Cortisol and the Polycystic Ovary Syndrome

Renato Pasquali; Alessandra Gambineri


Expert Rev Endocrinol Metab. 2012;7(5):555-566. 

In This Article

Cortisol & the HPA Axis Activity & Their Relationship to Stress & Eating Behavior: Implications for the Pathophysiology of PCOS

PCOS is associated with several psychological disturbances and reduced quality of life.[60] This may reflect the individual discomfort to the presence of signs (i.e., hirsutism) and symptoms (i.e., irregular menstruations). Obesity itself may have a significant psychopathological impact, and may lead to poorer psychological heath by producing body dissatisfaction and lower self esteem.[61,62] Collectively, these traits may lead to perceived chronic stress and subsequent maladaptive response, which per se may play some role in the pathophysiology and the development of metabolic alterations often associated with PCOS, and the subsequent susceptibility to develop metabolic and cardiovascular diseases.[24] The authors have described a specific phenotype of obesity related to poor coping to a stressful event, which is characterized by rapid weight gain and increased daily UFC excretion rates.[63] This phenotype of obesity, which is characterized by specific pathophysiological mechanisms, may be associated with changes in dietary habits and food choice.[64]

Given the very high prevalence of obesity and psychopathological traits in women with PCOS, the potential association with alterations of the HPA axis, chronic stress and eating behavior or nutrient intake should not be underestimated. This first implies the knowledge of the physiological interaction between the HPA axis and the digestive tract and, second, the interpretation of the neuroendocrine circuits linking the activation of the hypothalamic nuclei regulating the HPA axis (see previous paragraph) and those involved in the regulation of food intake, the reward system and the response to stress.[65] A strong interaction between the HPA axis and the brain–gut axis is well known, although much more information is needed to understand the tuned mechanism involved in this complex network.[66] For example, both food intake and the light–dark cycle have been found to represent independent synchronizers for the circadian periodicity of cortisol secretion in experimental animals.[67] Furthermore, there is evidence that in both animals and humans meal timing, food composition and the length of the fasting state exert an important effect on cortisol secretion.[68] A protein-rich intake may induce a sustained cortisol increase, whereas negligible effects have been found after a carbohydrate-rich meal;[69,70] however, in obese subjects these findings are still controversial, because both altered[71] and normal[16] cortisol responses to standard mixed meals have been reported. In a study performed in obese women with different patterns of body fat distribution, the authors showed that those with abdominal obesity were characterized by a significantly lower cortisol response to a high lipid–protein meal and a significantly higher cortisol response to a high carbohydrate meal, compared with a group of weight-matched women with peripheral obesity.[72] These findings suggest that the activation of the HPA axis following the ingestion of large amounts of carbohydrates may have some pathophysiological relevance, specifically in women with the abdominal obesity phenotype. There are, however, few studies in women with PCOS. Hyperandrogenism and acne have been associated with poorer body satisfaction, and hirsutism combined with BMI have been linked with increased psychological distress.[73–75] Furthermore, problems with neuroticism and withholding anger have been found to be more frequent in women with PCOS than in the control population.[76] In addition, women with PCOS have been found to have higher levels of depression and overall psychological morbidity, and decreased quality of life in overall health and sex.[77] All the conditions cited earlier may have some relevance in the development of a pathological allostatic load, consistent with a maladaptive response to chronic stress, which explains the association between features of PCOS and metabolic comorbidities, such as abdominal obesity. This may be partly explained by an increased activity of the HPA axis, a key hormonal component of body maladaptation to stress. There are no studies focused on the potential role of chronic stress exposure in the pathophysiology of PCOS and its metabolic comorbidities. One controlled study investigated the neuroendocrine and immune cell response following a public speaking test – which has been proved to induce reproducible and pronounced responses of the HPA axis as well as changes in cytokine levels – showed that both PCOS women and weight-matched controls had comparable increases in state anxiety, blood pressure and C-reactive protein levels, whereas ACTH and cortisol, as well as heart rate responses, were significantly higher in PCOS women, together with a reduced upregulation of IL-6.[60] More interestingly, there are studies focusing on the relationship between psychological distress, hyperandrogenemia and menstrual disturbances and their association with greater food cravings and high fat and sweets in hyperandrogenic young women, relatively independent of BMI.[78] In a long list of experimental studies performed in laboratory animals, food craving and so-called 'comfort food' abuse have been clearly related to the exposure to chronic stress and poor coping.[65] There are impressive arguments to support that this may also occur in humans.[79] Whether this may apply also to women with PCOS, particularly those with associated obesity, has never been investigated. Preliminary data from the authors' group have shown that there is some potential difference between obese women with and without PCOS in both dietary intake and food choice. The authors have shown that diet did not differ between the two groups as regards energy, macronutrient and advanced glycosylated end product intake, except for a lower percentage of energy from lipids and a higher intake of fiber by PCOS women. By contrast, PCOS women were characterized by a higher consumption of cheese and high-glycemic index starchy sweets and a preference for raw oil rather than other cooked fats compared with controls. The PCOS or control status influenced some of the relationships between dietary components, food choices and metabolic parameters, particularly glucose-stimulated insulin and HDL-cholesterol.[80] The authors' findings support the hypothesis that specific foods may influence metabolic and hormonal patterns in women with PCOS. Future research activity should be devoted to investigate whether dietary patterns may be influenced by psychopathological factors or chronic stress exposure (both activating the HPA axis) and on their relationship with androgen status and metabolic parameters.