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

Discussion

It has been previously reported that women in the menopausal transition have increased levels of urinary cortisol.[30] The menopausal transition is a complex endocrine phase in which alteration in estrogens, progesterone, and their ratio may occur. Sex steroids may potentially affect adrenal activity. Whereas some data indicate a stimulatory effect of estradiol on cortisol,[40] data obtained in postmenopausal women show that estrogens either reduce[41] or do not affect levels of cortisol.[42,43] The present study indicates that levels of cortisol are associated with the Greene Climacteric Scale total score. All complaints, including vasomotor symptoms and specific evaluation of psychological symptoms such as anxiety by STAI and depression by the Zung scale, were directly related to 24-hour urinary cortisol values, a good index of the activity of the hypothalamus-pituitary-adrenal axis.[23,31,37] Several pieces of evidence indicate that depression and anxiety, whose scores increase in perimenopause and early postmenopause,[21] can be associated with elevated adrenocortical activity.[22,23] The same can be hypothesized for vasomotor symptoms, when considering that cortisol level increases in association with every single hot flash.[19] Also, sleep disturbance, another feature of the perimenopause to postmenopause is associated, in the following day, with an increase in cortisol level.[25] When all these features are considered together in a single evaluation, as the one furnished by the Greene Climacteric Scale, they are associated with 24-hour urinary cortisol level. The association is stronger for the whole scale than for each single subscale, including the one for vasomotor symptoms that is, however, constituted by only two questions and not so reliable as it would have been a weekly diary. The association between the Greene Climacteric Scale score and 24-hour urinary cortisol level seems to furnish the biological bases for considering the menopausal transition a stressful condition associated, in a dose-dependent fashion, with increased activity of the adrenal axis.

In accordance with previous reports,[26,27] the 24-hour urinary cortisol level is associated also with increasing BMI. Accordingly, a common endocrine mechanism, that is, an increase in adrenal cortisol level, is associated with complaints of the menopausal transition and body fatness.

An increased cortisol level is believed to play a pivotal role in the aging process[44,45] and induces several detrimental effects on human biological functions. It deteriorates immune response;[46] favors degeneration of hippocampus neurons, impairing memory and cognitive function;[47–49] and accelerates bone loss.[22] It also promotes the metabolic syndrome and diabetes,[50,51] thereby increasing the risk for atherosclerosis and cardiovascular disease.[12,52,53] Indeed, in the present study, we found that an increased 24-hour urinary cortisol level is associated with known risk factors for atherosclerosis and cardiovascular disease, such as a decrease in HDL-cholesterol level and an increase in insulin resistance.

Recent data indicate that atherosclerosis and risk factors for cardiovascular diseases can be augmented in symptomatic postmenopausal women.[8–12] These observational data seem to suggest that cortisol elevation may represent one of the links between increased disturbances of the menopausal transition and increased cardiovascular risk.

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