A novel method to detect dysfunction of stress-response-mechanism in women with ovarian dysfunction: implications of circadian rhythm in salivary cortisol for diagnosis and treatment

Abstract

Stress causes various diseases, including infertility and ovarian dysfunction. Stress response is controlled by hypothalamo-pituitary-adrenocortical (HPA) axis and sympathoadrenal system (SAS). We analyzed HPA axis and SAS in various types of ovarian dysfunction. Prospective study. A total of 157 women with ovarian dysfunction according to abnormalities in the basal body temperature and 7 normal volunteers were studied. The patients were classified to 8 groups: PCOS, 49 women; PCOS with habitual abortion, 7; low body weight, 10; elevated FSH, 24; elevated PRL, 6; endometriosis, 10; high age, 4; and idiopathic, 47. HPA axis was analyzed by the circadian rhythm of salivary cortisol and dexamethasone suppression test (DST) on cycle days 3–7. The circadian rhythm was classified into normal (N) type and 4 abnormal types: low-morning (LM), plateau (P), V-shaped (V), and flat (F) types. SAS was analyzed by measuring plasma catecholamines. Pregnancy rates in IVF was compared between normal and abnormal circadian rhythms of salivary cortisol. The incidence of abnormal circadian rhythm in salivary cortisol was significantly higher in women with ovarian dysfunction than in normal volunteers (48% vs. 0%) The incidence was high in PCOS with habitual abortion (86%), low body weight (60%) and PCOS (53%), and moderate in elevated PRL (50%), idiopathic (47%) and elevated FSH (42%), and low in endometriosis (30%) and high age (0%). DST was worsened in types N, LM, P, V and F in this order. The incidence of elevated catecholamines was prominently high in PCOS with habitual abortion (86%), compared with other groups of ovarian dysfunction (0%–27%) and normal volunteers (0%). IVF pregnancy rates were significantly higher in women with normal cortisol rhythm than in those with abnormal cortisol rhythm. Abnormal HPA axis was identified by the circadian rhythm of salivary cortisol in half of women with ovarian dysfunction, especially more frequently in PCOS and low body weight. Abnormal SAS was prominent in PCOS with habitual abortion. Analysis of circadian rhythm in salivary cortisol is a novel and useful method to diagnose dysfunction of stress-response-mechanism in ovarian dysfunction and habitual abortion, and probably to assess effectiveness of stress managements and pharmacological treatments against these disorders.