ArticleThe European respiratory journal2009
Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females.
Article in The European respiratory journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01884051 (Hormonal, Metabolic, and Signaling Interaction in Pulmonary Arterial Hypertension), which is not on this map. Cited by 121 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Hormonal, Metabolic, and Signaling Interaction in Pulmonary Arterial Hypertension
Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- A systematic review of genetic mutations in pulmonary arterial hypertension.BMC medical genetics · 2017Pooled it
- Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.American journal of respiratory and critical care medicine · 2017Trial
- Trial
- Trends and future projections of the disease burden of pulmonary arterial Hypertension-related heart failure in China and G20 countries: Based on the global burden of disease 2023 database.International journal of cardiology. Cardiovascular risk and prevention · 2026Article
- Sex-specific insights in atherosclerosis and pulmonary arterial hypertension: an overlooked comorbidity.Frontiers in cardiovascular medicine · 2026Review
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Estrogen and Cyp1b1 Regulate Pparγ in Pulmonary Hypertension Through a Ubiquitin-Dependent Mechanism.Pulmonary circulation · 2025Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Hemodynamic and Clinical Profiles of Pulmonary Arterial Hypertension Patients with GDF2 and BMPR2 Variants.International journal of molecular sciences · 2024Article
- Sex-biased TGFβ signalling in pulmonary arterial hypertension.Cardiovascular research · 2023Review
- Portopulmonary Hypertension: An Updated Review.Transplantation direct · 2023Review
- MicroRNA and lncRNA as the Future of Pulmonary Arterial Hypertension Treatment.International journal of molecular sciences · 2023Review
- SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.American journal of respiratory and critical care medicine · 2023Article
- Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma.Scientific reports · 2023Article
- Vascular stiffening in aging females with a hypertension-induced HIF2A gain-of-function mutation.Bioengineering & translational medicine · 2023Article
- Pathophysiology and new advances in pulmonary hypertension.BMJ medicine · 2023Review
- Polychlorinated Biphenyls and Pulmonary Hypertension.International journal of environmental research and public health · 2022Article
- Pulmonary Arterial Hypertension: Emerging Principles of Precision Medicine across Basic Science to Clinical Practice.Reviews in cardiovascular medicine · 2022Article
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in bone morphogenetic protein receptor type 2 (BMPR2) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. In addition, gene expression data implicating the oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. We examined genetic and metabolic markers of altered oestrogen metabolism in subjects with a BMPR2 mutation. Genotypes for CYP1B1 Asn453Ser (N453S) were determined for 140 BMPR2 mutation carriers (86 females and 54 males). Nested from those subjects, a case-control study of urinary oestrogen metabolite levels (2-hydroxyoestrogen (2-OHE) and 16alpha-hydroxyoestrone (16alpha-OHE(1))) was conducted in females (five affected mutation carriers versus six unaffected mutation carriers). Among females, there was four-fold higher penetrance among subjects homozygous for the wild-type genotype (N/N) than those with N/S or S/S genotypes (p = 0.005). Consistent with this finding, the 2-OHE/16alpha-OHE(1) ratio was 2.3-fold lower in affected mutation carriers compared to unaffected mutation carriers (p = 0.006). Our findings suggest that variations in oestrogens and oestrogen metabolism modify FPAH risk. Further investigation of the role of oestrogens in this disease with profound sex bias may yield new insights and, perhaps, therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.