PAH Risk, Mortality Increased by Disturbances in Male Sex Hormones

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Higher testosterone and progesterone were both associated with a reduced risk for PAH
Higher testosterone and progesterone were both associated with a reduced risk for PAH

Men with high estradiol and a higher estradiol/testosterone ratio as well as lower testosterone and progesterone concentrations had an increased risk for pulmonary arterial hypertension (PAH) and all-cause mortality, according to a study published in Hypertension.

A total of 95 male patients with idiopathic PAH and 95 healthy controls were included in the prospective cohort study and followed for up to 65 months or until death, whichever came first. At baseline, investigators collected demographic and anthropometric data, 6-minute walk test distance (6MWD) results, and data on pituitary-gonadal axis hormone levels. In addition, all patients underwent transthoracic echocardiography and right heart catheterization at baseline. All-cause mortality comprised the primary end point.

In patients with PAH, plasma levels of sex hormones were abnormally higher than in controls. Specifically, patients with PAH vs controls had higher estradiol (154.00 vs 105.70 pmol/L; P <.001) and estradiol/testosterone ratio (14.60 vs 7.52; P <.001). Patients with PAH also had lower testosterone (8.63 vs 14.13 ng/mL; P =.02) and progesterone (0.32 vs 0.68 ng/mL; P <.001) levels compared with controls.

Having higher estradiol and estradiol/testosterone levels was significantly associated with an increased risk for PAH (odds ratio per ln estradiol, 3.55; P <.001; odds ratio per ln estradiol/ testosterone, 4.30; P <.001). Conversely, having higher testosterone and progesterone were both associated with a reduced risk for PAH (odds ratio per ln testosterone, 0.48; P =.003; odds ratio per ln progesterone, 0.09; P <.001).

Participants with higher estradiol concentrations also demonstrated an increased risk for all-cause mortality after adjustment for patient-specific baseline characteristics and PAH treatment strategy (hazard ratio per ln estradiol, 2.02; P =.007). In addition, patients with PAH who had an estradiol level ≥145.55 pmol/L had a significantly worse 5-year survival rate vs PAH with lower estradiol concentrations (38.6% vs 68.2%; log-rank test P =.001).

The observational nature of the study precluded the researchers' ability to determine causal factors associated with sex hormones and all-cause mortality in patients with PAH.

“Our finding may provide strong evidence that higher estradiol plays [a] detrimental role in the initiation and progression of PAH and suggest [that] sex hormone imbalance plays a contributing role in the pathophysiology of PAH,” the investigators concluded.

Reference

Wu WH, Yuan P, Zhang SJ, et al. Impact of pituitary-gonadal axis hormones on pulmonary arterial hypertension in men [published online April 30, 2018]. Hypertension. doi:10.1161/HYPERTENSIONAHA.118.10963

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