Hormonal Modulation of Subjective Sleep Quality and Perivascular Space Volume Across the Menstrual Cycle: An Observational Dense-Sampling Study.

Background: Hormonal fluctuations during the menstrual cycle (and their suppression) are accompanied by altered mood, cognition, and sleep, yet their relationship to subjective sleep quality and glymphatic function - a sleep-dependent brain waste-clearance pathway that involves perivascular spaces (PVS) - is unclear. Methods: We examined daily oestradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), subjective sleep quality, and MRI-derived PVS volume (PVSV) in a single healthy woman across two 30-day periods: during her physiological menstrual cycle and, one year later, under oral contraceptive pill (OCP) use. We employed linear regression models to examine whether hormones are associated with sleep quality and PVSV, and whether they moderate the sleep quality-PVSV association during the physiological menstrual cycle. Subsequently, we conducted permutation-based Spearman rank correlations to assess whether day-to-day changes in sleep quality were associated with corresponding changes in PVSV across the physiological menstrual cycle and OCP use. False discovery rate (FDR) correction was used to control for multiple comparisons. Findings: Higher LH levels were associated with poorer sleep quality during the physiological cycle (b=2·15, 95% CI 0·64 to 3·67, p Interpretation: Ovulation is characterized by poor sleep quality and reduced PVSV, potentially reflecting noradrenergic modulation. The association between sleep quality and PVSV day-to-day changes is shaped by the hormonal milieu, being absent under OCP. PVSV increase associated with poor sleep may reflect elevated sleep pressure promoting vasomotor-mediated cerebrospinal fluid inflow.