Testosterone consistently improved self-reported walking ability, modestly improved 6MWD in all men participating in the Testosterone Trials, but did not affect falls. However, there needs to be consideration for the potential that hormones which we introduce to the body (e.g. contraception and HRT) may worsen hypermobility symptoms. The symptoms listed in bold are also often caused by or linked to hypermobility, and the combination of the two causes can amplify the severity of the symptoms. The hormonal changes that happen at puberty, during the menstrual cycle, perimenopause and menopause, or with various other conditions such as polycystic ovarian syndrome or endometriosis, can cause a wide range of symptoms. Given that hypermobile people already have lax joints and rely on muscle control to help stabilise those joints, it is not surprising that this effect can be amplified in some hypermobile people. There are questions about the impact of synthetic oestrogens as well, for example, in the combined pill with research showing that they may impact joint stability, particularly in individuals with hypermobility. The PF-10 scores improved significantly more in men treated with testosterone than in men treated with placebo among men whose baseline 6MWS was ≥1.2 m/sec (treatment effect 4.9, 95% CI (2.2, 7.7) PFigure 3). Adherence to assigned treatment in men enrolled in the PFT, assessed by weighing the returned bottles and comparing it to the expected weight based on the prescribed dose, was high in both the testosterone and placebo groups (means 97% and 92%), respectively, with fewer than 5% of men with compliance135%). The primary analysis was performed using random effects models for longitudinal data, which included visit time as a categorical variable and a single main effect for treatment, and included balancing factors and baseline value of the 6-minute walking distance as fixed effect covariates. Our expectation was that men who walked more slowly and perceived mobility problems would be more likely to benefit from testosterone treatment than men who were functioning at a higher level. While this trial aims to demonstrate that testosterone safely and effectively promotes gains in muscle strength and physical function in a group of older men with mobility limitations, the design has taken into consideration many of the conceptual and methodological hurdles facing clinical trials of anabolic, function promoting therapies. The TOM study will target older men with low testosterone levels who meet an operational definition of mobility limitations that includes self-reported and objectively demonstrated limitations in physical function and mobility. Testosterone treatment of older men with mobility limitation who have clearly low testosterone levels consistently improves self-reported mobility but has a modest effect on walking speed. Testosterone also likely improved 6MWD but the treatment effect was modest and appeared to be related to baseline gait speed, the self-reported mobility limitation, and changes in testosterone and hemoglobin levels. Testosterone’s effect on mobility measures in older men with low testosterone were related to baseline gait speed and self-reported mobility limitation, and changes in testosterone and hemoglobin levels. Despite the clear anabolic effects of testosterone in older subjects, its administration has not consistently translated into improvements in muscle strength or when studied, physical function or mobility 24, 27–33. Unique aspects of the TOM Trial include selection of men with self-reported as well as objectively demonstrable functional limitations, community-based screening and recruitment, adjustment of testosterone dose to ensure serum testosterone levels in the target range while maintaining blinding, and inclusion of a range of self-reported and performance-based physical function measures as outcomes. 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. 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 anabolic effects of testosterone on skeletal muscle mass and muscle strength are well recognized, but it is not known whether testosterone improves physical function and mobility or reduces the risk of falls in older men. In summary, testosterone administration in older men with mobility limitation consistently improved self-reported measures of physical function and likely improved mobility, but did not affect fall frequency. 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. By restoring testosterone levels to a normal range, TRT helps in the production of synovial fluid, improving joint lubrication and reducing friction. In the TOM study, we hypothesize that more challenging tasks such as walking an intermediate distance and climbing a flight of stairs while carrying a moderate load, and the selected lift and lower measure, will display higher ceilings and therefore better discriminate among subjects of differing abilities and be more sensitive to change. To address this issue, the TOM study will employ a reliable and proven method for measuring dynamic muscle strength that the investigative team has used in older individuals and shown to be androgen-resposnive ; the leg press 1RM. Given the considerable variability in testosterone levels during replacement therapy, a unique aspect of the methods described here includes adjusting the testosterone dose to achieve the desired increment in circulating levels. This calculation is based on a 0.05 type I error rate, statistical power of 90%, and prior work by our laboratory supporting a testosterone-mediated increase of 245 N (25 kg) in bilateral leg press strength following the 6 month intervention and a standard deviation of the treatment effect of 540 N (55 kg) .
