Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes ...and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED.
This study aimed to determine the effect of testosterone replacement with long‒acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open‒label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits.
The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double‒blind placebo‒controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52‒week open‒label follow on.
The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self‒reported quality of life.
Testosterone replacement therapy with long‒acting TU improved all domains of sexual function at 30 weeks (erectile function EF, P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological scores. All responses in sexual function continued to improve significantly up to 18 months with an improvement in EF score of 4.31 from baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors, there was no change during the double‒blind phase but a nine‒point improvement in EF domain during 52‒week open‒label treatment. After 30 weeks, 46% vs. 17% of patients on active therapy vs. placebo felt that the treatment had improved their health, reaching 70% after open‒label therapy. Less obese and older patients responded better to testosterone therapy. There were no significant adverse events.
TU significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks and more significantly after 52‒week open‒label extension. Improvement was most marked in less obese patient and those without coexisting depression. In men with type 2 diabetes, trials of therapy may need to be given for much longer than 3–6 months suggested in current guidelines.
Background: The study was conducted to assess the effects of the digestible dietary energy level on some reproductive characteristics in African giant rat. Methods: Sixteen young males were randomly ...distributed into 4 groups of 4 animals each. To each group was attributed randomly one of the 4 dietary energy levels (3600 Kcal/kg, 3800 Kcal/kg, 4000 Kcal/kg or 4200 Kcal/kg). The daily distribution of experimental diets last six months, ie ended when cricetoma were 8 months old. At the end of that period, all animals were sacrificed. Results: Results showed an increase in testes weight with the augmentation of dietary digestible energy level (0.79 + or - 0.13, 0.88 + or - 0.17, 1.02 + or - 0.28 and 1.02 + or - 0.16 respectively for 3600 Kcal/kg, 3800 Kcal/kg, 4000 Kcal/kg and 4200 Kcal/kg). The serum testosterone level, the sperm mobility (76.67, 62, 63 and 57%) and count per cauda epididymis (18.25 + or - 3.75, 16.38 + or - 4.19, 10.83 + or - 2.02 and 10.13 + or - 2.9) and per gram cauda epididymis (39.09 + or - 11.82, 27.01 + or - 4.23, 15.41 + or - 3.31 and 17.40 + or - 7.28) significantly (p<0.05) decreased with the increasing level of digestible energy in the feed. Conclusions: The dietary digestible energy level that gave the higher reproductive performances in male African giant rat was 3600 Kcal/kg DM. Keywords: African giant rat, Cauda epididymal sperm characteristics dietary energy level, Genital organs, Testosterone concentration
Abstract Context The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a ...dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency. Patient summary In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.
Lessons From the Testosterone Trials Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
Endocrine reviews,
2018-June, Letnik:
39, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract
The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled,
double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of
increasing the ...testosterone levels of older men with low testosterone. Testosterone
treatment increased the median testosterone level from unequivocally low at baseline to
midnormal for young men after 3 months and maintained that level until month 12. In the
Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile
function. In the Physical Function Trial, testosterone did not increase the distance
walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants,
testosterone did increase the distance walked. In the Vitality Trial, testosterone did not
increase energy but slightly improved mood and depressive symptoms. In the Cognitive
Function Trial, testosterone did not improve cognitive function. In the Anemia Trial,
testosterone increased hemoglobin in both men who had anemia of a known cause and in men
with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral
density and the estimated strength of the spine and hip. In the Cardiovascular Trial,
testosterone increased the coronary artery noncalcified plaque volume as assessed using
computed tomographic angiography. Although testosterone was not associated with more
cardiovascular or prostate adverse events than placebo, a trial of a much larger number of
men for a much longer period would be necessary to determine whether testosterone
increases cardiovascular or prostate risk.
The Testosterone Trials were conducted to determine if testosterone treatment would
benefit older men with low testosterone. This report describes the Trials' development and
results and the lessons learned.
Testosterone, the notorious male hormone has been surrounded by many dark rumors for several decades, leading to the avoidance of it by numerous health care professionals and patients. However, ...recent research has shown that the data with regard to several side effects reported in the past are mostly inaccurate and that the benefits of testosterone replacement therapy reach far beyond the restoration of libido, and include many vital body functions which are impaired when testosterone levels decrease. This book reveals the multiple pathways by which testosterone benefits the male in order to widen the outlook of new and innovative potential applications of testosterone replacement therapy in a broad range of fields.
IMPORTANCE: Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown. OBJECTIVE: To determine the effect of testosterone administration on ...subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Testosterone’s Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012. INTERVENTIONS: One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES: Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health–related quality of life. RESULTS: Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, −0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, −10.8 Agatston units/year; 95% CI, −45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group. CONCLUSIONS AND RELEVANCE: Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00287586
Objective
To evaluate the efficacy and safety of long‐acting i.m. testosterone undecanoate (TU) in Malaysian men with testosterone deficiency (TD).
Patients and Methods
A total of 120 men, aged 40–70 ...years, with TD (serum total testosterone TT ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo.
In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study.
Participants were seen six times in the 48‐week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone‐binding globulin, liver function test, prostate‐ specific antigen (PSA) and adverse events.
Results
The mean (sd) age of the participants was 53.4 (7.6) years.
A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48‐week period.
Two men in the placebo arm and one man in the treatment arm developed myocardial infarction.
Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne.
Overall, TU injections were well tolerated.
Conclusions
TU significantly increases serum testosterone in men with TD.
PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits.
There was no significant adverse reaction that led to the cessation of treatment.