The study intervention is a daily application of a transdermal gel containing either placebo or 100 mg testosterone (Testim 1%, Auxilium Pharmaceuticals, Norristown, PA) for 6 months (24 weeks). The gradual but progressive decrease in serum testosterone from age 20 to 80 14–16 and indisputable evidence that testosterone supplementation increases skeletal muscle mass not only in states of health 17, 18, but also disease 19–22 and older age 23–26, have underscored its potential as a function promoting anabolic therapy. The causality of limitations in physical function and mobility is without doubt complex and multifactorial. The socioeconomic costs of these sequelae and the aging epidemic have exposed an unmet need for therapies to improve physical function and mobility in older individuals. Limitations in physical function and mobility consequent to advancing age represent a far-reaching public health burden in the United States; a society in which 20% of the population will be 65 years of age or older in 2030. The primary objective is to determine whether testosterone therapy improves maximal voluntary muscle strength as quantified by the one repetition maximum. Some individuals may notice positive changes within a few weeks, while others may take several months. The timeframe for experiencing improvements in joint health and mobility with TRT can vary from person to person. While TRT can be beneficial for joint health, it is essential to consider potential risks and side effects. This can alleviate joint pain, stiffness, and enhance overall mobility. Without sufficient testosterone, cartilage may become less effective in cushioning the joints, leading to discomfort and limited range of motion. Oestrogen and testosterone both play roles in serum production and skin hydration. Testosterone and oestrogen may also play a role in overall metabolic function. Oestrogen, progesterone, and testosterone are all thought to be important for strong, healthy immune responses. The association of PGIC with treatment was assessed in a random effects proportional odds model, adjusted for balancing factors. The participants were assigned to receive testosterone or placebo gel for one year using the method of minimization (21). The participants initially applied either 5-g 1% testosterone gel (AndroGel 1%, AbbVie Pharmaceuticals, North Chicago, IL) containing 50-mg testosterone or an equivalent amount of placebo gel daily on the skin. The exclusion criteria have been published (17); briefly, they included conditions that could potentially be worsened by testosterone treatment or would preclude assessment of primary or secondary outcomes. The study protocol was approved by the institutional review boards of the University of Pennsylvania and each of the 12 trial sites. If the participants qualified for any of the three main trials, they could participate in one or more of the other trials. Briefly, the participants had to meet eligibility requirements for one or more of the three main trials (Sexual Function, Physical Function, and Vitality). 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. Unlike many previous trials, which enrolled healthy older men without functional limitations, PFT enrolled men who not only had self-reported mobility limitation, but also had slow gait speed assessed objectively using the 6-minute walk test. While there is a consensus that testosterone replacement of androgen-deficient men increases fat-free mass, its effects on muscle performance and physical function have been inconsistent across trials. A fundamental shortcoming of two recent trials that studied the effects of testosterone replacement on aspects of strength, physical function and mobility in older men with low testosterone levels was the failure to induce appreciable changes in circulating levels of testosterone 32, 33. The TOM study is the first, single-site, placebo-controlled, randomized clinical trial designed to comprehensively determine the effects of testosterone administration on muscle strength and physical function in older men with mobility limitations. This has been neglected in the design of similar and recent studies that failed to induce meaningful changes in testosterone levels and not surprisingly, reported no improvements in muscle strength or physical function and mobility 32, 33. The Testosterone Trials (The TTrials) were a set of seven coordinated placebo-controlled trials, designed to determine the efficacy of testosterone in improving sexual function, physical function, vitality, and other outcomes in older men with unequivocally low testosterone levels and low libido, mobility limitation and/or low vitality (17–19). We report detailed results of The Physical Function Trial (PFT), one of seven Testosterone Trials (TTrials), which determined testosterone’s effects on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) in older men with self-reported mobility limitation and walking speed These observations underscore the importance of the methods described here that will allow monitoring of testosterone levels during therapy and adjustment of the testosterone dose by an unblinded physician and also insure masking of other study personnel and the participants. Additional trials will need to be performed to establish meaningful improvements in physical function and other health-related outcomes. We have recently observed, however, that older subjects with self-reported and objective limitations in mobility demonstrate significantly lower muscle strength than those without . To date, studies of testosterone replacement in older men have either excluded objective measures of physical function or suffered methodological shortcomings. In comparison to previous studies of testosterone administration in older subjects who were higher functioning and community dwelling, the inclusion of individuals with mobility limitations presents a significant recruitment challenge. This study will provide a framework from which future clinical trials of anabolic function promoting therapies can be developed. Sign up for muscle-building workouts, expert weight loss advice, and nutritious meal plans, delivered to your email daily. It’s important to consult with a healthcare professional to determine if TRT is suitable for you and to manage any potential risks or side effects. By promoting the production of synovial fluid and maintaining bone density, TRT can alleviate joint discomfort and enhance mobility. Testosterone plays a significant role in joint health and mobility for men. Adhering to the prescribed treatment plan and maintaining a healthy lifestyle, including regular exercise and a balanced diet, can help optimize the benefits of TRT for joint health. The Patient Global Impression of Change scores indicated a significantly positive impact of testosterone on participant’s perception of improvement in his walking ability overall and separately in men enrolled and not enrolled in the PFT. Thus, testosterone should probably not be started specifically to improve physical function, but men who are treated with testosterone for other reasons may experience some improvement in physical function. The overall treatment effect on 6MWD was small, but not dissimilar from that of a physical activity intervention in older adults with mobility limitation (29). Additionally, we included a patient global impression of change to corroborate whether the patients perceived their walking speed to have improved. We asked men at each visit whether they perceived any changes in their walking ability since the start of the trial using a 7-point scale ranging from "much worse" to "much better" (PGIC).
