6587 Circulating androgen and estrogen metabolites associated with self-reported sleep quality and vasomotor symptoms in the Women’s Health Initiative Observational Study
Authors: Arabi A H , Trabert B , Allison M , Anderson G , Chervenak J , Crandall C J , Gass M , Gorzelitz J , LeBlanc E S , Lieman H , Pfeiffer R M , Wactawski-Wende J , Wild R A , Xu X , Michels K A 
Published: October 2024

Disclosure: A.H. Arabi: None. B. Trabert: None. M. Allison: None. G. Anderson: None. J. Chervenak: None. C.J. Crandall: None. M. Gass: None. J. Gorzelitz: None. E.S. LeBlanc: None. H. Lieman: None. R.M. Pfeiffer: None. J. Wactawski-Wende: None. R.A. Wild: None. X. Xu: None. K.A. Michels: None.

Sleep and vasomotor symptoms such as hot flashes, affect quality of life for many peri- and post-menopausal women. Decreases in estradiol concentrations may contribute to these symptoms, but the roles of other sex hormones are unclear. We compared circulating concentrations of androgens, estrogens, and their metabolites in women with and without menopause-associated sleep quality concerns and vasomotor symptoms. Previously, highly sensitive liquid chromatography-tandem mass spectrometry assays were used to measure over 20 hormones and their metabolites among women in a nested case-control study (n=1,817) from the Women’s Health Initiative-Observational Study. At enrollment, these women answered questionnaires about their current experiences with menopause-associated symptoms and provided serum. Inverse probability weighting was used to correct for the sampling of women from the original cohort. Linear regression, adjusted for confounders and stratified by menopausal hormone therapy (MHT) use, was used to estimate geometric mean hormone concentrations and percent differences in the means associated with reporting sleep quality symptoms, including a score derived from the frequency of the symptoms. Women also reported the presence or absence of night sweats and hot flashes. Among women not using MHT (n=936), those who reported the poorest sleep quality had lower concentrations of several androgens compared to those who reported no or mild sleep disturbances (e.g., androsterone (ADT) -9.9% difference, confidence interval [CI] -17.8, -1.3%). Women who reported the poorest sleep quality did not have lower concentrations of estrogens. Multiple sleep quality symptoms were also associated with lower androgen levels (e.g., frequent restlessness of sleep: ADT -9.1% difference, CI -17.2, -0.2%) compared to patients who did not report these symptoms. Among women not using MHT, the 25% who reported any night sweats had lower concentrations of several estrogen metabolites compared to women who did not report these symptoms (e.g., 2-methoxyestradiol -17.4% difference, CI -27.5, -5.8%). Higher levels of several androgens were also suggested among these women (e.g., nights sweats: ADT-glucuronide 19.3% difference, CI -1.2, 44.0%). A similar pattern of hormone associations was observed in the group reporting hot flashes. Women using MHT (n=881) who reported night sweats (20%) also had lower concentrations of some estrogens, as well as higher concentrations of androgens that cannot undergo aromatization into estrogens (e.g., ADT-glucuronide 33.1% difference, CI 10.7, 60.1%). This suggests that even among women expected to have sufficient estrogen levels from an exogenous source, those reporting vasomotor symptoms may have unique androgen metabolism. Androgens and their metabolites may play a more substantial role in menopause-related sleep symptoms than previously noted.

Presentation: 6/3/2024