Table 2.
Major findings from studies investigating gender differences, sex hormones, or sex hormone pathway components in human PAH.
| Study finding | References |
|---|---|
| General findings | |
| ↑ Susceptibility to PAH development in women | See Table 1 |
| ↑ Pulmonary vascular remodeling in female PAH patients | (390) |
| ↑ Survival in female PAH patients | (28, 167, 170, 175, 307, 365) |
| ↓ Hemodynamic alterations in female PAH patients (↓ RAP, ↓ mPAP, ↑ CI) | (365, 445) |
| ↑ RVEF in female PAH patients | (175, 192,405) |
| ↑ Improvement in RVEF in females after initiation of PAH treatment responsible for survival advantage in females | (175) |
| ↑ Response to treatment with endothelin receptor antagonists or intravenous prostacyclins in female PAH patients | (108, 118) |
| ↑ Response to treatment with tadalafil in male PAH patients | (258) |
| Menopause is risk factor for scleroderma-associated PAH (SSc-PAH); HT attenuates SSc-PAH | (30, 363) |
| Findings specific to sex hormone signaling | |
| Altered estrogen metabolism ↑ penetrance of hereditary PAH; ↓ urine 2-hydroxyestradiol/16α-hydroxyestrone ratios in patients with hereditary PAH vs. unaffected BMPR2 mutation carriers |
(12) |
| ↑ ESR1 mRNA expression in PAH patients | (331, 391) |
| SNPs in ESR1 and CYP19A1 associated with ↑ risk for development of portopulmonary hypertension; SNPs in CYP19A1 associated with ↑ E2 plasma levels |
(340) |
| E2 plasma levels correlate negatively with 6MWD and functional class in male and female PAH patients | (19, 441) |
| ↑ E2 and E2/testosterone ratio and ↓ testosterone and γ progesterone associated with ↑ risk of PAH in males; ↑ E2 associated with ↑ mortality in male patients | (471) |
| Genetic variations in E2 metabolism and androgen signaling associated with RV morphology in a gender-specific manner (MESA-RV, healthy cohort) | (443) |
| Aromatase inhibition safe and ↑ 6MWD in postmenopausal and male PAH patients (small proof-of-concept study) | (193) |
| Lower DHEA-S levels in men and postmenopausal women with PAH compared to matched controls; lower DHEA-S associated with more severe PAH, RV dysfunction | (19, 441) |
| Lower DHEA-S and metabolites associated with poor survival | (19) |
| Open-label DHEA treatment in small (n = 8) study of COPD-PH improved 6MWD and hemodynamics | (90) |
The upper section lists general findings; the lower section lists findings related to the study of specific sex hormones. BMPR2, bone morphogenetic protein receptor 2 gene; CI, cardiac index; CYP19A1, aromatase gene; ESR1, estrogen receptor α gene; HT, hormone therapy; mPAP, mean pulmonary artery pressure; RAP, right atrial pressure; RVEF, right ventricular ejection fraction; SNP, single-nucleotide polymorphism; 6MWD, six-minute walking distance.