The hypothalamic-pituitary-adrenal axis and the female reproductive system

The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the 'hypothalamic' amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period

Blood Pressure in Children and Adolescents with Cushing's Syndrome before and after Surgical Cure

Approximately half of children and adolescents with Cushing's syndrome develop hypertension. To examine the role of hypercortisolism in the pathogenesis of hypertension in young patients and to establish its reversibility, we studied 31 hypertensive children and adolescents with Cushing's syndrome (systolic, diastolic, and/or mean blood pressure more than 2 SD U for age and sex) from a total of 63 patients before, and for a period of 1 yr after surgical cure. Preoperatively, 93.5%, 42%, and 45% of these patients presented with an increase of the systolic, diastolic, and mean blood pressure, respectively. The systolic blood pressure remained increased in 30.7%, 15.8%, and 5.5% of patients at 3, 6, and 12 months after surgical cure, respectively. The diastolic and mean blood pressure completely normalized by 3 months after surgical cure. A significant, positive correlation was observed between the systolic blood pressure and the duration of the disease, but no correlation was seen with the 24-h urinary free cortisol values and/or the patients' body mass indices. The lack of correlation between 24-h urinary free cortisol values and blood pressure suggests that hypercortisolism influences blood pressure through multiple pathways. The positive correlation between the systolic blood pressure and the duration of the disease points towards the deleterious effects of prolonged hypercortisolism and the significance of early diagnosis and treatment. The fact that the blood pressure normalized within a year from the correction of hypercortisolism suggests that, as a rule, young patients with hypercortisolism do not develop essential hypertension