Placebo-treated Men Research Articles

Under the influence: exogenous testosterone influences men's cross-sex perceptions of sexual interest.

The sexual misperception bias is a cognitive bias in which men tend to overestimate sexual interest from women, potentially shaped by evolutionary mating strategies. Testosterone, often linked to mating behaviors, might play a role in sustaining sexual overperceptions. To explore this possibility, we conducted a placebo-controlled study with 190 heterosexual men, administering either 11 mg of testosterone or a placebo. Participants interacted with an attractive female confederate, while naïve raters assessed the confederate's affiliative behaviors. Our findings suggest that exogenous testosterone did not broadly impact sexual overperception. However, we found that affiliative behavior from the confederate was positively correlated with perceived sexual interest among testosterone-treated, but not placebo-treated men. In addition, we found that this effect among testosterone-treated men was contingent on their self-perceived attractiveness. Specifically, the confederate's affiliative behaviors were positively correlated with perceived sexual interest, but only for testosterone-treated men with average or above average self-perceived attractiveness. Furthermore, our data revealed that men's tendency to project their own short-term and long-term mating interests increases as a function of self-perceived attractiveness, and this coupling is enhanced by testosterone for long-term interest. Taken together, these results suggest that testosterone may potentiate existing biases, particularly when sexual motivation is high, and bias perceptions of friendly behavior when engaging in cross-sex mindreading. This study adds to the understanding of the neuroendocrine bases of social cognition, suggesting that testosterone can affect men's perceptions of potential mates.

Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism

The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown. To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes. This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022. Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion. The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes. Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes. In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism. ClinicalTrials.gov Identifier: NCT03518034.

Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy.

The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood. We assessed the effects of testosterone-replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial. A randomized, placebo-controlled, double-blind study was conducted at 316 trial sites. Participants included men, aged 45 to 80 years, with 2 fasting testosterone levels less than 300 ng/dL, 1 or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated 3 subgroups of participants: (1) men with rigorously defined, late-life-onset, low-grade persistent depressive disorder (LG-PDD, previously "dysthymia"); (2) all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and (3) all randomly assigned men. Intervention included 1.62% transdermal testosterone or placebo gel. Outcome measures included the proportions of participants (1) meeting criteria for LG-PDD or (2) with significant depressive symptoms; and changes in depressive symptoms, energy, sleep quality, and cognition in testosterone-treated vs placebo-treated men in the 3 subgroups. Of 5204 randomly assigned participants, 2643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met rigorous criteria for LG-PDD. Among those with LG-PDD, there was no significant difference in any outcome measure between the TRT and placebo groups, possibly reflecting low statistical power. In men with significant depressive symptoms (n = 2643) and in all randomly assigned participants (n = 5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. Depressive symptoms are common in middle-aged and older men with hypogonadism but LG-PDD is uncommon. TRT is associated with small improvements in mood and energy in hypogonadal men with and without significant depressive symptoms.

Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism

Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood. To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia. This randomized, placebo-controlled trial included men with hypogonadism at 316 US sites enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. Eligible participants were aged 45 to 80 years, with 2 testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March and August 2023. Participants were randomized with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration. Proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. Secondary end points included incidence of anemia among men who were not anemic. Binary end points were analyzed using repeated-measures log-binomial regression. A total of 5204 men were included, 815 with anemia (mean [SD] age, 64.8 [7.7] years; 247 Black [30.3%], 544 White [66.7%], 24 other [2.9%]) and 4379 without anemia (mean [SD] age, 63.0 [7.9] years; 629 Black [14.4%], 3603 White [82.3%], 147 other [3.4%]). Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs 38 of 97 [39.2%]) (P = .002). Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level. In middle-aged and older men with hypogonadism and anemia, TRT was more efficacious than placebo in correcting anemia. Among men who were not anemic, a smaller proportion of testosterone-treated men developed anemia than placebo-treated men. ClinicalTrials.gov Identifier: NCT03518034.

Changes in white adipose tissue gene expression in a randomized control trial of dieting obese men with lowered serum testosterone alone or in combination with testosterone treatment.

The aim of this study was to determine early weight loss-associated changes in subcutaneous abdominal white adipose tissue (WAT) gene expression in obese men with lowered serum testosterone by RNA next-generation sequencing. Fourteen men, mean age (IQR) 51.6 years (43.4-54.5), BMI 38.3 kg/m2 (34.6-40.8) and total testosterone 8.4 nmol/L (7.5-9.5) provided subcutaneous WAT samples at baseline and after 2 weeks of a very low energy diet. Body weight loss was similar in participants receiving testosterone (n = 6), -5.27 kg [95% CI -6.17; -4.26], and placebo (n = 8), -4.57 kg [95% CI -6.10; -3.55], p = 0.86. In placebo-treated men, of the 14,410 genes expressed in subcutaneous WAT, four genes, Angiopoietin-like 4, Semaphorin 3 G, Neuropilin 2 and Angiopoietin 4, were upregulated (adjusted false discovery rate P < 0.05). In an exploratory analysis comparing men receiving testosterone and placebo, the most-upregulated gene in the testosterone group (exploratory p < 0.0005) was the neuropeptide y receptor 2. In obese men, dieting is associated with upregulation of WAT-expressed Angiopoietin-like 4, a secreted protein that regulates lipid metabolism, Semaphorin 3 G, a proposed adipocyte differentiation factor and secreted adipokine, and its receptor Neuropilin 2, as well as Angiopoietin 4, a vascular integrity factor. In an exploratory analysis, testosterone was associated with the upregulation of neuropeptide y receptor 2, a receptor involved in appetite regulation. Further studies are needed to confirm these observations and their potential biological implications. clinicaltrials.gov, Identifier NCT01616732, Registration date: June 8, 2012.

Effect of testosterone replacement on measures of mobility in older men with mobility limitation and low testosterone concentrations: secondary analyses of the Testosterone Trials

The Physical Function Trial (PFT) was one of seven Testosterone Trials (TTrials), the aim of which was to assess the effect of testosterone on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) in older men with low testosterone concentrations, self-reported mobility limitation, and walking speed of less than 1·2 m/s. Using data from the PFT and the overall TTrials study population, we also aimed to identify whether the effect of testosterone on mobility differed according to baseline walking speed, mobility limitation, or other participant-level factors. The TTrials included 790 men aged 65 years or older and with an average of two total testosterone concentrations below 275 ng/dL (9·5 nmol/L), of whom 390 had mobility limitation and a walking speed below 1·2 m/s and were enrolled in the PFT. Participants were assigned (by minimisation method) to 1% testosterone gel or placebo gel daily for 12 months, with participants and study staff masked to intervention allocation. The primary outcome of the PFT was an increase in 6 min walk test (6MWT) distance of 50 m or more. Here we report data for absolute change in 6MWT distance and physical component of Short Form-36 (PF10), and for PGIC and falls. Data are reported for men enrolled in the PFT and those who were not, and for all men in TTrials; data are also reported according to baseline walking speed and mobility limitation. Analyses were done in a modified intention-to-treat population in all patients who were allocated to treatment, had a baseline assessment, and at least one post-intervention assessment. The TTrials are registered with ClinicalTrials.gov, number NCT00799617. The TTrials took place between April 28, 2011 and June 16, 2014. Of 790 TTrials participants, 395 were allocated to testosterone and 395 to placebo; of the 390 participants enrolled in the PFT, 193 were allocated to testosterone and 197 to placebo. As reported previously, 6MWT distance improved significantly more in the testosterone than in the placebo group among all men in the TTrials, but not in those who were enrolled in the PFT; among TTrials participants not enrolled in the PFT, 6MWT distance improved with a treatment effect of 8·9 m (95% CI 2·2-15·6; p=0·010). As reported previously, PF10 improved more in the testosterone group than in the placebo group in all men in TTrials and in men enrolled in the PFT; among those not enrolled in the PFT, PF10 improved with an effect size of 4·0 (1·5-6·5; p=0·0019). Testosterone-treated men with baseline walking speed of 1·2 m/s or higher had significantly greater improvements in 6MWT distance (treatment effect 14·2 m, 6·5-21·9; p=0·0004) and PF10 (4·9, 2·2-7·7; p=0·0005) than placebo-treated men. Testosterone-treated men reporting mobility limitation showed significantly more improvement in 6MWT distance (7·6 m, 1·0-14·1; p=0·0237) and PF10 (3·6, 1·3-5·9; p=0·0018) than placebo-treated men. Men in the testosterone group were more likely to perceive improvement in their walking ability (PGIC) than men in the placebo group, both for men enrolled in the PFT (effect size 2·21, 1·35-3·63; p=0·0018) and those not enrolled in the PFT (3·01, 1·61-5·63; p=0·0006). Changes in 6MWT distance were significantly associated with changes in testosterone, free testosterone, dihydrotestosterone, and haemoglobin concentrations. Fall frequency during the intervention period was identical in the two treatment groups of the TTrials (103 [27%] of 380 analysed in both groups had at least one fall). Testosterone therapy consistently improved self-reported walking ability, modestly improved 6MWT distance (across all TTtrials participants), but did not affect falls. The effect of testosterone on mobility measures were related to baseline gait speed and self-reported mobility limitation, and changes in testosterone and haemoglobin concentrations. US National Institute on Aging and AbbVie.

Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials

BackgroundLimited information is available on the performance characteristics of 2 questionnaires commonly used in clinical research, the Psychosexual Daily Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II Assessment, especially in older men with low testosterone (T) and impaired sexual function. AimTo determine reliability of PDQ and DISF-II by assessing the correlation within and between domains in the questionnaires and to define clinically meaningful changes in sexual activity (PDQ question 4 [Q4]) and desire (DISF-II sexual desire domain [SDD]) domains. MethodsData from 470 men participating in the T Trials were used to calculate Spearman correlation coefficients of individual items and total score among questionnaires to determine convergent and construct validity. Clinically meaningful changes for sexual desire and activity were determined by randomly dividing the sample into training and validation sets. Anchor- and distribution-based clinically meaningful change criteria were defined in the training set, and selected changes were evaluated in the validation set. OutcomesValidity of the PDQ and DISF-II and clinically meaningful changes in sexual desire and activity were determined in older men in T Trials. ResultsModerate to strong correlations were shown within and between domains from different questionnaires. Using Patient Global Impression of Change as an anchor, clinically meaningful change in PDQ sexual activity was ≥0.6, and in DISF-SDD was ≥5.0. Applying these change cut-points to the validation set, a greater proportion of T-treated men achieved clinically meaningful improvement in their sexual desire and activity compared to placebo-treated men. Clinical ImplicationsThe PDQ-Q4 and DISF-II-SDD can be used to reliably assess clinically meaningful changes in sexual activity and sexual desire in hypogonadal men treated with T. Strengths & LimitationsStrengths of this study include a large sample size, long trial duration, and inclusion of men with low libido and unequivocally low T levels. Limitations include using data from a single study that enrolled only older hypogonadal men, and only 1 anchor for both sexual desire and activity. ConclusionModerate to strong correlations were demonstrated within and between different sexual domains of the PDQ and DISF-II confirming construct and convergent validity. Clinically meaningful improvement in elderly hypogonadal men was change of ≥0.6 score in the PDQ-Q4 and ≥5.0 in the DISF-SDD. Improvements in sexual activity and desire in the T Trials were modest but clinically meaningful.Wang C, Stephens-Shields AJ, DeRogatis LR, et al. Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials. J Sex Med 2018;15:997–1009.

The Testosterone Trials: What the Results Mean for Healthcare Providers and for Science

The purpose of this review was to assess the results of the Testosterone (T) Trials with regard to their clinical and scientific implications. The T Trials investigated 1 year of T gel versus placebo in 790 men 65 years and older with unequivocally low serum T concentrations (< 275 ng/dl). Safety monitoring was performed for an additional year. Primary results were improvement over placebo for sexual desire, sexual activity, erection quality, physical activity, and mood. Vitality improved with some instruments, but not all. Improvement was noted in bone density and anemia. Coronary CT provided mixed results—coronary calcium scores were unchanged whereas volume of non-calcified plaque increased more in the testosterone group. There were no worrisome safety concerns. Major adverse cardiovascular events over 2 years occurred in 9 testosterone-treated men and 16 placebo-treated men. The T Trials provide high-level evidence of strong, broad benefits of T therapy, without substantive safety concerns.

The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment

Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30kg/m2 ) and a repeated total testosterone level <12nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82weeks [74; 90] in men previously receiving testosterone (cases) and 81weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1kg/m2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5kg/m2 (-0.8, -0.3), P<.0001 compared to controls. The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82weeks after testosterone treatment cessation.

Predictors of clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or placebo: An exploratory post-hoc analysis of COU-AA-302 trial data.

e16529 Background: A post-hoc analysis of COU-AA-302 trial data showed that brief pain inventory (BPI), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bone metastases were predictors for overall survival in men with mCRPC treated with AA+P. This study aimed to identify baseline predictors of other clinical outcomes. Methods: COU-AA-302 trial data were used to develop predictive models for prostate-specific antigen (PSA) progression, Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration, and opiate use. Associations between baseline factors and outcomes were first assessed using multivariable Cox models among AA+P patients (Step 1). In Step 2, interaction testing was conducted between treatment (AA+P vs. placebo) and each potential predictor (P &lt; 0.2) identified in Step 1. Final Cox models included predictors and any significant interactions (p &lt; 0.05). Results: A total of 1,034 men (525 AA+P; 509 placebo) were included in the analysis. Baseline BPI, PSA, LDH, and ALP were predictors of PSA progression and opiate use regardless of AA+P or placebo with higher values indicating higher risks (all P &lt; 0.05). Younger age, shorter time from luteinizing hormone-releasing hormone to randomization, higher Gleason score, and lower PSA at diagnosis were also associated with higher risks of opiate use: (all P &lt; 0.05). For ECOG PS deterioration, higher baseline BPI, PSA, LDH, and Gleason score, older age, and lower baseline ECOG were associated with higher risks regardless of AA+P or placebo (all P &lt; 0.05). Baseline ALP and site of metastasis also predicted ECOG PS deterioration but the effect varied by treatment (lower risk in AA+P versus placebo; both interactions’ P &lt; 0.05). Conclusions: Predictors of PSA progression, ECOG PS deterioration, and opiate use were identified in AA+P and placebo-treated men with mCRPC. No predictors were associated with worse outcomes for AA+P versus placebo, while the negative impact of certain predictors on ECOG PS was favorably modified by AA+P. Further study is needed on the relationship between AA+P and prognostic factors.

Effect of pumpkin seed oil on hair growth in men with androgenetic alopecia: a randomized, double-blind, placebo-controlled trial.

Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase and to have antiandrogenic effects on rats. This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of PSO for treatment of hair growth in male patients with mild to moderate androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per day or a placebo for 24 weeks. Change over time in scalp hair growth was evaluated by four outcomes: assessment of standardized clinical photographs by a blinded investigator; patient self-assessment scores; scalp hair thickness; and scalp hair counts. Reports of adverse events were collected throughout the study. After 24 weeks of treatment, self-rated improvement score and self-rated satisfaction scores in the PSO-treated group were higher than in the placebo group (P = 0.013, 0.003). The PSO-treated group had more hair after treatment than at baseline, compared to the placebo group (P < 0.001). Mean hair count increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases of 10% were observed in placebo-treated men (P < 0.001). Adverse effects were not different in the two groups.

The effect of PSA frequency and duration on PSA doubling time (PSADT) calculations in men with biochemically recurrent prostate cancer (BRPC) after definitive local therapy.

4559 Background: The prognostic nature of PSADT in men with BRPC makes it an attractive intermediate endpoint for assessing novel therapies in these patients. Although a number of investigational agents appear to favorably modulate PSADT, slowing in PSADT has also been observed in placebo-treated men. We aimed to determine whether PSADT calculations could be influenced by the frequency and duration of PSA measurements. Methods: We performed a retrospective analysis of men with BRPC who chose to defer hormonal therapy. Eligible men were those with PSA values ≥0.2 ng/mL and at least 6 values taken on average 3 mo apart, and whose local prostate cancer therapy was completed ≥1 year prior. To examine the influence of PSA frequency and duration on PSADT, we calculated median PSADT using different subsets of available PSA values (e.g. each vs every other; and first 3 vs. remaining PSA values). Results: After a median follow-up of 58 mo (range, 6-185 mo), 213 men with BRPC had ≥6 PSA values and 127 men had ≥9 PSA values for analysis. Men (77% white, 23% black/other) had a median age of 61 y with Gleason score distribution as follows (≤6: 30%; 7: 40%; ≥8: 18%; NOS: 12%). For men with ≥6 data points: PSADT calculated using earlier values ranged from 13.2 to 16.6 mo, compared to 16.6 to 17.8 mo, respectively, for the remaining values (within-patient change range: 0.6-1.2 mo). For men with ≥9 data points: PSADT calculated using earlier values ranged from 15.3 to 19.9 mo compared to 22.1 to 22.3 mo, respectively, for the remaining values (within-patient change range: 3.5 to 4.5 mo). When we examined the frequency of PSADT by using every other value, we found little difference (22.3 vs 22.1 mo). Conclusions: These data show that PSADT appears to increase even in the absence of therapy, and may be influenced by duration of PSA follow up. This finding explains PSADT slowing on placebo arms and calls into question the utility of PSADT as a surrogate endpoint. Placebo-controlled trials and the use of standard clinical endpoints are recommended to screen novel agents in men with BRPC to mitigate bias because of natural PSADT variability.

Effect of monthly ibandronate on hip structural geometry in men with low bone density

Hip structural analysis (HSA) performed in a subset of participants from the STudy Researching Osteoporosis iN Guys (STRONG) demonstrated that 1 year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density. HSA was performed on dual-energy X-ray absorptiometry (DXA) images in a subset of participants from the STRONG to examine the impact of monthly ibandronate on geometric properties of the hip in men with low bone density. This prespecified subgroup analysis evaluated men in the intent-to-treat population of STRONG with baseline and 12-month DXA data. Cross-sectional geometric parameters of the femoral shaft (FS), intertrochanter region (IT), and narrow neck (NN) were calculated from femoral DXA scans. All analyses were exploratory. Treatment differences were evaluated using analysis of covariance, which adjusted for baseline parameter value, testosterone level, and treatment. HSA was performed on DXA scans from 89 men (34 placebo; 55 monthly ibandronate). Significant increases in average cortical thickness and cross-sectional area and decreases (i.e., improvements) in the buckling ratio were observed at the FS and IT at 12 months for ibandronate-treated men compared with placebo-treated men. No significant differences were observed between ibandronate and placebo for any NN HSA parameters. One year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density, suggesting that ibandronate may improve resistance to axial compressive forces and bending forces at the hip.

The effect of alcohol on sexual risk-taking among young men and women

The current study investigated the effects of alcohol and gender on the intentions of engaging in sexual risk-taking. Young adults (101 men, 99 women) were randomly assigned to the alcohol, placebo, or no-alcohol conditions. Participants listened to an audiotaped scenario that presented a romantic situation between a man and a woman who had just met. Participants were asked to imagine that they were one of the individuals in the scenario and then judged their intentions to engage in sexual risk-taking. Similar previous studies (e.g., Abbey, Saenz, & Buck, 2005) employing a vignette in which the couple had known each other prior to the romantic encounter found that intoxicated individuals reported a greater willingness to engage in sexual activity than those in the placebo and control groups. In contrast, the current study's results showed that intoxicated and placebo-treated women reported a greater intention of engaging in sex than sober women ( b = 4.92, t = 2.42, p < 05). Conversely, intoxicated and placebo-treated men reported less willingness to engage in sex than sober men ( b = −4.66, t = −2.14, p < .05). Neither alcohol nor gender predicted participants' intention to use a condom if they chose to engage in sex. However, those who used condoms more frequently were more likely to report intending to use a condom in this scenario ( b = −1.60, t = −2.17, p < .05). The results demonstrated the complex processes underlying the effects of alcohol on engaging in casual sex by revealing a gender-specific psychological effect of alcohol.

A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog

The effects of testosterone (T) and estradiol (E(2)) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E(2) on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0+/-8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E(2) were suppressed. In the second phase of the study, either micronized E(2) 1mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E(2) would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E(2)-treated men, exhibited a trend towards improvement in their scores on both the immediate (p=.075) and delayed recall (p=.095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E(2)-treated men on both the immediate (p=.020) and delayed recall (p=.016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E(2) failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer.

A Randomized, Double-Blind, Placebo-Controlled Study of Testosterone Treatment in Hypogonadal Older Men With Subthreshold Depression

Hypogonadism and subthreshold depression are common conditions in elderly men. The objective of this study was to examine the effect of testosterone treatment in older, hypogonadal men with subthreshold depression. A randomized, double-blind, placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older (N = 33) with screening total testosterone levels of <or= 280 ng/dL and subthreshold depression (dysthymia or minor depression, according to DSM-IV). Recruitment for the study was conducted from November 2002 through May 2005. Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks, followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel. The primary outcome measure was the change in the Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of the double-blind phase. Secondary outcome measures were remission of subthreshold depression (defined a priori as a HAM-D score <or= 7) and changes in the Hopkins Symptom Checklist depression scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the short-form 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. At the end of the double-blind phase, testosterone-treated men had a greater reduction in HAM-D scores (p = .024) and a higher remission rate of subthreshold depression (52.9% vs. 18.8%, p = .041) than did placebo-treated men, but there were no differences in other secondary outcome measures between groups. At the end of the open-label phase, the testosterone group had sustained improvement, the control group improved, and there were no differences between groups in any outcome measures. These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism. Larger studies are needed to corroborate these findings. clinicaltrials.gov Identifier: NCT00202462.

Oral Sildenafil Citrate (Viagra) for Erectile Dysfunction: A Systematic Review and Meta-analysis of Harms

To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case–cohort analysis

In the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not reduce plasma viraemia after infection, and HIV-1 incidence was higher in vaccine-treated than in placebo-treated men with pre-existing adenovirus serotype 5 (Ad5) immunity. We assessed vaccine-induced immunity and its potential contributions to infection risk. To assess immunogenicity, we characterised HIV-specific T cells ex vivo with validated interferon-gamma ELISPOT and intracellular cytokine staining assays, using a case-cohort design. To establish effects of vaccine and pre-existing Ad5 immunity on infection risk, we undertook flow cytometric studies to measure Ad5-specific T cells and circulating activated (Ki-67+/BcL-2(lo)) CD4+ T cells expressing CCR5. We detected interferon-gamma-secreting HIV-specific T cells (range 163/10(6) to 686/10(6) peripheral blood mononuclear cells) ex vivo by ELISPOT in 77% (258/354) of people receiving vaccine; 218 of 354 (62%) recognised two to three HIV proteins. We identified HIV-specific CD4+ T cells by intracellular cytokine staining in 58 of 142 (41%) people. In those with reactive CD4+ T cells, the median percentage of CD4+ T cells expressing interleukin 2 was 88%, and the median co-expression of interferon gamma or tumor necrosis factor alpha (TNFalpha), or both, was 72%. We noted HIV-specific CD8+ T cells (range 0.4-1.0%) in 117 of 160 (73%) participants, expressing predominantly either interferon gamma alone or with TNFalpha. Vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile, did not differ between vaccinated male cases (before infection) and non-cases. Ad5-specific T cells were lower in cases than in non-cases in several subgroup analyses. The percentage of circulating Ki-67+BcL-2(lo)/CCR5+CD4+ T cells did not differ between cases and non-cases. Consistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells. Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial.

Preliminary evidence for gender‐specific effects of topiramate as a potential aid to smoking cessation

Study aims were threefold: (i) to determine the feasibility, potential efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine potential predictors of abstinence including gender; and (iii) to explore topiramate's effects on tobacco withdrawal and post-cessation weight gain. Randomized, double-blind, placebo-controlled, 11-week clinical trial with a 6-week dosage titration period and 5 weeks of maintenance treatment. Single-site, out-patient, randomized clinical trial. Thirty-eight adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes per day and who were motivated to try to quit smoking. Random assignment to receive either topiramate (n = 43) up to 200 mg daily in divided doses or placebo (n = 44) orally combined with brief counseling over an 11-week period. Carbon monoxide (CO)-confirmed 4-week prolonged abstinence rate during weeks 8-11. Changes in tobacco withdrawal, body weight and safety parameters were also assessed. Overall, no significant increase in the prolonged abstinence rate was detected, but logistic regression analysis indicated significant gender-specific differences. Men treated with topiramate were nearly 16 times more likely to quit smoking than women on topiramate [37.5% versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal scores than both women taking topiramate and men on placebo. On average, male cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were significantly higher in the topiramate group (topiramate 23% versus placebo 2%). The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue, difficulty with concentration/attention and nervousness. Topiramate produced gender-specific effects on smoking cessation. Male smokers had markedly greater quit rates than female smokers and men were roughly four times more likely to quit smoking when treated with topiramate as compared to placebo. Topiramate was fairly well tolerated, although higher discontinuation rates were seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine withdrawal and preventing post-cessation weight gain might make it a promising agent for treating tobacco addiction, at least in men.

Effect of Growth Hormone Replacement on BMD in Adult-Onset Growth Hormone Deficiency

To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. We randomized 67 men and women to receive GH (n=33) or placebo (n=34) for 2 yr. The GH dose was initially 2 microg/kg body weight/d, increased gradually to a maximum of 12 microg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. BMD of the lumbar spine in the entire group increased by 2.9 +/- 3.9% above baseline in the GH-treated subjects, which was significantly (p=0.037) greater than the 1.4 +/- 4.5% increase in the placebo-treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 +/- 4.3% above baseline, which was significantly (p=0.001) greater than that in placebo-treated men (0.4 +/- 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD.