Latest Updates
May 2013
- Testosterone treatment and sleep disorders
Key Points
- Cautionary statements about testosterone therapy have appeared in the scientific literature despite a lack of convincing evidence that testosterone causes and/or aggravates obstructive sleep apnea (OSA)
- A conclusion from a review from 2007 indicated that the link between testosterone therapy and OSA was weak (due to methodological issues in many studies often involving low patient numbers) and that further studies in this area were needed
- OSA may affect up to 25% of middle-aged men, many of whom are obese. Men with both OSA and obesity are likely to be at greatest risk for androgen deficiency
- A randomized study was designed to assess sleep and breathing effects of testosterone treatment (1,000 mg testosterone undecanoate or placebo at 0, 6 and 12 weeks) as an adjunct to weight loss in obese men with severe OSA (n=67)
- The results showed that testosterone therapy in obese men with OSA mildly worsened sleep disordered breathing (oxygen desaturation index [ODI] was worsened by 10.3 events/h, p=0.03; nocturnal hypoxemia worsened by 6.1%, p=0.01) after 7 weeks (but not 18 weeks) irrespective of initial testosterone concentrations
- Although statistically significant, these acute changes in sleep measures were small in magnitude and did not result in a worsening in subjective sleepiness
- Obese patients with OSA requiring testosterone therapy should continue to be cautiously monitored and assessed on an individual basis
- Lifestyle modification to achieve weight loss should remain the first-line therapy for all obese men with OSA
April 2013
- Testosterone may be beneficial for metabolic syndrome-associated prostate inflammation
Key Points
- There is evidence of a strong and independent association between obesity/metabolic syndrome and BPH/LUTS; one of their common denominators is hypogonadism
- As the prevalence of this condition increases the management of metabolic syndrome is considered a major challenge to global public health. An effective way to combat metabolic syndrome and its related consequences is through primary prevention. However, examination of metabolic syndrome molecular pathways and prostatic diseases may offer new therapeutic perspectives for these conditions
- In a rabbit model of metabolic syndrome overt hypogonadism was induced and characterized by low testosterone along with prostate, seminal vesicle, and testis hypotrophy when compared with controls. In this model, prostatic mRNA levels of several inflammatory markers (e.g., IL-8, IL-1β, TNF-α and IL-6) were upregulated as was the expression of fibrotic and myofibroblast activation markers (including TGFβ1, αSMA, RhoA, ROCK1 and ROCK2)
- Testosterone prevented (and did not induce) prostatic diseases and normalized markers of metabolic syndrome in HFD-treated rabbits. In addition, oral treatment with INT-747 also significantly (p<0.05) normalized fasting glucose, glucose tolerance, and decreased visceral fat in HFD-treated rabbits
- Whereas testosterone treatment normalized prostate fibrosis and levels of HFD-upregulated mRNA of all the prostatic inflammatory markers plus expression of fibrotic and myofibroblast activation markers, INT-747 treatment had no effect on these parameters suggesting that the positive effect of testosterone on the prostate gland is not via a metabolic syndrome component
- It is evident that testosterone protects rabbit prostate from metabolic syndrome-induced prostatic hypoxia, fibrosis and inflammation, thus providing new insights and perspectives for prevention and intervention in BPH/LUTS
March 2013
- Testosterone for the treatment of obesity in hypogonadal men
Key Points
- T is an important factor in the etiology of obesity, MetS, T2DM and CVD, with sub-normal T levels increasing the accumulation of fat deposits, particularly abdominal (visceral) fat
- Lifestyle changes (diet and exercise) are typically recommended by physicians to combat obesity but the often transient effects are only marginally successful and of limited clinical benefit
- T treatment in hypogonadal men reverses fat accumulation with a significant improvement in lean body mass, insulin sensitivity and markers of cardiovascular risk
- Medical professionals are largely unaware of the potential benefit and contribution of T in combating obesity and managing MetS in hypogonadal men, with many physicians fearing an increased risk of PCa and CVD (despite the lack of supportive evidence)
- Combined with lifestyle changes, T may be a useful tool for the treatment of obesity in hypogonadal men; it also improves mood levels and vitality, while reducing fatigue, and may motivate men to adhere to diet and exercise regimens designed to combat obesity
February 2013
- Long-acting testosterone undecanoate is well tolerated in men with hypogonadism in daily clinical practice
Key Points
- TU was well tolerated in men with hypogonadism. Adverse drug reactions (ADRs) related to TU therapy were rare (5.8%)
- Only 1 patient (0.1%) reported an ADR that was considered serious (prostate enlargement and urinary retention)
- The number of men who discontinued from the study was relatively low (17.5%)
- Overall, ADRs were associated with treatment discontinuation in 31 patients
- No cases of prostate cancer were observed with TU treatment
- Hematocrit levels increased slightly from a baseline level of 42.8 ± 6.6% to 44.5 ± 6.1% after the last TU injection (Visit 5; p <0.0001) but remained below 50% (the recommended limit for testosterone treatment in men with androgen deficiency)2
- Adverse cardiac events were reported in seven patients, all of whom had preexisting cardiovascular impairment
- TU was well tolerated in men with hypogonadism. Adverse drug reactions (ADRs) related to TU therapy were rare (5.8%)
November 2012
- Changes in the worldwide diagnosis and treatment of testosterone deficiency between 2006 and 2010
Key Points
- The majority of physicians surveyed (82%) would regularly use laboratory measurements of total testosterone to diagnose testosterone deficiency
- Physicians consider the main symptoms of testosterone deficiency to be erectile dysfunction, lack of libido, fatigue, loss of power, depression, weight gain and loss of hair/reduced body hair
- There was an increased awareness among physicians of depression and weight gain as clinical symptoms of low testosterone
- For 70% of the physicians surveyed, the severity of the symptoms experienced was considered a more significant reason to start testosterone treatment than the laboratory value of testosterone
- In 2010, significantly more physicians expressed concern about the adverse effects of testosterone treatment compared with 2006 (78% vs 54%)
- Eleven percent of patients eligible for testosterone therapy did not receive treatment due to these concerns
- The proportion of patients diagnosed with erectile dysfunction who have testosterone deficiency ranged from 41% to 63% depending on the country
- These patients were more likely in 2010 to be treated with phosphodiesterase type 5 (PDE5) inhibitor monotherapy or testosterone plus PDE5 inhibitors than in 2006.
October 2012
- Efficacy and safety of long-acting testosterone undecanoate in men with hypogonadism in daily clinical practice
Key Points
- Mean trough serum total T increased from 9.6 nmol/L at baseline to 17.3 nmol/L before the fifth injection (p<0.0001)
- The proportion of patients with a high/very high libido increased from 10% at baseline to 61% at injection 5 (overall p<0.0001)
- Significant improvements over each injection interval were seen in the overall levels of vigor/vitality, mood and ability to concentrate (p<0.0001 for each)
- The proportion of patients reporting moderate, severe or extremely severe ED was significantly decreased from baseline at the time of the fifth TU injection, from 65% to 19% (p<0.0001)
- Statistically significant reduction in waist circumference (Figure 1)
- Adverse drug reactions related to TU therapy were rare (5.8%).
- Effects of long-acting testosterone undecanoate on quality of life in Asian men with testosterone deficiency syndrome
Key Points
- Serum total testosterone increased from 8.9 nmol/L (256.5 ng/dL) at baseline to 23.7 nmol/L (683.0 ng/dL) at week 48 in the testosterone group (p<0.001) and from 9.1 nmol/L (262.3 ng/dL) to 11.2 nmol/L (322.8) ng/dL in the placebo group (p<0.001; between group difference p<0.001)
- At week 48 unadjusted quality of life scores of men in the testosterone treatment group improved significantly in five out of the eight domains on the Short-Form-12 survey
- Physical health composite scores improved 4.0 points in the treatment group compared to 0.8 points in the placebo group (F=3.652, p=0.027)
- Mental health composite scores improved 4.4 points in the treatment group compared to 1.0 point in the placebo group (F=4.514, p=0.018)
- After adjusting for baseline differences, significant improvement was observed in vitality and social functioning domains and mental health composite scores, but not in physical health composite scores
- No significant adverse events were observed.
September 2012
- Effects of long-term long-acting testosterone undecanoate on bone mineral density in men with late-onset hypogonadism and metabolic syndrome
Key Points
- Bone mineral density (BMD) improved significantly (by approximately 5% per year) in men treated with testosterone undecanoate for 36 months, but there was no improvement in BMD in the control group
- At 36 months:
- Lumbar BMD was 1.053±0.145 g/cm2 in the testosterone replacement therapy (TRT) group versus 0.866±0.109 g/cm2 in controls (p<0.002 vs testosterone undecanoate)
- Femoral BMD was 0.989±0.109 g/cm2 versus 0.823±0.126 g/cm2 in controls (p<0.003 vs testosterone undecanoate)
- There was a direct correlation between change in total testosterone levels and change in BMD at the lumbar site (r2 = 0.66, p<0.0001) and femoral site (r2 = 0.52, p<0.0001)
- There was a significant reduction in high-sensitivity C-reactive protein (hs-CRP) levels in the TRT, but not the untreated control, group after 12, 24 and 36 months
- No relationship between improvement in BMD and estradiol levels was observed
- No serious testosterone undecanoate-related adverse events were reported.
August 2012
- Retrospective observational study finds hypogonadism prevalent in men with sexual dysfunction and related to a range of chronic illnesses
Key Points
- The prevalence of hypogonadism among men with sexual dysfunction and common medical causes of ED ranged from 30.8−64.3%
- Hypogonadism was prevalent among men who used alcohol excessively or who smoked
- The prevalence of hypogonadism was also substantial among men receiving medication for anxiety or depression and in men with work-related stress
- The highest prevalence of hypogonadism was observed in men in their 50’s and 60’s
- A significant association between the medical or psychiatric causes of ED and hypogonadism was limited to hypertension, tobacco abuse, sleep apnea and work stress
- In a retrospective observational cohort study testosterone therapy was associated with decreased mortality in men with low testosterone levels compared with no testosterone treatment
This observational, retrospective cohort study based on a clinical database that included seven Veteran Affairs medical centres in the US was the first to examine the association between testosterone treatment and mortality in men with low testosterone levels.1
July 2012
- Effects of long-acting testosterone undecanoate on health-related quality of life in hypogonadal men: results of a randomized, double-blind study
This randomized, double-blind, placebo-controlled study evaluated the effect of long-acting testosterone treatment in Malaysian men with low testosterone levels, assessing treatment effects using the Aging Male Symptoms (AMS) scale.
May 2012
- Examining the role of testosterone in the etiology and treatment of obesity, the metabolic syndrome and diabetes in hypogonadal men
The review looks beyond the role of testosterone in the male reproductive system and sexual functioning to consider its significance in the development and treatment of obesity, a condition that is acknowledged to be reaching global epidemic proportions. - Rational approach to categorizing testosterone levels using community-based reference ranges
This study1 generated reference limits for total and free testosterone levels in a community-based sample of nonobese healthy young (19-40 years) men enrolled in the Framingham Heart Study third generation cohort.
April 2012
- Time-course of biological effects of testosterone replacement therapy
This article reviewed the published literature of studies analyzing the effects of testosterone administration in hypogonadal men to estimate the onset or time-dependency effects of testosterone.
- Current knowledge on testosterone deficiency with practical recommendations for diagnosis and treatment
This article aimed to provide practical recommendations for the diagnosis of testosterone deficiency (TD) and information on the benefits and risks of testosterone replacement in middle-aged and older men through a comprehensive review of epidemiological and clinical studies.
March 2012
- Data strongly suggests a relationship between testosterone deficiency and frailty in elderly men
This review aimed to discuss the relationship between low testosterone level and frailty in elderly men and to evaluate the data which show that treatment of frail hypgonadal men with testosterone replacement therapy (TRT) improves physical functioning and reduces some common risk factors for cardiovascular disease.1
December 2011
- Long-acting testosterone undecanoate (TU) injection, but not oral TU, improves metabolic parameters
This randomized, double-blind, double-dummy study was the first clinical trial to compare the efficacy and safety of long-term testosterone replacement therapy using two different preparations of testosterone undecanoate (TU), in hypogonadal men with metabolic syndrome (MetS) and/or type 2 diabetes mellitus (T2DM).1
- Endocrine aspects of the diagnosis and treatment of male sexual dysfunction: new ISSM Guidelines
This article is a summary of the report by the Endocrine Aspects of Male Sexual Dysfunctions international experts Committee aimed to provide guidelines based on best evidence for the diagnosis and treatment of endocrine-related male sexual dysfunction.1
June 2011
- The addition of testosterone therapy improves erectile function in hypogonadal men who fail to respond to phosphodiesterase type 5 inhibitor (PDE5-I) therapy alone
This study aimed to confirm that testosterone replacement therapy (Testogel®, Androgel®) improved erectile function in men with erectile dysfunction (ED) who were nonresponders to phosphodiesterase type 5 inhibitors (PDE5-Is).
May 2011
- Meta-analysis supports association between metabolic syndrome and hypogonadism; testosterone replacement therapy may improve metabolic control and reduce central obesity
A systematic review and meta-analysis of available prospective and cross-sectional studies comparing androgen levels in men with or without metabolic syndrome (MetS) was performed to analyse the relationship between androgen levels and MetS.
April 2011
- Testosterone replacement therapy improves body composition, insulin resistance and markers of atherosclerosis in men with low testosterone and metabolic syndrome
Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study.
March 2011
- Low testosterone is common in men with coronary heart disease and negatively impacts survival
A total of 930 men (mean age 61 years) were followed in a prospective cohort study for a mean of 6.9 years to determine the prevalence of testosterone deficiency and to investigate the effect of serum testosterone levels on survival in men with confirmed coronary disease.
February 2011
- Study shows testosterone (T) improves body composition and hip bone mineral density in elderly men with low T
Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. J Svartberg, I Agledahl, Y Figenschau, T Sildnes, K Waterloo and R Jorde. International Journal of Impotence Research. 2008:20;378–387.
December 2010
- Largest international trial indicates that testosterone replacement therapy is an effective and well tolerated treatment for male hypogonadism in daily clinical practice
IPASS: Final data from the worldwide largest study of the tolerability and effectiveness of injectable testosterone undecanoate (TU) for the treatment of male hypogonadism involving 1493 patients. M Zitzmann, JU Hanisch, A Mattern, M Maggi. A presentation to the Men’s Health World Congress, 2010.
November 2010
- Exercise performance in men with stable angina improved by testosterone over 12 month period
Long term benefits of testosterone replacement therapy on angina threshold and atheroma in men. - Testosterone improves depression and quality of life scores in hypogonadal men
Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome.
August 2010
- Testosterone improves functional performance in elderly men with chronic heart failure
Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure. - Testosterone reduces visceral fat and increases muscle mass in non-obese men aged ≥55 years
Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Allan CA, Strauss BJG, Burger HG, Forbes EA, McLachlan RI. J Clin Endocrinol Metab 2008;93(1):139-146 - Testogel reduces fat and improves body composition and quality of life scores
Testosterone therapy improves body composition and quality of life in men with late-onset hypogonadism: A large, randomized, placebo-controlled study. Bouloux P-M, Kelly J, Hiemeyer F. The Aging Male 2008; 11(1):1-41.
