Estrogen exposure, obesity and thyroid disease in women with severe pulmonary hypertension

Abstract

Severe pulmonary hypertension is a lethal group of disorders which preferentially afflicts women. It appears that in recent years the patient profile has shifted towards older, obese, and postmenopausal women, suggesting that endocrine factors may be important. Several studies have revealed an increased prevalence of thyroid disease in these patients, but no studies have evaluated for a coexistence of endocrine factors. In particular, no studies have attempted to evaluate for concurrent thyroid disease, obesity and long-term estrogen exposure in patients.88 patients attending the Pulmonary Hypertension Association 8th International meeting completed a questionnaire and were interviewed. Information was collected regarding reproductive history, height, weight, and previous diagnosis of thyroid disease.46% met criteria for obesity. 41% reported a diagnosis of thyroid disease. 81% of women reported prior use of hormone therapy. 70% reported greater than 10 years of exogenous hormone use. 74% of female patients reported two or more of potentially disease modifying endocrine factors (obesity, thyroid disease or estrogen therapy).The coexistent high prevalence in our cohort of exogenous estrogen exposure, thyroid disease and obesity suggests that an interaction of multiple endocrine factors might contribute to the pathogenesis of pulmonary hypertension and may represent epigenetic modifiers in genetically-susceptible individuals.

Relationship between Digit Ratio and Idiopathic Pulmonary Arterial Hypertension in Japanese Women

“…To date, sex remains the most powerful modifier of disease development, as demonstrated by the high prevalence of IPAH in females between the age of 35 and 50 years. Some clinical studies of PAH indicated that abnormalities in estrogen metabolism may play a pathogenic role of PAH [10]. In contrast to these clinical studies, most animal studies have shown that female sex and estrogen supplementation can have a protective effect against PAH.…”

The estrogen paradox in pulmonary arterial hypertension

“…However, it seems to contradict the female predominance that is observed in idiopathic PAH. Moreover, Sweeney and Voelkel (49) showed that early and long term estrogen exposure might be correlated with an increased risk of the development of PAH (49). Here we ask the question: Is estrogen a friend or a foe?…”

“…Thus, the female predominance in PAH and the adverse effects of estrogen suggest that this hormone has the theoretical potential to negatively affect PAH. A heterogenous cohort of obese women with pulmonary hypertension reported an unusually high incidence of exogenous estrogen use (49), further complicating the interpretation of estrogen's effects on the pulmonary vascular disease. Unfortunately, definitive epidemiological studies about the risks of exogenous estrogens in PAH are near impossible given the rare nature of the disease and its predilection for the young.…”

Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: is it safe?

“…Estrogen-induced rescue of severe pre-existing PH seems to be associated with stimulation of cardiopulmonary neoangiogenesis, suppression of inflammation, fibrosis and right ventricular hypertrophy, most likely mediated through ER-β [23]. Human studies in postmenopausal women also suggest a protective role of estrogen in PH [24,25]; nevertheless, contradictory data exist [26,27]. Interestingly, the only publication on the use of ART in a patient with primary pulmonary hypertension did not report any complications [28].…”