protocolSection identificationModule nctId: NCT06306404, orgStudyIdInfo id: NL86165.100.24, briefTitle: Improving Sleep and Mood in the Peri-menopause, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-06-01, primaryCompletionDateStruct date: 2028-06-01, completionDateStruct date: 2028-06-01, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: VU University of Amsterdam, class: OTHER, collaborators name: ZonMw: The Netherlands Organisation for Health Research and Development, collaborators name: Netherlands Brain Foundation, collaborators name: Purplexus, descriptionModule briefSummary: The perimenopause is known as a vulnerable period for some women, with noticeable somatic and psychological issues. Aside from climacteric symptoms, insomnia and depression are common. About half of women during the peri-menopausal period experience sleep problems like problems falling asleep, awakening during the night and being unable to return to sleep. This is often attributed to vasomotor symptoms, but this is not the only reason of poor sleep (Joffe et al., 2010). Also, the peri-menopausal period is a critical time for the occurrence of new onset and recurrent depressions (Cohen et al., 2006). It has been suggested that fluctuations in estradiol may increase the risk for depression by altering neuronal functions in the brain. But there are also indications that the risk for depression increases by indirect effects, such as the increase in insomnia. Poor sleep has increasingly been recognized as the key modifiable factor affecting mental issues like depression (Van Someren, 2021). While antidepressants and psychotherapies continue to be the treatments of choice for depression, and Cognitive Behavioral Therapy for sleep (CBTi) for insomnia, preclinical and clinical data support the benefits of estrogen-based therapies to improve mood, sleep and other menopause-related symptoms (Gordon et al. 2018). Transdermal estradiol patches, which provide a stable release of estradiol and lead to more stable blood levels, have been suggested to have a positive effect on sleep (Joffe et al., 2020) and depressive symptoms (Gordon et al., 2018) in randomized controlled trials. However, it is currently unclear if the relation between improvement in mood and estradiol patches is mediated by improvement in sleep problems, and if the effect of estradiol patches on sleep problems is more effective during peri-menopause than the current evidence-based sleep interventions of CBTi, preferably in combination with Circadian Rhythm Support (CRS). The aim of the study is to pinpoint the determinants of complaints about sleep and mood and how they respond to Menopausal Hormone Treatment (MHT) with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.Measurements will be conducted at baseline (T0), 2 months (T1) and 4 months (T3), with questionnaires, sleep measurements (EEG sleepband and actigraph) and skin conductance (to measure hot flushes). Participants will be recruited via www.slaapregister.nl and via OLVG outpatient clinic population of peri-menopausal women seeking help for climacteric complaints (like hot flushes, feeling bloated, increase in weight), including sleep problems. The participants are adults between 40-55 years old, with an Insomnia Severity Index score ≥10 and Climacteric Green Scale score ≥ 13.They have the self-considered capability to complete online questionnaires and diaries in Dutch.The intervention will be MHT (estradiol transdermal patches 50 mcg (Systen), in combination with 200 mg progesterone (Utrogestan tablets for 2 weeks, adjusted to the menstrual cycle to prevent endometrium carcinoma according to the international MHT guidelines), with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS., conditionsModule conditions: Menopause, conditions: Insomnia, designModule studyType: INTERVENTIONAL, phases: PHASE4, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: SINGLE, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 222, type: ESTIMATED, armsInterventionsModule interventions name: Estrogens and Progestogens, interventions name: Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy, outcomesModule primaryOutcomes measure: The primary outcome variable is the difference between the groups in the within-subject change in insomnia severity at T1 (2 months) and T2 (4 months) relative to T0 (baseline)., eligibilityModule sex: FEMALE, minimumAge: 40 Years, maximumAge: 55 Years, stdAges: ADULT, contactsLocationsModule, hasResults: False