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 po****tion, 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. Comparison of change in 6-minute walking distance and PF10 scores between testosterone and… Comparison of change in 6-minute walking distance and PF10 scores in men enrolled… 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. 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. With a one-year intervention period, the TTrials also are among the longest testosterone trials. By repeated monitoring of testosterone levels and blinded dose adjustments, we were able to raise and maintain testosterone levels in the mid-normal range for healthy young men. The TTrials included men with unequivocally low testosterone levels, measured using LC-MS/MS. By recruiting subjects who report and demonstrate mobility limitations independent of potential cause (e.g., muscle weakness, balance disorders, joint pain), we may undermine the potential salutary effects of testosterone therapy on muscle strength and therefore, physical function. The TOM study is a clinical trial planned to comprehensively examine the potential therapeutic benefits of testosterone administration on prevalent and disabling consequences of aging, namely, impairments in muscle strength and limitations in physical function and mobility. The primary objective of this study is to determine whether testosterone therapy in older men with low testosterone levels and mobility limitations will increase maximal voluntary muscle strength as measured by the 1 repetition maximum. In the clinical trial described herein we aim to comprehensively examine the therapeutic potential of the prototypical androgen, testosterone, on muscle strength and physical function in older men with mobility limitations. The change in PF10 from baseline in men treated with testosterone was not significantly related to the change in total and free testosterone, DHT and estradiol level (data not shown). Serum free testosterone, DHT and estradiol concentrations also increased in the testosterone group, but did not change in the placebo group. The men enrolled in the PFT were on average older, had higher BMI, were more likely to have comorbid conditions, and, as expected, had slower gait speed and lower PF10 score than those not enrolled in this trial. The two intervention groups were similar in their baseline characteristics among men enrolled and not enrolled in the PFT (Table 1), among men whose baseline gait speed was Supplementary tables 1 and 2). Among the 390 men who were enrolled in the PFT, 35 withdrew prior to month 12, 13 in the testosterone group and 22 in the placebo group (CONSORT diagram; Figure 1). As described (19), among 790 men who were enrolled in the TTrials, 390 were enrolled in the PFT; 193 men were allocated to the testosterone arm and 197 to the placebo arm. 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. In addition to optimizing the methods to detect change in the primary and secondary outcome measures, another distinction of the TOM study is the administration and tailoring of the testosterone dose to restore circulating levels to the mid-normal range. Measures of muscle performance and physical function will also be performed at the study midpoint (3 months) and at the end of the 6-month treatment period. This is a single-site, placebo-controlled, randomized clinical trial that will enroll a total of 252 community dwelling older men aged 65 and older who have low total (less than 350 ng/dL by liquid chromatography tandem mass spectrometry, LC-MS/MS) or free testosterone (less than 50 pg/mL) levels and who self-report and demonstrate limitations in physical mobility. 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.
