The Effects of 17β-estradiol on Skeletal Muscle

• Status: Withdrawn
• Trial end date: 2018-08-14
• Target enrollment: 0
• Participant gender: Male

Summary

The maintenance of skeletal muscle mass and function is critical for healthy aging. Muscle loss with disuse, termed muscle disuse muscle atrophy, leads to impaired functional capacity, the onset of insulin resistance, as well as a heightened risk for morbidity and mortality. With advancing age there is a chronic wasting of muscle. This is especially true in women, where rapid rates of decline in muscle mass and greater anabolic resistance are experienced around the time of menopause, despite higher protein synthesis rates. As women have a longer life expectancy, they are particularly venerable to age-related frailty and morbidity.

Skeletal muscle protein turnover serves to maintain the optimal function of proteins and also provides plasticity of the tissue during altered demands such as during increased loading or unloading of the muscle. Reduced periods of physical activity also have a similar, albeit milder, impact on skeletal muscle and most, people will likely experience multiple bouts of skeletal muscle disuse during their lifetime from which some, particularly older adult women, will fail to fully recover. Thus, muscle disuse atrophy is a significant and continuing problem as reclamation of lost muscle mass, strength/function, and potentially metabolic health (particularly insulin-induced glucose disposal), following disuse is oftentimes incomplete and may be further exacerbated after menopause.

Previous evidence has demonstrated that in the loss of muscle mass is less pronounced in post-menopausal women when receiving hormone replacement therapy. Skeletal muscle has estrogen-β-receptors on the cell membrane, in the cytoplasm and on the nuclear membrane, and therefore a direct mechanistic link between low estrogen levels and a decrease MPS. Interestingly, despite higher rates of protein synthesis, older women still lose muscle mass with advancing age. It has been suggested that the negative muscle protein balance is due to an enhanced rate of MPB. Insulin is a potent inhibitor of MPB and estrogen has been shown to enhance insulin sensitivity in skeletal muscle. However, to our knowledge, no study has examined the efficacy of estrogen supplementation to attenuate the losses of skeletal muscle mass and function during a period of disuse. The findings of this investigation may yield critical data for those who wish to combat skeletal muscle disuse atrophy, particularly after menopause.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: McMaster University
• Treatments: Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol valerate; Polyestradiol phosphate

Criteria

Inclusion Criteria:

1. Generally healthy, non-smoking as assessed by questionnaire

2. Willing and able to provide informed consent

3. BMI between 22 and 29 kg/m2

Exclusion Criteria:

1. Any concurrent medical, orthopedic, or psychiatric condition that, in the opinion of the Investigators, would compromise the ability to comply with the study requirements

2. Significant orthopedic, cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude oral 17β-estradiol supplementation

3. Current illnesses which could interfere with the study (e.g. prolonged severe diarrhea, regurgitation, difficulty swallowing)

4. Excessive alcohol consumption (>21 units/week)

5. History of bleeding diathesis, platelet or coagulation disorders, or antiplatelet/anticoagulation therapy

6. Personal or family history of clotting disorder or deep vein thrombosis

7. Concomitant use of corticosteroids, testosterone replacement therapy (ingestion, injection, or transdermal), or any anabolic steroid