Regulation of Cervical Mucus Secretion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Regulation of Cervical Mucus Secretion (NCT02969590), a randomized phase 4 study. The primary outcome is Median Cervical Mucus Score - Baseline.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 4, randomized, single-masked crossover study, with enrollment of 5. Its status is Completed. The recorded start date is 2015-03-29 and the primary completion date is 2017-08-23. The sponsor is Oregon Health and Science University. These registry entries describe the study’s classification and timeline, but do not establish how each design feature was implemented.

The study summary describes suppressing natural hormone production with a drug and then replacing estrogen and progesterone. It also describes studying a common birth control pill that may affect cervical mucus, as well as cells in the cervix that produce mucus. The registered interventions are leuprolide acetate, estrogen and progesterone replacement, and progestin. The arm descriptions name Norethindrone and Estradiol, and refer to different orders of exposure. Some of these descriptions are truncated in the registry record, so the complete treatment schedules and procedures are not reported there.

A crossover design generally means that participants receive more than one intervention or condition in a sequence, allowing observations from the same participant under different conditions. That general design can make within-participant comparisons informative, but interpretation depends on details such as the sequence, timing, and handling of possible carryover. Those details are not reported in the registry record. The registry says the study was single-masked, but does not report who was masked or how masking was maintained.

The posted primary endpoint is explicitly labelled Baseline and presents results by Norethindrone and Estradiol group. It therefore supplies descriptive group summaries, not a reported crossover contrast. The record does not report a primary-outcome model, an estimate of a treatment-period effect, or a test of sequence or carryover effects. The record lists one secondary outcome, change in PGRMC1 during the menstrual cycle, but does not post a result for it.

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.

Before assignment: In order to qualify for the intervention phase, subjects needed to demonstrate an ovulatory menstrual cycle during the Screening Period.

Screening Period

Reasons for not completing this period:

Treatment Period 1

Treatment Period 2

Analysis population for the primary outcome, as defined in the registry: Data from one (1) subject were excluded from analyses because estradiol (E2) levels were consistent with patch noncompliance

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.

6. Primary Endpoint

The registry lists the primary outcome as Median Cervical Mucus Score - Baseline, measured over Baseline.

The primary endpoint is the median cervical mucus score at baseline. The registry describes the score as the Insler score, a clinical measure based on five mucus features: volume, spinnbarkeit or stretch, ferning, viscosity, and cellularity. The scale runs from 0 to 15 points. The record states that, under WHO guidelines, scores above 10 are considered mucus favoring penetration, while scores below 10 are considered unfavorable to penetration.

This endpoint is used to characterize cervical mucus in relation to its potential to permit sperm penetration. The score combines several observable features into a single measure, which gives a compact description of mucus status. A median describes the midpoint of the observed scores, while the inter-quartile range describes the spread of the middle portion of the observations. Neither summary gives the individual scores or their distribution in full.

The posted baseline median is 11.0 for the Norethindrone group, with an inter-quartile range of 9.0 to 12.0, and 13.0 for the Estradiol group, with an inter-quartile range of 12.0 to 13.0. The registry says data from one subject were excluded from analyses because estradiol levels were consistent with patch noncompliance. It does not report an inferential comparison for this endpoint, a confidence interval, or a treatment-effect estimate. The endpoint description explains what the score is intended to assess; it does not establish that a score or treatment causes a particular reproductive outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a median and inter-quartile range for the primary endpoint. These are descriptive statistics. A median identifies the middle of an ordered set of observations, and the inter-quartile range describes the span from the first to the third quartile. This approach can be useful for scores when the distribution may not be well represented by a mean and standard deviation. The posted summaries do not reveal every observed score, the distribution’s shape, or the uncertainty around a comparison.

What does the baseline label mean?

The endpoint is named Median Cervical Mucus Score - Baseline. A baseline value describes measurement at the designated starting point, rather than a change from baseline or an outcome measured after treatment. Although the study is registered as a crossover, the primary result reported in the record is a pair of baseline summaries. The registry does not report a treatment-period contrast or an analysis of repeated measurements. It would therefore be inappropriate to treat the baseline medians as a randomized estimate of treatment effect.

How should the score be understood?

The Insler score combines five features of cervical mucus into a score on a 15-point scale. The registry describes scores above 10 as mucus favoring penetration and scores below 10 as unfavorable to penetration. A score is a measured outcome, not a direct measure of pregnancy or fertility. Interpreting a median against a threshold does not reveal how many individuals had scores above or below that threshold. The posted summaries do not include counts by threshold category or individual observations.

What does a crossover design add?

General statistical explanation: a crossover design can allow each participant to contribute observations under different interventions, so comparisons may account for stable differences between participants. However, such interpretation depends on the treatment sequence, timing, period effects, and any carryover from one condition to another. The registry identifies the design as crossover and describes different intervention orders, but does not report the complete schedule, washout details, or analysis of period and sequence effects. No specific crossover analysis can be inferred from the design label alone.

What can randomization and masking establish?

The record identifies allocation as randomized and masking as single. Random allocation is intended to reduce systematic differences in assigned groups, while masking can reduce bias arising from knowledge of assignment. Those are general design aims, not guarantees that bias is absent. The registry does not report the randomization procedure, concealment details, who was masked, or whether masking was successful. It also does not report whether the primary baseline result was analyzed according to randomized assignment.

How should uncertainty be assessed?

General statistical explanation: an inferential comparison would normally report an estimate of the contrast and a measure of uncertainty, such as a confidence interval, with a method suited to the design and outcome. A confidence interval indicates the precision of an estimate under the model’s assumptions; it does not prove that a result is clinically important. A p-value assesses compatibility with a specified null hypothesis and model. Neither an estimate, confidence interval, nor p-value for the primary comparison is reported in the registry record. With small group summaries, the observed medians can be sensitive to individual observations, but uncertainty cannot be quantified from the posted summaries alone.

What is over-dispersion, and does it apply?

General statistical explanation: over-dispersion occurs when count data vary more than a statistical model assumes. In such settings, standard errors from a model that assumes less variability can be too small, making results appear more precise than they are. The posted primary outcome is a score summarized by medians and inter-quartile ranges, not a count outcome. The registry does not report a model for which over-dispersion could be assessed, so it is not possible to say that this issue was evaluated in the trial analysis.

What do the planning assumptions mean?

General statistical explanation: a sample-size planning illustration asks how many participants per arm might be needed under stated assumptions to detect a chosen effect with a chosen power and significance level. Such a calculation is prospective planning, not evidence that a completed trial had that power. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification. Any planning illustration should not be described as observed power or as an analysis of the trial’s actual precision.

The registry lists zero analyses, while reporting the primary endpoint summaries. This may reflect the registry’s analysis-reporting fields rather than a complete account of every analytic step, so it should not be used to infer what the investigators did outside the posted record. The methods used to produce the posted summaries, beyond their being medians and inter-quartile ranges, are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and one secondary outcome, change in PGRMC1 during the menstrual cycle. It does not report results for that secondary outcome. It also records zero analyses. The multiplicity strategy, including whether outcomes or comparisons were prioritized or adjusted for multiple testing, is not reported in the registry record. No family of statistical tests or adjustment procedure can be inferred from the list of outcomes alone.

For the primary outcome, the record gives baseline medians and inter-quartile ranges but no p-value, confidence interval, model specification, or formal comparison. The record does not report whether other candidate endpoints or subgroup analyses were considered. Thus, the available information is not enough to assess selective reporting or the extent to which the posted result was prespecified.

The primary endpoint population description says that data from one subject were excluded because estradiol levels were consistent with patch noncompliance. This exclusion is reported as a reason, but the registry does not provide the full analysis-population definition, participant flow, missing-data handling method, or a sensitivity analysis including excluded observations. It does not state whether other data were missing, how missing values were handled, or whether all randomized participants contributed to each outcome.

The distinction matters because exclusions and missing observations can affect a summary, particularly in a small study. This is a general statistical concern, not a claim that the reported result is biased. The registry record does not permit assessment of the direction or size of any such effect. The stated exclusion should be considered when reading the baseline summaries, while avoiding assumptions about unreported observations or analyses.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The adverse-event record reports zero serious adverse events in the Spontaneous Cycle group, with 5 at risk; zero in the Norethindrone (NET) group, with 4 at risk; and zero in the Estradiol (E2) group, with 4 at risk. It also reports zero other adverse events in each group, with the same group-specific numbers at risk. Deaths are reported as zero in each group. No top serious adverse-event terms are listed.

These are the figures recorded for the listed groups. A report of zero events means none were recorded in the relevant registry category and group; it does not establish that an event is impossible or that no unrecorded event occurred. The groups have small numbers at risk, so the absence of recorded events provides limited information about uncommon harms. The record does not report event definitions, collection procedures, severity grading beyond the serious-event category, or the observation period used for each adverse-event group.

The group-specific numbers at risk should not be combined into a total, particularly because the study is described as a crossover and the same participant may contribute in different periods. These safety entries are not a comparative statistical analysis and do not establish a difference between interventions.

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

The record contributes descriptive information about cervical mucus scores in a small randomized crossover study focused on hormonal regulation. Its primary posted result gives baseline medians of 11.0 for Norethindrone and 13.0 for Estradiol, with inter-quartile ranges of 9.0 to 12.0 and 12.0 to 13.0, respectively. Those values characterize the recorded baseline scores in the named groups.

The result does not establish that one intervention changed cervical mucus more than another. The primary endpoint is labelled Baseline, and no treatment-effect estimate, confidence interval, or statistical test is reported. The medians cannot show the full participant-level distribution or how many individual scores fell above or below the registry’s interpretive thresholds. The findings should not be extended to fertility, contraception, pregnancy, or other clinical outcomes that are not reported as results.

The registry describes a mechanistic research aim: understanding how estrogen and progesterone affect cervical mucus, alongside study of a common birth control pill and mucus-producing cervical cells. A study’s stated aim is not itself evidence that an intervention has a particular effect. The listed secondary outcome, change in PGRMC1 during the menstrual cycle, has no posted result in this record.

The study’s crossover and randomized design labels are relevant context, but the registry does not report enough analytic detail to assess treatment sequence, period effects, carryover, or the exact role of masking. Nor does it report a complete participant flow or the analysis plan. The posted data therefore support a narrow descriptive reading rather than a conclusion about comparative effectiveness or mechanism.

General statistical interpretation: a result can be informative even when it is imprecise, but precision requires an uncertainty estimate or enough underlying data to calculate one appropriately. Neither is available for the primary comparison in the registry record. The absence of an inferential result should not be converted into a claim that there is or is not a difference. It means the posted registry information does not quantify that question.

13. Why This Trial Matters Statistically

This study is statistically interesting because it examines a biological measurement that changes in relation to hormones and uses a crossover design. Such designs can be useful in mechanistic research when participants can be assessed under more than one condition. The registry’s description of distinct exposure orders suggests that sequence is relevant, but the record does not supply enough detail to evaluate how sequence or period effects were handled.

The primary endpoint also illustrates a distinction between a clinically interpretable measurement and an inferential result. The Insler score is described through observable mucus features and threshold interpretations. The posted medians and inter-quartile ranges show the central score and its middle spread, but do not provide a formal estimate of the contrast between conditions. A clear endpoint definition does not substitute for a reported analysis.

The small enrollment and the exclusion reported for patch noncompliance make transparency about analysis populations particularly important. The record states the exclusion reason and provides arm-level summaries, but does not fully reconcile enrollment with the reported group counts or explain all analysis decisions. This limits independent assessment of how robust the descriptive result may be.

The safety entries likewise illustrate why zero recorded events should be read in context. With small groups at risk and no detailed event-collection information in the record, the entries describe what was recorded without establishing the absence of risk. Overall, the registry record is most useful for clarifying the study’s question, design classification, endpoint definition, and posted descriptive result. It leaves key details about estimation, uncertainty, and analysis conduct unreported.

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 limitation of the posted result is that the primary outcome is a baseline summary, not a reported treatment contrast. Although the study is registered as randomized and crossover, the registry provides no estimate of change or difference attributable to treatment. It also reports no confidence interval, p-value, or model for the primary comparison. The precision of any treatment effect therefore cannot be assessed from the record.

The study enrolled 5, and the two primary-result groups each report n=3. The outcome description states that data from one subject were excluded because estradiol levels were consistent with patch noncompliance. The record does not explain fully how these figures relate to enrollment, how observations are represented across crossover periods, or whether any other data were missing. A complete participant flow and analysis-population definition are not reported.

The crossover label alone does not disclose treatment sequence, period timing, washout procedures, or how carryover and period effects were considered. The single-masked designation is not accompanied by information about who was masked or whether masking was maintained. The analysis plan, sample-size justification, and multiplicity approach are not reported in the registry record.

The outcome is a score that summarizes several mucus properties. The posted median and inter-quartile range do not reveal individual scores or counts at clinically described thresholds. The registry does not report the measurement procedures beyond the endpoint description, the reliability of scoring, or whether assessors were masked to treatment condition.

Finally, the record lists a secondary outcome but does not post its result, and its safety entries do not include detailed event definitions or observation periods. These gaps restrict interpretation to the descriptive information that is explicitly recorded; they do not establish that unreported procedures or analyses were absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Regulation of Cervical Mucus Secretion — NCT02969590.
• Registry record last updated 2019-10-18; status last verified 2019-10.
• Results first posted 2019-10-18.
• 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.

18. Record Summary

NCT02969590, titled Regulation of Cervical Mucus Secretion, is registered as a Phase 4 randomized, single-masked crossover study sponsored by Oregon Health and Science University. The record lists enrollment of 5, status Completed, and dates of 2015-03-29 for study start and 2017-08-23 for primary completion.

The primary outcome is median baseline cervical mucus score, assessed using the Insler score. The posted medians are 11.0 for Norethindrone and 13.0 for Estradiol, with inter-quartile ranges of 9.0 to 12.0 and 12.0 to 13.0. One subject’s data were excluded because estradiol levels were consistent with patch noncompliance. No inferential comparison is reported in the registry record.

The record lists change in PGRMC1 during the menstrual cycle as a secondary outcome, without a posted result. The safety entries report zero serious adverse events, zero other adverse events, and zero deaths in each listed group. Important details about the analysis plan, missing data, crossover procedures, and treatment-effect estimation are not reported in the registry record.