Females, Aging, Metabolism, and Exercise: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Females, Aging, Metabolism, and Exercise (NCT01712230), a randomized na study. The primary outcome is Change in Physical Activity Energy Expenditure (PAEE).

2. Clinical Question

The study description frames the question around energy expenditure during activity and also mentions energy use while sleeping, resting, and eating. The primary outcome, however, is specifically PAEE. Total fat mass and total fat-free mass were listed as secondary outcomes, but their numerical results are not reported in the registry record.

3. Trial Design

This was a randomized, triple-masked, parallel-group study with enrollment of 47. Its title is “Females, Aging, Metabolism, and Exercise,” and its official title is “Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women.” The registry lists obesity as the condition and University of Colorado, Denver as the sponsor. The study is marked completed. The listed start and primary-completion dates are 2012-10 and 2017-10.

There were three groups: placebo, GnRH agonist, and GnRH agonist plus exercise. The placebo group received monthly placebo injections for 6 months. The GnRH agonist group received monthly GnRH agonist injections for 6 months. The combination group received monthly GnRH agonist injections for 6 months plus supervised cardiovascular exercise. The record does not state the exercise frequency, session length, or adherence procedures beyond the compliance information associated with the outcome analysis.

Random allocation means that assignment to groups was intended to be determined by a random process; the precise sequence-generation and concealment procedures are not reported in the registry record. Triple masking indicates that masking was recorded, but which people were masked and how masking was maintained are not reported in the registry record. The parallel design means participants were assigned to a group rather than described as crossing between interventions.

The registry lists a primary outcome of change in PAEE from baseline to 6 months. Its posted arm-level results include 9 participants for placebo, 14 for GnRH agonist, and 11 for GnRH agonist plus exercise. These outcome counts should not be conflated with enrollment or with the distinct safety-group counts. The outcome population description notes withdrawals and exclusions,. The registry record does not report a sample-size justification, a detailed analysis plan, or numerical pairwise treatment estimates.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Placebo: One participant dropped because they got a new job. GnRH agonist+exercise: One participant dropped because of a health problem unrelated to the study. Results from five participants were not included in the analysis because they did not meet the exercise compliance threshold (completed \<70% of exercise sessions).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 47 women were enrolled in to the study, but only 42 completed the intervention. Baseline characteristics are reported for these 42 women. Primary and secondary outcome analyses were completed on 34 women who met the definition of compliance to the intervention (defined as completing \>70% of prescribed exercise sessions).

6. Primary Endpoint

The registry lists the primary outcome as Change in Physical Activity Energy Expenditure (PAEE), measured over Change from baseline to 6 months.

Physical activity energy expenditure, or PAEE, is the amount of energy attributed to physical activity. The registry defines it as total energy expenditure (TEE) minus resting energy expenditure (REE) minus the thermic effect of feeding (TEF). TEE was measured using doubly-labeled water, REE using indirect calorimetry, and TEF was estimated using a constant. The primary outcome was change in PAEE from baseline to 6 months, expressed in kcal/day.

This endpoint is used to focus on energy expenditure attributed to activity rather than total energy expenditure alone. In general, separating activity-related expenditure from resting expenditure and the energy cost of feeding can help address a more specific physiological question. The endpoint is an estimate derived from its component measurements and estimate; it is not a direct count of exercise sessions or a measure of fitness. The registry record does not report the value of the constant used for TEF or additional measurement details.

The posted results summarize change using a mean and standard error for each group. The standard error describes the precision of an estimated group mean; it is not a measure of the spread of individual participant outcomes. The registry does not post confidence limits for these arm-level estimates or numerical estimates of between-group differences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant has a numerical PAEE change, and the posted group summaries use means. A mean gives a central summary of observed values. It can be useful for comparing groups, but a mean alone does not convey how widely individual outcomes vary or how uncertain a group contrast is. The record reports standard errors alongside the means, which describe precision of each estimated mean rather than participant-level dispersion.

How to read the arm summaries

The placebo, GnRH agonist, and GnRH agonist plus exercise rows report separate mean changes. Those values are not adjusted effects and are not themselves pairwise comparisons. A treatment comparison would ordinarily be expressed as a contrast between groups, with an uncertainty measure and, where reported, a test result. The registry record does not report numerical contrasts, confidence intervals, or p-values for this endpoint. The posted comparison output indicates that values are missing or not estimable for a two-arm comparison. No new contrast can be recovered without doing a calculation, and the arm summaries alone should not be presented as a substitute for a sponsor-reported analysis.

What the standard error conveys

In general, the standard error describes how much an estimate such as a mean would be expected to vary across repeated samples under the assumptions of the analysis. A smaller standard error generally indicates greater precision, while a larger one indicates less precision. It is not the same as the standard deviation, which describes the spread of individual observations. The posted values are standard errors, and the registry does not provide standard deviations or confidence intervals for PAEE change. A confidence interval is generally a range that communicates uncertainty around an estimate under a specified method; without a posted interval or a documented analysis, its bounds should not be inferred from the displayed summaries.

How PAEE is constructed

The registry defines PAEE as TEE minus REE minus TEF. TEE was measured using doubly-labeled water, REE using indirect calorimetry, and TEF was estimated using a constant. In general, a derived endpoint combines information from its component measures, so its interpretation depends on how those components were obtained and on the estimation method. The registry gives the broad measurement approach but does not report the constant used for TEF, quality-control procedures, or further details needed to reproduce the endpoint calculation.

Change from baseline to 6 months describes the difference between a participant’s measurement at the starting point and the later measurement, as defined by the study. Summarizing these changes by group focuses on within-participant change before producing an arm mean. The record does not give the baseline and 6-month PAEE values separately, nor does it report a model that adjusts for baseline values or other covariates. The posted summaries therefore should be described as the arm-level mean changes, without attributing an adjustment or model that is not documented.

Randomization, masking, and comparison

Randomization is generally intended to reduce systematic differences between groups at the point of assignment. It does not ensure that every characteristic is balanced in a particular study, especially when the groups are limited in size. Masking is generally used to reduce the influence of expectations or knowledge of assignment on care, measurement, or assessment. Although this record labels the trial randomized and triple masked, it does not specify the people masked, the allocation procedure, or how the masking was implemented. A parallel-group design compares groups assigned to different regimens over the study period rather than using a crossover sequence, as far as the posted design label indicates.

Three groups allow distinct questions to be considered: the placebo group versus GnRH agonist alone, the placebo group versus GnRH agonist plus exercise, and the two GnRH agonist groups against one another. These are possible comparisons suggested by the groups, not a statement of which comparisons were prespecified or analyzed. The registry record does not report the planned contrast structure or a multiplicity procedure. Because the pairwise numerical results are not posted, the arm means do not establish the answer to any of these comparisons.

Planning illustrations are not trial outcomes

The page includes a sample-size section based on planning assumptions and the observed effect. Such values are planning illustrations: they describe sample sizes under stated assumptions, not the number of participants actually observed and not the trial’s original design justification. In general, a sample-size calculation depends on a target effect, variability, significance level, allocation, and a statistical approximation. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The registry record does not report that these were the trial’s original planning assumptions. These illustrations are not observed power and should not be read as evidence that a result is or is not statistically reliable.

Over-dispersion is a general concern when observed variation is greater than a model assumes: uncertainty can then be understated if the model fails to account for that extra variation. The posted outcome is continuous and reported with standard errors; the registry does not report an over-dispersion analysis or indicate that this issue was modeled. The available information is not enough to judge the adequacy of an unreported model. More broadly, the statistical analysis plan, handling of outliers, model diagnostics, and any adjustment for multiple outcomes are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo", "GnRH Agonist", "GnRH Agonist + Exercise")
n   <- c(9, 14, 11)
m   <- c(74.5, -10.2, 61)
sp  <- c(77.9, 63.6, 66.4)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo  9  74.500  233.700  -105.138  254.138
CARM  GnRH Agonist  14  -10.200  237.969  -147.599  127.199
CARM  GnRH Agonist + Exercise  11  61.000  220.224  -86.948  208.948

11. Multiplicity, Missing Data and Analysis Populations

The study has one listed primary outcome and two listed secondary outcomes: total fat mass and total fat-free mass. The registry record does not report numerical results for those secondary outcomes in the information. It also does not report whether the primary and secondary outcomes were tested as a family, whether any multiplicity adjustment was planned, or which pairwise comparisons were prespecified. When several outcomes or group comparisons are examined, multiplicity is a general statistical concern because the chance of at least one apparently notable result can increase across analyses. That concept does not show that an adjustment was or was not needed in this study; the analysis plan is not reported.

The registry outcome description notes one placebo participant who dropped because they got a new job and one participant in the GnRH agonist plus exercise group who dropped because of a health problem unrelated to the study. It also says results from five participants were not included because they did not meet the exercise compliance threshold. The recorded text specifies “completed <70” but does not make the unit clear in the posted text. The record does not report whether these participants were excluded from all analyses, how missing measurements were handled, or whether any sensitivity analyses assessed the effect of exclusions.

The outcome group counts are 9, 14, and 11, while the safety group counts differ. These are distinct summaries and should not be assumed to represent identical analysis populations. The registry record does not describe an intention-to-treat analysis, a per-protocol analysis, imputation, or another missing-data method. Without those details, the posted arm summaries can be described, but the influence of missing data and compliance-based exclusions cannot be assessed from the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety table reports serious adverse events for groups with 10 participants at risk in placebo, 14 in GnRH agonist, and 18 in GnRH agonist plus exercise. The number affected by a serious adverse event is 0 in each group. Deaths are also reported as 0 in each group. No serious adverse-event terms are listed in the posted information.

These figures describe the recorded safety groups, not the primary-outcome analysis groups. In particular, the safety counts differ from the PAEE outcome counts, so they should not be treated as the denominators for the outcome means. The registry also lists other adverse events: 3 affected in placebo, 4 in GnRH agonist, and 4 in GnRH agonist plus exercise, with the corresponding safety-group counts. These other events are distinct from serious adverse events.

In general, zero recorded serious events means none were reported in the stated group during the registry’s safety reporting, not that the possibility of such events is ruled out. The registry record does not provide further detail about event definitions, timing, severity criteria, or relatedness. These counts are descriptive and do not by themselves establish comparative safety.

13. What the Result Does, and Does Not, Mean

The posted results show the mean change in PAEE for each trial group over the stated period. The placebo mean change was 74.5 kcal/day, the GnRH agonist mean change was -10.2 kcal/day, and the GnRH agonist plus exercise mean change was 61.0 kcal/day. Each estimate is accompanied by a standard error, and the outcome counts are 9, 14, and 11, respectively. These summaries describe the observed analysis groups; they do not provide a direct estimate of the difference caused by assignment to one regimen rather than another.

The results do not, as posted, establish whether the groups differed statistically. The registry does not report numerical between-group estimates, confidence intervals, or p-values for the primary outcome, and the comparison output is unavailable because values are missing or not estimable for a two-arm comparison. The means should not be interpreted as proof of benefit, lack of benefit, or equivalence. A difference in the displayed means is not itself evidence that the corresponding population-level difference is precise or distinguishable from chance variation.

The study description raises a question about ovarian hormone reduction, energy expenditure, and exercise. The intervention groups provide a structure for examining these questions, but the available arm-level results do not isolate a causal effect of GnRH agonist or exercise. Such interpretation would require the relevant group contrasts and an account of the analysis, including how withdrawals and compliance-based exclusions were handled. Those details are not reported in the registry record.

The results also do not answer every energy-metabolism question in the study description. The primary endpoint is PAEE, while the description mentions resting, sleeping, and eating. The registry lists total fat mass and total fat-free mass as secondary outcomes, but their numerical results are not reported in the information. The posted PAEE values should therefore be kept distinct from claims about other energy expenditure measures, body composition, or clinical outcomes.

In general, a registry result is most informative when its estimate, uncertainty, comparison, and analysis population are all clear. Here, the arm means and standard errors offer a descriptive view, while the missing comparison results and incomplete analysis details limit inferential interpretation. The appropriate reading is narrow: these are the posted group summaries for this study, not a complete account of the statistical evidence for the study question.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question concerns a derived continuous measure and includes three groups representing placebo, GnRH agonist alone, and GnRH agonist with supervised exercise. That design makes the distinction between arm summaries and treatment contrasts especially important. A reader can see the mean change in each group, but the scientific comparison depends on estimates of differences between groups and their uncertainty. Those numerical comparisons are not reported in the registry record.

The endpoint also illustrates how measurement choices shape analysis. PAEE is calculated from total expenditure, resting expenditure, and an estimate of the thermic effect of feeding. Each component has a stated measurement or estimation approach, and the resulting endpoint is not simply a direct activity measurement. Statistical interpretation therefore depends on both the group comparison and the construction of the outcome. The registry gives the broad formula but not all details required to reproduce it.

The reported outcome population also matters. The record notes withdrawals and results excluded for not meeting an exercise compliance threshold, while the safety table uses different group counts from the PAEE analysis. These distinctions are relevant to how representative the posted means are of all enrolled participants and to how a reader interprets any intended comparison. The missing-data and analysis-population procedures are not reported.

Finally, this record highlights the limits of registry summaries. The posted means and standard errors support a descriptive account, but they do not replace a full statistical analysis with contrasts, confidence intervals, and a clear account of exclusions and multiplicity. Reading the record carefully means separating what is numerically shown from what would require additional analysis or documentation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpretation is that only arm-level means and standard errors are reported. The registry record does not report between-group estimates, confidence intervals, or p-values for PAEE change. As a result, the posted results do not quantify the precision of the treatment contrasts needed to answer the principal comparative question.

The outcome populations are not fully described. The record mentions one participant dropping from placebo, one dropping from GnRH agonist plus exercise, and results from five participants omitted for not meeting an exercise compliance threshold. The text states “completed <70” but does not make the unit clear. It does not report the analysis population definition, the handling of missing measurements, or sensitivity analyses. The safety group counts also differ from the outcome counts, so the two sets of figures should not be combined.

Important design and analysis details are not reported in the registry record, including eligibility criteria, allocation procedures, which parties were masked, the statistical model, baseline adjustment, the planned comparison structure, multiplicity handling, and the sample-size justification. The exercise schedule is also not detailed. The record gives a broad formula and measurement methods for PAEE but not the constant used for TEF or other information needed to reproduce the endpoint.

Only the primary outcome values are described. Although total fat mass and total fat-free mass are listed as secondary outcomes, their numerical results are not reported in the information summarized. The results therefore cannot support conclusions about those measures or about other energy expenditure components mentioned in the study description. These reporting gaps constrain interpretation; they do not establish that the unreported methods or results were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Females, Aging, Metabolism, and Exercise — NCT01712230.
• Registry record last updated 2019-11-22; status last verified 2019-11.
• Results first posted 2019-11-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed randomized, triple-masked, parallel-group study with enrollment of 47. The three groups received placebo, GnRH agonist, or GnRH agonist plus supervised cardiovascular exercise; the injection regimens were monthly for 6 months.

The primary outcome was change in PAEE from baseline to 6 months, in kcal/day. The posted mean changes were 74.5 for placebo, -10.2 for GnRH agonist, and 61.0 for GnRH agonist plus exercise, with standard errors of 77.9, 63.6, and 66.4, respectively. Outcome counts were 9, 14, and 11. Numerical between-group analyses are not reported in the registry record.

The record notes withdrawals and compliance-based exclusions, and lists total fat mass and total fat-free mass as secondary outcomes without numerical results. Serious adverse events and deaths were reported as 0 in each safety group. Missing analysis details and the absence of reported contrasts limit interpretation of the posted outcome summaries.