Costs of Hypogonadism
September 29, 2012
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.
Testosterone and Mortality in Hypogonadal Men
July 25, 2012
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.
Characteristics of Androgen Deficiency in Late-Onset Hypogonadism
June 12, 2012
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.
Higher Serum Testosterone Levels Associated with Decreased Loss of Lean Body Mass
May 31, 2012
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.
Testosterone is Positively Correlated with Safer Sex in Young Men
April 25, 2012
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.
Testosterone and Metabolic Syndrome
April 20, 2012
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.
Effect of Testosterone and 5α-Reductase Inhibitors on Lean Mass
March 25, 2012
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.
ISMH launches TDS-Public Awarness Campaign "Let´s talk balls" in Sweden
November 11, 2011
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:
1090 Vienna, Austria
Tel +43/ (0)1 / 904 78 12
Fax +43/ (0)1 / 409 60 11
Low Testosterone Predicts Mortality from Cardiovascular Disease
November 11, 2011
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.
Testosterone Deficiency as a Risk Factor for Cardiovascular Disease
September 26, 2011
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.
The Impact of Hypogonadism and Autonomic Dysfunction on Fatigue, Emotional Function, and Sexual Desire in Male Patients With Advanced Cancer
July 12, 2011
A Pilot Study Strasser F, et al./Cancer 2006;107:2949–57.
BACKGROUND. The objective of this study was to determine whether hypogonadism and autonomic dysfunction contribute substantially to cancer-related fatigue, decreased sexual desire, and depression inmale patients with advanced, incurable cancer.
METHODS. Forty-eight patients who had received no major antineoplastic intervention for at least 2 weeks were tested for autonomic dysfunction by using Ewing tests. Total and free testosterone levels were measured. Multivariate analyses were performed to test the relation of these factors with the Functional Assessment of Cancer Therapy (FACT) (the Functional Assessment of Anorexia/Cachexia Therapy [FAACT] scale and the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] subscale), the Hospital Anxiety and Depression Scale (HADS), the Edmonton Symptom Assessment Scale, the Sexual Desire Inventory, and sexual function (Cancer Rehabilitation Evaluation System subscale). Common causes for fatigue (anemia, depression,malnutrition, symptomdistress, and medications) also were considered.
RESULTS. Thirty-eight of 47 patients (81%) had autonomic dysfunction, although it was not associated significantly with the other variables examined. Twenty-nine of 45 patients (64%) had a low level of free testosterone (hypogonadism), which was correlated with the HADS Anxiety score (P ..002), the FACT Emotional Well-Being score (P ..02), and the HADS Depression score (P ..04). Hypogonadal men also had lower scores on the FACT Functional Well-Being scale (P ..01) and the FACIT-F subscale (P ..05). Men who reported symptoms related to weight loss (FAACTscale) had significantly lower levels of free testosterone (r . 0.34; P ..02) but did not differ from the other group in actual weight loss (P ..22). The total testosterone level was not appropriate for screening of hypogonadism unless the patients had values <100 ng/ mL. Logistic regression analysis failed to reveal a distinct multivariate model of autonomic dysfunction or hypogonadism that predicted clinical outcomes.
CONCLUSIONS. Hypogonadism is a frequent condition in patients with advanced, incurable cancer and is associated with negative mood, fatigue, and symptoms related to anorexia/cachexia.
COMMENT. Patients with advanced cancer frequently are hypogonadal, and also experience autonomic dysfunction. The results from this cross-sectional pilot study of men with advanced cancer indicated that hypogonadism, but not autonomic dysfunction, was associated strongly with fatigue, depression, and sexual dysfunction. Hypogonadism in men with advanced cancer appears to be mediated centrally, as demonstrated by the lack of elevated LH or FSH. Elevated inflammatory cytokines, particularly IL-6, are common in patients with advanced cancer and are associated with fatigue, depression, anorexia/cachexia, reduced free testosterone. Whether testosterone supplement does ameriolate fatigue and depression in cancer patients is not extensively studied in a large doble-blind randormized studies.Hypogonadal men with cancer who do not have hormone-sensitive tumors should be included in a clinical trial to determine the efficacy, dosage, and optimal means of administering testosterone replacement therapy.
Low serum testosterone and frailty in older men and women
July 12, 2011
I.-C. Wu et al. / Maturitas 67 (2010) 348–352
BACKGROUND. Frail older persons are at high risk of morbidity and mortality, and are characterized by body composition alterations. Serum testosterone, which regulates body composition, declines with age. We investigated the relation between serum testosterone level and physiological frailty in both older menand women.
METHODS.This was a cross-sectional study of 108 adults 65 years old or older. Frailty status was determined by hand-grip strength, weight change, walking speed, exhaustion, and activity levels, and was classified as frail (3 or more deficits), pre-frail (1 or 2 deficits), or robust (no deficit) according to the Fried criteria. Serum total testosterone (TT) and sex-hormone-binding globulin were measured while free testosterone (FT) was estimated.
RESULTS. Median (range) TT and FT were lower in frail than in pre-frail and robust men (TT: (frail) 15.7 [2.4–26.9] vs. (pre-frail) 19.4 [7.2–39.9] and (robust) 25.9 [13.2–35.2] nmol/L, P = 0.03; FT: 230.0 [35.9–299.0] vs. 272.0 [86.7–411.0] and 303.0 [267.0–396.0] pmol/L, P = 0.02) and women (TT: 0.31 [0.10–0.51] vs. 0.47 [0.14–1.55] and 0.45 [0.36–1.25] nmol/L, P = 0.02; FT: 4.59 [0.46–6.63] vs. 4.66 [1.57–15.10] and 6.65 [3.91–21.00] pmol/L, P = 0.03). After adjusting for age, comorbidities, body mass index, and serum albumin in ordinal logistic regression model, odds ratios of being frail were significantly higher for those participants whose TT and FT levels were in the lowest tertile compared to the highest tertile in men (TT: odds ratio [OR] 3.29, 95% confidence interval [CI] 1.14–9.50; FT: OR 3.44, 95% CI 1.05–11.22) and in women (TT: OR 6.69, 95% CI 1.84–24.31; FT: OR 4.86, 95% CI 1.31–18.08).
CONCLUSIONS. Low serum testosterone levels were independently associated with frailty in the elderly Taiwanese.
COMMENT. Recent studies on large cohort have shown that low testosterone level is a significant risk factor for the premature death. However little has been known for the significance of testosterone elevel in post-menopausal women. This study from Taiwan showed that low testosterone level is associated with fraility in older women as well as men. Future studies focusing on women in larger cohort would be awaited to conform the significance of testosterone level as a biomarker.
Testosterone Therapy in Men with Untreated Prostate Cancer
March 29, 2011
Historically, testosterone has been associated with beneficial effects in aging men, but also with the concern of potential for growth of prostate cancer. This notion comes from previous research by Morgentaler and colleagues that observed regression of prostate cancer caused by androgen deprivation yielding a decreased serum PSA level, while normalization of testosterone in men who are androgen-deprived caused a rise in PSA levels. However, more recent retrospective trials of small numbers of men found no biochemical recurrence of prostate cancer with testosterone replacement after an average period of 4.5 years.
This month in the Journal of Urology, Morgentaler and colleagues report their findings from a study of 13 men with symptomatic testosterone deficiency with prostate cancer (Gleason score 6 in 12 men; 7 in 1 man). Their results suggest that testosterone replacement in these men with localized prostate cancer did not cause tumor progression over a time frame of 1 to 8 years. While previous studies suggest that testosterone replacement causes rapid prostate cancer growth in androgen deprived men, data is still conflicting with regard to prostate cancer growth trends in hormonally intact men.
While the major limitations of this study include its small sample size and lack control factors, it is landmark in that it is the first study to assess a group of men with untreated prostate cancer who concomitantly took testosterone replacement therapy for greater than one year. Nonetheless, its conclusions are in line with the theory that serum androgen concentrations in men with testosterone deficiency can maintain androgen-mediated growth of prostate cancer and the addition of exogenous testosterone does not yield additional tumor growth.
Reference: Morgentaler A, Lipshultz LI, Bennett R, et al. Testosterone therapy in men with untreated prostate cancer. J Urology 2010;185:1256-61.
Male Pattern Baldness and Prostate Cancer Risk
March 17, 2011
A novel study conducted in France recently evaluated the potential link between androgenic alopecia and prostate cancer risk. Current estimates posit that over 50% of men will experience androgenic alopecia during their lifetime. Until now, evidence has been conflicting regarding this potential association. A case-control study of 669 subjects (388 with a history of prostate cancer and 281 without) found that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01], yet the specific pattern of hair loss was not determined to be a predictor of hair loss. Moreover, there was no association found between early-onset alopecia and an earlier diagnosis of prostate cancer, or with the development of more aggressive prostate cancer tumors.
The authors admit the possibility of selective recall bias in this study, yet retrospective self-reporting of male balding patterns has been validated across previous studies. As androgenic alopecia can impact self-perception, it was felt that since most men remember developing baldness at an early age. Similarly, the authors did not control for increased risk factors of prostate cancer including African heritage, yet family history was stratified in both case subjects and controls.
Data is abundant with regard to aging men and androgenic alopecia as well as the development of prostate cancer. To date, there is no statistical evidence to support a direct cause-and-effect relationship between alopecia and the development of prostate cancer at any age. As with previous studies, this is retrospective study cannot prove a direct causal relationship. Future research will focus on the identification of specific genetic markers to prove such a relationship.
Reference: Yassa M, Saliou M, De Rycke Y, et al. Male pattern baldness and the risk of prostate cancer. Annals of Oncology, February 2011.
Effects of Testosterone in Frail Elderly Men
February 17, 2011
Short-term testosterone replacement has been shown to improve muscle mass and strength in frail and elderly men, but until now these effects have not been evaluated post-treatment. The authors sought to assess the long-term effects of testosterone therapy in 274 frail men aged 65-90 with low endogenous testosterone levels and conducted a single-center, randomized, double-blind, placebo-controlled trial to investigate the effects of 6 months of testosterone therapy on muscle strength, body composition, physical function, and overall quality of life.
After a period of 6 months, mean testosterone levels increased with statistical significance, in addition to increases in lean muscle mass and subjective improvements in somatic and sexual symptoms. After 12 months however, no significant differences in the treatment and control groups remained evident. While the authors concluded that 6 months of treatment with replacement testosterone offered improvements in lean body mass, muscle strength, and quality of life, these changes were not maintained at 6 months post-treatment. The decline in muscle mass and strength post-treatment suggests that testosterone replacement for a period of 6 months may not be sufficient to improve overall frailty in this population. Moreover, the effects of increasing serum testosterone levels to within the physiologic range in a 6-month period may have been too short to sustain significant and lasting symptomatic improvements.
The optimal duration of treatment with testosterone replacement therapy to achieve lasting improvements in lean muscle mass and quality of life remains unknown, yet it is imperative for clinicians to offer a multi-disciplinary approach to the treatment of frail middle-aged and elderly men that includes resistance exercise, appropriate diet and pharmacologic agents.
Reference: O'Connell MDL, Roberts SA, Srinivas-Shankar U, et al. Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment intermediate-frail and frail elderly men? J Clin Endocrinol Metab 2011; 96(2):454-458.