Menopause at Young Ages Linked to Higher PH Risk in UK Study

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Women who reach menopause prematurely — meaning before age 40 — are two times more likely to develop pulmonary hypertension (PH) than those who do not, a study found.

Analysis of medical records covering over 150,000 women registered in the U.K. Biobank also showed that this risk was not associated with the presence of other health conditions, with current or past tobacco smoking, or with body mass index (a measure of body fat based on height and weight).

The younger the age at menopause, the higher the risk of PH, its researchers reported, adding that the use of menopausal hormone therapy did not change this risk.

Their study, “Association of premature menopause with incident pulmonary hypertension: A cohort study,” was published in Plos One.

More women than men are affected by PH, and the cause is suggested to be related to the levels of female sex hormones.

Premature menopause, which occurs before the age of 40, has been linked to a higher risk of developing several cardiovascular disorders. Of note, menopause is characterized by a marked decrease in levels of estrogen and other sex hormones.

However, whether premature menopause could be a risk factor for PH was unclear.

A team of researchers led by Pradeep Natarajan, MD, director of Preventive Cardiology at Massachusetts General Hospital and an assistant professor of medicine at Harvard Medical School, analyzed medical records from the U.K. Biobank. This database holds information that includes blood pressure and lung function covering more than  500,000 U.K. residents.

Biobank participants were recruited from 2006–10, and all underwent regular examinations. Follow-up exams for this study extended for a median of 11.1 years, with data collected through March or May 2020.

Researchers initially looked at records of postmenopausal women, ages 40 to 69, without pre-existing PH, congenital (from birth onward) heart disease, or very low measures of lung health.

Among the 136,715 women identified, 5,201 (3.8%) had premature menopause, while 131,514 women (96.2%) did not (control group). Among all these women, 447 (0.33%) developed PH over time — 38 (0.73%) among those with premature menopause, and 409 (0.31%) among those with menopause at normal ages.

Analysis revealed that premature menopause was independently associated with PH with a hazard ratio (HR) of 2.13. In these rations, values higher than one represent an increased risk. HR was obtained after adjusting the results for several parameters, including age, race, smoking habits, body mass index, blood pressure, antihypertensive medication use, type 2 diabetes, obstructive sleep apnea, heart failure, venous thromboembolism (blood clots that start in a vein), or the use of menopausal hormone therapy.

Age at menopause, however, was found to be directly related to PH risk. “Risk of PH appeared to increase progressively with younger age at menopause,” the researchers wrote.

Women reaching menopause before age 30 had a hazard ratio of 4.82 for PH and those before age 35 a HR of 4.46, when compared with women who experienced menopause after age 50.

“In a large cohort of postmenopausal women, menopause before age 40 years was independently associated with 2-fold risk of PH. Further increase in PH risk was observed with progressively earlier age at menopause,” the researchers wrote.

The use of hormone replacement therapy at menopause — or the duration of its use — “did not modify the association of premature menopause with PH,” the researchers added.

Thus, “premature menopause may represent an independent risk factor for PH,” the team concluded, adding that “further investigation of the role of sex hormones in PH is needed to elucidate pathobiology [the nature of the disease] and identify novel therapeutic targets.”

The team also noted that 95% of the group analyzed was white, and further studies will be needed to determine whether these results are valid for other racial and ethnic groups.