Low-normal Testosterone Levels Research Articles

Effects of Testosterone Replacement Therapy on Muscle Strength in Older Men with Low to Low-Normal Testosterone Levels: A Systematic Review and Meta‐Analysis

Background: Previous studies and meta-analyses have explored the relationship among testosterone, muscle strength, and physical function, to the best of our knowledge, no meta-analysis has investigated the effects of testosterone replacement therapy (TRT) on subgroup of relatively hypogonadal older men. Objective: The aim of this study was to evaluate the effect of TRT in older men with low testosterone levels. Methods: PubMed, Embase, and Web of Science were systematically searched for articles published between January 1990 and April 2020. We included randomized controlled studies that investigated the effect of TRT and included older men (age >60 years) with relatively low testosterone levels. Studies were extracted following the PRISMA flowchart, and the included randomized controlled trials were evaluated using RoB 2.0. Our main outcome was muscle strength changes after TRT evaluated using a metaregression of confounding factors. Secondary outcomes included changes in physical performance and the risk ratio of adverse events. Random-effects meta-analyses of TRT on muscle strength and physical function were performed. Results: Thirteen studies with 2,043 patients were included. The mean age of subjects in various studies ranged from 65.9 years to 76 years. Transdermal testosterone dosages ranged from 5 to 10 g/day, while intramuscular options were 125 mg/week or 200 mg every 2 weeks. Oral testosterone supplementation was given at 160 mg/day in one study. Pooled meta‐analyses revealed greater muscle strength improvement after TRT compared with placebo (Hedges’ g = 0.21; 95% CI: = 0.15–0.28). Intramuscular administration of TRT had greater efficacy (Hedges’ g = 0.74; 95% CI: = 0.34–1.14) than transdermal and oral TRT (p < 0.001). A metaregression revealed that baseline serum total testosterone was associated with muscle strength improvement (β = −0.004, p = 0.002). The risk ratios of adverse events, including elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer, were not significantly different. Conclusion: TRT improved muscle strength in older, relatively hypogonadal men. The effect was more pronounced in populations with lower baseline testosterone levels.

PERMANENT LOW NORMAL TESTOSTERONE LEVELS AND SEMINOLOGICAL DAMAGES IN MEN FROM 37 TO 45 YEARS OLD

In our practice, we are increasingly seeing men aged from 37 to 45 years' old who have permanent low normal testosterone levels. Aim: We set out to investigate whether there is an association between permanent low normal testosterone levels and negative change in seminal fluid parameters in young men. Patients and Methods: For the period from January 2013 to December 2015 at the Andrology office at Hospital "St. Sofia" we examined 73 men aged 37 to 45 years with normal or elevated body mass index, permanent low normal testosterone level, and negative change in seminal fluid parameters. In order to compare the results we obtained, at the very beginning of the study we selected a control group of 20 healthy men of the same age. Results: We obtained, although within reference ranges, significantly lower values for total testosterone in the 73 men with negative change in seminal fluid parameters, compared with those in the control group without seminal damages (p&lt;0.001) We found a high correlation relationship between the level of testosterone and the results of the first (r = 0.614, p&lt;0.001) and second spermograms (r = 0.662, p&lt;0.001). Conclusions: 1. Our study shows that in a number of men at a young age, some decrease in normal testosteronе secretion occurs, with a concomitant negative change in seminal fluid parameters, which is remarkably different from the same parameters in their peers with a high normal testosterone level. 2. We identify permanent low normal testosterone, overweight and obesity as predictors, signaling a possible negative change in seminal fluid parameters. 3. We can say that if obesity plays some role in seminal damages, the mechanism in most cases is most likely related to the sustained permanent low normal testosterone level, as a result of increased adipose tissue.

PERMANENT LOW NORMAL TESTOSTERONE AND LOWER URINARY TRACT SYMPTOMS IN MEN 35 - 45 YEARS OF AGE

In our outpatient practice, we are increasingly seeing men aged 35 to 45 years who have permanent low normal testosterone levels. Aim We set out to investigate whether there is an association between permanent low normal testosterone levels and lower urinary tract symptoms in young men. Patients and Methods For the period from January 2013 to December 2015 at the Andrology office at Hospital "St. Sofia", we examined 73 men aged 35 to 45 years with normal or elevated body mass index, permanent low normal testosterone level and micturition disorders. In order to compare the results we obtained, at the very beginning of the study, we selected a control group of 20 healthy men of the same age. Results We obtained, although within reference ranges, significantly lower values for total testosterone in the 73 men with micturition disorders we studied, compared with those in the control group without micturition disorders. Conclusions 1. Our study shows that in some men at a young age, some deviation in normal testosteronе secretion occurs, with a concomitant decrease in maximum urine flow, which is remarkably different from the same indicator in their peers with a high normal testosterone level. 2. We identify permanent low normal testosterone, overweight, and obesity as predictors of initial lower urinary tract symptoms in young men. 3. According to our study, the altered E2/T ratio is also relevant to the initial onset of lower urinary tract symptoms in young men.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

The anabolic applications of androgens in older adults with functional limitations.

Aging is associated with a progressive decrease in skeletal muscle mass, strength and power and impairment of physical function. Serum testosterone concentrations in men decrease with advancing age due to defects at all levels of the hypothalamic-pituitary-testicular axis. Testosterone administration increases skeletal muscle mass, strength and power in older men with low or low normal testosterone levels, but the effects on performance-based measures of physical function have been inconsistent. Adequately powered randomized trials are needed to determine the long-term safety and efficacy of testosterone in improving physical function and quality of life in older adults with functional limitations.

What are the benefits and harms of testosterone therapy for male sexual dysfunction?-a systematic review.

The role of Testosterone Therapy (TTh) in the management of male sexual dysfunction remains unclear. Objective of the authors was to systematically review the relevant literature assessing the benefits and harms of TTh in men with sexual dysfunction. EMBASE, MEDLINE, Cochrane Systematic Reviews-Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane HTA, DARE, HEED), Google Scholar, WHO international Clinical Trials Registry Platform Search Portal, CINAHL databases and clinicaltrial.gov were searched systematically in March 2015 and an updated search was performed in March 2016. Randomized and non-randomized comparative studies assessing the benefits and harms of TTh in hypogonadal, borderline eugonadal and eugonadal men suffering from sexual dysfunction were included. Risk of bias and confounding assessments were performed. A narrative synthesis was undertaken. Of the 6410 abstracts identified, 36 studies were judged to be eligible for inclusion, including 25 randomized clinical trials (RCTs) and 11 non-randomized comparative studies (NRCSs), recruiting a total of 4944 patients. RCTs were judged to have low or unclear risk of bias, while NRCSs had high risk of bias and thus, overall quality of evidence was judged to be at least unclear. Based on the evidence mainly provided by the RCTs included in this systematic review, TTh could be considered for men with low or low-normal testosterone levels and problems with their sexual desire, erectile function and satisfaction derived from intercourse and overall sexual life. The exact testosterone formulation, dosage and duration of treatment remain to be clarified, while the safety profile of TTh also remains unclear. TTh could be used with caution in hypogonadal and most probably borderline eugonadal men to manage disorders of sexual desire, erectile function and sexual satisfaction. The overall low-to-moderate evidence quality highlights the need for robust and adequately designed clinical trials.

Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels.

Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.

Testosterone does not affect agrin cleavage in mobility-limited older men despite improvement in physical function.

In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C-terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility-limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial. We analyzed the difference in change in serum CAF levels between testosterone and placebo groups, as well as its association with muscle strength and physical function. Association of change in serum CAF levels with serum total (TT) and free testosterone (FT) was also evaluated. Men randomized to testosterone experienced significant improvement in muscle strength and physical function (assessed by loaded stair-climbing power). However; testosterone administration was not associated with a reduction in serum CAF levels (effect size=-50.3pm; 95% CI=-162.1 to 61.5pm; p=0.374); there was no association between changes in CAF levels with changes in TT (p=0.670) or FT (p=0.747). There was no association between changes in serum CAF levels with improvement in either muscle strength or stair-climbing power. In conclusion, testosterone treatment in mobility-limited older men with low to low-normal testosterone levels did not reduce serum CAF levels. Additionally, testosterone-induced improvements in muscle strength and physical function were not associated with changes in serum CAF concentrations. These findings suggest that improvement in physical function with testosterone replacement in older men with mobility limitations and elevated CAF levels is mediated by mechanisms other than stabilization of the NMJ.

Effect of Megestrol Acetate and Testosterone on Body Composition and Hormonal Responses in COPD Cachexia.

Background: Underweight chronic obstructive pulmonary disease (COPD) patients with involuntary weight loss have a poor prognosis; no effective therapy is currently available. We conducted the first clinical trial seeking to determine whether combination therapy with an appetite stimulant and an anabolic steroid would have beneficial effects on body composition for patients with COPD cachexia. Methods: We conducted a 12-week pilot study in which 4 men and 5 women (age 64±10 y, forced expiratory volume in 1 second [FEV1] 31±9 %pred., body mass index [BMI] 18±3 kg/m2) with low-normal testosterone levels (average 532±45ng/dl in men and 12.4±5.3ng/dl in women) and weight loss ≥10 lbs over the previous year were treated with oral megestrol acetate 800mg/day plus weekly testosterone enanthate injections, initially 125 mg in men and 40 mg in women, with doses subsequently adjusted targeting circulating nadir testosterone levels of 850 and 300 ng/dl, respectively. Results: On treatment, nadir testosterone level increases averaged 160±250 ng/dl (NS) in men and 322±49 (p<0.001) ng/dl in women. Body weight increased in all individuals, with average end-intervention weight gain of 3.1±2.2 kg (p<0.005). Two women and 2 men had COPD exacerbations and did not complete the 12-week study. In the 5 individuals who completed, dual energy x ray absorptiometry (DEXA) scans revealed an average 2.0±1.5 kg lean mass and 2.3±1.7 kg fat mass increase (each p<0.05). No adverse effects of treatment were detected. Conclusions: Combination therapy reversed the trajectory of involuntary weight loss and increased lean mass in cachectic COPD patients. Though the interventions were apparently well tolerated, participant drop-out rate was high. Larger randomized placebo-controlled long-term studies with functional outcomes are needed.

Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition

Purpose. We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. Methods. Double-blinded, placebo-controlled study in 54 men aged 60–78 years with bioavailable testosterone < 7.3 nmol/L and waist > 94 cm randomized to TT (gel, 50–100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. Outcomes. sCD36, total and regional fat mass were established by Dual X-ray absorptiometry and magnetic resonance imaging. Data are presented as median (quartiles). Kruskal-Wallis and Mann-Whitney tests were performed on delta values at 0, 3 and 6 months. Results. ST + placebo decreased sCD36 levels by 21% [from 0.80 (0.68–1.22) to 0.63 (0.51–0.73) rel. units] vs. TT and vs. placebo (p < 0.05). ST + placebo did not change bioavailable testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta central fat mass (r = 0.84). Conclusions. Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass.

Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels

ImportanceTestosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.ObjectiveTo determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels.Design, Setting, and ParticipantsTestosterone’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.InterventionsOne 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 MeasuresCoprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health–related quality of life.ResultsBaseline 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 RelevanceAmong 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 Registrationclinicaltrials.gov Identifier: NCT00287586

Mechanical Muscle Function and Lean Body Mass During Supervised Strength Training and Testosterone Therapy in Aging Men with Low‐Normal Testosterone Levels

To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study. Randomized, double-blind, placebo-controlled. Odense, Denmark. Men aged 60 to 78, with bioavailable testosterone levels of less than 7.3 nmol/L and a waist circumference greater than 94 cm were randomized to testosterone (50-100 mg/d, n = 22) placebo (n = 23) or strength training (n = 23) for 24 weeks. The strength training group was randomized to addition of testosterone or placebo after 12 weeks. Subjects performed supervised strength training (2-3 sets with 6- to 10-repetition maximum loads, 3 times per week). Testosterone levels, maximal voluntary contraction and rate of force development, and LBM were obtained at 0 and at Weeks 12 and 24 of the intervention. No changes in any variables were recorded with placebo. In the strength training group, maximal voluntary contraction increased 8% after 12 weeks (P = .005). During the following 12 weeks of strength training rate of force development increased by 10% (P = .04) and maximal voluntary contraction further increased (P < .001). Mechanical muscle function was unchanged in men receiving only testosterone for 24 weeks. LBM increased only in men receiving testosterone (P = .004). Strength training in aging men with low-normal testosterone levels may improve mechanical muscle function, but this effect occurs without a significant increase in LBM. Clinically, only the combination of testosterone therapy and strength training resulted in an increase in mechanical muscle function and LBM.

Effects of Testosterone and Progressive Resistance Exercise in Healthy, Highly Functioning Older Men With Low-Normal Testosterone Levels

Aging in men is associated with reduced testosterone (T) levels and physiological changes leading to frailty, but the benefits of T supplementation are inconclusive.We studied the effects of T supplementation with and without progressive resistance training (PRT) on functional performance, strength, and body composition.We recruited 167 generally healthy community-dwelling older men (66 ± 5 years) with low-normal baseline total T levels (200-350 ng/dL).Subjects were randomized to placebo or transdermal T gel [2 doses targeting either a lower (400-550 ng/dL) or higher (600-1000 ng/dL) T range] and to either PRT or no exercise for 12 months.The primary outcome was functional performance, whereas secondary outcomes were strength and body composition.A total of 143 men completed the study. At 12 months, total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group. In the PRT group, function and strength were not different between T- and placebo-treated subjects, despite greater improvements in fat mass (P = .04) and fat-free mass (P = .01) with T. In the non-PRT group, T did not improve function but improved fat mass (P = .005), fat-free mass (P = .03), and upper body strength (P = .03) compared with placebo. There were fewer cardiovascular events in the T-treated groups compared with placebo.T supplementation was well tolerated and improved body composition but had no effect on functional performance. T supplementation improved upper body strength only in nonexercisers compared with placebo.

Synergetic effect of testosterone and phophodiesterase-5 inhibitors

Testosterone deficiency seems to impair the clinical response tophophodiesterase-5 (PDE-5) inhibitors in patients with erectile dysfunction (ED). In hypogonadal men, testosterone repletion was associated with enhanced sexual function in patients who failed initial treatment with sildenafil or tadalafil. We conducted a systematic review of studies that evaluated combination therapy of testosterone and PDE-5 inhibitors in patients with ED and low, low-normal testosterone levels who failed monotherapy. The studies we examine are heterogeneous with several methodological drawbacks and that, overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone &lt;300 ng/dL (10.4 nmol/L) who failed monotherapy. Further studies, with a randomized placebo-controlled and double blind design, are needed to describe the appropriate target patient group, testosterone cut-off and to define the optimal dose and duration of combination therapy.

Synergetic effect of testosterone and phophodiesterase-5 inhibitors in hypogonadal men with erectile dysfunction: A systematic review

Testosterone deficiency seems to impair the clinical response to phophodiesterase-5 (PDE-5) inhibitors in patients with erectile dysfunction (ED). In hypogonadal men, testosterone repletion was associated with enhanced sexual function in patients who failed initial treatment with sildenafil or tadalafil. We conducted a systematic review of studies that evaluated combination therapy of testosterone and PDE-5 inhibitors in patients with ED and low, low-normal testosterone levels who failed monotherapy. The studies we examine are heterogeneous with several methodological drawbacks and that, overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone <300 ng/dL (10.4 nmol/L) who failed monotherapy. Further studies, with a randomized placebo-controlled and double blind design, are needed to describe the appropriate target patient group, testosterone cut-off and to define the optimal dose and duration of combination therapy.

A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50–80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males’ Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5–7.5 mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28 ± 0.15 kg (mean ± SE) and FM decreased by 1.16 ± 0.16 kg, with minor changes with placebo (LBM +0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.

Testosterone therapy decreases subcutaneous fat and adiponectin in aging men

Testosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l, and a waist circumference >94 cm. Central fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), and thigh subcutaneous fat area (TFA) were measured by magnetic resonance imaging. Adiponectin levels were measured using an in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. LEFM was decreased (b = -0.47 kg, P = 0.07) while CFM did not change significantly (b = -0.66 kg, P = 0.10) during testosterone therapy. SAT (b = -3.0%, P = 0.018) and TFA (b = -3.0%, P < 0.001) decreased, while VAT (b = 1.0%, P = 0.54) remained unchanged. Adiponectin levels decreased during testosterone therapy (b = -1.3 mg/l, P = 0.001). Testosterone therapy decreased subcutaneous fat on the abdomen and lower extremities, but visceral fat was unchanged. Moreover, adiponectin levels were significantly decreased during testosterone therapy.

Testosterone Gel Replacement Improves Sexual Function in Depressed Men Taking Serotonergic Antidepressants: A Randomized, Placebo-Controlled Clinical Trial

Testosterone replacement is the most effective treatment for sexual dysfunction in hypogonadal men. Comorbid depression and antidepressant side effects may reduce its influence. The authors conducted a 6-week, double-blind, placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level. A total of 100 men were enrolled at 2 study sites (Boston, Massachusetts, USA, and Tel Aviv, Israel). The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function (IIEF). Complete pre- and posttrial IIEF data were available for 63 subjects. Men randomized to testosterone (n = 31) and placebo (n = 32) were similar in age, baseline testosterone levels, and baseline IIEF scores. At study termination, men randomized to placebo showed virtually no change from baseline in mean (95% CI) IIEF score (−0.7 [−6.5, 5.2]), whereas those receiving testosterone exhibited a substantial increase (15.8 [8.5, 23.1]). The estimated mean difference between groups was 16.8 [7.5, 26.1]; p = .001 by linear regression with adjustment for age and study site. There were also significant between-group differences in each of the 5 IIEF subscales, as well as on the single question involving ejaculatory ability (p ≤ .03 in all cases). Effect sizes in these comparisons remained little changed, and generally remained statistically significant, when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale. It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels, suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone. In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants, treatment with exogenous testosterone was associated with a significant improvement in sexual function, particularly including ejaculatory ability.

Groin Pain- Distance Running

HISTORY: A 41-year-old ultra-distance runner developed progressive aching pain deep in the right groin with running over a 1-month period. The pain would gradually worsen with longer distance runs. He was running his usual 70 miles per week at the time of pain onset. He has completed multiple 100-mile runs throughout the last 10 years without prior injuries. PHYSICAL EXAMINATION: Examination revealed a slightly antalgic gait with reduced step length on the right, normal and symmetric lower extremity ROM, leg length, strength, and sensation. He had tenderness near the right pubic ramus and ischial tuberosity. DIFFERENTIAL DIAGNOSIS: 1. Tendinopathy of adductors or proximal hamstring. 2. Bone stress reaction or fracture of pubic ramus. 3. Intra-articular hip pathology. TESTS AND RESULTS: Right hip anterior-posterior and lateral x-ray: -Faint linear sclerosis and cortical irregularity at the right inferior pubic ramus Pelvis MRI: -Low signal intensity fracture line through the right inferior pubic ramus, with associated bone marrow edema -No evidence of labral or tendon pathology. DEXA Scan: -Lowest z-score= -1.9 standard deviations in the right femoral neck consistent with low bone mass. Laboratory and historical work-up for secondary causes of low bone mass revealed: -Vitamin D deficiency and low-normal testosterone levels -Vegan diet for the last year -History of childhood asthma and several courses of steroids for exacerbations in childhood -History of SSRI use for depression FINAL/WORKING DIAGNOSIS: Grade 4 fatigue fracture of the right inferior pubic ramus in setting of multi-factorial low bone mass in an ultra-distance male runner. TREATMENT AND OUTCOMES 1. Crutches for 12 weeks, based on symptoms. Recumbent bike or swimming to maintain fitness. 2. Supplemented Calcium (1500mg/day) and Vitamin D (ergocalciferol 50000 units weekly) 3. Liberalized diet to include meat and dairy. 4. He replaced his SSRI with buproprion for depression. 5. Repeat x-ray at 12 weeks showed increasing sclerosis indicative of early bony healing. 6. Tenderness nearly resolved by 12 weeks. 7. Anticipate initiation of ROM and non-impact loading exercise at 15 weeks. 8. Incremental return to running by 24 weeks, expecting normal strength, ROM, improved bone density and painless running by that time.

Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males’ Symptoms rating scale (AMS) questionnaires

First, to assess the association between the concentration of serum testosterone and the symptoms of testosterone deficiency according to two screening questionnaires. Second, to investigate the effects in elderly men with a low-normal testosterone concentration of testosterone supplementation over a period of 6 months on symptoms of testosterone deficiency according to the screening questionnaires. A total of 587 men between 60 and 80 years of age with an eligible serum testosterone measurement and completion of the screening questionnaires were included in the study. Of these 587 men, 237 men with testosterone levels <13·7 nmol/l were included in a double-blind, randomized, placebo-controlled trial of testosterone supplementation. One hundred and sixty milligrams per day of oral testosterone undecanoate or a matching placebo for 6 months. The Androgen Deficiency in Ageing Males (ADAM) and the Ageing Males' Symptoms rating scale (AMS) questionnaires. There was no significant association between the total testosterone concentration and the scores on the two questionnaires. However, age was significantly associated with the scores on the ADAM (OR 1·14, 95% CI 1·05-1·23) and the AMS (OR 1·03, 95% CI 1·01-1·08) questionnaire. After supplementation with testosterone, there were no effects on the scores on the two questionnaires in the testosterone group compared with the placebo group. The findings do not support the use of the ADAM or AMS questionnaire in the evaluation of late-onset hypogonadism in ageing men. Moreover, 6 months of oral testosterone supplementation had no significant effect on scores of the ADAM and AMS questionnaire in this group of elderly men with low-normal testosterone levels.