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Objectives: Sarcopenia is defined using a variety of different muscle variables, muscle mass adjustment techniques and cut offs for each variable. The objectives of this thesis were to assess how operational differences in sarcopenia definitions impact the agreement between definitions and the association between sarcopenia and health outcomes such as falls. Methods: A list of sarcopenia definitions was developed which captured the combinations of muscle variables, muscle mass adjustment techniques, and cut offs used in the literature based on a systematic review conducted for this thesis. These definitions were applied to participants taking part in the Canadian Longitudinal Study on Aging, a national study of participants aged 45 to 85 years at baseline. The agreement between the definitions and the association of each definition with falls was assessed. Findings: Both the combination of muscle variables as well as the different muscle mass adjustment techniques generally had limited agreement. Sarcopenia definitions including muscle mass and muscle strength were associated with falls in males, but none of the sarcopenia definitions were associated with falls in females. Area under the curve analyses revealed that even sarcopenia definitions associated with more than two times the odds of falling in males, had a small impact on identifying fallers with values ≤0.56. Conclusions: The results of this thesis show that the existing range of definitions used to define sarcopenia are not equivalent based on the limited agreement and inconsistent association of sarcopenia with falls. The results also show that sarcopenia may have limitations as clinically useful diagnosis for identifying fallers with area under the curve values for all definitions showing that the identification of fallers based on sarcopenic status was at best, modestly better than chance alone. Thesis Doctor of Philosophy (PhD) Definitions for sarcopenia differ in terms of which muscle variables are included, how muscle mass is adjusted, and which cut offs to use for each variables. This thesis assessed the impact of different methods of operationalizing sarcopenia on the proportion of sarcopenic participants, agreement between definitions, and the strength of the association between sarcopenia and falls. The variables used to operationalize sarcopenia as well as different techniques for adjusting muscle mass resulted in poor agreement between definitions. In males, these factors impacted which definitions were significantly associated with falls, and in females, sarcopenia was not associated with falls for any definition. For all definitions, sarcopenia status poorly discriminated between those that would or would not fall. Together, these results show that different sarcopenia definitions are not equivalent and that a standard definition is required. However, this thesis also shows that more work is required to determine the clinical utility of sarcopenia.

Key Points Question In postmenopausal women 50 years or older, is estrogen-based hormone therapy associated with reduced loss of lean body mass compared with no hormone therapy? Findings In this systematic review and meta-analysis of 12 studies comprising 4474 postmenopausal women, those who received estrogen-based hormone therapy lost less lean body mass compared with women who received no hormone therapy and women who received placebo, but this finding was not statistically significant. Meaning The importance of muscle retention in aging women is crucial, but these findings suggest that interventions other than hormone therapy should be explored., This systematic review and meta-analysis evaluates results of 12 randomized clinical trials, comparing changes in lean body mass in 4474 postmenopausal women who were vs were not receiving estrogen-based hormone therapy., Importance Hormone therapy (HT) has been suggested for protection against age-related muscle weakness in women. However, the potential for HT-associated health risks necessitates a better understanding of the direction and magnitude of the association between HT and health outcomes, such as lean body mass (LBM). Objective To determine whether HT was associated with reduced LBM loss compared with not receiving HT among postmenopausal women aged 50 years and older. Data Sources MEDLINE, Embase, AgeLine, CINAHL, and SportDiscus (searched from inception until April 25, 2018). Study Selection For this systematic review and meta-analysis, randomized clinical trials including postmenopausal women undergoing HT and control groups of women not receiving HT were selected by 2 reviewers. Studies were included if LBM or fat-free mass were measured as an outcome. Studies with participants from hospitals, long-term care facilities, or with specific diseases were excluded. Data Extraction and Synthesis Information regarding study characteristics and outcome measures were extracted by 1 reviewer and verified by another. Risk of bias was evaluated. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to abstract data and assess data quality/validity. Data were pooled using a fixed-effects model. Main Outcomes and Measures The primary study outcome was the overall absolute change in LBM (measured in kilograms), captured by dual-energy x-ray absorptiometry, dual-photon absorptiometry, or bioelectrical impedance analysis imaging. Results Of 8961 studies that met selection criteria, 12 were included, with a total of 4474 recruited participants. Of the participants, mean (SD) age was 59.0 (6.1) years. Data on ethnicity were collected by 2 of the studies. Of the 22 HT intervention arms, 15 used estrogen-progesterone combination HT and 7 used estrogen-only HT. Control participants were women who received no HT at all or who received placebo. The median follow-up duration was 2 years (range, 6 months to 6 years). Seven treatment arms showed a loss of LBM, and 14 were protective. Overall, HT users lost 0.06 kg (95% CI, –0.05 to 0.18) less LBM compared with control participants, but the difference was not statistically significant (P = .26). The results were unchanged when stratified based on treatment type and dosage, duration of follow-up, time since menopause, study quality, and type of LBM measurement, with HT users losing between 0.06 kg more to 0.20 kg less LBM compared with control participants for all strata. The quality of evidence based on GRADE was low. Conclusions and Relevance This systematic review and meta-analysis did not show a significant beneficial or detrimental association of HT with muscle mass. Although muscle retention in aging women is of crucial importance, these findings suggest that interventions other than HT should be explored.