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 The Effects of Aging and Estrogen on the Pituitary (NCT00386022), a randomized phase 2, phase 3 study. The primary outcome is Pituitary Response to GnRH.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00386022 |
| Phase | Phase 2, Phase 3 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Younger and older postmenopausal women. The registry record describes the condition as healthy and lists 19 participants enrolled.
Intervention
Graded doses of GnRH after administration of the GnRH antagonist NAL-GLU, with or without a transdermal estrogen patch.
Comparator
The record identifies younger and older postmenopausal women as the groups, and describes treatment with or without an estrogen patch. It does not report a single direct comparison or the detailed assignment sequence for these conditions.
Primary question
How do aging and low-dose estrogen relate to the pituitary response to GnRH, measured by peak-to-nadir changes in LH and FSH after GnRH doses?
The study focuses on pituitary response rather than a clinical disease outcome. Its stated purpose is to examine how hypothalamic signaling to the pituitary and the resulting secretion of reproductive hormones change with aging. The listed primary outcome describes baseline LH and FSH responses to each of 4 GnRH doses, expressed as percent change from nadir to peak. The stated timeframe is the peak hormone level within 2 hours after GnRH doses.
The arm descriptions indicate that both younger and older postmenopausal women received graded GnRH doses after NAL-GLU administration, with or without a transdermal estrogen patch. The registry record does not specify a single outcome contrast that combines these groups and treatment conditions. It also does not provide numerical response estimates, so the direction and magnitude of any age- or estrogen-associated difference are not reported in the registry record. The question can therefore be described from the study design and outcome definition, but not answered quantitatively from the posted results.
3. Trial Design
The registry record identifies this as a randomized study with no masking and a sequential model. Its phase is listed as Phase 2 and Phase 3. Enrollment is 19, and the condition is described as healthy. The record names Massachusetts General Hospital as sponsor. The study start is listed as 2002-01 and primary completion as 2012-01; its status is recorded as unknown.
The two named groups are younger postmenopausal women and older postmenopausal women. For both, the intervention description includes graded doses of GnRH following administration of the NAL-GLU GnRH antagonist, with or without a transdermal estrogen patch. The listed interventions are GnRH, NAL-GLU GnRH antagonist, and estrogen patch. These descriptions establish the broad intervention components, but do not specify the detailed sequence, timing, dose levels, or allocation of each treatment condition. Those details are not reported in the registry record.
Randomization indicates that chance was used in assigning at least some aspect of the study, but the record does not explain what was randomized or how assignments were generated. No masking means the study is recorded as unmasked; the record does not say which people knew treatment assignments. The sequential model is named, but its operational meaning, visit order, and any rules for moving between conditions are not reported in the registry record. These omissions limit reconstruction of the exact comparison and of how repeated responses were collected.
The primary outcome description refers to responses across 4 GnRH doses and identifies LH and FSH. The record lists 2 outcome measures and 8 analyses, while noting that the primary outcome has several categories or time points and is not reduced to one comparison. Consequently, the design is better understood as a set of physiological response measurements across conditions than as a record containing one clearly specified numerical treatment contrast.
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.
Baseline
| Stage | Younger PMW | Older PMW |
|---|---|---|
| STARTED | 10 | 9 |
| All Doses of GnRH | 10 | 9 |
| COMPLETED | 10 | 9 |
| NOT COMPLETED | 0 | 0 |
Plus Estrogen
| Stage | Younger PMW | Older PMW |
|---|---|---|
| STARTED | 10 | 9 |
| Estrogen Patch | 8 | 9 |
| All Doses GnRH | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 2 | 1 |
Reasons for not completing this period:
| Reason | Younger PMW | Older PMW |
|---|---|---|
| Lost to Follow-up | 2 | 0 |
| Adverse Event | 0 | 1 |
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: Healthy postmenopausal women who experienced their last menstrual period a minimum of 12 months previously and met all inclusion and exclusion criteria.
| Characteristic | Unit | Younger PMW | Older PMW | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 9 | 19 | |
| Age, Continuous | years | 52.9 (SD 2.46) | 72.8 (SD 2.88) | 61.9 (SD 10.6) |
| Sex: Female, Male: Female | Participants | 10 | 9 | 19 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 7 | 9 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 10 | 9 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Pituitary Response to GnRH, measured over Peak hormone level within 2 hours post GnRH doses.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | Percent change |
| Endpoint classification | Continuous Endpoint |
The listed primary outcome is titled “Pituitary Response to GnRH.” It measures LH and FSH responses to each of 4 GnRH doses. The response is described as the peak-to-nadir amplitude expressed as percent change from nadir, with the peak hormone level assessed within 2 hours after GnRH doses. The outcome parameter is a mean, and the stated dispersion measure is the standard error.
These hormones are used in this study as indicators of the pituitary’s response to GnRH stimulation. Measuring the change from nadir to peak describes the size of the measured response within the specified timeframe. Considering different GnRH doses can describe how the response varies across stimulation levels; examining younger and older groups and conditions with or without estrogen relates the response to the study’s aging and estrogen questions. This is a general explanation of the measurement’s statistical and physiological role, not a claim about the findings.
The registry record does not give the numerical means or standard errors for these responses. It also does not provide a single contrast, estimate of between-group difference, confidence interval, or p-value. Since the outcome encompasses hormone measures, dose categories, and time-related details, its definition alone cannot establish the direction or precision of an age or estrogen association. Numerical primary-outcome results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives a clear description of the intended physiological measurement but does not report numerical primary-outcome results. It identifies mean responses and standard errors for LH and FSH after each of 4 GnRH doses, with peak hormone levels assessed within 2 hours. It does not state the observed means, standard errors, between-group contrasts, confidence intervals, or p-values. As a result, the posted results do not establish whether responses differed by age or by estrogen condition, nor how large or precise any such difference might be.
The outcome is not a single comparison in the registry record. It includes multiple hormone and dose categories, and the record notes that the primary outcome has several categories or time points and is not reduced to one comparison. This matters for interpretation: a conclusion depends on which response is compared, which group or condition is the reference, and whether the comparison accounts for the set of measurements. The relevant comparison specification and numerical analyses are not reported in the registry record.
The words “mean” and “standard error” describe the planned or recorded summary format, but do not by themselves communicate the observed response or its uncertainty. In general, a mean summarizes a group’s average measurement, while a standard error describes the precision of an estimated mean. It is not a measure of how much individual measurements vary. Without the actual estimates and their context, readers cannot assess precision or determine whether an apparent difference is compatible with a range of values.
The enrollment of 19 gives the overall number recorded as enrolled, while the safety groups list 10 younger and 9 older participants at risk. These counts do not supply the number contributing to each hormone analysis, and the analysis populations are not reported in the registry record. The record lists 8 analyses but does not describe which participants or observations were included in each one.
Thus, the statistical interpretation must remain limited to the outcome definition, the design labels, and the safety counts. The absence of reported primary-outcome estimates is not evidence that there was no difference. It means the magnitude, direction, and precision of the physiological response comparisons cannot be determined from the registry record.
9. Statistical Methods Explained
The registry record identifies a continuous outcome summarized by a mean and standard error. The primary response is described as peak-to-nadir amplitude expressed as percent change from nadir. This is a summary of a measured hormone response, rather than a count of events or a time-to-event outcome. No numerical outcome estimate is reported in the registry record, so there is no reported mean or standard error to interpret for the primary measure.
What does a mean describe?
In general, a mean is an average across the observations included in an analysis. For this study, the outcome description concerns LH and FSH responses after GnRH doses. An average can summarize the group response, but it does not show the full range of individual responses. The registry record does not give the underlying observations or the number included in each hormone, dose, age, or estrogen-condition analysis.
What does a standard error describe?
In general, a standard error describes the precision of an estimated mean: smaller standard errors indicate less sampling uncertainty in that estimate, while larger standard errors indicate more. It should not be read as the spread of individual measurements. A standard deviation is typically used to describe individual-level spread; no standard deviation is reported in the registry record. Nor are confidence intervals reported. Without the mean and its standard error, the degree of precision cannot be assessed for the primary outcome.
Why does the response definition matter?
The outcome uses the peak-to-nadir amplitude, expressed as percent change from nadir, and specifies a peak hormone level within 2 hours after GnRH doses. In general, a response measure depends on how the starting or reference value and the peak are defined. The registry record describes the measure but does not provide the values used to obtain each response or numerical estimates for the resulting summaries. The endpoint definition therefore supports understanding of what was intended to be measured, not reconstruction of the observed response.
How should the multiple response categories be understood?
The outcome description includes LH and FSH, responses to each of 4 GnRH doses, and a stated timeframe. The registry record lists 2 outcome measures and 8 analyses, and says the primary outcome has several categories or time points and is not reduced to one comparison. In general, multiple analyses can address distinct scientific questions, but interpretation requires knowing which contrast each analysis estimates. The record does not report those contrast definitions or the numerical results. It also does not report whether any adjustment for multiple comparisons was used.
Multiplicity is a general statistical concern when many outcomes, time points, or comparisons are examined: the chance of a nominally notable result can increase if the set of analyses is not accounted for. This does not mean an adjustment was necessarily required or omitted in this study. The analysis plan and any multiplicity procedure are not reported in the registry record, so the approach cannot be evaluated.
What does randomization contribute?
In general, random assignment can reduce systematic differences between assigned groups, provided the allocation process is appropriate and the analysis respects it. The study is labeled randomized, but the record does not specify what aspect of the sequential study was randomized, how allocation was generated, or how assignments were concealed. No masking is recorded. These labels alone do not establish the details of implementation or the comparability of the analyzed groups.
The sample-size assumptions describe a planning illustration, not an observed-power calculation or a report of the trial’s design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The record says such illustrations for this type of outcome are expressed as participants per arm. It does not report the trial’s own sample-size justification, the effect fractions, or numerical planning results. These planning assumptions should not be mistaken for evidence about the study’s actual power or findings.
No inferential test, adjustment method, model specification, or handling of repeated hormone responses is described in the registry record. General methods for continuous outcomes may include comparisons of means or models that account for repeated measurements, but naming a sequential design and a mean summary does not establish which method was used. The actual statistical analysis plan and its implementation are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 2 outcome measures and 8 analyses. It describes the primary outcome as having several categories or time points and explicitly does not reduce it to one comparison. The listed hormone responses span LH and FSH and each of 4 GnRH doses. The particular contrasts represented by the 8 analyses are not reported in the registry record.
Whether and how the analyses accounted for multiplicity is not reported in the registry record. In general, examining multiple outcomes or comparisons can complicate interpretation because each test addresses a different question, and unadjusted tests can make chance findings more likely across a collection of tests. This general issue does not establish that any particular adjustment was required or that the study did or did not use one. Without the analysis plan and reported estimates, readers cannot assess how multiplicity was handled.
Missing-data procedures are not reported in the registry record. It does not state whether any hormone measurements were missing, how missing observations were treated, or whether participants with incomplete measurements were included in particular analyses. The analysis populations are also not reported. The enrollment count and safety-group denominators should not be assumed to equal the number contributing to every outcome analysis.
The record does not describe an intention-to-treat population, a per-protocol population, or another named analysis set. It also does not report sensitivity analyses for missing data. These omissions prevent assessment of whether the reported analyses, if any, retained participants according to their randomized assignment or used another inclusion rule. Because the numerical primary-outcome results and analysis details are not reported in the registry record, the effects of missingness, exclusions, and multiple testing 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 |
|---|---|---|---|
| Younger PMW | 0 | 10 | 0.0% |
| Older PMW | 1 | 9 | 11.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Younger PMW | 0 of 10 |
| Older PMW | 0 of 9 |
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 |
|---|---|
| Younger PMW | 2 of 10 |
| Older PMW | 0 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Younger PMW | Older PMW |
|---|---|---|---|
| New Onset Rapid Atrial Fibrillation | Cardiac disorders | 0 of 10 | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Younger PMW | Older PMW |
|---|---|---|---|
| fall | Musculoskeletal and connective tissue disorders | 1 of 10 | 0 of 9 |
| genital herpes diagnosis | Infections and infestations | 1 of 10 | 0 of 9 |
Serious events with the highest arm-level rate: new onset rapid atrial fibrillation (11.1%).
The safety record lists serious adverse events and other adverse events separately for younger and older postmenopausal women. In the younger group, 0 of 10 participants at risk had a serious adverse event, and 2 of 10 had an event in the “other” category. In the older group, 1 of 9 participants at risk had a serious adverse event, and 0 of 9 had an event in the “other” category. Deaths are listed as 0 in both groups. These are the registry’s reported counts; the record does not give further definitions for the “other” category.
The listed top serious-event term is “New Onset Rapid Atrial Fibrillation,” with 11.1% reported. The registry record does not provide additional event-level context, timing, attribution, or a comparison adjusted for other factors. A count or percentage describes events recorded in the study groups; by itself, it does not establish that an intervention caused an event or that the groups differ reliably in risk. With the safety information limited to these counts and the listed term, broader conclusions about safety are not supported by the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study’s question, broad design, outcome definition, and some safety counts. It describes a randomized, unmasked, sequential study of younger and older postmenopausal women and a pituitary response to GnRH, with estrogen patch conditions included in the intervention descriptions. It does not provide numerical primary-outcome results. Therefore, the record does not show the direction, size, or precision of any age-related or estrogen-related difference in LH or FSH response.
This distinction is important: a missing numerical result is not a null result. Without outcome estimates and uncertainty measures, it is not possible to conclude that responses were the same, different, or meaningfully related to the intervention conditions. The listed safety counts provide limited descriptive information, but do not establish a causal connection between a treatment and an event.
The endpoint is a physiological measurement rather than a reported clinical outcome. In general, a measured hormone response can address a biological question without directly answering questions about symptoms, disease, or other outcomes that are not listed. The registry record does not report such outcomes or provide evidence about their effects.
The study’s enrollment and design labels also do not substitute for the missing analyses. The record does not report which participants contributed to each hormone analysis, the analysis methods, confidence intervals, p-values, or multiplicity handling. Conclusions should therefore be confined to what is documented: the study was intended to examine pituitary responses in relation to aging and estrogen, and its registry entry contains limited safety counts. The main response findings are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because its stated question concerns a measured biological response across age groups and estrogen conditions, rather than a single conventional clinical outcome. The primary outcome description includes LH and FSH, responses to each of 4 GnRH doses, and a peak hormone level within 2 hours. That structure makes the analysis question dependent on which hormone, dose, group, and condition are being compared.
General statistical interpretation benefits from separating the outcome’s definition from its results. A mean and standard error can describe an average response and its precision, but they are useful only when the estimates and the analysis populations are reported. The registry record provides the summary format without numerical primary-outcome estimates. Consequently, the biological question is identifiable, but the evidence needed to judge the observed response and its uncertainty is not available in the registry record.
The study also illustrates why a collection of response categories requires transparent contrast definitions and a clear account of multiplicity. The registry lists 8 analyses and notes that the primary outcome has several categories or time points, but does not report the analysis details or any multiplicity procedure. That limits the ability to distinguish a prespecified primary comparison from additional analyses.
Finally, the safety counts illustrate the difference between descriptive reporting and causal inference. Counts can document events within groups, but interpretation depends on definitions, follow-up, and context that are not fully described in the registry record. The statistical importance of the entry lies in the questions it sets up and in the need for complete outcome and analysis reporting to evaluate them.
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 main trial-specific limitation for statistical interpretation is that numerical primary-outcome results are not reported in the registry record. Although the outcome is defined as mean LH and FSH response with standard error, the actual estimates, their uncertainty, and the relevant between-group or between-condition contrasts are absent. The direction and magnitude of the response comparisons therefore cannot be assessed.
Enrollment is 19, and the safety groups list 10 younger and 9 older postmenopausal women at risk. The registry record does not report the number contributing to each hormone analysis. It is not possible to determine from these counts whether every participant contributed complete measurements across the doses and conditions.
The primary outcome includes several categories or time points and is not reduced to one comparison. The record lists 8 analyses but does not identify the contrasts, statistical models, or any adjustment for multiple comparisons. It also does not describe missing-data handling, the analysis populations, or sensitivity analyses. These gaps limit reproducibility and make it difficult to evaluate how the analyses relate to the stated question.
Although the design is labeled randomized and sequential, the randomization process and sequence are not described in detail. Masking is recorded as none, but the record does not identify who knew assignments. Doses, timing, and detailed allocation across conditions are not reported in the registry record. The study status is listed as unknown. These are limitations of the available registry description; they do not establish what was or was not done outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effects of Aging and Estrogen on the Pituitary — NCT00386022.
- Registry record last updated 2017-04-13; status last verified 2017-04.
- Results first posted 2017-04-13.
- 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
NCT00386022 is a randomized, unmasked, sequential study listed as Phase 2 and Phase 3, with 19 participants enrolled. It concerns younger and older postmenopausal women and examines pituitary responses after graded GnRH doses following NAL-GLU GnRH antagonist administration, with or without a transdermal estrogen patch.
The primary outcome is described as mean LH and FSH peak-to-nadir amplitude, expressed as percent change from nadir, with peak hormone level assessed within 2 hours after GnRH doses. The record lists 2 outcome measures and 8 analyses but does not report numerical primary-outcome results or a single comparison. Safety counts include 1 serious adverse event in the older group and none in the younger group, with 0 deaths in both groups. The study status is unknown, and key analysis details are not reported in the registry record.