Hormonal Modulation of Subjective Sleep Quality and Perivascular Space Volume Across the Menstrual Cycle: An Observational Dense-Sampling Study
- 1Institute of Neuroscience and Medicine, Research Center Juelich
Abstract
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, pFDR=0.028), while FSH moderated the sleep quality-PVSV association (b=-92.98, 95% CI -160.15 to -25.81, pFDR=0.034), suggesting that lower FSH was associated with lower PVSV, whereas this association reversed at elevated FSH levels characteristic of the periovulatory window. During the physiological menstrual cycle, day-to-day decreases in sleep quality were associated with synchronous increases in PVSV, driven by centrum semiovale PVSV ({rho}=0.55, 95% CI 0.30 to 0.67, pperm=0.0095). This association was absent during OCP use and differed between hormonal milieus ({Delta} {rho}=0.72, p=0.040). 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.
Related
- Menstrual cycle and hormonal contraceptive intake alter the electrophysiological signature of selective auditory spatial attention
- Cellular and spatial context of genetic convergence between insomnia liability and DTI ALPS perivascular diffusivity
- Clearing perivascular light chain-derived amyloid to counteract aging-associated decline in liver regeneration
- Spatial transcriptomic mapping of anti-MDA5 dermatomyositis reveals perivascular enrichment of type I interferon responses and immune activation
- Perivascular fibroblasts locally regulate the vasomotor dynamics of pial arterioles
BibTeX
@misc{apter2026hormonal,
title = {{Hormonal Modulation of Subjective Sleep Quality and Perivascular Space Volume Across the Menstrual Cycle: An Observational Dense-Sampling Study}},
author = {D. Apter and J. D. Elberse and L. Stankeviciute and S. Weis and D. Elmenhorst and J. J. Iliff and S. B. Eickhoff and C. Heller and M. Tahmasian},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749189},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749189v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Hormonal Modulation of Subjective Sleep Quality and Perivascular Space Volume Across the Menstrual Cycle: An Observational Dense-Sampling Study
AU - D. Apter
AU - J. D. Elberse
AU - L. Stankeviciute
AU - S. Weis
AU - D. Elmenhorst
AU - J. J. Iliff
AU - S. B. Eickhoff
AU - C. Heller
AU - M. Tahmasian
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749189
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749189v1
AB - 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, pFDR=0.028), while FSH moderated the sleep quality-PVSV association (b=-92.98, 95% CI -160.15 to -25.81, pFDR=0.034), suggesting that lower FSH was associated with lower PVSV, whereas this association reversed at elevated FSH levels characteristic of the periovulatory window. During the physiological menstrual cycle, day-to-day decreases in sleep quality were associated with synchronous increases in PVSV, driven by centrum semiovale PVSV ({rho}=0.55, 95% CI 0.30 to 0.67, pperm=0.0095). This association was absent during OCP use and differed between hormonal milieus ({Delta} {rho}=0.72, p=0.040). 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.
ER -