Impact of severity of illness on the function of the hypothalamo-pituitary-gonadal axis in postmenopausal women with acute severe illness: Implications for predicting disease outcome

Abstract

Background:While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients.Methods:Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization.Results:There was an independent negative association between the FSH and the SAPS II score (beta = −0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = −0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015).Conclusion:FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay.

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China

“…Accordingly, a prospective study, which evaluated sex differences in respiratory physiology and the development of chronic obstructive pulmonary disease (COPD), reported that early menopause was associated with greater risk of COPD-related hospitalization or death [ 14 ]. Meanwhile, E2 in critically ill or injured adults was independently associated with mortality [ 15 , 16 ], and low E2 was a diagnostic feature for prolonged hospital stay in critically ill surgical and trauma patients [ 17 ]. In addition, because menstruation could be affected by factors such as body mass index, drug intake, environment, and emotion [ 18 ], aside from the periodic fluctuation of sex hormones, further study of sex hormones was performed to more objectively evaluate the effect of sex difference.…”