Endo-App Pain Benefits May Not Last, Letter Warns

A letter published in Archives of Gynecology and Obstetrics questions whether the reported benefits of the Endo-App, a digital intervention for endometriosis-related pain, are truly sustained. Writing in response to a real-world analysis by Nigdelis and colleagues, Zahide Küçük argues that the study’s improvements in selected outcomes do not yet establish a durable, clinically meaningful, or app-specific effect, and she lays out several analytical and clinical reasons for caution.

The central concern involves the study’s follow-up structure. Analyses at three months and at six to seven months were conducted separately among participants with paired baseline-to-follow-up observations, and the original authors noted that only some overlap may have occurred between respondents at the two time points. Because the three-month and six-to-seven-month groups were never directly compared, the later findings cannot demonstrate persistence or further improvement beyond month three. They may instead reflect a different, highly self-selected subgroup, a concern sharpened by the drop from 143 respondents at three months to only 55 at six to seven months.

The magnitude of the reported pain improvement is also modest, according to the letter. Self-reported average pain fell by 0.80 points at three months and 0.85 points at six to seven months, relative decreases of roughly 14 percent, with small effect sizes corresponding to a Cohen’s d of 0.28 at both time points. In chronic pain research, a reduction of about two points or 30 percent on a numerical rating scale has commonly corresponded to clinically important improvement, although a specific threshold for endometriosis-related pain is not well established. The letter notes that the observed mean reduction appears modest at the group level, while not excluding the possibility that individual patients may still benefit from the app as part of multimodal management.

Sick days and days requiring medical assistance did decrease significantly at six to seven months, with p values of 0.04 and 0.03 respectively. However, the letter characterizes these as indirect measures of disease burden rather than direct measures of symptom intensity, and it argues their nominal significance should be weighed against the number of outcomes tested.

Medication outcomes face a further measurement problem. Counting only the number of days on which pain medication was required does not establish comparable analgesic exposure, since nonsteroidal anti-inflammatory drugs differ substantially in duration of action, dose, dosing frequency, and anti-inflammatory potency. The broad term pain medication may also include paracetamol, which has no clinically meaningful anti-inflammatory activity, meaning one treatment day was counted identically regardless of the agent or cumulative exposure. Because analgesics and hormonal therapies are established components of endometriosis pain management, unmeasured differences or changes in these treatments could confound a small change in subjective pain.

The letter also raises concerns about how the pain phenotype was characterized. Fibromyalgia and other chronic overlapping pain conditions can coexist with endometriosis and are associated with greater pain severity, interference, and overall burden. Without documenting fibromyalgia, central sensitization, or other independent sources of pain, a single global pain score cannot confidently be interpreted as reflecting improvement specifically in endometriosis-related pain.

Statistical multiplicity adds another layer of caution. Six outcomes were examined at two follow-up points without adjustment, and the nominally significant six-to-seven-month findings, with p values between 0.02 and 0.04, would not remain significant under a simple Bonferroni threshold of approximately 0.004. While such a correction may be conservative, the clustering of borderline p values, the letter argues, warrants an explicitly exploratory interpretation of the secondary outcomes.

The original authors did acknowledge important limitations, including attrition, the lack of a concurrent control group, and limited information on concomitant treatments. The letter contends these limitations remain directly relevant to causal interpretation: expectancy effects, self-monitoring, natural symptom fluctuation, regression to the mean, and treatment changes cannot be distinguished from an app-specific effect in an uncontrolled design.

As possible next steps, the letter proposes a reanalysis restricted to participants with observations at all three time points to better characterize within-patient trajectories, along with a responder analysis using a prespecified threshold such as a 30 percent or two-point reduction on the numerical rating scale, and multiplicity-adjusted analyses or explicitly exploratory framing for secondary outcomes.

Taken together, the correspondence concludes that the available data suggest a modest improvement in selected outcomes but do not yet establish that the Endo-App produces a sustained, clinically meaningful, or app-specific effect, and that longitudinal within-patient and responder analyses would help clarify the durability and clinical relevance of the observed changes.

Subject of Research: A critique of real-world evidence for sustained pain benefits of the Endo-App in endometriosis

Article Title: Is the reported benefit of the Endo-App truly sustained?

Article References: Küçük, Z. (2026). Is the reported benefit of the Endo-App truly sustained?. Archives of Gynecology and Obstetrics, 313(1), Article 280. https://doi.org/10.1007/s00404-026-08582-1

Image Credits: AI Generated

DOI: 10.1007/s00404-026-08582-1

Keywords: endometriosis, Endo-App, digital health, chronic pain, statistical significance, attrition, pain measurement, correspondence, clinical research, effect size, reported, benefit