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 Hormone Replacement and Neural Cardiovascular Control in Postmenopausal Women (NCT01633814), a randomized na study. The primary outcome is Change in Carotid Baroreflex Sensitivity (Bpm/mmHg).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01633814 |
| Phase | NA |
| Condition | Menopause, Aging, Blood Pressure |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Missouri-Columbia |
| Results posted | Yes |
2. Clinical Question
Population
Older postmenopausal women. The registry lists menopause, aging and blood pressure among the conditions studied. Enrollment was four.
Intervention
Transdermal estradiol, described as a delivery rate of 100 µg day-1. The study summary also refers to estrogen combined with progesterone and progesterone alone, although these are not listed as registry interventions.
Comparator
A placebo patch. The record describes a randomized crossover design, but does not report the treatment sequence or further details about how periods were arranged.
Primary question
How does carotid baroreflex sensitivity change after the hormone conditions compared with placebo? The registry reports no results for this endpoint, so the treatment comparison cannot be assessed from the posted results.
The study rationale concerns blood pressure responses to exercise in older women. The registry summary says these responses may be exaggerated, and notes that a greater exercise-related blood pressure response has been associated with stroke and mortality in otherwise healthy individuals. It describes estrogen and progesterone as possible influences on cardiovascular responsiveness, with the arterial baroreflex and feedback from exercising muscle as potential mechanisms.
The stated research purpose includes examining baroreflex function and the exercise pressor reflex after hormone treatment and placebo. The registered primary outcome is narrower: change in carotid baroreflex sensitivity, measured in beats per minute per millimetre of mercury. The record does not establish whether any effect was observed, how large it was, or how uncertain an estimate might be. Those outcomes are not reported in the registry record.
3. Trial Design
The record describes a randomized, single-masked, crossover study sponsored by the University of Missouri-Columbia. It lists four participants as enrolled and gives a status of terminated. The study start is recorded as 2011-09 and primary completion as 2015-08. The reason for termination is not reported in the registry record.
In a crossover design, participants receive more than one study condition in sequence, so each participant may contribute measurements under multiple conditions. General statistical context: this structure can allow comparisons within the same participant, but the interpretation depends on treatment order, timing, and whether effects from an earlier condition persist into a later one. The registry record does not describe the sequence, period length, washout arrangements, or methods for addressing order or carryover effects.
The listed interventions are transdermal estradiol and placebo. Estradiol is described as having a delivery rate of 100 µg day-1, and the placebo as a patch. The study summary and primary outcome timeframe also mention estrogen plus progesterone and progesterone alone. How those conditions relate to the listed interventions is not reported in the registry record. The specific masking arrangement—such as who was masked—is also not reported.
The primary outcome timeframe refers to measurements within one week before and then after one month of transdermal estrogen alone, transdermal estrogen plus progesterone, progesterone alone, and placebo. The registry does not report the planned allocation sequence or enough detail to reconstruct the full treatment schedule. It also does not report a sample-size justification or the reason the study ended.
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 | Transdermal Estradiol or Placebo |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Results are not available due to all members of the study having left the institution and not having made results available.
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: Total enrollment was 4 women. Study was terminated prematurely early due to poor enrollment and the fact that the PI was moving to another institution. No data was analyzed.
| Characteristic | Unit | Transdermal Estradiol or Placebo |
|---|---|---|
| Participants analysed | 4 | |
| Age, Customized: 50 - 80 years of age | Participants | 0 |
| Sex: Female, Male: Female | Participants | — |
| Sex: Female, Male: Male | Participants | — |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Change in Carotid Baroreflex Sensitivity (Bpm/mmHg), measured over Within one week prior to and then after one month of transdermal estrogen alone, transdermal estrogen plus progesterone, progesterone alone and placebo..
| 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 outcome is change in carotid baroreflex sensitivity, expressed in beats per minute per millimetre of mercury. The registry describes measuring this sensitivity with neck pressure and neck suction. A variable-pressure collar is placed around the anterior two thirds of the neck to alter pressure across the carotid sinus.
In general, the baroreflex is a cardiovascular control mechanism that responds to changes in pressure. Measuring its sensitivity provides an estimate of how strongly heart-rate responses change in relation to a pressure stimulus. The study rationale identifies the arterial baroreflex as one potential mechanism influencing blood pressure during exercise, making its function relevant to the stated research question. This general rationale does not establish that a change in the measured endpoint would necessarily correspond to a particular clinical outcome.
The registry timeframe describes measurement within one week before and then after one month of the listed hormone conditions and placebo. The endpoint description does not give observed values, a treatment contrast, or a measure of uncertainty. It explicitly states that results are unavailable because all study members had left the institution and results had not been made available. Therefore, the direction and magnitude of any change are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry record contains no available primary outcome results. It identifies carotid baroreflex sensitivity as the primary endpoint and describes how it was to be measured, but supplies no outcome values or comparison estimates. There is consequently no posted estimate from which to describe the size or direction of a treatment difference, and no statistical uncertainty measure with which to judge precision.
The study enrolled four participants and is listed as terminated. These registry entries describe the record but do not explain why the study ended or establish whether the planned treatment conditions were completed. The reason for termination and the number of participants contributing to each outcome measurement are not reported in the registry record. Enrollment alone cannot establish that every enrolled participant contributed data to every condition.
The registry lists two outcome measures and zero analyses. Its primary outcome population text states that results are unavailable because all members of the study had left the institution and had not made results available. This is a lack of posted findings, not evidence that the treatments had identical effects or that the outcome did not change. No conclusion about the primary comparison can be drawn from the absence of results.
In general, an estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data under the statistical model and assumptions used. Neither an estimate nor a confidence interval is reported for this primary endpoint. A p-value, test statistic, and analysis model are also not reported in the registry record. Statistical significance, precision, and the contribution of individual participants therefore cannot be assessed from the posted information.
The crossover design could, in principle, support within-participant comparisons. General statistical context: those comparisons require measurements under the relevant conditions and a suitable account of treatment order and possible carryover. Since the record does not provide outcome data or the analysis approach, it is not possible to tell how the crossover structure was used or whether its assumptions were examined.
The registry rationale links exercise blood pressure, cardiovascular reflexes, and hormone levels as a research question. It does not report findings that confirm or refute those proposed relationships. Nor does the absence of findings show that either treatment is beneficial or harmful. The defensible reading is limited: this was a small, terminated registered study with an identified primary endpoint, but no available outcome results.
9. Statistical Methods Explained
What does a crossover design mean?
In general, a crossover study assigns participants to receive multiple conditions in sequence. Rather than comparing only separate groups of people, an analysis may compare measurements from the same participant under different conditions. This can account for stable differences between participants, provided the relevant measurements are available and the design and analysis appropriately handle the sequence of conditions.
For this study, the registry lists randomized allocation and a crossover model. It does not report treatment sequences, the number or duration of periods, washout arrangements, or the method used to account for order. Those details matter because responses in one period may be influenced by the condition received earlier. Whether this occurred, and how it would affect the results, cannot be assessed from the registry record.
What does randomization tell the reader?
In general, randomization uses a chance-based process to allocate treatment order or assignment. Its purpose is to reduce systematic differences associated with assignment. The record says the study was randomized but does not describe the sequence-generation method, concealment, or implementation. It therefore does not allow a detailed assessment of how randomization was carried out. The single-masked designation is also recorded, but who was masked is not reported.
What is the primary endpoint measuring?
The registered primary endpoint is change in carotid baroreflex sensitivity, with a unit of beats per minute per millimetre of mercury. The measurement description refers to applying neck pressure and neck suction with a variable-pressure collar. In general, a sensitivity measure relates a response to a stimulus; in this case, the endpoint is intended to characterize heart-rate response in relation to a pressure stimulus. The record describes a measurement method but gives no resulting values.
The timeframe refers to measurements within one week before and then after one month of four conditions: estrogen alone, estrogen plus progesterone, progesterone alone, and placebo. However, only transdermal estradiol and placebo appear in the listed interventions. The relationship between the additional conditions in the endpoint description and the listed interventions is not reported in the registry record.
How should planning calculations be understood?
In general, a sample-size calculation is a planning exercise that depends on assumptions about the effect to detect, variability, significance level, allocation, and statistical model. The record’s planning note describes a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of an observed effect. Such illustrations describe hypothetical planning scenarios; they are not observed power and do not establish that the study was designed with those assumptions.
The registry does not report a sample-size justification for the trial. It also reports no primary endpoint result from which the treatment effect or its variability could be assessed. Thus, a planning illustration cannot be read as evidence of an observed treatment effect or as a substitute for outcome data. The record does not report an interim analysis plan or any interim analysis results.
What can be inferred without an analysis?
In general, an analysis of a crossover endpoint would need to specify how the outcome is summarized and how the within-participant and treatment-period structure is handled. The record lists zero analyses and provides no statistical model, estimate, confidence interval, test statistic, or p-value for the primary endpoint. It is not reported whether the analysis would adjust for period, sequence, or other factors.
General statistical context: a confidence interval conveys uncertainty around an estimated effect; a point estimate alone does not show how precisely the effect is known. Neither is available for this outcome. The small enrollment and the lack of posted results leave no basis for evaluating the stability of an estimate, even if an analysis had been planned. No unadjusted recalculation can be made from the posted information because the required outcome summaries are absent.
10. Multiplicity, Missing Data and Analysis Populations
The record lists two outcome measures but does not report the complete outcome list or identify the second measure in the available details. It names carotid baroreflex sensitivity as the primary outcome. The number of analyses is listed as zero, and no analysis results or statistical plan are reported.
Multiplicity concerns arise in general when several outcomes, treatment contrasts, time points, or analyses are examined. Without a reported analysis plan, it is not possible to determine whether any multiplicity adjustment was planned or whether a particular result would have been designated as primary in the analysis. An adjustment method, if any, is not reported in the registry record.
The record does not describe missing-data handling, participant-level exclusions, or the analysis population. Although enrollment was four, the number contributing to each endpoint or treatment condition is not reported. The primary outcome text says that results were unavailable because all study members had left the institution and had not made results available. That statement explains why the registry has no findings; it does not describe participant-level missingness or establish why data were unavailable for each person.
In general, analysis populations may include all randomized participants, those receiving treatment, or participants with evaluable measurements, depending on the study plan. The registry does not specify which population was intended for the primary analysis. It also does not report whether participants completed all crossover periods. Consequently, the impact of incomplete data, exclusions, or deviations from the intended treatment sequence cannot be evaluated.
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 |
|---|---|---|---|
| Transdermal Estradiol or Placebo | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Transdermal Estradiol or Placebo | 0 of 4 |
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 |
|---|---|
| Transdermal Estradiol or Placebo | 0 of 4 |
The safety record lists a group titled “Transdermal Estradiol or Placebo.” Four participants were recorded as at risk for serious adverse events, with zero affected; four were recorded as at risk for other adverse events, with zero affected. Deaths are listed as zero. No serious adverse-event terms are listed.
These figures describe the registry’s recorded safety counts; they do not provide event descriptions, timing, severity beyond the serious-versus-other grouping, or an account of how events were collected. The record does not clarify how the combined estradiol-or-placebo group relates to the crossover periods, nor does it provide treatment-specific safety counts. No event counts should therefore be attributed separately to estradiol or placebo based on this entry.
In general, zero recorded events in a small study does not establish that an event cannot occur or that the treatments have equivalent safety. Such counts describe only the recorded participants and the safety information entered in the registry. The record does not report the safety observation period or additional details needed to interpret the completeness of event ascertainment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, single-masked crossover study was registered to examine hormone conditions and cardiovascular reflexes in older postmenopausal women. Its primary endpoint was change in carotid baroreflex sensitivity, and the record describes a neck-pressure and neck-suction measurement approach. It also records four participants enrolled and a terminated status.
It does not establish what happened to the primary endpoint. No values, treatment contrasts, uncertainty intervals, or analysis results are available. The result cannot be interpreted as showing an increase, a decrease, or no change in baroreflex sensitivity. Lack of posted results is not the same as a finding of no effect.
The registry rationale connects hormone levels with cardiovascular responses to exercise and identifies the baroreflex and exercise pressor reflex as possible mechanisms. Those statements explain the research question; they are not findings from this trial. The record does not report results for the exercise pressor reflex or enough information to evaluate any relationship between the proposed mechanisms and exercise blood pressure.
In general, an observed statistical difference would need to be interpreted in light of its magnitude, precision, study design, and data completeness. Those elements are unavailable for the primary outcome. The study’s small enrollment and terminated status further limit what can be learned from the record, but the extent of their effect on any planned analysis cannot be quantified because no analysis is posted.
Accordingly, the record supports a description of the study’s question, design labels, intervention descriptions, enrollment, and recorded safety counts. It does not support a conclusion that estradiol or placebo changed baroreflex sensitivity, nor does it establish a clinical benefit, harm, or absence of effect.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the distinction between a registered research question and an interpretable result. The record names a primary endpoint and gives a measurement description, but no primary outcome results are available. Without an estimate and its uncertainty, readers cannot judge the direction, magnitude, or precision of a treatment comparison.
The crossover model also makes design details important. General statistical context: repeated measurements within participants can be informative, but their interpretation depends on treatment sequence, timing, and the possibility that one condition affects measurements in a later period. Those details and the analysis method are not reported. The design label alone cannot show how the data were analyzed or whether period-related issues were addressed.
The enrollment of four and the terminated status provide context for the scale and completion of the study, but they do not reveal the number of usable measurements or why the study ended. The record’s absence of analysis results prevents assessment of whether the intended comparisons were estimable. It also prevents evaluation of precision or model assumptions.
The safety counts are similarly bounded: the registry records zero affected participants in the listed serious and other adverse-event categories, but does not give treatment-specific counts or further ascertainment detail. In general, such counts should not be mistaken for a complete estimate of risk.
Statistically, the most informative conclusion is about the limits of the record: it documents a focused mechanistic question and a planned endpoint, but does not make the treatment effects assessable. This distinction helps prevent missing results from being misread as evidence of no difference.
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 direct limitation is the absence of primary outcome results. The registry states that results are unavailable because all study members had left the institution and had not made results available. No endpoint values, treatment contrasts, uncertainty measures, or analysis results are reported.
Enrollment was four, and the study status is terminated. The reason for termination is not reported in the registry record. Nor does the record state how many participants completed each condition or contributed measurements to the primary endpoint. The enrolled count therefore cannot be treated as the number analyzed.
The design description is incomplete for evaluating the crossover structure. Treatment sequences, period timing, washout arrangements, and methods for handling order or carryover effects are not reported. The record identifies the study as single-masked but does not state who was masked. It also does not provide the randomization procedure or an analysis plan.
The intervention descriptions are not fully aligned: the listed interventions are transdermal estradiol and placebo, while the primary outcome timeframe and study summary also refer to estrogen plus progesterone and progesterone alone. How those conditions fit into the registered intervention structure is not reported. The second outcome measure is not described in the available record details.
Finally, the safety entry does not give treatment-specific counts, event timing, or the observation period. These omissions, together with absent outcome findings, prevent a detailed assessment of efficacy, safety, data completeness, and statistical precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hormone Replacement and Neural Cardiovascular Control in Postmenopausal Women — NCT01633814.
- Registry record last updated 2017-08-10; status last verified 2017-06.
- Results first posted 2017-08-10.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a randomized, single-masked crossover study sponsored by the University of Missouri-Columbia, with four participants enrolled and status listed as terminated. The study start is 2011-09 and primary completion is 2015-08. The reason for termination is not reported in the registry record.
The listed interventions are transdermal estradiol and placebo. The primary endpoint is change in carotid baroreflex sensitivity, measured using neck pressure and neck suction. The record reports that primary outcome results are unavailable. It lists zero analyses and two outcome measures.
Safety counts list four participants at risk and zero affected for serious adverse events, four at risk and zero affected for other adverse events, and zero deaths. No serious adverse-event terms are listed. The record does not provide treatment-specific safety counts or primary outcome estimates.