Anastrozole Administration in Elderly Hypogonadal Men: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anastrozole Administration in Elderly Hypogonadal Men (NCT00136695), a randomized phase 2 study. The primary outcome is Change in Lean Body Mass.

2. Clinical Question

The question is about a measured body-composition outcome, not a direct measure of symptoms, function, or long-term health. The registry describes the study’s purpose as assessing the effects of sustained aromatase inhibitor therapy in elderly men with mild hypogonadism. The primary outcome focuses on the difference between groups in change in lean body mass during the stated follow-up timeframe.

The posted group means are changes from baseline: -2000.0 grams for anastrozole and -1500.0 grams for placebo. The reported mean difference, expressed as anastrozole relative to placebo, is -500.0 grams. The confidence interval and unadjusted p-value provide information about the precision and statistical evidence associated with that estimate. They do not, by themselves, establish the clinical importance of the difference or explain why it occurred.

The registry record does not report eligibility details beyond the population description, the method used to measure lean body mass, or additional primary-question outcomes. These details would be needed to interpret the finding in greater clinical and methodological context.

3. Trial Design

The registry describes a completed phase 2, randomized, triple-masked, parallel-group study sponsored by Massachusetts General Hospital. The study compares anastrozole with placebo in elderly men with mild hypogonadism. The record lists enrollment as 88. For the posted primary outcome, the reported arm counts are 34 for anastrozole and 35 for placebo; these outcome-specific counts should not be assumed to account for every enrolled participant.

The study began in 2004-10, and primary completion is recorded as 2008-10. The primary outcome timeframe is baseline and 1 year. The intervention is listed as anastrozole, and the comparator as placebo. The registry identifies the design as parallel, meaning the record describes separate groups assigned to the study arms rather than a crossover arrangement.

Randomization and triple masking are stated, but the registry record does not report how the random sequence was generated, how assignment was concealed, or which groups of people were masked. It also does not report details of treatment dosing, adherence, co-interventions, or the procedures used to maintain masking. The record’s allocation description establishes random assignment, but it does not specify an allocation ratio for the trial itself. Equal allocation is an assumption used for the separate planning illustration, not a reported trial-design feature.

The primary outcome is continuous, summarized as a mean with standard deviation. The registry record reports one outcome measure and no posted secondary outcome measures. It does not report a protocol-level analysis plan, a sample-size justification, or the original design assumptions. The trial’s completed status indicates that the registry lists it as completed; it does not resolve the missing methodological details or supply information about all enrolled participants’ outcome availability.

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

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 Change in Lean Body Mass, measured over Baseline and 1 year.

The primary endpoint is change in lean body mass, measured in grams from baseline to 1 year. Lean body mass is a continuous body-composition measure: values represent quantities on a numeric scale, rather than categories such as improved or not improved. The registry summarizes the outcome using a mean and standard deviation for each arm.

Change from baseline is used to describe how the measured quantity differs between the start of follow-up and the specified later assessment. Comparing the mean changes between randomized groups focuses the estimate on the difference in average change during follow-up. The posted means are -2000.0 grams for anastrozole and -1500.0 grams for placebo. The between-group mean difference is -500.0 grams, calculated with anastrozole relative to placebo.

A continuous endpoint preserves the scale of the measurement and allows the size and uncertainty of an average difference to be described. It does not show how individual participants’ values were distributed, whether the change was similar across participants, or how the measurement relates to symptoms or daily functioning. A group mean can conceal variation among individuals, so the standard deviations and confidence interval matter when interpreting the estimate.

The registry record does not report the measurement instrument, measurement procedures, or details of how the change score was calculated. It also does not report a threshold for a clinically important change. Accordingly, the result describes the posted mean change and its between-group statistical comparison, but the registry alone does not establish the practical importance of that difference.

7. Results Posted in the Registry

• Anastrozole: mean -2,000 versus -1,500 on control; difference -500.00 (95% CI -874.73 to -125.27), standardized effect d = -0.64; z-test p = 0.009.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, so the registry reports a mean change for each arm and a mean difference between arms. A mean gives the average observed change within a group. The mean difference compares those group averages on the original measurement scale, here grams. The comparison is defined as anastrozole relative to placebo. Its estimate is -500.0 grams.

What does the mean difference represent?

The mean difference is a contrast between group summaries, not a statement that every participant changed by that amount. The arm means are -2000.0 grams for anastrozole and -1500.0 grams for placebo. Individual outcomes can vary around those means. The registry reports standard deviations of 1000.0 grams and 500.0 grams, respectively; a standard deviation describes the spread of observed values around a group mean. It is not the uncertainty of the mean difference itself.

The comparison uses outcome counts of 34 and 35. The record reports a pooled standard deviation of 787.0 grams and an effect size of -0.635. These are summary statistics for the posted comparison. The pooled standard deviation combines information about variation across arms for a standardized description; the mean difference, rather than the standardized effect size, retains the original gram scale. The registry record does not report a clinical threshold against which either measure could be judged.

How should the p-value be read?

The unadjusted p-value is 0.009. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model, assuming the model and analysis conditions hold. It is not the probability that the null hypothesis is true, nor does it quantify the probability that the finding is due to chance. It also does not measure clinical importance. Here it is an unadjusted result; the registry record does not report a multiplicity adjustment or an analysis plan that would clarify how this comparison fits into the full set of planned analyses.

Random assignment supports a comparison between groups by reducing systematic differences in expectation, but it does not guarantee that all possible sources of imbalance are absent in a particular study. The registry identifies the study as randomized and triple-masked. It does not report the randomization procedure, concealment process, or which parties were masked. Those details therefore cannot be evaluated from this record.

Why does variability matter?

Continuous outcomes vary among participants. When variability is large relative to the difference in means, the estimate is less precise; when variability is smaller, the estimate can be more precise, all else being equal. The reported arm standard deviations describe observed spread, while the confidence interval for the mean difference describes uncertainty in the estimated contrast. These are related but distinct quantities.

General statistical methods often assume that observations are independent and that the model adequately represents the outcome distribution. The registry record does not report diagnostic checks, model details, or whether assumptions were assessed. Over-dispersion is a general concern when observed variation is greater than a model allows: standard errors can then be too small, making intervals too narrow and p-values too optimistic. The outcome is continuous, and the record does not identify an over-dispersed model; this concept is a general explanation, not a reported feature of this analysis.

What does recalculated mean?

The posted comparison is a simple unadjusted recalculation from the reported group summary statistics. It compares the group means without a reported covariate adjustment. The record does not flag a discrepancy between this calculation and a sponsor analysis. The registry record does not state whether a different primary analysis was prespecified or whether an adjusted estimate was also produced. Consequently, the recalculated contrast should be interpreted as the unadjusted comparison represented by the posted summary statistics, not as a full account of every analysis that may have been performed.

The confidence interval from -874.7 to -125.3 grams provides an interval estimate for the mean difference under the calculation’s assumptions. If the same design and analysis were repeated many times, a confidence interval procedure would cover the true parameter at its stated confidence level in the long run. For the individual study, it is not correct to interpret the interval as assigning a probability to each possible value. It conveys both the direction and precision of the estimate.

The registry reports one primary outcome measure and no secondary measures. That limited posted outcome set does not show whether there were other outcomes, repeated assessments, or analyses that were not entered. The statistical plan, missing-data methods, and analysis populations are not reported in the registry record. These omissions limit assessment of whether the posted analysis matches the original plan and how sensitive the estimate might be to analytic choices.

10. Confidence Intervals and Precision

The estimated mean difference in change in lean body mass is -500.0 grams for anastrozole relative to placebo. Its 95% confidence interval extends from -874.7 to -125.3 grams. The interval lies entirely below zero, so the range of values compatible with the reported unadjusted calculation points in the same direction as the estimate. This does not establish the clinical importance of any value in the interval.

A confidence interval communicates precision as well as direction. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty about the size of the underlying difference. The interval spans values with different magnitudes, so the estimate should not be treated as an exact value. It is also conditional on the analysis assumptions, including how the outcome data were summarized and compared.

The posted group standard deviations are 1000.0 grams for anastrozole and 500.0 grams for placebo. The outcome-specific counts are 34 and 35. Variation within groups and the amount of outcome information contribute to the uncertainty of the between-group estimate. The registry record does not provide an adjusted interval, an alternative model, or sensitivity analyses that could show how robust the precision is to other analytic choices.

The unadjusted p-value of 0.009 is consistent with the interval excluding zero, but a p-value and a confidence interval answer different questions. The p-value summarizes evidence relative to a null model; the interval gives a range of effect values compatible with the data and assumptions. Neither indicates the probability that the result is clinically meaningful. The record does not report a threshold for clinical importance, so precision can be described statistically but not translated into a judgment about practical importance from this information alone.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They illustrate the sample size associated with detecting specified fractions of the observed effect under the stated planning assumptions. For 100% of the observed effect, the illustration gives 39 participants per arm for 80% power and 53 participants per arm for 90% power. For 75% of the observed effect, it gives 70 participants per arm for 80% power and 93 participants per arm for 90% power. For 50% of the observed effect, it gives 156 participants per arm for 80% power and 209 participants per arm for 90% power.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial’s design assumptions and sample-size justification are not reported in the registry record; these planning assumptions describe the illustration, not the trial’s original design.

In general, power is the probability that a specified analysis will detect an effect of the assumed size if that effect exists, under the planning model and assumptions. The 80% power column uses one target probability of detection, while the 90% power column uses a higher target probability. Smaller effects are harder to distinguish from random variation, so the planning calculations require more participants per arm as the assumed effect becomes smaller. These figures are planning illustrations, not observed power. They do not describe the probability that this completed study’s result is correct or that a future study will reproduce it.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -500.000; pooled standard deviation σ = 787.022.
2. n = 2 × (1.96 + 0.842)² × 787.022² / -500.000² = 38.9, rounded up to 39 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -500                      # observed difference in means
sigma <- 787.021591237894                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(136695)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 39 (80% power), 53 (90% power)
 75% of observed effect: n per arm = 70 (80% power), 93 (90% power)
 50% of observed effect: n per arm = 156 (80% power), 209 (90% power)
power.t.test: 39.9 
Simulated power at n = 39 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, change in lean body mass, and no posted secondary outcome measures. It does not report a multiplicity plan. Multiplicity arises when several outcomes, time points, subgroup comparisons, or statistical analyses are considered: the chance of at least one apparently unusual result can increase as the number of comparisons grows. A prespecified strategy can address that issue, but no such strategy is described in the registry record.

The posted p-value is unadjusted. The record does not report whether other analyses were performed, whether there were additional outcomes that were not posted, or how the primary comparison was selected. The absence of secondary results in the registry record should not be taken to mean that no other outcomes were collected or analyzed. Without the protocol or statistical analysis plan, the full analysis family and any planned corrections cannot be assessed.

Missing-data handling is also not reported in the registry record. The outcome-specific counts are 34 for anastrozole and 35 for placebo, but the record does not explain whether those counts reflect all randomized participants with available measurements, a particular analysis population, or another reporting convention. It does not describe withdrawals, missing measurements, imputation, or sensitivity analyses. The enrollment figure is 88, but the record does not reconcile enrollment with the outcome-specific counts.

The analysis population is not defined. The registry record does not say whether the comparison followed an intention-to-treat principle, included only participants with observed outcome data, or used another population. It also does not report exclusions after randomization or protocol deviations. These omissions make it difficult to evaluate how missingness and analysis-population choices may affect the estimate. The posted means, confidence interval, and unadjusted p-value can still be described, but their interpretation should remain limited to the reported summary comparison.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatic cancer (2.9%), hepatitis a (2.9%), pulmonary embolism (2.9%), embolic stroke (2.9%), prostate cancer (2.9%).

The registry reports serious adverse event figures by arm. In the anastrozole arm, 4 of 34 participants are listed as affected; in the placebo arm, 1 of 35 is listed as affected. These are counts and at-risk denominators, not estimates of a causal treatment effect. The registry also lists the leading serious adverse event terms with a percentage of 2.9% for each: pancreatic cancer, hepatitis A, pulmonary embolism, embolic stroke, and prostate cancer. The record does not identify an arm beside each term in this list.

For other adverse events, the registry lists 3 of 34 affected in the anastrozole arm and 3 of 35 in the placebo arm. The record does not define the “other” category in further detail. Death counts are not reported in the registry record.

These figures describe the safety entries posted in the registry; they do not establish whether an event was caused by the study intervention. The record does not provide event-level timing, severity details beyond the serious-event designation, exposure duration for each participant, or a comparative statistical analysis. Small event counts can be especially imprecise, and the figures should be read as descriptive reporting rather than as a definitive comparison of safety.

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

The posted primary result is a mean difference of -500.0 grams in change in lean body mass, comparing anastrozole with placebo from baseline to 1 year. The 95% confidence interval ranges from -874.7 to -125.3 grams, and the unadjusted p-value is 0.009. The group means are -2000.0 grams for anastrozole and -1500.0 grams for placebo. These figures describe the recorded outcome and the statistical comparison based on the posted summary data.

The result does not, on its own, show why the group averages differed. Nor does it establish whether the difference matters to participants’ health, symptoms, or functioning. The registry record does not report a threshold for clinically important change, patient-reported outcomes, or a link between lean body mass and outcomes that participants would directly experience. Statistical evidence against a zero difference is not the same as evidence of an important effect.

The result also does not establish that the finding applies to people outside the studied population. The record describes elderly men with mild hypogonadism, but does not provide detailed eligibility criteria or characteristics that would allow assessment of how representative the participants were. It does not report the study’s dosing details, adherence, missing-data approach, or analysis-population definition. Those factors could affect interpretation of the observed estimate.

The safety entries are descriptive and limited. Serious adverse events are reported as counts by arm, and the listed event terms are not mapped to a specific arm in the record. No causal attribution or comparative safety analysis is reported. Similarly, the absence of posted secondary outcomes does not establish that other outcomes were not measured.

Overall, the registry record supports a precise description of the posted primary comparison: the estimated mean change was lower in the anastrozole arm on the stated scale, with an interval that excludes zero under the unadjusted calculation. It does not establish clinical benefit or harm, explain mechanisms, resolve limitations in reporting, or provide a basis for individual treatment decisions.

16. Why This Trial Matters Statistically

This trial is statistically informative because it reports a continuous primary outcome as group means, standard deviations, a between-group mean difference, a confidence interval, and an unadjusted p-value. Together, these quantities show more than whether a statistical test crossed a threshold: they describe the direction, scale, variability, and uncertainty of the comparison. The interval from -874.7 to -125.3 grams makes the range of estimates compatible with the reported calculation visible.

The study also illustrates why endpoint scale matters. The mean difference is stated in grams, which is directly interpretable on the outcome’s measurement scale. A standardized effect size is also reported, but it does not replace the raw-scale estimate or establish whether the difference matters clinically. Statistical interpretation benefits from keeping effect magnitude, uncertainty, and clinical meaning distinct.

Another useful statistical point is that the posted comparison is unadjusted and the registry does not report a multiplicity plan, missing-data method, or analysis population. These omissions do not invalidate the reported calculation, but they limit how fully readers can evaluate its place in the trial’s analysis strategy. Randomization and masking are recorded, while procedural details that would help assess implementation are not.

The planning illustrations show how assumed effect size and desired power relate to required participants per arm under stated assumptions. They also make clear that detecting smaller effects requires more participants. These calculations are distinct from the original trial design, whose justification is not reported, and they are not observed power.

Finally, the record juxtaposes an enrollment figure with smaller outcome-specific arm counts without explaining the relationship. Recognizing that distinction prevents readers from treating the enrollment entry as the analysis denominator for the primary result. The trial therefore offers a useful example of reading effect estimates carefully while distinguishing the information reported from important methodological details that remain unavailable.

17. 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 registry record leaves several trial-specific limitations and reporting questions unresolved. It gives enrollment as 88 but reports outcome-specific arm counts of 34 for anastrozole and 35 for placebo, without explaining the relationship between enrollment and the primary-outcome analysis. The record does not describe participant flow, withdrawals, missing measurements, or whether the posted outcome counts represent the full analysis population.

Although the study is identified as randomized and triple-masked, the randomization procedure, allocation concealment, and identities of the masked groups are not reported. Dosing, treatment adherence, concomitant care, and procedures for maintaining masking are also not described. These omissions restrict assessment of how the intervention and comparator were delivered.

The primary result is an unadjusted comparison. The registry record does not report an adjusted analysis, prespecified covariates, an analysis plan, or sensitivity analyses. It also does not report a multiplicity strategy. Since no secondary outcome measures are posted, the record cannot show whether other endpoints were collected or analyzed. The original sample-size rationale is not reported, and the planning illustration should not be mistaken for that rationale.

For the endpoint itself, the record does not describe the measurement instrument or specify a threshold for clinically important change. The safety entries provide counts and event terms but do not report detailed timing, attribution, or a comparative analysis. These gaps mean that the reported result is best interpreted narrowly as a summary comparison of change in lean body mass, rather than as a complete account of efficacy, safety, or clinical relevance.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Anastrozole Administration in Elderly Hypogonadal Men — NCT00136695.
• Registry record last updated 2022-09-13; status last verified 2022-08.
• Results first posted 2017-01-27.
• 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.

21. Record Summary

The registry record describes a completed phase 2 randomized, triple-masked, parallel-group study of anastrozole versus placebo in elderly men with mild hypogonadism. Massachusetts General Hospital is listed as sponsor. Enrollment is recorded as 88; the primary outcome is change in lean body mass in grams from baseline to 1 year.

The posted arm means are -2000.0 grams for anastrozole and -1500.0 grams for placebo. The mean difference is -500.0 grams, with a 95% confidence interval from -874.7 to -125.3 grams and an unadjusted p-value of 0.009. Outcome-specific counts are 34 and 35. No secondary outcome measures are posted. Serious and other adverse event counts are reported by arm, while deaths are not reported in the registry record.

The record does not report the trial’s original sample-size justification, detailed statistical plan, missing-data methods, or analysis-population definition. The posted result therefore supports interpretation of the stated unadjusted primary comparison, with those reporting limitations in mind.