untreated. It correlates with different symptoms such as loss of enthusiasm, abdominal weight gain, depressed mood, lack of energy or low sex drive. Hypogonadism for example is associated with the metabolic syndrome (Makhsida N. et al., J Urol 2005;174(3):827-834), diabetes (Maric C et al, Am J Physiol Renal Physiol 2009;269 (4):F680-F688; Grossmann M et al, Curr Opin Endocrinol Diabetes Obes 2010; 17:247–256) and atherosclerosis (Svartberg J et al, J Int Med 2006;259:576-582).

    Why does the ISMH run a campaign about hypogonadism?

    There are three main topics in the field of men´s health: prostate health, erectile dysfunction and hypogonadism/TDS. The ISMH choose hypogonadism/TDS for the campaign as it is often correlated with other severe disease as diabetes, obesity, atherosclerosis or cardiovascular disease. Furthermore men with hypogonadism do have a lower life expectancy than men with normal testosterone level (Khaw K-T et al., Circulation 2007;116: 2694-2701, Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR, Arch Intern Med. 2006;166:1660-1665).

     What is the purpose of the campaign?

    Many men have testosterone deficiency without knowing it. They are suffering from non-specific symptoms and most have no idea that apathy, irritability, lethargy and loss of libido may be due to hypogonadism caused by low levels of testosterone. Almost nobody knows that testosterone production is decreasing with increasing visceral fat while, at the same time, testosterone is needed to metabolize visceral fat. It is a vicious circle. More informed men can make better decision in regard to their health when they are aware of the consequences.

    The aim of the campaign is to help men and their partners recognize that certain changes they may be experiencing might not be due just to aging, make them ask a doctor about it and help to prevent long-term effects like the metabolic syndrome.

    Men are not likely to talk or read about their health problems and go to the doctor. This is why the campaign is being displayed in daily newspapers, finance and sport magazines. With the football a key visual was chosen that grabs the attention of many men in a more humorous way trying to channel their interest towards the important taboo afflicted health topic of hypogonadism.

    What are GPs interested in/aware of when it comes to TDS?

    Hypogonadism/TDS awareness amongst health care professional is usually low, treatment rates in Europe are about ¼ compared to the US. However, interest and knowledge of GPs are increasing along with the growing scientific understanding that hypogonadism is no life style issue and not part of the normal aging process. Hypogonadism caused by low levels of testosterone is often associated with serious health issues in men (Muller M et al, European Journal of Endocrinology 2003; 149 583–589; Mulligan T et al, Int J Clin Pract 2006; 60, 7, 762–769). This is the reason why the ISMH is requesting more international studies on testosterone and related medical conditions. The call for more research was one of the results of the ISMH consensus conference 2010 in New York. The ISMH runs a number of educational initiatives and more efforts are planned in the next future.

    Who came up with the idea to start this campaign?

    The concept was formed during the ISMH consensus conference on hypogonadism and testosterone replacement therapy (TRT) in New York in 2010 (Traish A et al, Am J Med 2011; 124: 578-587; Wang C et al, Diab Care 2011; 34: 1669-1675). This scientific meeting of 25 international experts was also attended by many pharmaceutical companies including Bayer. The current campaign about symptoms of hypogonadism caused by low levels of testosterone in Sweden is a logical result of this conference and the publications resulting from this meeting. It is part of the ISMH's mission to improve the health of men and empower them to pursue healthier lives. Bayer is named as the sponsor for this campaign, but the ISMH is responsible for content and the wording of the campaign. Additionally, the campaign is not related to any product but suggests to men with symptoms to consult their doctors. Other industry partners would be very welcome as these would help to increase the impact of this awareness campaign on the TDS/hypogonadism.

    You can contact us through our website (http://www.ismh.org/en/contact/) or our bureau in Vienna:

    Lazarettgasse 9/5
    1090 Vienna, Austria
    Tel +43/ (0)1 / 904 78 12
    Fax +43/ (0)1 / 409 60 11
    E-Mail office@ismh.org

  • November 11, 2011 – 11:52

    Low Testosterone Predicts Mortality from Cardiovascular Disease

    The Health in Men Study is a population-based cohort study of men aged 65 years and older in Australia.  The authors of this study hypothesized that men with low serum free testosterone (T) or elevated luteinizing hormone (LH) are at increased risk of all-cause mortality attributable to cardiovascular disease (CVD) and not other potential causes, over a 5-year period.

    In this trial, sex hormones exhibited direct relationships with all-cause mortality, as the relationship between low free T, elevated sex hormone binding globulin (SHBG), and elevated LH were statistically significant in association with cardiovascular mortality.  While there was a noticeable relationship between total T and increased mortality, this relationship did not reach statistical significance.  Overall, men with both low free T and high LH were at greatest risk of cardiovascular mortality.  Higher T levels were associated with lung cancer, and elevated SHBG levels were associated with non-CVD mortality.

    The study concluded that low serum free T may predict mortality from CVD, yet a true cause-and-effect relationship cannot be exclusively determined.  The authors postulate that prevention and early treatment of androgen deficiency syndrome may improve CV outcomes, but not necessarily mortality from other outcomes.

    This study can be contrasted with a previous trial published in 2010 with men who received T supplementation (Basaria S, et al.  NEJM 2010).  This trial examined 209 men at mean 74 years of age, all of whom had a high prevalence of hypertension, diabetes mellitus, hyperlipidemia, and obesity.  The conclusions stated that use of T gel in these men was associated with increased risk of adverse CV events, questioning the safety of T supplementation.  Additional and more rigorous trials are needed to better elucidate more clear relationships between T and cardiovascular mortality risks.

    Hyde Z, Norman PE, Flicker L, et al.  Low free testosterone predicts mortality from cardiovascular disease but not other causes: The Health in Men Study.  J Clin Endocrinol Metab published ahead of print as doi:10.1210/jc.2011-1617.