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 Reproductive Hormonal Alterations in Obesity (NCT01457703), a non-randomized na study. The primary outcome is Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01457703 |
| Phase | NA |
| Condition | Obesity |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 62 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled women with obesity and women in a normal-weight BMI range. The arm descriptions specify BMI ≥30 kg/m2 for the obesity group and BMI 18-25 kg/m2 for the normal-weight group. Both groups were described as having a history of regular menstrual cycles, with different cycle-length ranges in the arm descriptions. The primary Aim 1 outcome description says 10 women in each BMI group completed the procedures and contributed data for those analyses.
Intervention
This was a physiological investigation using medications to probe reproductive hormone responses, not a randomized comparison of therapies. Aim 1 used gonadorelin-GnRH, the GnRH antagonist cetrorelix, and recombinant LH. Aim 2 used GnRH or gonadorelin and letrozole. The study description explains that medication challenges were intended to assess pituitary hormone responses and responses related to estrogen feedback.
Comparator
The comparison was between the BMI-defined groups: women with obesity and women in the normal-weight range. Allocation was nonrandomized and masking was absent. The groups therefore should not be read as randomized treatment arms or as like-for-like controls. The registry record describes comparisons between the groups but does not report adjustment for differences between them.
Primary question
The primary Aim 1 question was whether LH pulse amplitude differed between the obese and normal-weight groups during a 12 hour study visit. LH pulse amplitude was measured hourly and averaged over the visit. The study's broader aims concerned reproductive hormone regulation, including pituitary sensitivity and estradiol negative feedback. The registry record does not report the observed LH pulse-amplitude values or an estimate of the between-group difference, so the direction and precision of the primary comparison cannot be assessed from the posted results.
3. Trial Design
This completed study, registered as NCT01457703, is titled “Reproductive Hormonal Alterations in Obesity.” It was conducted by the University of Colorado, Denver. The registry lists a start of 2010-06 and primary completion in 2013-07. The listed phase is NA. Its design is nonrandomized, parallel, and unmasked. These features describe a group-comparison physiology study rather than a randomized trial assigning participants to competing treatments.
The two groups were defined by BMI: BMI ≥30 kg/m2 and BMI 18-25 kg/m2. The arm descriptions also specify regular menstrual-cycle histories, with cycles every 25-40 days in the obesity group and every 25-35 days in the normal-weight group. The registry lists enrollment of 62. That enrollment figure should not be confused with the population contributing to the primary Aim 1 analyses: the outcome description states that 10 obese and 10 normal-weight women completed the Aim 1 procedures and contributed data for those analyses.
The study had two aims. Aim 1 used gonadorelin-GnRH, cetrorelix, and recombinant LH. Aim 2 used GnRH or gonadorelin and letrozole. The stated hypotheses concerned pituitary sensitivity to exogenous GnRH, clearance of exogenous LH, and sensitivity to estradiol negative feedback. These interventions were used as physiological probes; the registry does not describe random assignment between medication regimens.
The primary outcome was change in LH pulse amplitude in Aim 1. The registry also lists changes in FSH in Aim 1 and Aim 2 among the secondary outcomes. Further details about the sequence and timing of each medication procedure, eligibility criteria beyond the listed BMI and menstrual history, and handling of participants who did not complete procedures 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 | BMI ≥30 kg/m2 | BMI 18-25 kg/m2 |
|---|---|---|
| STARTED | 29 | 33 |
| COMPLETED | 23 | 22 |
| NOT COMPLETED | 6 | 11 |
Reasons for not completing this period:
| Reason | BMI ≥30 kg/m2 | BMI 18-25 kg/m2 |
|---|---|---|
| Screen Failure | 5 | 7 |
| Withdrawal by Subject | 1 | 4 |
Analysis population for the primary outcome, as defined in the registry: This study was divided into two aims, and 10 obese and 10 normal weight women completed the study procedures and contributed data for analyses related to Aim 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.
| Characteristic | Unit | BMI ≥30 kg/m2 | BMI 18-25 kg/m2 | Total |
|---|---|---|---|---|
| Participants analysed | 29 | 33 | 62 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 29 | 33 | 62 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Gender: Female | Participants | 29 | 33 | 62 |
| Gender: Male | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 5 | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 24 | 28 | 52 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 | 6 | 14 |
| Race (NIH/OMB): White | Participants | 15 | 19 | 34 |
| Race (NIH/OMB): More than one race | Participants | 2 | 6 | 8 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 | 2 | 5 |
| Region of Enrollment: United States | participants | 29 | 33 | 62 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1), measured over Measured hourly and averaged over the 12 hour study visit.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Inter-Quartile Range |
| Unit | IU/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is LH pulse amplitude in Aim 1. LH is a pituitary hormone involved in reproductive function, and pulse amplitude describes the size of hormone pulses rather than simply the average concentration across all measurements. The registry says LH pulse amplitude was measured hourly during a 12 hour study visit, then averaged over that visit, with the obese and normal-weight groups compared.
Repeated measurements across a visit can characterize a changing hormone pattern that a single measurement might not capture. Averaging the hourly amplitude measurements gives a participant-level summary for the visit, which can then be compared between the BMI groups. The endpoint is therefore relevant to the study's stated question about reproductive hormone regulation and its hypothesis concerning pituitary responses.
The registry identifies the unit as IU/L, the parameter as mean, and the dispersion as inter-quartile range. These labels describe how the outcome was intended to be summarized; the actual group summaries are not reported in the registry record. No numerical estimate of the difference, confidence interval, or statistical test for the primary outcome is reported there. The endpoint's measurement description can therefore be understood, but its observed between-group result and precision cannot be evaluated from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint is clearly described, but its observed results are not. The registry record gives no group-specific LH pulse-amplitude summary, no estimated difference between the groups, and no confidence interval or p-value for Aim 1. It is therefore not possible to determine from the posted results whether LH pulse amplitude was higher, lower, or similar in one group, or how precisely a difference was estimated. The outcome description reports that participants completed the Aim 1 procedures, but it does not supply outcome values.
The study's stated hypotheses provide context, not findings. They propose that obese women may have reduced pituitary sensitivity to exogenous GnRH with normal clearance of exogenous LH, and increased sensitivity to estradiol negative feedback that would be reversed by an aromatase inhibitor. The registry record does not report results for those hypotheses. The listed secondary outcomes are changes in FSH in Aim 1 and Aim 2; their observed values and statistical comparisons are likewise not reported in the registry record.
General statistical interpretation: a group difference is an estimate based on observed measurements, while a confidence interval describes the range of values compatible with the data under the method's assumptions. A p-value addresses compatibility with a specified null model; it does not describe the size or clinical importance of an effect. None of those inferential quantities for the primary endpoint appears in the registry record, so no claim about statistical significance, effect size, or precision is justified.
The study was nonrandomized and unmasked. As a general matter, observed differences between nonrandomized groups can reflect both the feature defining the groups and other differences between participants. Random allocation is one way to reduce some sources of confounding, but it was not used. The registry record does not report an adjusted analysis or a plan for controlling confounding, so any causal interpretation would go beyond the record.
The registry lists enrollment of 62, while its primary outcome description identifies 10 obese and 10 normal-weight women who completed the Aim 1 procedures and contributed data for those analyses. These figures refer to different stated aspects of the record and should not be treated as interchangeable. The registry does not explain the relationship between the overall enrollment and the Aim 1 analysis population. No sample-size justification is reported. Any sample-size illustrations based on the observed effect are planning illustrations, not observed power and not a substitute for the missing result estimates.
9. Statistical Methods Explained
The registry record describes a nonrandomized, parallel-group study and gives a primary outcome definition, but it does not report the primary outcome results or a statistical analysis plan. General explanations below clarify how the stated measurements and common statistical tools are interpreted; they do not imply that a particular method was used in this study.
What does an average of repeated measurements represent?
The primary outcome was measured hourly during a 12 hour visit and averaged over the visit. In general, summarizing repeated measurements can make a series of observations easier to compare between participants. The resulting summary represents the measured pattern over that visit, not every fluctuation or measurement taken separately. This distinction matters for a hormone that is described in terms of pulses: an average pulse-amplitude summary is not the same thing as a single LH concentration measured at one time.
The registry lists the endpoint parameter as mean and its dispersion as inter-quartile range. A mean describes a central value through averaging, while the inter-quartile range describes the spread across the middle portion of a distribution. They provide different information: the mean characterizes location, and the inter-quartile range characterizes variability. The registry does not report the actual summaries, so their values and the distribution of participant-level measurements cannot be assessed.
What would a between-group estimate show?
In general, a between-group estimate expresses the observed contrast in an outcome between the groups being compared. The estimate's scale and direction depend on how the comparison is defined. A confidence interval adds information about precision by showing a range of values compatible with the data and analysis assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. A confidence interval does not establish that an effect is important, and it does not remove bias arising from study design or measurement.
No between-group estimate or confidence interval for the primary outcome is reported in the registry record. Thus, the endpoint definition alone cannot establish either the magnitude or direction of a difference. Nor can the listed sample population be used to infer a p-value or the precision of an estimate.
Why does nonrandomized allocation matter?
As a general statistical principle, randomization can make measured and unmeasured participant characteristics more comparable across assigned groups, on average. Here, group membership was defined by BMI and allocation was nonrandomized. Consequently, any group contrast could be associated with other characteristics that differ between the groups. Adjustment for measured covariates can sometimes address some observed differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report covariate adjustment, matching, stratification, or another method to address this issue.
Masking is listed as absent. In general, lack of masking can affect some aspects of measurement or conduct, depending on the outcome and procedures. The registry does not explain whether measurement personnel were aware of group status or how potential observer effects were managed. Because LH pulse amplitude is a laboratory-measured outcome, its specific susceptibility to such effects cannot be determined from the record.
How should sample-size illustrations be read?
General sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions about variability, significance level, allocation, and analysis. The registry's stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect expressed as a fraction of the observed effect. These are planning assumptions, not a report of the study's original design justification.
A sample-size illustration based on an observed effect is retrospective and conditional on that observed estimate. It does not show the probability that the completed study detected an effect, and it is not observed power. No sample-size justification is reported in the registry record. The record also does not report the statistical test, the model used to estimate the primary contrast, or any method for deriving uncertainty intervals.
What does over-dispersion mean in general?
For count outcomes, over-dispersion means that the observed variability exceeds what a simple model assumes. A model that ignores such extra variability may give uncertainty estimates that are too small. This study's stated primary outcome is a continuous hormone measure, not a count endpoint, and the registry does not report an over-dispersion model or a model for the primary analysis. The general concept should not be taken as evidence that it applied to the reported analysis.
Overall, the registry supports a description of the endpoint and study design, but not a reconstruction of the statistical analysis. The actual summaries, model specifications, inferential results, and diagnostic checks are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study describes two aims and lists a primary LH outcome for Aim 1, along with secondary FSH outcomes in Aim 1 and Aim 2. The brief description also states two hypotheses involving responses to GnRH, LH clearance, and estradiol negative feedback. When a study examines multiple outcomes or hypotheses, the chance of obtaining at least one apparently unusual result can increase if each is tested separately. General approaches to address multiplicity include designating a primary analysis in advance, adjusting inference across a family of tests, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy or explain how the stated hypotheses and outcome measures were grouped for inference.
The primary outcome description identifies the Aim 1 contributing population as 10 obese and 10 normal-weight women who completed the procedures. The registry does not give equivalent analysis-population information for each secondary outcome. It also does not report how missing observations, incomplete visits, or participants who did not complete procedures were handled. The relation between overall enrollment and the primary Aim 1 population is not explained in the registry record.
No intention-to-treat or per-protocol analysis population is specified. Because allocation was nonrandomized, an intention-to-treat framework for assigned interventions is not directly described by the record. The registry also does not report an interim-analysis plan, missing-data assumptions, imputation method, or sensitivity analyses. These absences limit the ability to assess whether the posted outcome population and any analyses would be vulnerable to selection or missing-data bias. They do not establish that such procedures were or were not performed outside the registry record.
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 |
|---|---|---|---|
| BMI ≥30 kg/m2 | 0 | 29 | 0.0% |
| BMI 18-25 kg/m2 | 0 | 33 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BMI ≥30 kg/m2 | 0 of 29 |
| BMI 18-25 kg/m2 | 0 of 33 |
The registry lists serious adverse events for the BMI ≥30 kg/m2 group and the BMI 18-25 kg/m2 group. For each group, 29 participants are listed as at risk and 0 as affected by a serious adverse event. The other adverse-event fields also list 29 and 33 participants at risk, respectively, with 0 affected in each group. These figures describe the registry's recorded event counts; they do not demonstrate that no event could occur or that the groups have equivalent safety profiles.
The registry lists no serious adverse-event terms. Death counts are recorded as null rather than as a numerical zero, so deaths are not reported in the registry record. A null entry should not be interpreted as evidence that no deaths occurred. The record does not provide event definitions, event-specific follow-up detail, or an explanation of how adverse events were collected.
These safety counts arise in a nonrandomized study with BMI-defined groups, not from a randomized safety comparison. The group counts therefore should not be interpreted as a causal comparison of medication safety. The registry's adverse-event figures are limited to the events and fields recorded in the entry; they do not describe unreported events or establish the absence of risk.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, nonrandomized study examined reproductive hormone responses in women in two BMI groups. It identifies the primary Aim 1 endpoint as LH pulse amplitude measured hourly and averaged over a 12 hour visit. It also describes medication challenges intended to examine aspects of pituitary and ovarian hormone regulation. Those details explain the scientific question and measurement approach, but they are not themselves evidence of a between-group result.
The posted record does not include numerical results for the primary endpoint, an estimate of the group contrast, or measures of inferential uncertainty. It also does not report results for the listed FSH outcomes or the stated mechanistic hypotheses. Consequently, the record cannot establish whether the measured outcomes differed between groups, how large any difference was, or how precisely a difference was estimated. No conclusion about statistical significance can be drawn from the information recorded.
The study's nonrandomized design also limits causal interpretation. The groups were defined by BMI rather than created by random assignment, and the registry does not describe adjustment for possible confounding. A group difference, if one were reported, would be an association in this design unless additional assumptions and evidence supported a causal explanation. The registry record does not establish that other relevant participant characteristics were comparable.
The Aim 1 population description is specific, but the record does not explain how it relates to overall enrollment or provide analysis-population details for the other outcomes. Safety entries record zero affected participants for the listed adverse-event categories, but deaths are not reported in the registry record and the event information is limited. These limitations do not negate the study's descriptive value; they define what can and cannot be concluded from the posted record. The study offers a framework for investigating reproductive hormone physiology, while the missing outcome estimates prevent evaluation of its findings.
13. Why This Trial Matters Statistically
This study is statistically notable because its main question concerns a physiological pattern rather than a single hormone measurement. LH pulse amplitude was measured repeatedly during a study visit, then averaged for comparison between BMI groups. Such a design highlights an important distinction in biostatistics: measurement timing and the choice of summary determine which features of a biological process are represented in an endpoint. A single concentration and a repeated-measure pulse-amplitude summary answer different questions.
The study also illustrates the interpretive limits of a nonrandomized group comparison. BMI defines the groups, but other participant characteristics may also differ. Statistical adjustment can address measured covariates under assumptions, yet it does not make group membership randomized or automatically eliminate confounding. Clear reporting of the analysis population, adjustment strategy, and uncertainty would be important for judging the strength of any comparison. Those details are not reported in the registry record.
Another statistical lesson is the distinction between a well-specified research question and an evaluable result. The registry describes the Aim 1 endpoint, secondary FSH outcomes, and mechanistic hypotheses, but does not report the observed outcome summaries or inferential estimates. Without those results, readers cannot assess direction, magnitude, or precision. A design description is useful context, but it cannot replace transparent reporting of estimates and uncertainty.
Finally, the registry identifies an Aim 1 contributing population that differs in scope from the overall enrollment figure, without explaining that relationship. This emphasizes why reporting participant flow and analysis populations matters, particularly in studies with multiple aims and procedures. The record supports careful discussion of design and measurement, while also making clear that outcome-level statistical interpretation is limited.
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 central limitation for statistical interpretation is that the registry record does not report the primary LH pulse-amplitude results. No group summaries, between-group estimate, confidence interval, or p-value is listed. Without these, the effect's direction, magnitude, and precision cannot be evaluated. The same absence applies to the listed secondary FSH outcomes and the hypotheses about GnRH response, LH clearance, and estradiol negative feedback.
The design was nonrandomized and unmasked. Groups were defined by BMI, so any observed contrast could reflect differences beyond BMI. The registry does not report covariate adjustment or another approach to address confounding. It also does not describe whether outcome measurement was performed with awareness of group membership. These gaps prevent assessment of how design-related biases were handled.
Participant accounting is incomplete in the registry record. Overall enrollment is listed as 62, while the primary Aim 1 description identifies 10 obese and 10 normal-weight women who completed procedures and contributed data. The record does not explain the relationship between these figures, describe reasons for noncompletion, or state how incomplete or missing measurements were treated. Analysis populations for secondary outcomes are not reported.
The statistical plan is also not described. The test or model for the primary comparison, any adjustment for multiple outcomes, missing-data methods, and interim analyses are not reported in the registry record. No sample-size justification is reported. Finally, safety information is limited to the recorded event counts; death entries are null, and event definitions and collection details are not given. These limitations constrain conclusions from the registry entry rather than establishing that unreported procedures were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reproductive Hormonal Alterations in Obesity — NCT01457703.
- Registry record last updated 2017-01-12; status last verified 2016-11.
- Results first posted 2015-03-25.
- 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
NCT01457703, “Reproductive Hormonal Alterations in Obesity,” is a completed, nonrandomized, parallel, unmasked study sponsored by the University of Colorado, Denver. The registry lists enrollment of 62 and identifies two BMI-defined groups. The study used medication challenges across Aim 1 and Aim 2 to investigate reproductive hormone responses.
The primary Aim 1 outcome was LH pulse amplitude measured hourly and averaged over a 12 hour visit. The outcome description states that 10 obese and 10 normal-weight women completed Aim 1 procedures and contributed data for those analyses. Secondary outcomes include changes in FSH in Aim 1 and Aim 2.
The registry record does not report outcome estimates, inferential results, a statistical analysis plan, or a sample-size justification. Serious and other adverse-event fields list 0 affected participants in both groups; deaths are not reported in the registry record. The design and endpoint are described, but the posted information does not permit an assessment of the primary result's direction or precision.