None listed
Conditions
Brief summary
Endogenous testosterone has been associated with increased lean mass and exercise performance in young and elderly women and testosterone therapy increased lean mass in two pilot randomized controlled trials. However, our systematic review and meta-analyses found no effect of exogenous testosterone on muscle strength or performance, as prior studies have been small (<20 participants per group) and of short duration (6-16 weeks). The aim of this two-arm parallel-group randomized placebo-controlled trial is to determine whether testosterone therapy results in significant gains in muscular power over placebo in postmenopausal women. Participants will be randomly allocated to receive either transdermal testosterone or identical placebo for 26 weeks. The primary outcome will be body weight-corrected power (watts/kg) determined from the maximal vertical jump test on a Leonardo Mechanography Ground Reaction Force Platform (Novotec Medical GmbH). This innovative technology allows for measurement of force, velocity and centre of gravity/sway. It is reproducible and appropriate for older women. Secondary outcomes include grip strength, balance, proprioception, coordination, performance, endurance, and fatiguing (all measured using Leonardo Mechanography), body composition, bone mineral density (BMD), and health-related quality of life. This study addresses the conditions highlighted in the National Women’s Health Strategy 2020-2030 as being of the greatest significance and urgency for older women, who are notably underrepresented in research. It will generate new knowledge in testosterone action and therapy in relation to the preservation of muscle mass and function in postmenopausal women, and potentially provide evidence for novel approaches to prolong the morbidity-free life span of Australian women. This study will provide much needed reference data, presently lacking, for the effect of transdermal testosterone on preservation of muscle mass and function, which will inform the design of future studies of testosterone and other potential therapies. The findings will lead to high impact publications, and potentially transformative interventions ensured by Prof Davis’s standing as the world expert on testosterone in women.
Interventions
Application of active treatment, 1% testosterone cream, 0.5ml (10mg/ml), or placebo cream
applied transdermally daily to upper thigh or lower torso by participant for 6 months.
Compliance will be assessed by collection and weighing of returned cream containers at week 12 and week 26 after commencement of treatment.
Participants will be provided with and asked to self-administer vitamin D3 oral capsule, 1000IU/day for 26 weeks.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
55 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Naturally postmenopausal women, aged 55-70 years, who are not taking medications that might influence hormone levels or muscle/bone health. Participants must be agreeable to taking vitamin D3 1000 IU/day and making no meaningful change in their exercise regime or diet over the course of the study. Participants will be required to have a body mass index between 18 and 35 kg/m2, a clinically acceptable mammogram in the preceding 2 years and clinically acceptable cervical screening test results within the preceding 5 years.
Exclusion criteria
1. Body mass index <18 or >35 kg/m2 2. Current or recent (in the past 12 months) use of systemic estrogen replacement therapy or tibolone (vaginal estrogen permitted) 3. Current or recent (in the past 12 months) use of antiandrogens 4. Use of any drugs affecting bone metabolism such as bisphosphonates, denosumab, systemic corticosteroids, antineoplastic drugs, thiazide diuretics, anti-epileptic drugs, and heparin in the last 5 years 5. History of testosterone or dehydroepiandrosterone treatment in the last 5 years 6. Plans to commence a weight reduction diet for the duration of the study 7. Known allergy to almonds (a constituent of the cream) 8. Severe chronic skin disease (such as eczema or psoriasis) that is likely to interfere with transdermal drug absorption 9. Intolerance to transdermal testosterone 10. Clinically significant infection requiring systemic antibiotics 11. Undiagnosed vaginal bleeding 12. Evidence of clinical hyperandrogenism (hirsutism, androgenic alopecia, or acne) as assessed by the recruiting clinician 13. Taking herbal remedies, grapefruit juice, or medications known to be strong inducers or inhibitors of cytochrome P450 3A4 or known to interact with testosterone metabolism or reproductive hormone levels. 14. Use of protein supplementation is permitted but participants will be restricted from commencing new any new protein supplement or increasing their consumption. 15. History of smoking within the past year, active substance abuse, or alcohol consumption of more than two standard drinks per day 16. Severe musculoskeletal, neurological, or metabolic disease which might influence the results of the study 17. Present or previous systemic cancer diagnosis in the last 5 years 18. Donation of blood within the last 6 weeks or plasma within 7 days of the first dosing in this study 19. Abnormal thyroid function (abnormal thyroid stimulating hormone (TSH) value confirmed by a free T4 outside laboratory range) 20. Being considered by a chief investigator to be unsuitable for participation in the study
Outcome results
None listed