This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women (NCT01126801), a randomized phase 2 study. The primary outcome is Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01126801 |
| Phase | Phase 2 |
| Condition | Menopausal Depression |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Quadruple |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Early postmenopausal women, with and without frequent hot flashes. The registry lists menopausal depression as the condition. It does not report further eligibility details or how participants were classified by hot-flash frequency.
Intervention
Estradiol therapy. The registry does not report the dose, route, schedule, or duration of treatment.
Comparator
Placebo control. The record names this comparator but does not describe its formulation or administration.
Primary question
Whether mood, measured with the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS), improved from baseline to study end over one month. The protocol summary also frames hot flashes as a possible intermediary in menopause-associated depression.
The question combines a treatment comparison with an interest in whether frequent hot flashes help explain mood symptoms. The summary says the controlled study was intended to determine whether hot flashes were an important intermediary. However, the registry record does not report a formal mediation analysis, a comparison of hot-flash subgroups, or results that could address either question. It also does not state whether the primary mood comparison was planned separately within hot-flash groups.
Although the registry describes randomized estradiol and placebo arms, only one subject per arm had data collected, and those data were withheld to preserve privacy. No participants were analyzed. Thus the clinical question is clear at the level of the study’s stated purpose, but the posted record does not provide an answer about mood change or the role of hot flashes.
3. Trial Design
This was a Phase 2 study with randomized allocation and quadruple masking according to the registry. The interventions are listed as estradiol and placebo control, and the record’s summary describes a controlled study in early postmenopausal women with and without frequent hot flashes. Enrollment is recorded as 2. The study began in 2010-05, had primary completion in 2011-02, and is listed as terminated.
There is an important design-label inconsistency: the registry lists the model as single group while also listing randomized allocation and two named intervention arms. The record does not explain this discrepancy. The arm descriptions are blank, so details such as dose, treatment schedule, and how the arms were operationalized are not reported in the registry record. The meaning of quadruple masking is not explained, and the identities of the masked parties are not reported.
The primary outcome was mood improvement measured by clinician-rated MADRS from baseline to study end, with a one-month timeframe. A secondary outcome was improvement measured by the self-rated Beck Depression Inventory (BDI) over the same general baseline-to-end interval. The registry lists two outcome measures, but no analyses are posted.
Recruitment difficulty led to termination. The record states that data from only one subject per arm were collected and were not reported to preserve subject privacy. It also states that no participants were analyzed. Consequently, the planned randomized comparison did not yield a public outcome analysis. Details of the randomization procedure, allocation concealment, study visits, and the statistical plan are not reported in the registry record.
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
| Stage | Estradiol | Placebo |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: No participants were analyzed since the study was terminated due to difficulty recruiting subjects. Because data from only one subject per arm were collected, these data are not reported to preserve subject privacy.
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.
| Characteristic | Unit | Estradiol | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Continuous | years | 50 (SD 0) | 55 (SD 0) | 52.5 (SD 3.5) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Improvement of Mood, Measured by the Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) From Baseline to Study End., measured over one month.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was improvement in mood, measured using the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to study end. The registry gives the timeframe as one month. A change-based endpoint asks whether a participant’s measured mood symptoms differ between the starting assessment and the later assessment; the intended outcome is change over that interval, rather than a single score at one time alone.
In general, a clinician-rated scale can provide a structured way to assess mood symptoms across participants and visits. Using a baseline measure gives a reference point for describing subsequent change. Those are general features of change endpoints; the registry does not report the MADRS scoring details, assessment procedures, threshold for meaningful improvement, or exact calculation of the endpoint.
The outcome is relevant to the study’s stated focus on mood in early postmenopausal women. However, the posted record gives no MADRS values, change estimates, uncertainty intervals, or comparison between estradiol and placebo. Although the registry says one subject per arm had data collected, those data are not reported for privacy, and no participants were analyzed. The endpoint therefore describes what the study intended to measure, not a result demonstrating the size or direction of mood change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study intended to compare estradiol with placebo control and to examine mood in the context of frequent hot flashes. It does not report an outcome estimate for that comparison. The primary endpoint is identified as MADRS improvement from baseline to study end, but its numeric result is absent. The record says no participants were analyzed because the study was terminated after difficulty recruiting subjects.
Data were collected from one subject per arm, but those data were withheld to preserve subject privacy. This means the absence of posted outcome data should not be read as evidence that the groups had identical results, nor as evidence that mood improved or worsened. The direction and magnitude of any difference are unknown from the registry record. There is no reported confidence interval or other measure of precision. In general, a confidence interval indicates the range of effect sizes reasonably compatible with the data and analysis; without a reported estimate and interval, the precision of a treatment comparison cannot be judged.
Recruitment and the limited collected data also prevent meaningful assessment of variation across participants. A group average, even if it had been available, would not describe individual responses on its own. Here, no group-level result is posted at all. The registry’s enrollment figure is 2, but it separately states that no participants were analyzed. Enrollment should therefore not be mistaken for the number contributing to an analyzed treatment-effect estimate.
The stated scientific rationale includes whether hot flashes may be an intermediary in menopause-associated depression. The record does not report subgroup results by hot-flash frequency or a formal analysis of mediation. The study’s stated purpose therefore cannot be treated as evidence that hot flashes did, or did not, explain mood symptoms in the participants.
The safety entries list one subject at risk in each group, with zero serious adverse events and zero other adverse events recorded for each. These counts are descriptive registry entries, not a robust comparison of safety. Deaths are not reported in the registry record. The very small amount of collected data, the absence of reported outcomes, and termination for recruitment difficulty limit what can be inferred from both the efficacy and safety information.
Any sample-size material shown on the page should be read as planning illustration rather than evidence about the trial’s observed power or its original design. The record does not report a trial-specific sample-size justification. Because participant outcome data are withheld and no analysis is posted, readers cannot use the registry to verify an observed mood effect or judge its precision.
9. Statistical Methods Explained
The posted record identifies the study as randomized and quadruple masked, and it names estradiol and placebo control. Randomization is generally intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. Masking is generally intended to reduce the influence of treatment knowledge on participant experience, clinical care, or outcome assessment. These are general purposes, not descriptions of how this study implemented those safeguards. The randomization procedure, allocation concealment, and identities of the masked parties are not reported in the registry record.
What does the design label tell us?
The registry also labels the model as single group. That label sits uneasily beside the randomized allocation and the two named arms. The record does not explain whether the model label reflects a registry classification issue or a feature of the study design. It is therefore appropriate to report the labels as they appear, but not to resolve the inconsistency by guessing how participants were assigned or analyzed. Arm descriptions are blank, and details of estradiol and placebo administration are not reported.
What was intended to be measured?
The primary measure was improvement on clinician-rated MADRS from baseline to study end, over one month. The secondary measure was improvement on the self-rated BDI. In general, a baseline-to-follow-up outcome can be summarized as change within each group and then compared across groups. Alternatively, an analysis may compare follow-up values while accounting for baseline values. Those approaches can yield different estimates and require their own assumptions. The registry does not state which approach was planned, how scores were to be handled, or what constituted improvement.
The record lists two outcome measures and no analyses. It does not provide a model, test, effect measure, confidence-interval method, or missing-data procedure. The posted material also flags the primary outcome as having several categories or time points that were not reduced to one comparison. The record does not give enough detail to identify the categories or contrasts behind that flag. No single primary treatment-effect estimate is therefore to interpret.
How should uncertainty be understood?
In general, an estimate describes the effect seen in the analyzed data, while an uncertainty interval describes how imprecise that estimate may be. A small analyzed sample usually offers limited information about variation and can produce substantial uncertainty. In this study, the central limitation is more direct: no participants were analyzed and participant-level outcome data were withheld for privacy. There is no posted effect estimate or interval from which to assess uncertainty. It would be inappropriate to substitute an assumed effect or to infer that a lack of reported results means no effect.
Over-dispersion is a general concern when count data vary more than a simple statistical model expects; it can affect standard errors and inference for some count outcomes. The primary endpoint is a mood-scale change, and the record reports no analysis model or results. There is no basis in the registry record for saying that an over-dispersion adjustment was used or was relevant to the posted primary analysis. Likewise, no model assumptions can be checked from the unavailable data.
What do the planning illustrations mean?
Any sample-size calculations on the page are planning illustrations, not observed power and not evidence that the original study had a particular design target. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and effects defined as a stated fraction of the observed effect. For time-to-event tables, the stated convention is total events; for other tables, it is participants per arm. These general assumptions describe the illustrations, not a statistical plan reported for this trial. The trial’s own sample-size justification is not reported in the registry record.
A planning calculation asks how much information a hypothetical future study might need under specified assumptions. It does not show whether the present trial had adequate power, and it cannot repair missing outcome reporting. Where the observed effect used by an illustration is not visible in the posted endpoint results, readers cannot evaluate that input from this record. The calculations should not be interpreted as evidence that the treatment effect was observed with a particular degree of certainty.
Finally, the registry’s status and recruitment note matter for interpretation. The study was terminated because of difficulty recruiting subjects, and only one subject per arm had data collected. The record does not say that an interim efficacy analysis was conducted, and no interim analysis plan is reported. It also does not report protocol deviations, a prespecified analysis population, or a hierarchy for the primary and secondary outcomes. Those omissions do not establish what the investigators did outside the registry; they limit what can be concluded from the posted record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists MADRS improvement as the primary outcome and BDI improvement as a secondary outcome. It reports two outcome measures and zero analyses. It does not report a multiplicity strategy, such as how interpretation would account for examining more than one outcome or more than one contrast. The primary outcome is also flagged as having several categories or time points that were not reduced to one comparison. The record does not identify those categories or state which comparison would have been the principal one.
Multiplicity matters in general because repeated testing across outcomes, time points, or subgroups can increase the chance of apparently notable results arising by chance. That general concern cannot be quantified: the registry posts no outcome analyses and no statistical plan explaining which comparisons were intended. It would be speculative to describe a correction or testing hierarchy.
The analysis population is not described beyond the statement that no participants were analyzed. The registry says data from one subject per arm were collected, but not reported to preserve subject privacy. It does not describe the completeness of those data, reasons for any missing measurements, or how missing data would have been handled. Imputation, exclusion rules, and analysis of all randomized participants are not reported in the registry record. Therefore, there is no basis for assessing whether the reported population would have followed an intention-to-treat or another analysis principle.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Estradiol | 0 | 1 | 0.0% |
| Placebo | 0 | 1 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Estradiol | 0 of 1 |
| Placebo | 0 of 1 |
The registry’s adverse-event entries list one subject at risk in the estradiol group and one in the placebo group. For each group, the serious adverse-event count is 0 and the other adverse-event count is 0. The death entries are null, so deaths are not reported in the registry record. No serious adverse-event terms are listed.
These entries should be read as registry counts, not as evidence that either treatment has no safety risks. The record reports only one subject at risk per group, and it separately says that the study was terminated because of difficulty recruiting. With such limited exposure, the entries cannot characterize uncommon events or support a reliable comparison between groups. A zero count means no event was recorded in that category for the listed group; it does not establish that an event could not occur.
The record does not provide event definitions, observation duration for safety, or additional details about monitoring. Because deaths are not reported and outcome data were withheld for privacy, the safety information is especially limited. These figures describe what the registry lists and should not be used as a basis for treatment decisions.
12. What the Result Does, and Does Not, Mean
This record establishes that investigators planned a randomized, masked study of estradiol and placebo control in early postmenopausal women, with mood as the primary outcome and hot flashes as part of the scientific rationale. It also establishes that the study was terminated after difficulty recruiting subjects and that data from one subject per arm were collected but withheld to preserve privacy. No participants were analyzed.
It does not establish whether mood improved, whether estradiol and placebo differed, or whether hot flashes were an intermediary in menopause-associated depression. No primary outcome values, treatment-effect estimate, confidence interval, or analysis are posted. There is therefore no reported result whose direction or precision can be evaluated. Missing results are not the same as a finding of no difference, and the record does not justify claiming benefit, lack of benefit, or harm.
The very limited collected data also mean that the registry cannot show how well the planned comparison would generalize to a broader population. The record does not provide subgroup results for women with and without frequent hot flashes. Nor does it offer a formal test of the study’s proposed intermediary role for hot flashes. These questions remain unanswered by the posted results.
The adverse-event entries report zero serious and zero other adverse events in each group, with one subject at risk per group; deaths are not reported in the registry record. Those counts are too limited to characterize safety. Overall, the record is informative about the study’s purpose, design labels, termination, and reporting constraints, but it is not an interpretable efficacy or safety comparison.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a clearly stated research question and an answer that can be supported by posted data. The registry gives a focused clinical rationale: assess mood in early postmenopausal women and consider whether frequent hot flashes are relevant to menopause-associated depression. It names a primary mood measure and a comparison between estradiol and placebo control. Yet recruitment difficulty led to termination before an analyzable result was reported.
The record also demonstrates why design metadata must be read carefully. Randomized allocation and quadruple masking appear alongside a single-group model label, without an explanation of the inconsistency. Rather than infer an unreported design detail, readers must recognize what the record does and does not resolve. Clear reporting of allocation, masking, analysis populations, endpoint definitions, and planned contrasts is important for evaluating a trial’s methods.
Finally, the case underscores that zero posted analyses is not a null treatment finding. Data were collected from one subject per arm but withheld for privacy, and no participants were analyzed. Without effect estimates and uncertainty intervals, readers cannot assess magnitude or precision. The study is therefore a useful example of how recruitment feasibility, privacy, and incomplete outcome reporting can sharply limit the statistical conclusions available from a registry record, even when the intended clinical question is understandable.
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 principal limitation is that the study produced no participant analysis in the posted record. Although data were collected from one subject per arm, the registry says they were not reported to preserve subject privacy. The primary and secondary mood outcomes therefore have no posted values or treatment comparisons. This prevents assessment of effect direction, magnitude, and precision.
Recruitment difficulty led to termination. The record does not explain recruitment barriers beyond that statement, and it does not provide a recruitment flow or further information about participant characteristics. Enrollment is recorded as 2, but that figure should not be treated as an analyzed sample because the record explicitly states that no participants were analyzed.
Design information is incomplete. Randomized allocation and quadruple masking are listed, but the model is also described as single group. The registry does not explain the discrepancy, identify masked parties, or provide arm descriptions. Dose, route, treatment schedule, and allocation procedures are not reported in the registry record. The record also does not provide a statistical analysis plan, sample-size justification, missing-data methods, or multiplicity approach.
The primary endpoint is described as MADRS improvement over one month, but score details and the intended summary contrast are not reported. The registry flags multiple categories or time points without reducing them to one comparison. No subgroup analysis by hot-flash frequency or mediation result is posted. Safety counts are based on one subject at risk per group, and deaths are not reported. Together, these limits mean that neither the planned mood comparison nor the broader mechanistic question can be evaluated from the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Estrogen and Hot Flashes on Mood in Postmenopausal Women — NCT01126801.
- Registry record last updated 2017-10-20; status last verified 2017-09.
- Results first posted 2016-08-22.
- 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.
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18. Record Summary
This Phase 2 study of estradiol and placebo control in early postmenopausal women is listed as randomized and quadruple masked, with a single-group model label. It was terminated after difficulty recruiting subjects. Enrollment is recorded as 2; the registry says data from one subject per arm were collected but withheld for privacy, and no participants were analyzed.
The primary outcome was clinician-rated MADRS improvement from baseline to study end over one month. BDI improvement was listed as a secondary outcome. No analyses or outcome estimates are posted, so the treatment comparison and the proposed role of hot flashes in menopause-associated depression cannot be assessed. The adverse-event entries list zero serious and zero other events for one subject at risk in each group; deaths are not reported in the registry record.