Increased Cortisol Level: A Possible Link Between Climacteric Symptoms and Cardiovascular Risk Factors

Angelo Cagnacci, MD, PhD; Marianna Cannoletta, MD; Simona Caretto, MD; Renata Zanin, MD; Anjeza Xholli, MD; Annibale Volpe, MD

Disclosures

Menopause. 2011;18(3):273-278. 

In This Article

Abstract and Introduction

Abstract

Objective: Vasomotor symptoms may increase the risk for cardiovascular diseases through still elusive mechanisms. Increased cortisol release may favor atherosclerosis. In this study, we tested whether vasomotor and psychological symptoms are associated with an increase in cortisol levels.
Methods: A cross-sectional investigation on women in early menopause enrolled consecutively between January and June 2009 was conducted. This study was set at a menopause outpatient service at University Hospital. Participants included 85 healthy women who were 6 months to 5 years postmenopause. The 24-hour urinary cortisol level and Greene Climacteric Scale scores were evaluated. Anthropometric parameters and fasting blood samples for the determination of high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, glucose, and insulin levels were measured. Body mass index, waist-to-hip ratio, and homeostatic model assessment of insulin resistance were calculated. The relation between Greene Climacteric Scale scores and 24-hour urinary cortisol level and between 24-hour urinary cortisol level and lipid levels or insulin resistance was determined.
Results: The Greene Climacteric Scale score for climacteric symptoms (coefficient of regression [CR], 1.343; 95% CI, 0.441–2.246) and body mass index (CR, 4.469; 95% CI, 1.259–7.678) explained 32.5% and 10.3%, respectively, of the variance in 24-hour urinary cortisol level (r = 0.428; P = 0.0003). Twenty-four-hour urinary cortisol level was inversely related to HDL-cholesterol level (CR, −0.065; 95% CI, −0.114 to −0.017; r = 0.283; P = 0.009) and was related to waist girth (CR, 0.685; 95% CI, 0.306–1.063) and homeostatic model assessment of insulin resistance (CR, 0.097; 95% CI, 0.032–0.162; r = 0.510; P = 0.0001).
Conclusions: In early postmenopausal women, the Greene Climacteric Scale score is associated with increased 24-hour urinary cortisol level. Increased cortisol level is associated with known risk factors for cardiovascular disease, such as insulin resistance and decreased HDL-cholesterol level.

Introduction

Perimenopause and early postmenopause represent a critical period characterized by altered ovarian function,[1,2] vasomotor symptoms, increased psychological symptoms, modifications of body weight and composition, and alterations of metabolic processes leading to a greater risk for metabolic syndrome and bone loss.[1–3] Although altered ovarian function represents the underlying phenomenon of the menopausal transition and early postmenopause,[4,5] recent evidence suggest that predisposition to the negative effect of hypoestrogenism may be present, and women with increased vasomotor symptoms may represent a subset of individuals more frequently developing long-term consequences, such as cardiovascular disease and osteoporosis. Indeed, women having vasomotor symptoms seem to have an increased body weight,[6,7] increased abdominal adiposity,[8] increased blood pressure,[9] decreased endothelium-dependent vasodilation,[10,11] increased aortic calcification,[10] an atherogenic lipid profile,[12] and a different vessel response to stimuli such as nitroglycerin[13] or estrogen administration.[14] Furthermore, they seem to have lower values of bone mineral density.[15,16]

Besides the fact that this evidence may indicate a different sensitivity of a subset of individuals to postmenopausal hypoestrogenism, whether the presence of vasomotor symptoms may contribute to influence the risk of these women is unclear. It has been hypothesized that higher values of calcitonin gene-related peptide[17] or decreased cardiac vagal control[18] may contribute to increase the cardiovascular risk in women with vasomotor symptoms. On the other hand, vasomotor symptoms are associated with increased hypothalamus-pituitary-adrenal axis activity, leading to increased cortisol level.[19] Psychological symptoms are related to vasomotor symptoms[3] and increase in the menopausal transition[20,21] and can be associated with increased cortisol level.[22,23] Similarly, sleep disturbances[24] and increased adiposity,[4–6] which exacerbate in the menopausal transition, can be associated with an increase in cortisol level.[25–27] Cortisol may have important metabolic implications by favoring insulin resistance and bone absorption.[28,29] An increase in urinary cortisol level was seen in women during the menopausal transition,[30] but whether this is associated with vasomotor and psychological symptoms and is higher in women with more severe symptoms were not ascertained.

It was the aim of the present study to evaluate whether, in early postmenopausal women, vasomotor and psychological symptoms are related to the activity of the hypothalamus-pituitary-adrenal axis and whether the latter is related to known risk factors for cardiovascular disease, such as lipoprotein modification or insulin resistance. Because of the pulsatile release and the diurnal and stress-induced variation in cortisol secretion, integrated daily hypothalamic-pituitary-adrenal activity was evaluated by measuring 24-hour urinary cortisol level, a good index of 24-hour free serum cortisol level.[29,31]

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