MHT and CBCTi trial protocol evaluates insomnia treatment in perimenopausal womenNew trial plans to test hormone therapy for menopause insomnia

Background: About half of the women experience insomnia during the perimenopause, a transitional phase characterised by fluctuations in sex hormones. Insomnia is known to increase the risk of other mental health problems. Therefore, addressing insomnia could potentially prevent or alleviate mental health issues. Unfortunately, it is currently unknown which treatment is most effective in alleviating insomnia during the perimenopause. The Sleeping Through Menopause trial is among the first study to investigate side-by-side two interventions; menopausal hormone therapy (MHT) and combined cognitive behavioural and circadian therapy for insomnia (CBCTi). The primary aim of this study is to evaluate the effectiveness of CBCTi and MHT on insomnia symptoms. Methods: We plan a repeated measurement, randomised controlled trial (RCT) in perimenopausal women who experience insomnia and climacteric symptoms. The study uses a web-based, nationwide recruitment approach, allowing participants from across the Netherlands to self-enroll via an open-access research website. After informed consent, 222 women will be randomly allocated to one of four conditions in a two-by-two treatment design: 1. MHT, 2. CBCTi, 3. MHT + CBCTi and 4. control. MHT consists of transdermal estradiol patches and progesterone tablets in standard doses. CBCTi addresses sleep and circadian behaviour and cognitive restructuring. The primary study outcome is the change in insomnia symptoms assessed with the Insomnia Severity Index (ISI) after 8 weeks (T1) and 15 weeks (T2) relative to baseline (T0). Secondary outcomes are other subjective sleep quality indicators, objective sleep estimated from actigraphy and headband EEG, changes in climacteric symptoms, hot flash frequency estimated from wrist electrodermal activity, other mental health complaints, and wellbeing and daytime functioning. Furthermore, baseline personal characteristics will be assessed, including the history of hormone-related mental health problems. Discussion: This study addresses the gap in research regarding optimal treatment for insomnia during the perimenopause, and how treatments alleviate or prevent other mental health problems and climacteric symptoms including hot flashes. Trial Registration: The study was prospectively registered in the National Library of Medicine on May 13th 2024 as Improving Sleep and Mood in Peri-Menopause (NCT06306404, https://clinicaltrials.gov/study/NCT06306404?cond=NCT06306404&rank=1).