Effects of Estrogen Deficiency on Energy Expenditure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Estrogen Deficiency on Energy Expenditure (NCT01846728), a na na study. The primary outcome is Brown Adipose Tissue Activity.

2. Clinical Question

3. Trial Design

NCT01846728 is a completed, single-group study sponsored by the University of Colorado, Denver. The registry lists enrollment of 6 and an intervention of estrogen suppression. The record gives the study start as 2013-04 and primary completion as 2015-10. It lists the phase and allocation as NA and masking as NONE. These entries do not establish details beyond what the registry reports.

The intervention description says Lupron is used to block normal production of ovarian hormones. Brown adipose tissue activity is planned for measurement at baseline and after 3 months of suppression. This makes the planned contrast a within-group before-and-after comparison. It is not a randomized comparison between participants receiving suppression and a separate control group. The registry explicitly identifies the design as single-group.

The record lists cold induced thermogenesis, fat mass, fat free mass, and resting energy expenditure as secondary outcomes. It states that there are 5 outcome measures and 5 analyses, but does not provide results for those outcomes in the registry record recorded for this trial. Eligibility criteria, recruitment details, participant characteristics, adherence, treatment discontinuation, and the analysis population are not reported in the registry record.

The registry record does not describe a prespecified statistical analysis plan, the method for handling repeated measurements, or any adjustment for participant characteristics. It also does not report whether there were protocol deviations or missing observations. The completion status indicates that the study is recorded as completed; it does not by itself establish that every planned assessment was obtained or that results were reported.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Brown Adipose Tissue Activity, measured over Baseline and after 3 months of suppression.

The primary endpoint is brown adipose tissue activity, measured as standard uptake value (SUV). The registry describes assessment using positron emission tomography/computer tomography (PET/CT) before and after 3 months of estrogen suppression. SUV is described as a mathematically derived ratio and a semiquantitative measure of tracer uptake in a region of interest. The description says the measure normalizes lesion activity to injected activity and a measure of volume of distribution, usually total body weight or lean body mass.

The endpoint is intended to quantify tissue activity relevant to the study's question about heat production. The registry's rationale is that estrogen suppression may affect the body's ability to produce heat, and brown adipose tissue activity is the primary measure used to investigate that question. The outcome is specified as a mean of a continuous measure, with standard deviation as its dispersion measure.

The record gives the measurement schedule and units but does not report the actual SUV values, their standard deviations, or the estimated change between baseline and follow-up. It also does not report whether the volume-of-distribution measure used for normalization was total body weight or lean body mass. Thus the endpoint definition can be described, but the observed magnitude and precision of any change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine what statistical comparisons would be relevant, but the registry record does not report the analysis plan or primary outcome results. The methods below explain general statistical concepts that help interpret the stated design; they do not imply that a particular method was used in this study.

What does a before-and-after comparison estimate?

In a single-group study, the central comparison is between measurements from the same participants at different times. For a continuous outcome such as SUV, an analysis might describe the average measurement at baseline and follow-up, and the average within-participant change. Pairing matters: the uncertainty of an average change depends on how the two measurements vary together within participants, not only on the separate spread at each time point.

The registry identifies the endpoint as a mean with standard deviation but does not give the observed means, standard deviations, or changes. It also does not say whether a paired analysis, a model for repeated measurements, or another approach was used. The reported endpoint summary type alone is not enough to reconstruct an analysis or its uncertainty.

What does a confidence interval communicate?

In general, a confidence interval describes the uncertainty around an estimated effect under the assumptions of the statistical method. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval does not show the probability that the specific estimated effect is the true effect. For this study, no confidence interval for the primary outcome is reported in the registry record, so its precision cannot be judged.

A p-value, if reported, would address how compatible the observed data are with a specified null model and its assumptions. It would not measure the size or importance of a change. The registry record does not report a primary-outcome p-value or state the test used. There is therefore no basis to characterize the primary result as statistically significant or not statistically significant.

Why does the single-group structure matter?

A comparison with baseline can show whether measurements differ over time within the observed group. It does not provide the counterfactual outcome: what the same participants' measurements would have been over that time without estrogen suppression. Without a concurrent comparison group, changes may reflect intervention exposure, time, measurement conditions, participant behavior, or other influences. Randomization and allocation to a control group are not described; the registry lists a single-group model and allocation as NA.

This limitation is distinct from statistical uncertainty. A confidence interval can quantify sampling uncertainty for an estimate, but it cannot remove systematic differences between a before-and-after comparison and a randomized comparison. Even a precisely estimated within-group change would not, by itself, prove that the intervention caused that change.

What can be learned from standard deviation?

In general, standard deviation describes the spread of individual observations around their mean. It is not the same as the uncertainty in the estimated mean. The standard error of a mean depends on both the variability of observations and the number of observations contributing to the estimate. For a paired change, the variation of the individual changes is relevant. The registry specifies standard deviation as the dispersion measure but does not report its value or how many participants contributed to each measurement.

Continuous outcomes can also have distributions that are skewed or contain influential observations. With a small group, summaries may be strongly affected by individual values. Inspection of the distribution and sensitivity analyses can be useful in general, but the registry record does not report individual-level data, diagnostic checks, or such analyses.

How should planning illustrations be read?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect; the record also distinguishes participant-per-arm planning for non-time-to-event outcomes from total-event planning for time-to-event outcomes. These are planning assumptions, not a description of this trial's single-group design. A planning illustration is not observed power, and it does not show that the study was designed with a particular power. No sample-size justification or trial-specific design calculation is reported in the registry record.

Because the primary outcome estimate is not reported, the observed effect underlying any such illustration cannot be evaluated from this record. Any projected planning values should not be interpreted as estimates of treatment effect, observed enrollment, or evidence that the trial can detect a clinically important difference.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcomes of cold induced thermogenesis, fat mass, fat free mass, and resting energy expenditure. It records 5 outcome measures and 5 analyses. The record does not explain whether these outcomes were all tested inferentially, whether some were exploratory, or which comparisons were prespecified. A statistical plan, including any approach to controlling multiplicity, is not reported in the registry record.

In general, examining multiple outcomes or analyses can increase the chance of obtaining at least one apparently notable result by chance if each is interpreted without regard to the others. Methods for addressing this issue depend on the prespecified questions and analysis plan. Since that plan and the outcome results are not reported, it is not possible to determine whether multiplicity was addressed or how it should affect interpretation.

The record does not describe missing-data handling, the number of participants with measurements at each time point, or whether analysis included all enrolled participants. Enrollment of 6 should not be assumed to equal the number contributing to every outcome analysis. General approaches to missing data make different assumptions, and the appropriate interpretation depends on why observations are missing and which method was used. Those details are not reported in the registry record.

The registry also does not state whether exclusions, protocol deviations, or sensitivity analyses occurred. Without these details, readers cannot assess whether the analyzed observations represent the enrolled group or whether conclusions depend on particular analysis choices.

11. 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 adverse-event record lists 0 serious adverse events among 6 participants at risk, 2 participants with other adverse events among 6 at risk, and 0 deaths in the Estrogen Suppression group. These counts are descriptive entries in the registry, not comparative risk estimates. The record does not provide event terms for the other adverse events, and it lists no top serious-event terms.

The serious-event count should be read as the number recorded in the specified group, not as proof that no serious event could occur. The registry does not give detailed information about event ascertainment, follow-up duration for safety, severity grading, relatedness to the intervention, or whether all participants completed safety follow-up. The listed at-risk count does not establish that every participant had identical observation time.

Because this is a single-group study, the figures do not compare event frequency with an untreated or active-control group. The counts therefore cannot establish whether the intervention caused or prevented an event, nor do they provide a precise estimate of uncommon harms. The record supports only a description of the reported counts and the limits of their interpretation.

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

The registry record describes a study designed to examine brown adipose tissue activity before and after estrogen suppression. Its broader rationale connects estrogen levels with the body's capacity to produce heat and with a possible pathway related to menopause-associated weight gain. That rationale is the question motivating the study, not a result established by the record.

The primary endpoint is SUV measured with PET/CT at baseline and after 3 months of suppression. The record provides an endpoint definition and measurement schedule, but does not report observed SUV values, an estimated change, uncertainty intervals, or a statistical test. Accordingly, it does not show whether activity changed, by how much it changed, or how precisely any change was estimated.

Even if a within-group change were reported, a single-group before-and-after design would not isolate the causal effect of estrogen suppression from other changes over time. A separate randomized comparator is not described. Statistical evidence about a within-group difference and evidence about a causal treatment effect are different questions.

The registry also does not report results for the listed secondary outcomes. Nor does it provide enough information to assess participant characteristics, missing observations, analysis populations, or the prespecified statistical approach. The absence of these details limits what can be inferred from the registry record; it should not be mistaken for evidence that no effects or events occurred.

The reported safety counts are similarly limited: the record lists no serious adverse events and no deaths, alongside 2 participants with other adverse events. Without event descriptions and a comparative group, these figures are descriptive rather than a basis for estimating comparative safety. Overall, the record clarifies the research question and planned measurement, but does not provide the outcome evidence needed to answer the primary question.

13. Why This Trial Matters Statistically

This study illustrates the distinction between specifying a biological question and reporting evidence that answers it. The registry identifies brown adipose tissue activity as the primary endpoint, states how it is to be measured, and gives a before-and-after schedule around estrogen suppression. Those details make the intended comparison understandable even though the observed results are not reported in the registry record.

The single-group structure is statistically important. Repeated measurements can be informative because each participant serves as their own baseline reference, but that structure does not replace a concurrent control group. A change over time may have several explanations, and statistical adjustment cannot recover the unobserved outcome that would have occurred without the intervention unless additional design or modeling assumptions are made.

The record also illustrates why reporting the estimate and its uncertainty matters. An endpoint name and a summary-statistic plan do not indicate the size, direction, or precision of an observed effect. Without those results, readers cannot judge whether measurements were consistent across participants or whether an average change may have been driven by individual observations.

Finally, planning illustrations must be separated from the actual design and results. The registry describes assumptions for a planning calculation, including equal allocation between two arms, while the recorded study model is single-group. Such assumptions do not establish the trial's power or explain its enrollment. Clear reporting of methods, analysis populations, outcome estimates, and uncertainty would be needed to connect the research question to a defensible statistical conclusion.

14. 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 most consequential limitation for interpreting this trial record is that the primary outcome result is not reported. The outcome definition and timing are available, but there are no observed SUV values, estimated changes, or measures of uncertainty. The listed secondary outcomes also lack reported results in the record.

The single-group before-and-after design has no separate comparator. Any observed temporal difference, if reported, could not on its own distinguish an intervention effect from other influences over time. The record does not describe randomization or a control condition, and it lists the study model as single-group.

Enrollment is recorded as 6, but participant characteristics and outcome-specific analysis counts are not reported. It is therefore not possible to determine how many participants contributed paired measurements or whether missing observations affected the analyses. Eligibility criteria, adherence, withdrawals, and protocol deviations are also not reported in the registry record.

The analysis methods are not described in enough detail to evaluate model choice, handling of repeated measurements, multiplicity, missing data, or sensitivity to influential values. The endpoint description also leaves unspecified whether total body weight or lean body mass was used for normalization of SUV. These gaps constrain reproducibility and assessment of measurement comparability.

Finally, the safety information is limited to aggregate counts, without event descriptions, attribution, or a comparison group. These limitations concern the available registry record and should not be taken as proof that the study did or did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Estrogen Deficiency on Energy Expenditure — NCT01846728.
• Registry record last updated 2019-11-18; status last verified 2019-10.
• Results first posted 2019-11-18.
• 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.

18. Record Summary

NCT01846728, titled “Effects of Estrogen Deficiency on Energy Expenditure,” is recorded as completed and sponsored by the University of Colorado, Denver. The registry lists enrollment of 6, obesity as the condition, and estrogen suppression using Lupron as the intervention. The design is single-group, with brown adipose tissue activity measured at baseline and after 3 months of suppression.

The primary endpoint is SUV measured using PET/CT, with mean and standard deviation specified. Secondary outcomes include cold induced thermogenesis, fat mass, fat free mass, and resting energy expenditure. The registry does not report the primary outcome results, secondary outcome results, detailed analysis methods, or analysis populations.

The adverse-event record lists 0 serious adverse events, 2 participants with other adverse events, and 0 deaths. These are descriptive counts without a concurrent comparator. The registry record establishes the study question and planned measurement, but does not provide results sufficient to estimate the observed change or its precision.