Hypothalamic-pituitary-adrenal axis, subjective, and thermal stress responses in midlife women with vasomotor symptoms.

OBJECTIVE: Dysregulated responses to experimental stress paradigms may indicate exposure to chronic stress. Vasomotor symptoms (VMS) are linked with diminished quality of life and psychological stress, but induced stress responsivity has received limited investigation. We examined whether women with and without VMS differ in their evoked hypothalamic-pituitary-adrenal axis, subjective, hemodynamic, and thermal stress responses. METHODS: A total of 37 midlife women (27 VMS+; 10 VMS-) completed 2 experimental stress paradigms: (1) Montreal Imaging Stress Task (MIST; computerized social-evaluative stressor) and (2) Quantitative Sensory Testing (QST; thermal stress task). Responses on a five-domain (range 0-50) Visual Analog Scale, salivary cortisol (hypothalamic-pituitary-adrenal axis), and hemodynamic indices (blood pressure, heart rate) were measured before and after each task to compare within-person change between groups. Thermal sensitivity was assessed on the QST. RESULTS: On the MIST, the VMS+ group showed a smaller cortisol release (0.01 vs 0.07 µg/dL; P = 0.046; corresponding to 54% vs 83% increases), and subjective stress response (21.2- vs 31.1-point Visual Analog Scale increase, P = 0.05; corresponding to 2427% vs 2863% increases) but no hemodynamic difference, compared to the VMS- group. The QST did not provoke stress responses via cortisol release or subjective report, but the VMS+ group tended to perceive heat at a higher temperature (38.5°C vs 36.4°C, P = 0.08). CONCLUSIONS: Women with VMS exhibited both diminished cortisol and subjective stress responses to the MIST, and reduced thermal sensitivity on QST compared to women without VMS. Dysregulated stress responsivity provides preliminary evidence suggesting that VMS may represent a chronic stress condition.

Cardiovascular reactivity and psychological hyperarousal in hot flash-associated insomnia disorder.

OBJECTIVES: Given the neurocognitive hyperarousal observed in patients with insomnia disorder and associations of nocturnal hot flashes with cardiovascular disease risk, we examined whether women with hot flash-associated insomnia disorder demonstrate exaggerated cardiovascular responsivity to acute stressors, and also a profile of psychological hyperarousal. METHODS: Peri and postmenopausal women with and without hot flash-associated insomnia disorder underwent assessments of cardiovascular autonomic responsivity to acute stress paradigms and psychological hyperarousal. Hemodynamic responses (heart rate, blood pressure) to nociceptive, social-evaluative, and cognitive stress paradigms were measured in the morning. Psychological hyperarousal was evaluated using questionnaires assessing daytime and presleep hyperarousal, anxiety, and sleep-related cognitions. RESULTS: Women (25 with and 15 without hot flash-associated insomnia) aged 53.4 ±â€Š4.8 years reported a range of insomnia symptoms. Resting-state hemodynamics were similar between groups. Heart rate and blood pressure responses to stress paradigms did not differ by group nor did they correlate with insomnia severity. Women with insomnia disorder had higher generalized anxiety disorder scores (mean 2.7 ±â€Š3.0 vs 1.0 ±â€Š1.4; P = 0.05) and sleep-related cognitions than those without insomnia (P ≤ 0.05). Insomnia symptom severity was moderately correlated with presleep and daytime hyperarousal, anxiety, and sleep-related cognition (all r ≥ 0.43). CONCLUSIONS: Though hot flash-associated insomnia is characterized by psychological hyperarousal before sleep and during the daytime, it does not relate to cardiovascular responsiveness to acute stressors. Our findings do not support the hypothesis that altered cardiovascular control is a potential mechanism by which hot flash-associated insomnia confers higher cardiovascular disease risk.

Independent Contributions of Nocturnal Hot Flashes and Sleep Disturbance to Depression in Estrogen-Deprived Women.

CONTEXT: Women are at increased risk for mood disturbance during the menopause transition. Hot flashes (HFs), sleep disruption, and fluctuating estradiol levels correlate with menopause-associated depression but co-occur, making cause and effect relationships difficult to disentangle. OBJECTIVE: Using a GnRH agonist (GnRHa) experimental model, we investigated whether depressive symptoms are associated with HFs and/or are explained by concomitant sleep fragmentation in the absence of estradiol fluctuation. DESIGN AND INTERVENTION: Depressive symptoms, objective polysomnographic sleep parameters, subjective sleep quality, serum estradiol, and HFs were assessed before and 4 weeks after open-label depot GnRHa (leuprolide 3.75-mg) administration. SETTING: Academic medical center. PARTICIPANTS: Twenty-nine healthy nondepressed premenopausal volunteers (mean age, 27.3 years). RESULTS: Serum estradiol was rapidly and uniformly suppressed. HFs developed in 69% of the subjects. On univariate analysis, worsening of mood was predicted by increases in time in light sleep (stage N1), number of transitions to wake, non-REM arousals, subjective sleep quality, and reductions in perceived sleep efficiency (all P < .045), as well as the number of nighttime (P = .006), but not daytime (P = .28), HFs reported. In adjusted models, the number of nighttime HFs reported, increases in non-REM arousals, time in stage N1, transitions to wake, and reduced sleep quality remained significant predictors of mood deterioration (P ≤ .05). CONCLUSIONS: Depressive symptoms emerged after estradiol withdrawal in association with objectively and subjectively measured sleep disturbance and the number of nighttime, but not daytime, HFs reported. Results suggest that sleep disruption and perceived nighttime HFs both contribute to vulnerability to menopause-associated depressive symptoms in hypoestrogenic women.