To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone (NCT00706719), a randomized phase 2 study. The primary outcome is Sperm Concentration.

2. Clinical Question

The study focused on sperm parameters in men with secondary hypogonadism who had previously used topical testosterone. Its stated purpose was to determine whether Androxal would affect sperm parameters, specifically count, concentration, and volume. The listed primary outcome is total sperm concentration. The registry record also lists luteinizing hormone and follicle stimulating hormone as secondary outcomes.

The treatment structure makes the washout history relevant to interpreting the question: the Androxal groups differed in whether participants had a previous 3 month period without topical testosterone. The record does not report enough numerical outcome information to describe changes in sperm concentration, compare the groups’ measurements, or assess the precision of any difference. It therefore supports a description of the study question and analysis population, but not a conclusion about the direction or size of an outcome contrast.

3. Trial Design

This was a randomized, open-label, fixed-dose, active-control, multicenter Phase IIB study, described in the registry as Phase 2. Its allocation model was parallel, and masking was listed as none. The study was designed to evaluate fertility in men with secondary hypogonadism who had previously been treated with topical testosterone. The registry lists an enrollment of 17 and a completed status.

The interventions were 25 mg Androxal and Testim 1%. The Testim group used gel applied topically for 6 months. One Androxal group took a daily 25 mg capsule for 6 months without a 3 month washout period. The other took the daily capsule for 6 months after a previous 3 month washout period of topical testosterone. These treatment descriptions establish three groups, but the registry record does not report the allocation process in further detail, including how randomization was generated or whether assignment was concealed.

The primary outcome was sperm concentration, measured at baseline, Month 3, Month 6, and Follow-Up (Month 7). The record says the primary outcome analysis included participants in Groups A and B who completed the study. It says no analysis was performed for Group C because only 1 participant completed the study. The registry record does not explain why this completion pattern occurred, how missing measurements were handled, or whether the analyzed population was specified before the data were examined.

The record lists five outcome measures and 20 analyses. It identifies luteinizing hormone and follicle stimulating hormone levels as secondary outcomes. It does not report the randomization ratio, the group-specific enrollment at randomization, a sample-size justification, a prespecified statistical analysis plan, or details of the multicenter sites. Those omissions limit assessment of the planned comparisons and the relationship between the intended and completed analyses.

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

Analysis population for the primary outcome, as defined in the registry: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.

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 Sperm Concentration, measured over Baseline, Month 3, Month 6, Follow-Up (Month 7).

The primary endpoint was total sperm concentration, expressed in millions sperm/mL. Sperm concentration describes the number of sperm within a specified volume of semen. It is one component of sperm parameters, the broader set of measures named in the study’s purpose. The registry record lists sperm count and volume in the study description as well, but identifies concentration as the primary outcome.

Repeated measurements were specified at baseline, Month 3, Month 6, and Follow-Up (Month 7). Baseline provides a reference measurement before the subsequent scheduled assessments; later measurements can describe the observed course over the treatment period and follow-up. General statistical context: repeated measurements can help characterize how an outcome changes over time, but interpretation depends on which participants contribute data at each time and how within-participant correlation is handled. The registry record does not report those modeling details.

The stated analysis population consisted of completers in Groups A and B. No primary outcome analysis was performed for Group C because only 1 participant completed the study. This restriction matters: a completer analysis describes the participants with study completion rather than necessarily representing everyone randomized. The registry record does not provide numerical sperm concentration results, estimates of change, group contrasts, confidence intervals, or p-values. Consequently, the endpoint’s clinical and statistical pattern cannot be described from the record’s posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several features of the study help define what a statistical comparison would mean, while the registry record leaves important analytic details unspecified. The explanations below describe general statistical concepts and distinguish them from what the record actually reports.

What does randomization contribute?

General: Random allocation is intended to make treatment groups comparable, on average, with respect to measured and unmeasured factors at the point of assignment. It can support causal interpretation when allocation is implemented as planned and participants are analyzed in a way that preserves the randomized comparison. The registry identifies the study as randomized, but does not report the sequence-generation method, allocation concealment, or the allocation ratio. It also does not report enough participant-flow information to assess how the completed-case analysis may have changed group comparability.

The study was open-label, with masking listed as none. General: When participants and study personnel know the assigned treatment, behavior, co-interventions, measurement, or reporting can potentially be influenced by treatment knowledge. Whether such influences affected this study is not reported in the registry record. Sperm concentration is a laboratory measure, but the record does not say whether laboratory personnel were blinded to group assignment or describe specimen collection and measurement procedures.

How should repeated measurements be understood?

The primary endpoint was assessed at baseline, Month 3, Month 6, and Follow-Up (Month 7). General: Repeated measurements on the same participant are correlated; they are not independent observations. A statistical method that treats every measurement as unrelated can misstate uncertainty. Longitudinal approaches can account for within-participant correlation and make use of measurements over time, but their interpretation depends on the chosen model, assumptions, and handling of incomplete records.

The registry record does not report whether the primary analysis compared values at individual time points, changes from baseline, an overall time pattern, or a treatment-by-time contrast. It does not identify a repeated-measures model, covariance structure, transformation, or adjustment for baseline. These details are not reported in the registry record, so the actual analytic approach cannot be reconstructed from the outcome description alone.

What do means and standard deviations convey?

The primary outcome is described as a mean with standard deviation. General: A mean gives a measure of the center of observed values, while a standard deviation describes the spread of individual values around that center. They answer different questions: the mean describes an average level, and the standard deviation describes variability among measurements. Neither directly gives the precision of a group comparison. Precision is commonly communicated with a confidence interval for an estimate, which shows a range of values reasonably compatible with the data and statistical model. The registry record does not report means, standard deviations, or confidence intervals for this endpoint.

General: If a continuous outcome is strongly skewed or contains extreme observations, the mean and standard deviation may not fully describe its distribution. Other summaries or modeling choices may then be considered. The record does not report the observed distribution of sperm concentration or whether diagnostic checks informed the analysis. No distributional assumptions beyond the stated summary can be inferred.

Why do analysis populations matter?

The registry says the primary outcome analysis included participants in Groups A and B who completed the study. It says Group C was not analyzed because only 1 participant completed it. General: A completer analysis uses outcome information from participants who reached the specified completion point. It can be easier to interpret as a description of observed completers, but it may not preserve the balance created by randomization if completion is associated with treatment or outcome. An intention-to-treat approach instead aims to analyze participants according to randomized assignment, although missing outcomes still require explicit handling.

The record does not state whether an intention-to-treat analysis or another analysis population was defined, whether imputation was used, or how partial follow-up data were treated. It also does not explain whether participants were excluded for reasons other than failure to complete. These omissions prevent assessment of the possible effects of missing outcome data.

What can be learned from multiple analyses?

The registry lists five outcome measures and 20 analyses. General: When many outcomes, time points, or group contrasts are examined, the chance of at least one apparently unusual result can increase if each test is interpreted separately without a prespecified strategy. Statistical approaches to multiplicity can control specified error rates, but the appropriate method depends on the family of comparisons and the study’s objectives. The registry record does not report whether a hierarchy, adjustment procedure, or other multiplicity plan was used.

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. General: Such calculations can illustrate what sample size might be needed under specified assumptions; they do not demonstrate the power actually achieved by a completed trial. The registry record does not report the study’s own sample-size justification. Because numerical primary outcome estimates are not reported in the record, the planning illustration cannot be treated as evidence about the outcome or its precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and 20 analyses, but does not report how these outcomes and analyses were prioritized or whether a formal multiplicity plan was used. In a study with multiple outcomes, time points, or contrasts, separate tests can create multiple opportunities for a nominally unusual result. General: Prespecified testing hierarchies or statistical adjustments can address particular multiplicity concerns, but their interpretation depends on which comparisons are included in the testing family. That information is not reported in the registry record. Numerical p-values for the primary outcome are also not reported, so the role of multiplicity in interpreting a primary result cannot be assessed.

The registry identifies the primary outcome analysis population as completers in Groups A and B. Group C was not analyzed for that outcome because only 1 participant completed the study. This is an explicit restriction in the record, but the reasons for noncompletion and the number of participants with measurements at each time point are not reported in the registry record. The record does not describe whether participants with partial follow-up contributed available measurements or whether any missing values were imputed.

General: Missing data can affect both the estimate and its uncertainty, especially when the probability of a missing measurement is related to treatment assignment or the unobserved outcome. Analyses that use only complete cases can be unbiased under some conditions, but those conditions cannot be checked without information about missingness and its causes. The record does not report sensitivity analyses or a missing-data assumption.

The registry record also does not state whether the primary analysis population was defined before outcome data were examined, whether an intention-to-treat analysis was conducted, or how protocol deviations were handled. These gaps limit assessment of whether the analyzed participants reflect the randomized groups and how robust the results would be to alternative handling of incomplete data. No numerical result is available in the record to compare across analysis populations.

11. 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.

Most frequent non-serious adverse event terms

The serious adverse event counts reported for Group A Testim, Group B Androxal no Wash Out, and Androxal Wash Out were 0 among 5 at risk, 0 among 7 at risk, and 0 among 5 at risk, respectively. These figures describe the registry’s reported counts for the listed groups; they do not establish that serious events could not occur or that the treatments have equivalent safety. A zero count in a small group is compatible with uncertainty about the underlying event risk.

For other adverse events, the registry reports 0 among 5 at risk in Group A Testim, 2 among 7 at risk in Group B Androxal no Wash Out, and 4 among 5 at risk in the Androxal Wash Out group. These are counts of participants reported as affected, not event rates calculated for comparison. The record does not provide event descriptions for these other adverse events in the registry record for this analysis, nor does it give timing, severity, or attribution details. Serious adverse event terms are not listed.

Death counts are not reported in the registry record. The safety figures should be read as descriptive counts for the groups and denominators shown, not as a controlled estimate of comparative risk. The record does not report a statistical safety comparison or enough detail to assess differences in exposure or follow-up.

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

The study addresses an important measurement question within a specific population: men with secondary hypogonadism previously treated with topical testosterone. It compares daily 25 mg Androxal, under two different washout histories, with Testim 1% gel. Sperm concentration was the primary outcome, with measurements specified at baseline, Month 3, Month 6, and Follow-Up (Month 7). This design description clarifies the scope of the question but does not tell readers what happened to the measured endpoint.

The registry record does not report numerical sperm concentration results or a statistical comparison. It therefore does not establish the size, direction, or precision of any change or group difference. It also does not support a claim that one intervention did or did not affect sperm concentration. The absence of reported numerical results is an information limitation, not evidence of no difference.

The primary analysis used completers in Groups A and B, while Group C was not analyzed because only 1 participant completed it. As a result, the posted primary-outcome description does not provide a complete analysis across all three groups. Without participant flow, reasons for noncompletion, and a description of missing-data methods, it is not possible to judge how much the analyzed population may differ from the randomized population.

General: Statistical significance and practical importance are distinct. A p-value, if reported, would summarize how compatible the data are with a specified statistical model under a null hypothesis; it would not by itself communicate the size or practical relevance of an effect. A confidence interval would help show the precision of an estimate. Neither numerical p-values nor confidence intervals for the primary outcome are reported in the registry record, so those aspects cannot be evaluated.

The record also does not report the study’s own sample-size justification. Planning illustrations based on an observed effect are not observed power and cannot replace estimates from the trial. The appropriate conclusion is limited: the registry describes a randomized comparison and a planned longitudinal sperm concentration endpoint, but the numerical primary outcome findings needed to characterize the result are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way its treatment groups distinguish washout history. The two Androxal regimens used the same stated daily dose and 6 month treatment duration, but differed in whether participants had a previous 3 month washout period after topical testosterone. The active-control group used Testim 1% gel for 6 months. That structure makes the treatment history relevant when defining the comparison, and cautions against treating the two Androxal groups as interchangeable without examining their separate results.

The primary outcome is longitudinal rather than a single isolated measurement: sperm concentration was scheduled at baseline, Month 3, Month 6, and Follow-Up (Month 7). General: Analyses of longitudinal outcomes need to distinguish changes over time from differences between groups, and should account for the fact that measurements from the same participant are related. Clear reporting of time-specific estimates, contrasts, and uncertainty would help readers understand both the trajectory and the between-group comparison. The registry record does not provide those estimates or the analysis method used.

The stated completer analysis and the lack of a primary analysis for Group C are also consequential. They make the analysis population central to interpretation, rather than a technical detail. The registry does not report enough information about missingness, participant flow, or sensitivity analyses to assess the effect of this restriction.

Finally, the record lists multiple outcomes and analyses but does not report a multiplicity strategy. Together with the absence of numerical endpoint results, that makes it impossible to evaluate the statistical strength of any specific finding. The trial matters statistically as an example of why study design, analysis population, longitudinal methods, and complete outcome reporting must be considered together.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation of the registry record for interpreting this trial is that it does not report numerical results for the primary endpoint. Means, standard deviations, estimated changes, group contrasts, confidence intervals, and p-values are not reported in the registry record. Without them, the observed outcome pattern and its precision cannot be described.

The primary outcome analysis was limited to completers in Groups A and B. The record states that Group C was not analyzed because only 1 participant completed the study, but does not provide an explanation for the completion pattern. It also does not report participant counts with available measurements at each scheduled assessment, reasons for withdrawal, or the handling of partial follow-up. These omissions limit assessment of missing-data bias and the representativeness of the analyzed participants.

The study was open-label, with no masking listed. The record does not say whether laboratory staff assessing sperm concentration were blinded to assignment, or provide details about specimen collection, laboratory methods, or quality control. It also does not report the randomization sequence method, allocation concealment, or allocation ratio. These are relevant details for evaluating how the planned randomized comparison was implemented.

The record identifies five outcome measures and 20 analyses but does not state which analyses were prespecified or whether multiplicity was addressed. It does not report a sample-size justification or a full statistical analysis plan, including the method for repeated measurements and any adjustment for baseline. The listed design information is therefore insufficient to reconstruct the analysis or assess whether it followed a prespecified plan.

The safety record gives counts but does not include event descriptions for other adverse events, exposure detail, or death counts. These limitations are specific to the information reported in the registry record and should not be mistaken for evidence about unreported outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone — NCT00706719.
• Registry record last updated 2015-08-19; status last verified 2015-07.
• Results first posted 2010-10-08.
• 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

NCT00706719 is a completed randomized, open-label, parallel Phase 2 study described in its official title as Phase IIB. It enrolled 17 participants with secondary hypogonadism previously treated with topical testosterone. The trial compared daily 25 mg Androxal for 6 months, with or without a previous 3 month washout period, against Testim 1% gel applied for 6 months.

The primary outcome was total sperm concentration in millions sperm/mL at baseline, Month 3, Month 6, and Follow-Up (Month 7). The registry states that the primary analysis included completers in Groups A and B; Group C was not analyzed because only 1 participant completed the study. Numerical primary outcome findings are not reported in the registry record. The record also lists luteinizing hormone and follicle stimulating hormone levels as secondary outcomes, five outcome measures, and 20 analyses. It does not report the statistical analysis plan, sample-size justification, multiplicity procedure, or missing-data methods.