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The role of anxiety and hormonal changes in menopausal hot flashes

Freeman, Ellen W PhD1,2; Sammel, Mary D ScD3; Lin, Hui MS4; Gracia, Clarisa R MD1; Kapoor, Shiv PhD5; Ferdousi, Tahmina PhD4

doi: 10.1097/01.GME.0000142440.49698.B7

Objective: To estimate the association of anxiety with menopausal hot flashes in the early transition to menopause.

Design: A randomly identified, population-based cohort of midlife women followed up for 6 years to assess reproductive hormones and other physical, emotional, and behavioral factors. At enrollment, the women were premenopausal, aged 35 to 47 years, and had regular menstrual cycles in the normal range. Enrollment was stratified to obtain equal numbers of African American (n = 219) and white (n = 217) women.

Results: At the 6-year endpoint, 32% of the women were in the early transition stage and 20% reached the late menopausal transition or were postmenopausal. Reports of hot flashes increased with the transition stages, which were determined by bleeding patterns. At endpoint, hot flashes were reported by 37% of the premenopausal women, 48% of those in the early transition, 63% of women in the late transition, and 79% of the postmenopausal women. Anxiety scores were significantly associated with the occurrence of hot flashes and were also significantly associated with the severity and frequency of hot flashes (each outcome at P < 0.001). Compared with women in the normal anxiety range, women with moderate anxiety were nearly three times more likely to report hot flashes and women with high anxiety were nearly five times more likely to report hot flashes. Anxiety remained strongly associated with hot flashes after adjusting for menopause stage, depressive symptoms, smoking, body mass index, estradiol, race, age, and time. In a predictive model, anxiety levels at the previous assessment period and the change in anxiety from the previous assessment period significantly predicted hot flashes (P < 0.001).

Conclusions: Anxiety is strongly associated with menopausal hot flashes after adjusting for other variables including menopause stage, smoking, and estradiol levels. Anxiety preceded hot flashes in this cohort. Additional studies are needed to examine the duration of menopausal hot flashes and to determine whether treatments that target anxiety effectively reduce menopausal hot flashes.

Anxiety is strongly associated with reports of menopause hot flashes. Anxiety preceded the hot flashes in this cohort, and the association remained after adjusting for other important factors including menopausal stage, smoking, depressive symptoms, and estradiol levels. These findings suggest that anxiety may be a potential target in the clinical management of hot flashes.

From the Departments of 1Obstetrics/Gynecology and 2Psychiatry, the 3Center for Clinical Epidemiology and Biostatistics, the 4Center for Research in Reproduction and Women's Health, and the 5General Clinical Research Center, University of Pennsylvania, Philadelphia, PA.

Received April 20, 2004; revised and accepted July 27, 2004.

This study was supported by grants from the National Institutes of Health (RO1-AG-12745 to Dr. Freeman, and 2MO1RR-00040-37, General Clinical Research Center).

Address correspondence to: Ellen W. Freeman, PhD, Department of Obstetrics/Gynecology, 3701 Market Street, Suite 820, Philadelphia, PA 19104-5509. E-mail:

©2005The North American Menopause Society