{"paper_id":"89c5b445-3ff0-40c2-8338-8b70517ea504","body_text":"Vol.:(0123456789)\nArchives of Gynecology and Obstetrics (2025) 311:1721–1731 \nhttps://doi.org/10.1007/s00404-025-08000-y\nRESEARCH\nVirtual reality‑based pain control in endometriosis: \na questionnaire‑based pilot study of applications for relaxation \nand physical activity\nViktoria Pakebusch1  · Barbara Schlisio2  · Birgitt Schönfisch1  · Sara Y . Brucker1  · Bernhard Krämer1  · \nJürgen Andress1 \nReceived: 13 February 2025 / Accepted: 3 March 2025 / Published online: 25 March 2025 \n© The Author(s) 2025\nAbstract\nPurpose Virtual reality (VR) based technology may offer new avenues in the management of chronic endometriosis-related \npain. Our prospective, 14-week, open, three-phase, cross-over pilot study investigated whether the use of VR technol-\nogy equipped with a relaxation-inducing application (VR-R) or an activity-stimulating application (VR-A) could change \nendometriosis-related chronic pelvic pain levels and impairment of daily life.\nMethods 23 women aged 32.7 (SD 8.2) with endometriosis-related pelvic pain were each assigned to a permutated sequence \nof three 4-week phases: (A) the VR-R, (B) VR-A, and (C) intervention-free control phases. Phases were separated by two \ninterspersed 1-week washout phases. Main outcome measures included: momentary, average, and maximum pain intensities \non a 0–10 numerical rating scale (NRS); the Pain Disability Index (PDI) score; the Pain Catastrophizing Scale (PCS) score; \nsleep quality (Medical Outcomes Study Sleep Scale (MOS-SS) score); the Depression Anxiety Stress Scales (DASS) score; \nand the general health-related quality-of-life score (Short Form (12) Health Survey (SF-12)).\nResults Compared to baseline, VR-R use showed statistically significant positive effects for several scores (NRS “average \npain”; PDI “total score”; PCS “total score” and the “magnification”, “rumination”, and “helplessness” subscores; MOSS-SS \n“index I and II”; and the DASS “depression” and “stress” subscores), whereas VR-A yielded significant positive changes \nonly for PDI “total score”; PCS “total score” and the “helplessness” and “magnification” subscores; MOSS-SS “index II”; \nand DASS “depression” and “stress”. As four scale scores also showed significant improvements for control, a comparison \nof the effects was performed to offset a potential placebo-like effect by comparing difference from baseline against control. \nThis analysis yielded significantly greater positive effects only for VR-R: PCS “total score” and “helplessness”; MOSS-SS \n“index I” and “index II”; and the three DASS subscores “depression”, “anxiety”, and “stress”. SF-12 showed no significant \nchanges in either analysis.\nConclusions VR-R and VR-A showed positive effects on several pain and quality-of-life scores, which were significant for \nsome scores compared to baseline. For VR-R, some of these improvements were indeed significantly greater than under \ncontrol conditions, while the effects with VR-A were not. Larger studies are needed to corroborate these findings.\nTrial registration DRKS00030189.\nKeywords Chronic pain management · Benign gynecological disease · Nonpharmacological treatment · Supportive care · \nImmersive visual technology\nAbbreviations\nDASS  Depression anxiety and stress scale\nMOS-SS  Medical outcome study-sleep scale\nNRS  Numerical rating scale\nNS  Not significant\nPCS  Pain catastrophizing scale\nPDI  Pain disability index\nPRN  Pro re nata (as needed)\nSF-12  Short form health survey SF-12\nVR  Virtual realty\nVR-A  VR activity\nVR-R  VR relaxationViktoria Pakebusch and Barbara Schlisio are joint first authors.\nExtended author information available on the last page of the article\n\n1722 Archives of Gynecology and Obstetrics (2025) 311:1721–1731\nWhat does this study add to the clinical work \nA cross-over pilot study of relaxation- or physical \nactivity-inducing virtual reality technology showed \nimprovements in endometriosis-related chronic pain \nand quality of life using scales to measure pain and \nother parameters.\nIntroduction\nEndometriosis is a common benign but chronic disease in \nwomen of reproductive age, in which endometrial cells grow \noutside the uterine cavity, forming lesions within the uterine \nwall (adenomyosis) and in extrauterine sites, such as the \novaries, fallopian tubes, and abdominal tissues, including \nthe bladder, intestines, peritoneum, and diaphragm [1 –5]. \nSymptoms, if present, vary greatly from patient to patient [6, \n7] and typically include chronic pelvic pain with or without \nlower back or abdominal pain, dysmenorrhea, dyspareunia, \ndysuria, dyschezia, ovulation pain (mittelschmerz), and pain \nduring physical activity. As symptoms tend to be unspecific, \nendometriosis often remains undiagnosed for many months \nand even up to years [1 , 3, 8–10]. Endometriosis-related \nchronic pain is often severe and can significantly affect the \ndaily life of patients. The resulting medical costs and loss of \nproductivity are also of considerable economic importance \ndue to the frequency of the disease [11– 14]. Furthermore, \nendometriosis can cause infertility [15, 16] and patients \nwith endometriosis often suffer from depression, anxiety \nand sleep disorders [17].\nTreatment options typically include analgesics, surgery, \nhormonal therapy, and complementary medical treatments \n[1–3, 18– 21]. Nonpharmacologic and nonsurgical \napproaches to the management of chronic pain include \npsychotherapy, distraction techniques, and physical activity \n[22].\nWith the advent of virtual reality (VR) based technology \nin recent years, new avenues are currently also being \nexplored in the management of chronic endometriosis \npain [23, 24]. More generally, VR has been shown to be \neffective in the treatment of chronic pain associated with \nother diseases, or in the treatment of comorbidities such as \nanxiety and depression, as recent meta-analyses have shown \n[25, 26].\nAgainst this backdrop, we sought to investigate the \npotential beneficial effects of using VR headsets equipped \nwith relaxation  (HypnoVR ®) and activity (SyncVR  Fit®) \napplications on self-reported endometriosis-related chronic \npain, pain-related disability in everyday life, health-related \nand overall quality of life, and the general well-being of \nendometriosis patients.\nMethods\nStudy population\nEligible for inclusion were women aged at least 18 years \nwith a histologically confirmed diagnosis of endometriosis, \nreporting endometriosis-related severe pelvic pain with pre-\nstudy baseline ratings of at least 5 points on visual numerical \nrating scale (NRS). Recruitment occurred during routine \noutpatient visits to our university level-3 endometriosis \ncenter. Baseline ratings were derived from patient-reported \nNRS ratings for the preceding four weeks. Further eligibility \ncriteria included the willingness not to have surgery or begin \na new drug or nondrug treatment (opioid or nonopioid \nanalgesic, acupuncture, behavioral therapy, massages, \netc.) during study participation. Inclusion also required an \nadequate knowledge of German and the assurance that the \nstudy devices would be used according to manufacturers’ \ninstructions.\nExclusion criteria included serious mental illness (e.g., \npsychosis, schizophrenia, or bipolar disorder) and major \ndepression based on screening with the aid of the study \nquestionnaires and the Depression Anxiety Stress Scales \n(DASS). Starting regular use of opioid analgesics within \nseven days preceding study entry was also an exclusion \ncriterion.\nStudy objectives\nThe aim of this study was to investigate whether the use of \nVR technology with a relaxation application  (HypnoVR®) \nor an activity application (SyncVR  Fit®) had an effect on \nthe reported pain level and endometriosis pain-related \nimpairment of daily life.\nPrimarily, we investigated momentary, average, and \nmaximum pain intensity per day. Secondary objectives \nincluded recording (1) pain-related disability as measured \nusing the Pain Disability Index (PDI); (2) sleep quality as \nmeasured using the Medical Outcome Study–Sleep Scale \n(MOS-SS); and (3) general health-related quality of life as \nmeasured using the 12-item Short Form (12) Health Survey \n(SF-12).\nStudy design, devices, and interventions\nStudy design. This study was a prospective, 14-week, open, \nthree-phase, cross-over pilot study with 1-week washout \nperiods interspersed between phases. Each participant \nsequentially completed a four-week intervention phase with \n\n1723Archives of Gynecology and Obstetrics (2025) 311:1721–1731 \neach of the two study devices, and a four-week intervention-\nfree control phase. The sequence of the two intervention \nphases and the control phase was permutated, yielding an \nallocation plan with six different sequences. Participants \nwere consecutively included and assigned to one of the six \npredetermined intervention/control sequences in accordance \nwith the allocation plan. Questionnaires were completed \nat baseline and after each study phase. Additionally, \nparticipants were provided with a paper-based pain diary \nfor daily completion (see below). Participants had four \ninterviews, one at the initial visit (eligibility assessment \nand baseline data collection) and one after completing each \nstudy phase.\nThe study protocol received prior approval from the \nethics committee of the medical faculty of Tübingen \nUniversity Hospital, Tübingen, Germany (approval \nnumber 893/2021B01) in accordance with the ICH-GCP \nguidelines, the Declaration of Helsinki, and all relevant \nlaws and regulations. All participants gave their prior written \ninformed consent.\nStudy devices. Two virtual reality (VR) headsets were used \nas study devices: the Pico G2 4 K (Pico Technology Co., \nLtd, Beijing, China) with the pre-installed  HypnoVR ® \n(HypnoVR SAS, Lampertheim, France, www. hypno  vr. io/ \nen) application and the Pico Neo 3 Pro with the pre-installed \nSyncVR  Fit® (Amersfoort, The Netherlands, www. syncv  \nrmedi cal. com) application. Virtual experiences with the \n HypnoVR® included, e.g., a journey through space and a \ndeep-sea dive for virtual reality-induced relaxation (VR-R), \nwhereas the SyncVR  Fit® offered virtual reality-induced \nactivity (VR-A) by motivating participants to be physically \nactive and, e.g., perform guided body movements or play \nsoccer in a virtual stadium. Examples of the 3D-immersive \nVR environments provided by the VR-R and VR-A applica-\ntions are shown in Figs.  1 and 2. \nStudy interventions. These consisted in using the assigned \nVR device for 15–20 min three times a week, completing \nthe relevant online questionnaires described below, and \ndocumenting the experience in an electronic pain diary \nonline. In addition, pro re nata (PRN, as needed) use \nwas permitted, but needed to be recorded. During the \ncontrol phase, participants were required to complete the \nquestionnaires and keep their pain diary.\nData collection\nQuestionnaires. Table  1 lists the questionnaires used to \nrecord basic demographic and medication-related data \nas well as three pain-related questionnaires and three \nquestionnaires pertaining to quality of sleep, quality of \nlife, and mental health. Participants were requested to \ncomplete the questionnaires at the same time of day (7 pm, \nif possible).\nParticipants used a secure web-based survey platform \n (Unipark®, Tivian XI GmbH, Cologne, Germany; www.  \nunipa rk. com) hosting the NRS, PDI, PCS, MOS-SS, DASS, \nand SF-12 questionnaires to record their pain ratings, \nadditional self-assessments, and use of pain medication. No \npersonal data were stored on the  Unipark® platform.\nPain diary. Participants were instructed to keep a purpose-\ndesigned, paper-based pain diary throughout the study \nduration (including washout periods), detailing momentary \npain at rest, average pain, and maximum pain intensity at \nthe same time of day (7 pm, if possible). They were also \nrequested to provide information on their medication \nFig. 1  Examples of 3D-immersive virtual reality environments for \nrelaxation (VR-R): a winter day (top), an ocean beach (middle), and \nan underwater landscape (bottom) (reproduced with kind permission \nfrom the rights owner)\n\n1724 Archives of Gynecology and Obstetrics (2025) 311:1721–1731\nrequirements, including PRN medication, and their \nmenstrual cycle, including typical cycle duration, duration of \nmenstruation, and whether they had experienced menstrual \nbleeding or spotting within the last 24 h.\nData analysis\nStatistical analysis was performed using R, Version 4.2.2. \nDescriptive statistics used numbers and percentages and \nmeans and standard deviations (SD). The difference to \nbaseline was assessed by paired Wilcoxon–Mann–Whitney \nrank test. To investigate the effects of treatments, the \ndifferences to baseline Δ B for VR-R and VR-A were \ncompared versus the Δ B for control. A linear model for \nPRN medication depending on the presence or absence \nof menstrual bleeding was formulated with participant as \nrandom factor. A significance level of 5% was chosen in \nall statistical tests.\nResults\nStudy population\nThe study was conducted between 10/2022 and 02/2023. \nOut of 25 eligible candidates meeting the inclusion criteria, \n2 discontinued study participation after completing the \nbaseline visit and the baseline questionnaire and were \ntherefore excluded from the study. Table  2 summarizes \nthe 23 participants’ baseline demographic and clinical \ncharacteristics.\nParticipants stated their occupations as: homemaker \n(1/23), student or apprentice (6/23), job seeker (1/23), \nfull-time worker (10/23), or part-time worker (5/23). None \nindicated being unable to work.\nEndometriosis-related pain had persisted for 1 to more \nthan 5 years in all participants at study initiation, with \n11 of 23 (48%) participants reporting comorbidities. \nSingle instances of other complaints reported by 12 of \n23 (52%) included cold symptoms, hormone fluctuations, \nexhaustion/fatigue, gastrointestinal complaints (bloating, \npain, food intolerance), headaches, sleep disorders, fears, \npalpitations, leg cramps, frequent urge to urinate, back \npain, dyspareunia, and hypothermia, amongst others.\nTreatment with hormones as contraceptives or \nendometriosis medications was reported by 12 out of 23 \n(52%). Reports of nonpharmacologic treatments for pain \nincluded physiotherapy (5 of 23 patients), psychotherapy \n(3 of 23), and acupuncture and relaxation techniques (5 \nof 23).\nFig. 2  Examples of 3D-immersive virtual reality environments induc-\ning physical activity (VR-A): throwing rings into a pyramid (top), \ncatching fireflies (middle), and throwing soccer balls (bottom) (repro-\nduced with kind permission from the rights owner)\n\n1725Archives of Gynecology and Obstetrics (2025) 311:1721–1731 \nCompleteness of data sets\nTwo participants did not complete the baseline question-\nnaire. One participant discontinued after the first phase and \nanother after the second phase. Pain diaries were missing \nfor two other participants. Due to the small number of par -\nticipants and since this was a pilot study, these participants \nwere not excluded.\nPain diary\nPain diary. Complete pain diaries were obtained from 21 \nout of 23 (91%) participants. Scatter diagram analysis of \nthe questionnaire and pain diary recordings of average \nand maximum pain matched well (with respective Pearson \ncorrelation coefficients of  rP = 0.84 and  rP = 0.90). VR-A \nand VR-R phases were not associated with any significant \ndifferences in diary-recorded pain scores averaged per \nparticipant when compared against control or each other.\nMenstrual bleeding. Momentary pain at rest, average \npain, and maximum pain averaged per participant were all \nsignificantly greater with menstrual bleeding than without \n(p = 0.027, p = 0.011, and p = 0.008, respectively).\nPRN medication. There was no significant difference in \nPRN medication averaged per participant in the presence or \nabsence of menstrual bleeding (p = 0.114). A linear model \nfor PRN medication depending on the presence or absence \nof bleeding with participant as random factor showed a \nsignificant difference (p < 0.001). These results demonstrate \nthe importance of collecting menstrual cycle data.\nFigure  3 shows an example of the time course of pain rat-\nings as reported by one participant during the study. Gener-\nally, pain ratings in all three pain categories increased with \nthe onset of menstruation, accompanied by increased con-\nsumption of PRN medication.\nTable 1  Study questionnaires\nDecreases in scores indicate improvement except with SF-12, where increases indicate improvement\nPRN pro re nata (as needed)\nQuestionnaire Purpose\nBasic questionnaire Collection of demographic data, including age, weight, height, previous and current analgesic \n(long-term or PRN) medication\nNumerical rating scale (NRS) for pain Subjective assessment of pain intensity on a 0–10 rating scale\nPain disability index (PDI) Self-assessment of chronic pain-related disruption of everyday life activities to measure \nsubjective pain-related disability\nPain catastrophizing scale (PCS) Measurement of exaggerated negative perception of pain, comprising 3 subscales \n(“magnification”, “rumination”, and “helplessness”)\nMedical Outcome Study–Sleep Scale (MOS-SS) Assessment of the quality and possible impairment of night sleep\nDepression Anxiety and Stress Scale (DASS) Determination of the probability of the presence of depressive disorder or anxiety disorder\nShort Form (12) Health Survey (SF-12) 12-item self-reported survey of general health-related quality of life\nTable 2  Baseline demographic and clinical characteristics of the \nstudy population (n = 23)\nSD standard deviation\n*Age is given as patient-reported full years\nMean (SD) \nor number | \npercentage\nDemographics\n Age at  baseline*, years 32.7 (8.2)\n Body mass index, kg/m 2 22.6 (4.4)\nEndometriosis\n Duration of endometriosis-related pain, years\n   < 1 0 | 0%\n  1–5 7 |30%\n   > 5 16 |70%\n Comorbidities (multiple entries possible)\n  Anxiety disorder 0|0%\n  Chronic lower back pain 2|9%\n  Chronic headaches 3|13%\n  Depression 3|13%\n  Other pain disorders 7|30%\n  No comorbidities 12|52%\nPain medication\n Opioids 3|13%\n Before study entry 3|13%\n After study entry 3|13%\n Nonopioids 21|91%\n Daily use 3|13%\n Occasional use 18|78%\nHormone treatment 12|52%\n Oral contraceptive 9|39%\n Hormonal intrauterine device 2|9%\n Vaginal ring 1|4%\n\n1726 Archives of Gynecology and Obstetrics (2025) 311:1721–1731\nQuestionnaires\nPain numerical rating scale\nThe pain NRS questionnaire measures momentary pain \nseverity and average and maximum pain during the pre-\nceding 4 weeks. Figure  4 shows that for average pain, the \nmean NRS value of 3.3 exhibited a significant difference \nversus baseline (4.4) for VR-R (p = 0.033), whereas VR-A \n(3.6) and control (3.8) did not. No significant differences in \nNRS scores versus baseline were observed for momentary \npain and maximum pain (data not shown). Comparisons \nof differences from baseline Δ B yielded no statistically \nsignificant effects for momentary, average, and maximum \npain on the NRS scale observed with either VR-A and \nVR-R versus control (Table  3).\nPain disability index (PDI)\nThe 7-item Pain Disability Index (PDI) questionnaire \nmeasures self-reported pain-related impairment [ 27]. PDI \nscores were significantly lower than baseline for VR-A, \nVR-R, and control (p = 0.008, p = 0.003, and p = 0.008, \nrespectively). Testing Δ B values of VR-A and VR-R versus \ncontrol yielded no statistically significant differences \n(p = 0.270 and p = 0.457, respectively).\nFig. 3  Example of a time course of participant-reported pain ratings in the diary throughout the study. Solid black line = maximum pain; dashed \nline = average pain; solid grey line = momentary pain; red dashes = days with menstrual bleeding; circles = PRN medications\nFig. 4  Average pain on the NRS \nscale as reported for baseline, \nvirtual reality-guided activity \n(VR-A) and relaxation (VR-R), \nand control\n\n\n1727Archives of Gynecology and Obstetrics (2025) 311:1721–1731 \nPain catastrophizing scale (PCS)\nThe 13-item Pain Catastrophizing Scale (PCS) measures the \nextent of pain catastrophizing, distinguishing 3 subscales: \n“rumination”, “magnification,” and “helplessness” [28, 29]. \nPCS total scores and all three PCS subscores for both VR \napplications differed significantly from baseline, as did the \ncontrol, with the exception of the “helplessness” subscore \nfor the control and the “rumination” subscore for VR-A.\nHowever, comparison of the differences from baseline \n(Δ B values) for the PCS total score and the PCS subscores \nof VR-A and VR-R against control showed no statistically \nsignificant effects, except for the PCS total score (p = 0.043) \nand the PCS “helplessness” subscore (p = 0.023) observed \nwith VR-R versus control.\nMedical outcomes study sleep scale (MOS‑SS)\nThe 12-item MOS-SS questionnaire measures sleep qual-\nity during the 4 weeks before questioning [30]. MOS-SS \nquestionnaire items are detailed in Supplementary Table 1 \nonline (based on [31]). MOS-SS scores for sleep disturbance \ndiffered significantly from baseline for VR-A, VR-R, and \ncontrol. For VR-R, the scores for somnolence, index I, and \nindex II also differed significantly from baseline; for VR-A, \nthe index II score differed significantly from baseline. Test-\ning Δ B values of VR-A and VR-R versus control yielded \nsignificant effects only for the index I and index II scores \n(p = 0.019 and p = 0.003, respectively).\nDepression anxiety stress scale (DASS)\nThe 21-item DASS self-report questionnaire comprises \n7 questions per subscale to assess signs of depression \n(DASS-D), anxiety (DASS-A), and stress (DASS-S) over \nthe past week [32, 33]. DASS -D and DASS-S subscores \nwere statistically significantly different from baseline \nfor both VR applications but not for control, whereas the \nDASS-A subscores were not significantly different. By \ncontrast, testing differences from baseline (Δ B values) \nVR-R versus control yielded significant effects for all 3 \nsubscores (p = 0.014 for DASS-D, p = 0.033 for DASS-A, \nand p = 0.004 for DASS-S).\nTable 3  Qualitative summary of \nquestionnaire results for virtual \nreality interventions and control \nversus baseline, and changes \nfrom baseline Δ B for virtual \nreality interventions versus \ncontrol\nNS not significant, NRS numerical rating scale, PDI pain disability index, PCS pain catastrophizing scale, \nMOSS-SS medical outcome study – sleep scale, DASS depression anxiety and stress scale, SF-12 short form \n(12) health survey SF-12, VR-R VR relaxation, VR-A VR activity\n*Significant increase or decrease in measured scores\nVR-R vs. \nbaseline n = 22\nVR-A vs. \nbaseline n = 21\nControl vs. \nbaseline n = 23\nChange from baseline Δ B\nVR-R vs. \ncontrol n = 22\nVR-A vs. \ncontrol \nn = 21\nPain on NRS scale (↓ = improvement)\n Momentary pain ↓ ↓ ↓ NS NS\n Average pain ↓* ↓ ↓ NS NS\n Maximum pain ↓  → ↓ NS NS\nPDI (↓ = improvement)\n Total score ↓* ↓* ↓* NS NS\nPCS (↓ = improvement)\n Total score ↓* ↓* ↓* Significant NS\n Helplessness ↓* ↓* ↓ Significant NS\n Magnification ↓* ↓* ↓* NS NS\n Rumination ↓* ↓ ↓* NS NS\nMOSS-SS (↓ = improvement)\n (Sleep) Index I ↓* ↓ ↓ Significant NS\n (Sleep) Index II ↓* ↓* ↓ Significant NS\nDASS (↓ is improvement)\n Depression ↓* ↓* ↓ Significant NS\n Anxiety ↓ ↓ ↑ Significant NS\n Stress ↓* ↓* ↓ Significant NS\nSF-12 (↑ = improvement)\n Physical health ↑ ↑ ↑ NS NS\n Mental health ↑ ↑ ↓ NS NS\n\n1728 Archives of Gynecology and Obstetrics (2025) 311:1721–1731\nSF‑12 health survey\nThe Short Form (12) Health Survey is a 12-item, self-\nreported health survey that provides physical health \nand mental health scores [34]. In our study, neither VR \napplication yielded statistically significant results, whether \ncomparisons were performed as scores versus baseline or \nΔ B versus control.\nSummary of results\nOverall, the results of our 14-week VR-based intervention \nstudy of pain disability; sleep; depression, anxiety, and \nstress; and physical and mental health demonstrates that, \ncompared versus baseline, both VR applications showed \nstatistically significant reductions in some of the scores for \nthe respective rating scales employed. Significant differences \nwere also seen for the control phase and baseline (Table  3).\nDiscussion\nPrincipal findings\nEndometriosis is often associated with severe chronic \npain. Patients with chronic pain tend to feel helpless and \ndependent on others, which in turn may trigger, inter \nalia, depression and anxiety [17]. Current guideline-\nbased standard pain treatments involving analgesics, \nhormone therapy, and surgery are frequently inadequate \nand may entail specific risks and considerable side effects. \nSupportive care also provides only limited relief and is often \nunsatisfactory [22]. Hence there is a need for new methods \nthat are readily available, have few side effects, and will help \nto restore patients’ sense of self-efficacy.\nWith the advent of VR technology, which immerses \nthe user in an alternative audio-visual reality, VR-based \ndistraction, relaxation, and physical activity interventions \nhave been found to be effective in the treatment of chronic \npain of various etiologies [25, 26]. The present study \ninvestigated the use of virtual reality applications in \nendometriosis patients with regard to pain, sleep quality, \nmental health, and quality of life. To our knowledge, our \nstudy was the first to compare the effects of two different VR \napplications, i.e., relaxation (VR-R) and activity (VR-A), \nagainst a VR intervention-free control phase in a cross-over \ndesign. Moreover, it was also the first study to run over a \nlonger period of 14 weeks in total to investigate medium-\nterm effects on the above-mentioned areas investigated.\nOur study showed that the use of VR-R led to significant \nimprovements in several pain and quality-of-life scores. \nAs improvements were also seen in the control phase, in \ncontrast to other studies [23, 24], we performed further \nanalyses which took into account the change from baseline \nΔ B in order to determine as precisely as possible the effect \nof the intervention as such, so as to differentiate the effect \nof the VR intervention from the effect of study participation \n(potential placebo-like effect in the control).\nWith VR-R, changes that were significantly greater than \ncontrol were thus observed for the PCS (“Total score” \nand the “helplessness” subscore), MOSS-SS (“index I” \nand “index II”), and DASS (“depression”, “anxiety”, \nand “stress”) scores. Positive effects were also observed \nfor “average pain”, PDI “total score”, and the PCS \n“magnification” and “rumination” subscores, although \nthese were not significant when compared to the changes \nin the control. With VR-A, improvements from baseline \nwere noted for the PDI (“total score”), PCS (“total score”, \n“helplessness”, and “magnification”), MOSS-SS (“index \nII”), DASS (“depression” and “stress”) scores, but these \nwere not significantly greater than the effects in the control.\nA comparison of the present study with previously \npublished data reveals clear differences. In 2022, Merlot \net al. [23] published the results of a randomized controlled \ntrial in 45 women with endometriosis-related chronic \npelvic pain. They investigated a single immersion-based \nVR intervention for pain treatment, followed by 6 pain \nrecordings over a period of 4 h. By contrast, we recorded 84 \npain scores and quality-of-life data items per participant in \na crossover design over a 14-week study period.\nA second study by Merlot et  al. published in 2023 \n[24] revisited the topic, expanding the study to 102 \nparticipants treated with immersive VR technology after \nrepeated use of VR, but again limited to 2–5 days starting \nfrom menstruation. The total of 4 measurements of pain \nperception were also only taken around the intervention \non the same day. Of particular note, the authors did not \naccount for the potential placebo-like effect in the control \ngroup, which in contrast to our study was a “control group” \nwith intervention but without immersive technology. \nNevertheless, the authors speak of a significant improvement \nin pain perception through the use of VR with immersive \ntechnology. By contrast, our present study attempted to \nanalyze the efficacy of both VR-R and VR-A as precisely \nas possible by addressing the potential influence of mere \nparticipation in the study.\nStrengths and limitations\nSeveral strengths and limitations of our study should be \nconsidered when interpreting our results. One strength is \nthat this was the first study to compare the effects of 4-week \nperiods of VR-based relaxation and VR-based exercise \ntherapy on pain and quality-of-life related parameters with \na 4-week VR intervention-free control phase. Also, the \ncrossover design enabled us to conduct this pilot study with \n\n1729Archives of Gynecology and Obstetrics (2025) 311:1721–1731 \na comparatively small number of participants. Furthermore, \nalthough treatment allocation was not randomized in the \nstrict sense, the preestablished allocation table eliminated \narbitrary assignment of consecutive patients to a specific \ntreatment sequence. Carry-over effects were minimized by \n1-week washout periods in between study phases. Of note, \ncompliance with study requirements was very high across \nall participants, which was reflected not least in the high \nquality of the data. Moreover, the pain diary entries matched \nclosely with the questionnaire responses. In addition, while \nfavoring VR-based relaxation, all participants stated they \nhad subjectively benefited from the study. Last, our study \npopulation was balanced with regard to hormone therapy, \nwith half of participants (52%) receiving hormones.\nA specific, and likely the most important limitation of the \nstudy was its small sample size of 23 participants, which may \nhave impacted the significance of the results and therefore \nwarrants special consideration in future, larger studies. \nHowever, this was a pilot study with a cross-over design, \nwhich allowed us to keep the sample size to a minimum. \nFurther sample-size considerations included the logistics \nof exchanging the high-cost devices between participants \nin the midst of the ongoing COVID-19 pandemic. In this \ncontext it is remarkable that only two of the 23 participants \ndiscontinued their participation. Due to the small sample \nsize, it was not possible to take the sequence of study phases \ninto account in the analysis. However, our findings show the \nimportance of varying the sequence of study phases, ideally \nto use all possible permutations equally often in the absence \nof randomization.\nConclusions\nVR-R was shown to have positive effects on a number of \npain and quality-of-life scores, which were significant for \nseveral scores when compared to baseline, and some of these \neffects were even shown to be significantly larger than those \nobserved in the control. Moreover, VR-A showed significant \npositive effects compared to baseline; however, in our small \nsample, these effects were not significantly greater than \nthose in the control. We conclude that VR-R may have a \ngreater impact than VR-A but concede that both VR options \nneed to be further explored in larger studies.\nSupplementary Information The online version contains supplemen-\ntary material available at https:// doi. org/ 10. 1007/ s00404- 025- 08000-y.\nAcknowledgements We are grateful to HypnoVR and SyncVR Medi-\ncal, who provided the headsets and software applications for the pur -\nposes of the present study. While both companies provided instructions \nand advice on the use of the study equipment, neither company had \na role in the design or conduct of the study, data analysis, data inter -\npretation, or manuscript writing. The authors retained full control of \nmanuscript content at all times. The present data and results are part of \nVP’s doctoral thesis, which at the time of writing was at the finalization \nstage and unpublished. VP is the principal author and has given consent \nto publish the data reported in this article.\nAuthor contributions V Pakebusch: Protocol/project development, \nData collection or management, Data analysis, Manuscript writing/\nediting; B Schlisio: Protocol/project development, Manuscript \nwriting/editing; B Schönfisch: Protocol/project development, Data \nanalysis, Manuscript writing/editing; SY Brucker: Manuscript \nwriting/editing; B Krämer: Manuscript writing/editing; J Andress: \nProtocol/project development, Data collection or management, Data \nanalysis, Manuscript writing/editing. The first draft of the manuscript \nwas written by Viktoria Pakebusch and Jürgen Andress. All authors \ncommented on earlier manuscript versions, and read and approved the \nfinal manuscript.\nFunding Open Access funding enabled and organized by Projekt \nDEAL. This research received no external funding.\nData availability No datasets were generated or analysed during the \ncurrent study.\nDeclarations \nConflict of interest The authors have no relevant financial or non-fi-\nnancial interests to disclose.\nEthical approval The study protocol received prior approval from the \nethics committee of the medical faculty of Tübingen University Hospi-\ntal, Tübingen, Germany (approval number 893/2021B01) in accordance \nwith the ICH-GCP guidelines, the Declaration of Helsinki, and all \nrelevant laws and regulations. All participants gave their prior written \ninformed consent to participate in the present study.\nOpen Access This article is licensed under a Creative Commons Attri-\nbution 4.0 International License, which permits use, sharing, adapta-\ntion, distribution and reproduction in any medium or format, as long \nas you give appropriate credit to the original author(s) and the source, \nprovide a link to the Creative Commons licence, and indicate if changes \nwere made. The images or other third party material in this article are \nincluded in the article’s Creative Commons licence, unless indicated \notherwise in a credit line to the material. If material is not included in \nthe article’s Creative Commons licence and your intended use is not \npermitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a \ncopy of this licence, visit http://creativecommons.org/licenses/by/4.0/.\nReferences\n 1. 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In: Leibniz-Institut für Psychologie \n(ZPID) (ed) Open Test Archive. ZPID, Trier\n 34. Morfeld M, Kirchberger I, Bullinger M (2011) SF-36 Fragebogen \nzum Gesundheitszustand: Deutsche Version des Short Form-36 \nHealth Survey, 2nd edn. Hogrefe Verlag, Göttingen\nPublisher's Note Springer Nature remains neutral with regard to \njurisdictional claims in published maps and institutional affiliations.\n\n1731Archives of Gynecology and Obstetrics (2025) 311:1721–1731 \nAuthors and Affiliations\nViktoria Pakebusch1  · Barbara Schlisio2  · Birgitt Schönfisch1  · Sara Y . Brucker1  · Bernhard Krämer1  · \nJürgen Andress1 \n * Jürgen Andress \n juergen.andress@med.uni-tuebingen.de\n Viktoria Pakebusch \n viktoria.pakebusch@med.uni-tuebingen.de\n Barbara Schlisio \n barbara.schlisio@med.uni-tuebingen.de\n Birgitt Schönfisch \n birgitt.schoenfisch@uni-tuebingen.de\n Sara Y. Brucker \n sara.brucker@med.uni-tuebingen.de\n Bernhard Krämer \n bernhard.kraemer@med.uni-tuebingen.de\n1 Department of Obstetrics and Gynecology, University \nof Tübingen, Calwerstr. 7, 72076 Tübingen, Germany\n2 Department of Anesthesiology and Intensive Care \nMedicine, University of Tübingen, Hoppe-Seyler-Str. 3, \n72076 Tübingen, Germany","source_license":"CC0","license_restricted":false}