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Symptoms in the Menopausal Transition

Hormone and Behavioral Correlates

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

OBJECTIVE: To estimate the association of headache, irritability, mood swings, anxiety, and concentration difficulties with menopausal stage and with reproductive hormones in the menopausal transition.

METHODS: Women in the Penn Ovarian Aging Study were assessed longitudinally for 9 years. Data were obtained from structured interviews, a validated symptom questionnaire, menstrual bleeding dates, and early follicular hormone measures of estradiol (E2), follicle-stimulating hormone (FSH), and testosterone. Menopausal stages were based on menstrual bleeding patterns. Other risk factors included history of depression, perceived stress, premenstrual syndrome, current smoking, age, and race. Generalized linear regression models for repeated measures were used to estimate associations among the variables with each symptom.

RESULTS: Headache decreased in the transition to menopause and was significantly associated with menopausal stage in univariable analysis (P=.002). Mood swings were inversely associated with mean FSH levels (P=.005). Irritability was inversely associated with mean levels of FSH (P=.017) and testosterone (P=.008). In multivariable models, the independent contributions of other covariates were strongly associated with these symptoms: premenstrual syndrome (P<.001) and perceived stress (P<.001) for irritability and mood swings; P=.018 for headache. There was 80% power with 0.05 alpha to detect a decrease of 13% or more in the prevalence of the symptoms in the postmenopausal stage compared with the premenopausal stage.

CONCLUSION: Headache significantly decreased in the transition to menopause. Irritability and mood swings also decreased in the menopausal transition as assessed by hormone levels. The findings indicate that these symptoms that are commonly linked with menopause diminish with the physiologic changes of the menopausal transition.

LEVEL OF EVIDENCE: II