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As a disease topic Men's Health covers a broad set of issues affecting men of all ages. Some of the issues requiring greater focus and more thorough dissemination of information amongst the healthcare community, are those that have the potential to go undetected in the early stages. These include, hypogonadism and erectile dysfunction.
Early detection and more regular health checks of these diseases, not only improve prognosis and efficacy of treatment outcomes, but also quality of life.
- Testosterone treatment and sleep disorders
- 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
- Testosterone may be beneficial for metabolic syndrome-associated prostate inflammation
- 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
- Testosterone for the treatment of obesity in hypogonadal men
- 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
- Long-acting testosterone undecanoate is well tolerated in men with hypogonadism in daily clinical practice
- 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
- Changes in the worldwide diagnosis and treatment of testosterone deficiency between 2006 and 2010
- 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.
- Efficacy and safety of long-acting testosterone undecanoate in men with hypogonadism in daily clinical practice
- 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
- 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.
- Effects of long-term long-acting testosterone undecanoate on bone mineral density in men with late-onset hypogonadism and metabolic syndrome
- 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.
- Data strongly suggests a relationship between testosterone deficiency and frailty in elderly men
The 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
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