Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes

Table 1 Medicine therapy targeting E2 metabolism for PH

Disease (models)	Intervention	Target	Effect	References
Hypoxia-PAH rat, patients with PAH (phase 2 randomized clinical trial)	Anastrozole	Decrease E2	Decrease pulmonary vascular remodeling, decrease right ventricular systolic pressure, increase the 6 min walk distance by 26 m	[180, 181]
Patients with PAH	Fulvestrant	Decrease 16α-OHE2	Increase right ventricular systolic pressure, improve right ventricular function and increase 6 min walk distance by 31 m	[182]
BMPR2 mutant mouse	Anastrozole + fulvestrant	Decrease E2	Reduce the percentage of muscularized pulmonary vessels and right ventricular systolic pressure	[183]
Hypoxia-PH rat	2-ME2	Increase 2-ME2	Mitigate the pulmonary angiogenesis, reduce pulmonary artery remodeling, right ventricular systolic pressure, right ventricular hypertrophy and oxidative stress	[69, 70, 77]
MCT-PAH rat	Wogonin	Increase HSD17B2 and 2-ME2	Retard PAH and inhibit EndMT	[184]
Patients with COPD	Crocus sativus L.	Decrease HSD17B2, increase HSD17B1 and 2-ME2	Improve inflammation	[185]

ISSN: 1689-1392