• September 29, 2012 – 11:30

    Costs of Hypogonadism

    Prevalence studies have shown that nearly 39% of men over the age of 45 presenting to primary care offices have signs and symptoms of hypogonadism.  While prior studies on male hypogonadism have demonstrated a significant economic and quality-of-life burden, these previous trials have not evaluated the direct or indirect impacts of hypogonadism on healthcare utilization and costs in US men.

    A recent study sought to compare direct healthcare and indirect (disability leave or medical absence) costs between privately insured US men with hypogonadism and controls without hypogonadism.  The study included a sample size of 4,269 employed men ages 35-64 with 2 or more hypogonadism diagnoses.  Employees and controls had a mean age of 51 years. 

    This study demonstrated that men with hypogonadism had higher statistically significant comorbidity rates compared to controls with respect to hyperlipidemia, hypertension, musculoskeletal pain, and human immunodeficiency virus infection, which are directly related to increased financial costs.  Men with hypogonadism had higher inpatient hospitalizations, emergency department visits, and prescription drug use compared to controls.  However, the inpatient and emergency department evaluations did not substantially increase annual medical care utilization.  Men with hypogonadism had higher direct and indirect costs compared to controls, $14,118 versus $5,272, respectively.

    The authors admit that this study has limitations relative to retrospective claims data analysis.  For example, controlling for a comorbid diagnosis of obesity is challenging secondary to infrequency of reporting in billing claims.  Thus, the authors used 2 or more comorbid conditions associated with hypogonadism in the test group.  It is also probable that patients with additional comorbidities are likely to be labeled as having hypogonadism as an incidental results of laboratory evaluation.  Since the analysis in this study examined men who held private insurance, it limits the ability to generalize across populations of hypogonadal men with Medicare or Medicaid.

    Reference: Kaltenboeck A, Foster S, Ivanova J, et al.  The direct and indirect costs among US privately insured employees with hypogonadism.  J Sex Med 2012;9:2438-2447.

  • 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.

  • June 12, 2012 – 21:44

    Characteristics of Androgen Deficiency in Late-Onset Hypogonadism

    Results from the European Male Aging Study (EMAS)

    The phenomenon of age-related decline in sexual function and testosterone continues to attract significant attention in men.  A recent study conducted across several European countries aimed to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having late-onset hypogonadism (LOH).

    Definitions of LOH have varied widely in the literature.  The authors in this study define LOH as the presence of three sexual symptoms – decreased libido and morning erections, coupled with erectile dysfunction.  In addition, the authors examined whether observed associations could be explained by other factors varying concurrently with (hypo)gonadal status.

    A sample of 3369 men aged 40 to 79 were recruited from 8 European centers.  A fasting blood sample was obtained from each subject to measure total testosterone (T) and estradiol, in addition to fasting lipids and glucose.  One-hundred fifty subjects were excluded due to known endocrine disorders.

    In this sample, 63 men (2.1%) were identified as meeting criteria for LOH (36 moderate and 27 severe).  These men were of age above subject average, more obese, had lower lean muscle mass, and in overall poorer health.  Men with severe LOH had larger abdominal waist circumference, insulin resistance, and metabolic syndrome (odds ratio = 9.94).

    The results of this study conclude that LOH is associated with multiple end-organ adverse effects, supporting the notion of such a defined syndrome in a minority of elder men, especially those with serum T < 8 nmol/liter.

    Reference:  Tajar A, Huhtaniemi IT, O'Neill TW, et al.  Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS).  J Clin Endocrinol Metab 2012;97:1508-1516.

  • May 31, 2012 – 22:29

    Higher Serum Testosterone Levels Associated with Decreased Loss of Lean Body Mass

    Previous research has determined that men are more likely than women to lose muscle mass and strength as they age, and this has been linked to declining endogenous serum testosterone (T) levels.  Similarly, exogenous T supplementation in older men is positively correlated with increases in lean body mass, improved muscle strength, and decreased fat mass.

    A prospective study of 1183 ambulatory men in the Osteoporotic Fractures in men study across 6 US centers measured serum total T, estradiol, and sex hormone binding globulin (SHBG) levels; physical strength via bilateral grip strength, various walking parameters, and timed chair stands; and body composition via DEXA scans over a 4.5 year period.  Nearly 40% of men who lost more than 2.0-kg in the follow-up period exhibited a decreased decline in lean appendicular mass at higher baseline T levels compared to men with lower or normal T levels.  Estradiol was not found to be correlated to body composition or changes in physical function or strength. 

    The authors concluded that higher levels of serum T were associated with decreased loss of lean muscle mass and lower extremity strength in men over 65 years of age.  Higher T levels were more strongly associated with preservation of appendicular lean mass, which may translate to health outcomes related to frailty.  The authors admit that higher T levels may not necessarily correlate with less decline in overall physical function.  A limitation of the study posits that not every factor which may impact sex hormones could be adequately controlled for, and that trials with longitudinal measurements of sex steroid hormones are needed to establish an association between serum levels and body composition and physical function.

    Reference: LeBlanc ES, Wang PY, Lee CG, et al.  Higher testosterone levels are associated with less loss of lean body mass in older men.  J Clin Endocrinol Metab 2011;96:3855-63.

  • April 25, 2012 – 20:51

    Testosterone is Positively Correlated with Safer Sex in Young Men

    Research over the past several decades has demonstrated associations between higher serum testosterone levels (T) and increased prevalence of substance abuse, number of sexual partners, frequency of sexual activity, and permissive attitudes regarding one's sexuality.  Previous research has also suggested that safer sex behaviors may be linked to higher T because they are the bolder choice and either carry social risk or convey social status, given that confidence and expressions of power have been tied to higher T levels.

    A recent study by van Anders and colleagues was to investigate whether levels of T were associated with individual variation in behaviorally relevant safer sex attitudes and attitudes about sexual risk-taking, to better understand biopsychosocial aspects of sexual health related to sexually transmitted infections (STI).

    Seventy-eight men male college freshmen were recruited for the Implications of Partnerships Around the College Transition (ImPACT) study, which sought to examine associations between hormonal, health, social, and sexual variables during the first year of college.  Correlations between salivary T levels and behaviorally-relevant safer sex attitudes were assessed via survey questionnaires.  Higher T levels were positively associated with safer attitudes toward sexual encounters, especially those attitudes most closely tied to STI risk avoidance.  One limitation of the study centers on how the safer sex likelihood composite, which was used to draw an association between T and risk behavior, is not a validated measurement tool and its internal consistency has been low.  However, the safer sex likelihood scale was created based on factors shown to be important for STI protection, and this along with additional survey data conclusions, suggests a significant value as a meaningful measure of safer sex attitudes.

    Reference:  van Anders SM, Goldley KL, Conley TD, et al.  Safer sex as the bolder choice: testosterone is positively correlated with safer sex behaviorally relevant attitudes in young men.  J Sex Med 2012;9:727–734.

  • April 20, 2012 – 21:13

    Testosterone and Metabolic Syndrome

    The relationship between serum testosterone (T) and the metabolic syndrome was examined in a systematic review of 20 manuscripts (13 cross sectional, 3 longitudinal and 4 randomized controlled studies).  Consistent outcomes of these papers were presented and compared.

    Metabolic Syndrome (MetS) is a cluster of risk factors including abdominal obesity, increased blood glucose and/or insulin resistance, dyslipidemia and hypertension.  MetS is associated with a two-fold increase of 5-10 year risk of cardiovascular (CV) diseases and five-fold increase in risk for type 2 diabetes (T2DM).  The presence of hypogonadism in men with MetS and erectile dysfunction (ED) is associated with a greater severity of symptoms of sexual dysfunction, other than ED.  ED and male hypogonadism have been recently recognized as possible predictors of forthcoming metabolic diseases and CV events.  ED subjects have been considered paradoxically “lucky” because this symptom might offer them the opportunity to screen for the presence of ED-associated morbidities, including hypogonadism.

    The specific mechanism through which hypogonadism might affect CV health have not been completely clarified, but both clinical and animal evidence shows that T exerts a favorable effect upon vascular reactivity, inflammation, cytokine production and adhesion molecule expressions, as well as on serum lipid concentration and hemostatic factors.  It has been speculated that the presence of hypogonadism and ED in subjects with MetS should alert clinicians that such people deserve a more intensive lifestyle changes at an early stage to delay progression to a higher risk category.  Unfortunately, no study has specifically evaluated this point in subjects with ED, whereas only a few RCTs on the metabolic effect of T replacement therapy in subjects with MetS have been published.

    MetS is significantly associated with an overall lower total testosterone (TT). This difference is more evident in studies conducted in subjects with ED than in those without. The association among MetS, hypogonadism and ED is well recognized; in fact the syndrome is highly prevalent in subjects with ED and low T.  The specific mechanisms linking MetS and male hypogonadism have not been completely clarified.  Low T could be considered one of the many adverse consequences of overweight and obesity.  On the other hand, hypogonadism could contribute to the accumulation of excess fat and to the reduction of insulin sensitive muscular mass, thus establishing a vicious cycle.  Insulin resistance has been recently considered the common pathogenic link between ED, MetS and male hypogonadism.

    Reference: Corona G, Monami M, et al.  Testosterone and metabolic syndrome.  J Sex Med 2011;8:272-283.

  • March 25, 2012 – 20:48

    Effect of Testosterone and 5α-Reductase Inhibitors on Lean Mass

    A recent study published in the Journal of the American Medical Association (JAMA) sought to determine whether 5α-reduction of testosterone to dihydrotestosterone (DHT) is required for promotion of fat-free body mass.  The 5α-Reductase Trial was a parallel-group, double-blind, randomized placebo-controlled trial of 139 men ages 18 to 50 who were given varying doses of testosterone enanthate plus placebo or dutasteride.  The primary outcomes measured were changes in fat-free body mass, muscle strength, sexual function, prostate volume, and hematocrit and serum lipid levels.

    One hundred and two men completed the 20-week intervention.  Ultimately, statistically significant changes in the aforementioned primary outcome categories was unchanged between study groups.  This trial suggests that conversion of testosterone to DHT is not necessary for mediating anabolic effects on muscle to minimize body fat composition.  This data is similar to previous studies that have reported no significant effects of 5α-reductase inhibition on muscle or bone mass.

    Reference:  Bhasin S, Travison TG, Storer TW, et al.  Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production.  JAMA 2012;307(9):931-940.

  • 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.

  • September 26, 2011 – 11:07

    Testosterone Deficiency as a Risk Factor for Cardiovascular Disease

    Male gender, diabetes mellitus, and obesity, are known risk factors for the development of cardiovascular disease. Increasing attention has been given in recent years to the link between testosterone deficiency and increased risk of cardiometabolic disease. Recent meta-analyses have demonstrated a correlation between metabolic syndrome (e.g., commonly defined as obesity, diabetes/insulin resistance, hypertension, dyslipoproteinemia and gout) and lower serum testosterone levels.

    Hypogonadotropic hypogonadism occurs in up to 33% of men with type 2 diabetes. The Massachusetts Male Aging Study found that low levels of testosterone and sex hormone binding globulin (SHBG) are independent risk factors for the development of type 2 diabetes. In addition, this study demonstrated that low serum testosterone predicts the development of metabolic syndrome.

    Declining serum testosterone levels throughout a man's life are associated with an increase in all-cause mortality and an increase in atherosclerosis, visceral obesity, insulin resistance, dyslipidemia, and hypertension, the key components of the metabolic syndrome. Prospective clinical trials in men with prostate cancer who have undergone androgen deprivation therapy have found increased cardiovascular risk by increasing body weight, reducing insulin sensitivity, and/or resulting in dyslipidemia.

    Reference: Ullah MI, Washington T, Kazi M, et al. Testosterone deficiency as a risk factor for cardiovascular disease. Horm Met Res 2001;43:153-164.