Effects of Testosterone Treatment in Older Men.

BACKGROUND: Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS: We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS: Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS: In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

Why Is the Electronic Health Record So Challenging for Research and Clinical Care?

BACKGROUND: The electronic health record (EHR) has become increasingly ubiquitous. At the same time, health professionals have been turning to this resource for access to data that is needed for the delivery of health care and for clinical research. There is little doubt that the EHR has made both of these functions easier than earlier days when we relied on paper-based clinical records. Coupled with modern database and data warehouse systems, high-speed networks, and the ability to share clinical data with others are large number of challenges that arguably limit the optimal use of the EHR OBJECTIVES: Our goal was to provide an exhaustive reference for those who use the EHR in clinical and research contexts, but also for health information systems professionals as they design, implement, and maintain EHR systems. METHODS: This study includes a panel of 24 biomedical informatics researchers, information technology professionals, and clinicians, all of whom have extensive experience in design, implementation, and maintenance of EHR systems, or in using the EHR as clinicians or researchers. All members of the panel are affiliated with Penn Medicine at the University of Pennsylvania and have experience with a variety of different EHR platforms and systems and how they have evolved over time. RESULTS: Each of the authors has shared their knowledge and experience in using the EHR in a suite of 20 short essays, each representing a specific challenge and classified according to a functional hierarchy of interlocking facets such as usability and usefulness, data quality, standards, governance, data integration, clinical care, and clinical research. CONCLUSION: We provide here a set of perspectives on the challenges posed by the EHR to clinical and research users.

Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials.

CONTEXT: The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear. OBJECTIVE: To test the hypotheses that baseline serum TT, FT, estradiol (E2), and sex hormone-binding globulin (SHBG) levels are independently associated with sexual function, vitality, and physical function in older symptomatic men with low testosterone levels participating in the Testosterone Trials (TTrials). DESIGN: Cross-sectional study of baseline measures in the TTrials. SETTING: The study was conducted at 12 sites in the United States. PARTICIPANTS: The 788 TTrials participants were ≥ 65 years and had evidence of sexual dysfunction, diminished vitality, and/or mobility disability, and an average of two TT < 275 ng/dL. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Question 4 of Psychosocial Daily Questionnaire (PDQ-Q4), the FACIT-Fatigue Scale, and the 6-minute walk test. RESULTS: Baseline serum TT and FT, but not E2 or SHBG levels had small, but statistically significant associations with validated measures of sexual desire, erectile function, and sexual activity. None of these hormones was significantly associated within or across trials with FACIT-Fatigue, PHQ-9 Depression or Physical Function-10 scores, or gait speed. CONCLUSIONS: FT and TT levels were consistently, independently, and positively associated, albeit to a small degree, with measures of sexual desire, erectile function, and sexual activity, but not with measures of vitality or physical function in symptomatic older men with low T who qualified for the TTrials.

Recruitment and Screening for the Testosterone Trials.

BACKGROUND: We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment. METHODS: Men were eligible if they were ≥65 years, had an average of two morning total T values <275 ng/dL with neither value >300 ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or low vitality. Men had to be eligible for and enroll in at least one of these three main trials (physical function, sexual function, vitality). RESULTS: Men were recruited primarily through mass mailings in 12 U.S. communities: 82% of men who contacted the sites did so in response to mailings. Men who responded were screened by telephone to ascertain eligibility. Of 51,085 telephone screens, 53.5% were eligible for further screening. Of 23,889 initial screening visits (SV1), 2,781 (11.6%) men were eligible for the second screening visit (SV2), which 2,261 (81.3%) completed. At SV2, 931 (41.2%) men met the criteria for one or more trials, the T level criterion and had no other exclusions. Of these, 790 (84.6%) were randomized; 99 (12.5%) in all three trials and 348 (44%) in two trials. Their mean age was 72 years and mean body mass index (BMI) was 31.0 kg/m(2). Mean (standard deviation) total T (ng/dL) was 212.0 (40.0). CONCLUSION: Despite the telephone screening to enrollment ratio of 65 to 1, we met the recruitment goals for each trial. Recruitment of symptomatic older men with low testosterone levels is difficult but feasible.