Association Between High Follicle Stimulating Hormone,Low Progesterone And IPAH In Women Of Reproductive Age

BACKGROUND:Pulmonary arterial hypertension is a potential fatal pulmonary vascular disease with special epidemiological characteristics.Females occurs predominantly with a 2 to 4 times higher incidence compared with adult males,but the prognosis of adult males is worse than that of female patients.Relationships between pituitary-gonadal axis hormones and pulmonary arterial hypertension has always been one of the focus of academic attention.However,data on serum concentrations of sex hormones in fertile female IPAH patients are still unknown.We measured hormone levels,aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of idiopathic pulmonary arterial hypertension(IPAH).METHODS:In the matched case-control study,serum concentrations of estradiol,testosterone,progesterone,follicle-stimulating hormone,luteinizing hormone were measured by an electrochemiluminescence immunoassay in 164 patients with incident IPAH and 133 age and body mass index matched healthy controls.Differences in sex hormones levels between IPAH patients and controls,and correlations between sex hormones and clinical characteristics were analyzed.In the prospective cohort study,Patients were followed up by telephone for death or lung transplantation.The effects of hormone levels on mortality were assessed in IPAH fertile female patients.RESULTS:In female with IPAH,serum follicle stimulating hormone,luteinizing hormone concentrations were increased,testosterone and progesterone concentrations were decreased in comparison with controls.After adjusted for age and body mass index,the odds ratios of having pulmonary arterial hypertension for follicle stimulating hormone,testosterone,and progesterone were 1.51(95%CI:1.06-2.16),0.42(95%CI:0.31-0.57),and 0.52(95%CI:0.43-0.63),respectively.Lower progesterone and testosterone levels were associated with more severe clinical features including elevated mean right atrial pressure,pulmonary vascular resistance,World Health Organization functional classification,and decreased six-minute walk distance and cardiac index.Higher follicle stimulating hormone was associated with decreased cardiac index.In the cohort study with a median follow up of 77-months,65 patients died.The hazard ratios for death after adjusting for baseline clinical characteristics and treatments among IPAH patients were 2.01(95%CI:1.22-3.30)for follicle stimulating hormone and 0.78(95%CI:0.62-0.98)for progesterone.The group of patients with lower follicle stimulating hormone and higher progesterone levels had significantly better survival(p=0.004,p=0.004).The group of patients with both lower follicle stimulating hormone and higher progesterone levels had the best survival(p=0.002).CONCLUSIONS:Changes in serum sex hormones concentrations are extensive in fertile female patients with IPAH.Higher follicle stimulating hormone and lower progesterone were significantly corelated with higher risk of disease and mortality of patients,suggesting that gonadotropins and sex hormones are linked in causation and mortality of IPAH.