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Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study.

ABSTRACT: Women's risk of obstructive sleep apnea (OSA) increases substantially during and after the menopausal transition, when depression risk is also elevated, raising the possibility that estrogen withdrawal contributes to OSA vulnerability, in turn contributing to mood disturbance. We examined the association between estradiol levels and OSA in depressed peri- and postmenopausal women.Thirty depressed peri-/postmenopausal women (mean body mass index [BMI] 30.82?kg/m) without known OSA completed routine polysomnography concurrent with serum estradiol levels. Estradiol in women with apnea-hypopnea indices (AHI) ?15 indicating moderate-to-severe OSA was compared against those with AHI less than 15 using logistic regression adjusting for age and BMI.Thirteen women (43%) had AHI ?15 (median AHI 21.6). Estradiol levels were lower (P?=?0.02) in those with OSA (median 19, interquartile range 9-25?pg/mL) than without OSA (median 29, interquartile range 19-66?pg/mL). On univariate analysis, higher estradiol was associated with reduced odds of OSA (odds ratio 0.95, 95% CI 0.90-0.99, P?=?0.04). After adjusting for age and BMI, estradiol levels remained associated with lower odds of OSA (odds ratio 0.90), but the association was no longer statistically significant (95% CI 0.76-1.05, P?=?0.18). Montgomery Åsberg Depression Rating Scale scores did not differ between those with and without OSA.These preliminary results suggest that, in addition to higher BMI and age, lower estradiol may be associated with increased OSA risk in depressed women during the peri- and postmenopause, raising the possibility that estradiol withdrawal associated with menopause influences upper-airway patency in women.

SUBMITTER: Galvan T

PROVIDER: S-EPMC5177515 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study.

Galvan Thania T Camuso Julia J Sullivan Kathryn K Kim Semmie S White David D Redline Susan S Joffe Hadine H

Menopause (New York, N.Y.) 20170101 1

<h4>Objective</h4>Women's risk of obstructive sleep apnea (OSA) increases substantially during and after the menopausal transition, when depression risk is also elevated, raising the possibility that estrogen withdrawal contributes to OSA vulnerability, in turn contributing to mood disturbance. We examined the association between estradiol levels and OSA in depressed peri- and postmenopausal women.<h4>Methods</h4>Thirty depressed peri-/postmenopausal women (mean body mass index [BMI] 30.82 kg/m) ...[more]

PMID: 27648659

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Project description:Purpose:An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. Subjects and Methods:After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. Results:The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (?=-0.47) with MEP amplitude percentage deviation in OSAS patients. Conclusion:The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Project description:Abstract Difficulty sleeping is a common complaint of postmenopausal women. In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL), was shown to reduce moderate to severe hot flush frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. In this analysis, the effect of the E2/P4 capsules on “difficulty sleeping” in postmenopausal women experiencing hot flushes, was assessed by the menopause-specific quality of life (MENQOL) questionnaire and also analyzed by age. The phase 3 REPLENISH trial (NCT01942668), evaluated 4 daily doses of E2/P4 capsules in postmenopausal women (40-65 years, intact uterus) with vasomotor symptoms (VMS). Women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy); women with fewer/less severe VMS were randomized to active E2/P4 doses only for endometrial safety. MENQOL was administered at baseline, week 12, and months 6 and 12. The “difficulty sleeping” item was rated using a 7-item Likert scale ranging from “Not at all bothered” (analysis score of 2) to “Extremely bothered” (analysis score of 8) if difficulty sleeping was experienced, if not experienced, the score for the analysis was set to 1. Changes from baseline to week 12, and months 6 and 12 in all women (MITT population) were analyzed by ANCOVA between each E2/P4 groups vs placebo and stratified by age (pre-specified FDA subgroup; <55 and 55+). Treatment groups in the MITT population (n=1833) were E2/P4 1/100 (n=416), 0.5/100 (n=422), 0.5/50 (n=421), 0.25/50 (n=423) or placebo (n=151). The MITT population had a mean age of 55 years; in the <55-year group (n=927) mean age was 51.2 years and in the ≥55-year group (n=906) mean age was 58.1 years. Mean baseline scores for the “difficulty sleeping” item ranged from 5.1 to 5.8 points. In the MITT population, difficulty sleeping significantly improved from baseline with the three highest E2/P4 doses (1/100, 0.5/100, 0.5/50) compared with placebo at all timepoints (all, P<0.05), except for 0.5/50 at month 6. In women <55 years, the sleep difficulty item significantly improved from baseline at all timepoints with two E2/P4 doses (1/100 and 0.5/50) vs placebo. In women 55+ years, significant improvements from baseline were observed at week 12 with three E2/P4 doses (1/100, 0.5/100, 0.5/50) vs placebo. In REPLENISH, women treated with E2/P4 capsules containing 1 or 0.5 mg E2 demonstrated significant and sustained improvements in the MENQOL difficulty sleeping assessment, especially those <55 years. These data warrant further evaluation.

Dataset Information

Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study.

Publications

Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study.

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