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. Also, the peri-menopausal period is a critical time for the occurrence of new
onset and recurrent depressions. 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. 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. 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 and depressive symptoms 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.