Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH. (NCT02389088), a non-randomized na study. The primary outcome is Estradiol During Phase I and Phase II.

2. Clinical Question

The registry describes an FSH stimulation test in both phases. In Phase I, r-FSH is administered intravenously at a dose of 150 IU, with blood samples obtained before and after administration. Phase II is described as repeating the FSH stimulation test after the washout. The reported outcome schedule includes measurements at 24 hours during Week 0, and at 0 and 24 hours during Weeks 5 and 6 after FSH stimulation, in both phases. The study therefore concerns hormone measurements over time and across treatment conditions within a single-group study, not a randomized comparison of separate groups.

3. Trial Design

This completed study is registered as NCT02389088 and is titled “Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH.” The registry lists polycystic ovary syndrome as the condition and the University of California, San Diego as the sponsor. The phase classification is listed as NA. Enrollment is 9. The study is described as nonrandomized, unmasked, and using a single-group model.

The design has Phase I and Phase II. The Phase I description states that 9 women with PCOS would undergo an FSH stimulation test. On study day one, r-FSH would be administered intravenously at 150 IU, with blood samples obtained before and after FSH administration. Each participant would then receive an intramuscular injection of Lupron 3.75 mg. The description of the dose is incomplete in the registry record, so its full intended duration or rationale is not reported there.

Women who participated in Phase I were to be studied again in Phase II after a washout of 2 months. The registry says the FSH stimulation test would be performed as described for Phase I, followed by an intramuscular Lupron injection. The primary outcome description identifies Phase I as without letrozole and Phase II as with letrozole. The registry record does not report a randomized assignment, masking, or a separate concurrent control group. It also does not give a complete account of the timing or dosing of letrozole.

The study start is listed as 2006-04, primary completion as 2013-01, and status as completed. These registry design details describe the intended structure, but do not establish how many participants completed both phases or contributed data to each outcome time. Those participant counts 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 - Phase I

Phase II - All Study Participants

Analysis population for the primary outcome, as defined in the registry: Phase I and Phase II - PCOS patients.

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: 9 PCOS women

6. Primary Endpoint

The registry lists the primary outcome as Estradiol During Phase I and Phase II, measured over At time 24 hours during Week 0 and times 0 and 24 hours during Weeks 5 and 6 after FSH stimulation for both Phase I and Phase II.

The primary endpoint is estradiol concentration, measured in pmol/L and summarized as a mean with standard deviation. The registry describes measurements during Phase I, without letrozole, and Phase II, with letrozole. The stated timing is 24 hours during Week 0 and 0 and 24 hours during Weeks 5 and 6 after FSH stimulation in both phases. The population for this outcome is described as PCOS patients in Phase I and Phase II.

Estradiol is the outcome because the study's stated purpose is to evaluate the effect of increased circulating androgens on estradiol production by granulosa cells in response to FSH stimulus. In general, measuring a hormone concentration after a stimulus can describe the observed response at specified times. Measurements at more than one time can also describe how the recorded concentrations vary over the study schedule. They do not, by themselves, establish why any difference occurred.

The registry record does not report the actual mean estradiol values, standard deviations, changes, confidence intervals, or tests of the primary outcome. It therefore does not allow a numerical estimate of the size or precision of the observed phase or time differences. The listed outcome definition and schedule explain what was intended to be measured, but are not outcome results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous outcome: estradiol concentration in pmol/L. It specifies the mean as the summary measure and standard deviation as the measure of dispersion. These choices indicate the form in which the outcome was intended to be described, but do not reveal the actual values or the statistical procedure used to compare phases. Numerical analyses and a statistical analysis plan are not reported in the registry record.

What does a mean and standard deviation describe?

In general, a mean summarizes the central level of measurements in a group. A standard deviation describes how spread out individual measurements are around that mean. They answer different questions: the mean concerns the average level, while the standard deviation concerns participant-to-participant variability. A mean alone does not show whether most observations are close to it or whether the measurements vary widely. The registry states that these summaries were used for the primary outcome, but does not report their values.

These summaries also do not show the uncertainty around an estimated phase difference. A confidence interval is a general statistical tool for expressing uncertainty about an estimate, with narrower intervals indicating greater precision under the method's assumptions. No confidence interval for estradiol or a phase contrast is reported in the registry record. Likewise, no p-value is reported for the primary outcome. Without an estimate and an uncertainty measure, neither the size nor precision of a possible phase difference can be assessed.

Why does the repeated-measures structure matter?

The outcome schedule includes multiple times during both Phase I and Phase II, and Phase II is intended to include women who participated in Phase I. Measurements from the same participant are generally related rather than independent. In general, an analysis of repeated measurements should account for this within-participant dependence. Treating related observations as independent can misstate uncertainty because it fails to reflect how measurements from one person tend to move together.

For a comparison between phases in the same participants, a paired analysis may be appropriate when its assumptions match the data and the study question. A paired analysis focuses on each participant's within-person difference, rather than treating the two phase measurements as if they came from unrelated groups. Other repeated-measures approaches can account for several times and phases together. The registry record does not report which approach, if any, was used. It also does not report the number of complete participant pairs or how missing time points were handled, so the feasibility and results of a paired analysis cannot be determined.

How should the nonrandomized design be understood?

The study is listed as nonrandomized, unmasked, and single-group. The primary outcome description distinguishes Phase I without letrozole from Phase II with letrozole, with the second phase following a washout. This is a sequential within-group comparison, not a randomized comparison between independent treatment groups. In general, random allocation helps balance measured and unmeasured influences between groups; without it, changes associated with treatment condition can be entangled with order, time, or other differences. The registry does not report an adjustment strategy to address such influences.

Repeated measurements can offer useful descriptive information, but their interpretation depends on the analysis population, timing, and completeness of observations. For example, if not all participants contribute measurements at every scheduled time, the set of participants behind each mean can differ. A comparison of means can then reflect both changes in measurements and changes in who contributed data. The registry record does not report counts by time point or explain whether missing measurements occurred.

What do the planning assumptions mean?

The registry's planning illustration is described as computed from the observed effect, rather than from the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. These are planning assumptions, not a report of how this single-group study was conducted. The record does not report the numerical illustration values or the numerical observed effect on which they were based.

In general, a sample-size calculation estimates how many participants might be needed under specified assumptions to detect an effect with a chosen statistical procedure. It does not establish that the study actually had that number, that the assumed effect is true, or that the study achieved a particular probability of detecting an effect. The planning values are not observed power. The stated equal allocation between two arms does not describe the study's single-group, sequential phase structure. Any planning illustration should therefore be read as a hypothetical design exercise rather than a description of the enrolled study.

Normal-approximation calculations rely on assumptions about how estimates behave, and the fit of those assumptions depends on the data and analysis. In general, small or highly variable datasets may make approximations less dependable; the registry does not provide enough outcome information to assess that issue for this study. The sample-size assumptions do not substitute for an analysis plan, and the absence of posted primary results means they cannot be used to infer an outcome.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Phase I - Week 0 - 24 Hours", "Phase I - Week 5 - 0 Hour", "Phase I - Week 5 - 24 Hour", "Phase I - Week 6 - 0 Hour", "Phase I - Week 6 - 24 Hour", "Phase II - Week 0 - 24 Hours")
n   <- c(9, 9, 9, 9, 9, 9)
m   <- c(451.7, 116, 247.2, 131.4, 347.5, 401.4)
sp  <- c(131, 27.8, 105.5, 20.2, 83.9, 103.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Phase I - Week 0 - 24 Hours  9  451.700  131.000  351.004  552.396
CARM  Phase I - Week 5 - 0 Hour  9  116.000  27.800  94.631  137.369
CARM  Phase I - Week 5 - 24 Hour  9  247.200  105.500  166.106  328.294
CARM  Phase I - Week 6 - 0 Hour  9  131.400  20.200  115.873  146.927
CARM  Phase I - Week 6 - 24 Hour  9  347.500  83.900  283.009  411.991
CARM  Phase II - Week 0 - 24 Hours  9  401.400  103.400  321.920  480.880

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and identifies estradiol during Phase I and Phase II as the primary outcome. It lists 0 analyses. No analysis plan, hierarchy among outcomes, or multiplicity adjustment is reported in the registry record. Multiplicity is a general concern when several outcomes, time points, or comparisons are examined: the more opportunities there are to find an apparently notable result, the more important it is to define which analyses are primary and how additional analyses will be interpreted. The outcome schedule includes more than one measurement time in each phase, but the registry does not state how these repeated measurements were combined or compared.

Missing-data methods are not reported in the registry record. The study description says that women who participated in Phase I would be studied again in Phase II, but it does not give the number contributing outcome data in either phase, at each time, or in both phases. It also does not describe whether any measurements were missing, why they might be missing, or how missing values would be handled. These details are needed to understand which observations inform each estimate and whether comparisons use the same participants.

The registry identifies PCOS patients in both phases as the primary outcome population, but does not report an analysis population definition, such as rules for inclusion based on participation or available measurements. It does not report exclusions, deviations from the described sequence, or whether any participants were omitted from an analysis. With no posted analysis results or population counts, the extent to which the analyzed participants correspond to the planned group cannot be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

For Phase I, the registry reports 9 participants at risk for serious adverse events and 0 affected; it also reports 9 at risk for other adverse events and 0 affected. For Phase II, it reports 9 at risk for serious adverse events and 0 affected, and 9 at risk for other adverse events and 0 affected. No serious adverse-event terms are listed. These are the recorded counts for the two phase categories, not a comparison of randomized groups.

Zero affected participants in a registry category means that no affected participants are recorded in that category for the phase. It should not be interpreted as proof that no event of any kind occurred, or that risks are absent. The record does not provide event descriptions, severity details beyond the serious/non-serious grouping, or information about how events were collected. Death counts are not reported in the registry record; a missing death count should not be read as a reported count of zero. The small enrolled group also means these counts alone cannot characterize uncommon events.

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

The registry record establishes that a study was completed with a planned enrollment of 9 women with PCOS and a two-phase, single-group design. It describes FSH stimulation and an estradiol outcome measured at specified times, with Phase I identified as without letrozole and Phase II as with letrozole. It also records no participants affected by serious or other adverse events in either phase, among 9 listed as at risk for each category. These registry entries describe the study structure and the safety counts recorded in the registry.

The record does not report numerical estradiol results. It therefore cannot show whether concentrations were higher, lower, or similar between phases, how much they varied, or whether any observed pattern was statistically precise. The absence of reported outcome estimates does not imply that there was no effect or that the phases were equivalent. Equivalence requires a defined margin and an analysis designed to assess it; neither is reported in the registry record.

Even if phase-specific measurements were available, the design would require cautious interpretation. Phase I and Phase II are not randomized arms, and the registry describes the second phase as following the first. Differences may be associated with the phase conditions, but the record does not establish that they are caused by letrozole or by circulating androgen changes alone. A phase comparison is also not necessarily a direct measure of an isolated granulosa-cell mechanism.

In general, statistical evidence is most informative when an estimate is accompanied by a measure of uncertainty and interpreted in light of the design. Those outcome estimates and uncertainty measures are not reported in the registry record. The appropriate reading is therefore limited: the planned biological question and measurement schedule are described, but the posted record does not support a numerical conclusion about the primary outcome or a causal conclusion about treatment effects.

14. Why This Trial Matters Statistically

This study raises a statistical question that often arises in endocrine research: how to describe a response measured repeatedly in the same participants under sequential study conditions. The registry's schedule includes estradiol measurements at multiple times in both phases. Such data can be informative about trajectories, but observations from one participant are related. A valid analysis must distinguish within-person change from variation between participants and must account for the timing and dependence of measurements.

The design also highlights the difference between a within-group phase comparison and a randomized controlled comparison. A repeated-measures design can make each participant a reference for their own measurements, which may reduce the influence of stable individual differences. At the same time, a fixed sequence without a separate randomized control group leaves order and time-related explanations entangled with phase. Statistical methods can describe patterns and quantify uncertainty, but cannot remove design limitations unless the required comparisons and data support doing so.

The record is also a useful reminder that endpoint definitions and outcome findings are distinct. The endpoint is named, its units and summary measures are specified, and its time points are described, yet numerical results and analyses are not reported. Without those results, readers cannot assess effect size, variability, or precision. A completed status does not itself supply evidence about the direction or magnitude of the outcome.

Finally, the stated sample-size assumptions are planning illustrations rather than a description of the actual study design. Distinguishing such calculations from observed results prevents a hypothetical design exercise from being mistaken for evidence that an effect was detected. The record illustrates why interpretation requires both an explicit analysis and enough reported information to evaluate it.

15. 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 of interpretation is that numerical primary outcome results are not reported in the registry record. The record gives the estradiol measurement units, summary type, and timing, but not means, standard deviations, contrasts, or uncertainty estimates. It is therefore not possible to assess the direction, size, variability, or precision of the outcome.

The design is nonrandomized, unmasked, and single-group. Phase I precedes Phase II in the description, and the phases differ in whether letrozole is present. Without randomization or a separate concurrent control group, a difference across phases cannot be attributed to the treatment condition alone. The record does not report an approach for accounting for phase order, time-related changes, or other potential influences.

The intended Phase II participants are women who participated in Phase I, but the number with data in both phases and at each time is not reported. The record does not describe missing measurements, exclusions, adherence, or analysis-population rules. Those omissions limit evaluation of whether phase comparisons would be based on the same participants and whether any available-data analysis could be biased.

Other important analytic details are also not reported in the registry record, including a statistical analysis plan, handling of multiple outcomes or times, confidence intervals, and hypothesis tests. The Phase I description is incomplete, and the Phase II account does not provide a complete description of letrozole dosing or administration. The record lists zero affected participants in the adverse-event categories, but does not provide event narratives or a reported death count. These limitations restrict both efficacy interpretation and the scope of safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH. — NCT02389088.
• Registry record last updated 2016-03-10; status last verified 2016-02.
• Results first posted 2015-09-28.
• 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.

19. Record Summary

NCT02389088 is a completed, nonrandomized, unmasked, single-group study sponsored by the University of California, San Diego. It enrolled 9 participants with polycystic ovary syndrome; the listed phase classification is NA. The study start is recorded as 2006-04 and primary completion as 2013-01.

The study describes Phase I without letrozole and Phase II with letrozole, with Phase II following a washout of 2 months. Both phases include an FSH stimulation test. The primary outcome is mean estradiol in pmol/L, with standard deviation, at the specified times in Weeks 0, 5, and 6. Numerical primary outcome results and analyses are not reported in the registry record.

The registry lists 4 outcome measures and 0 analyses. In each phase, 9 participants are listed at risk for serious and other adverse events, with 0 affected in both categories. Death counts are not reported in the registry record.