About Delores Lucia
Baseline measures will be completed over a series of 4 visits spanning a 2 week period. This initial dose of testosterone gel is expected to increase average serum total testosterone concentrations into the mid- to high-normal range in the testosterone treated group. As described in 3.9 Participant Safety, blood analyses and determination of adverse events will be performed at 2 weeks and then every 6 weeks for the duration of the study intervention An overview of the primary, secondary and tertiary outcome measures and testing schedule is provided in Table 1.Men reporting mobility limitation showed significantly more improvement in 6MWD and in PF10 than placebo-treated men. As with many aspects of hypermobility management, it can take trial and error, and support from a relevant health care professional to find the right approach for each individual. Studies on female athletes have indicated that the increased risk of injury may be due to a combination of changes in joint laxity, and changes in coordination and muscle control. Oestrogen and testosterone both help to maintain bone density and strength. Oestrogen, progestogen, relaxin and testosterone all impact the body in ways that are relevant to hypermobility.
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.
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.
Following study initiation and the assessment and adjustment of testosterone dosing at 2-weeks, subjects will be seen bimonthly for safety (detailed below), compliance and overall health assessments. If testosterone level is greater than 1000 ng/dL, the unblinded physician will decrease the dose to 5 g gel daily (one 5 g testosterone gel tube plus two placebo tubes). To maintain blinding, all subjects initially receive three tubes of the gel; those assigned to testosterone group receive two active testosterone gel tubes each containing 5 g testosterone gel (50 mg testosterone) plus one tube containing placebo gel, while those assigned to placebo group receive three tubes containing placebo gel. Eligible subjects will have summary scores ranging from 4 to 9 on the SPPB as these values represent moderate to mild mobility limitations and strongly predict subsequent disability . In addition, fatigue, affect, sense of well-being, and self-reported function and disability will be assessed by validated questionnaires. Eligible participants will be randomized to a placebo or testosterone intervention group for 6 months.
The observation that testosterone administration increases skeletal muscle mass and maximal voluntary muscle strength (1–9) has led to considerable pharmaceutical interest in applying testosterone as an anabolic therapy to improve physical function and to reduce the burden of disability in older men with mobility limitation. In this initial trial, we are confident that testosterone therapy will increase muscle mass and strength (primary outcome) and propose that this will translate into improvements in physical function (secondary outcomes). In contrast to recent trials of replacement therapy in older men that achieved only marginal increases in testosterone levels, this study aims to restore testosterone to the mid- to high-normal range. Subjects will perform laboratory-based measures of muscle performance, physical function and physical activity at baseline and following 3 and 6 months of treatment. The secondary aim of this study is to test whether testosterone administration mediates improvements in self-reported as well as performance-based measures of physical function, self-reported disability and habitual physical activity. A total of 252 community dwelling individuals aged 65 and older with low testosterone levels and self-reported limitations in mobility and short physical performance battery (SPPB) score between 4 and 9 will be randomized to receive either placebo or testosterone therapy for 6 months. Unlike previous trials, which often used surrogate endpoints such as lean body mass and muscle performance measures, the TTrials included physical function outcomes that were deemed patient-important and of public health significance.
Progesterone has muscle-relaxing properties – which may negatively affect exercise performance and coordination. Oestrogen helps preserve muscle mass and supports collagen creation. Relaxin is involved in bone remodelling and healing of injured ligaments and skeletal muscle.