Hormone therapy protects the heart by lowering inflammation

One way how hormone therapy with oestradiol may slow the progression of atherosclerotic cardiovascular disease (CVD) in postmenopausal women is through the reduction of inflammatory biomarkers, according to the ELITE* study presented at the NAMS 2020 Annual Meeting.

The cardioprotective benefit was only seen in women who initiated hormone therapy soon after the onset of menopause (within 6 years), but not those who started later (>10 years) — consistent with the primary results.

Previously, oestradiol therapy has been shown to delay the progression of artery wall thickening by preventing cholesterol deposits from accumulating in the arteries — with greater benefits seen in women who started hormone therapy earlier than those who started later.

In the recent study presented at NAMS, the researchers found that another mechanism mediating the protective benefits of hormone therapy might lie in the reduction of inflammation. [NAMS 2020, abstract S-12]

The levels of inflammatory biomarkers including E-selectin (p=0.002), ICAM-1 (p=0.03), IFNγ (p=0.03), and IL-8** (p=0.03) were significantly lower in women who received oestradiol therapy than those on placebo.

“These results suggest that the atheroprotective effects of hormone therapy in ELITE may partially be explained by hormone therapy-induced reduction of multiple biomarkers of inflammation,” observed the researchers.

When the analysis was stratified by the time of therapy initiation, women who started oestradiol therapy within 6 years of menopause onset saw a greater reduction in inflammatory biomarkers than those who started more than 10 years later. This was particularly so for ICAM-1 and IL-8. Only E-selectin showed an inverse relation, with a greater reduction in women who initiated therapy later than earlier. 

“The ELITE results, in context with decades of studies on hormone therapy and vascular degeneration, provides strong evidence that the CV benefits of hormone therapy are dependent on timing of initiation,” said study co-investigator Dr Howard Hodis, director of the Atherosclerosis Research Unit and professor of medicine and preventive medicine at the Keck School of Medicine in Los Angeles, California, US.

In the ELITE study, 643 healthy postmenopausal women were randomized to receive either oral 17β-oestradiol 1 mg/day or placebo for a mean duration of 5 years. the levels of a panel of 14 inflammatory biomarkers were assessed using serum samples collected from a subset of women (n=535) with complete data available at baseline, 12 and 36 months of follow-up.

“This study helps us better understand the potential physiologic mechanisms that could explain why hormone therapy slows progression of heart disease early after menopause, but not in women more distant from the menopause transition,” said NAMS medical director Dr Stephanie Faubion from Mayo Clinic, Rochester, Minnesota, US.

“Additional research is needed to more fully understand how time since menopause alters the impact of hormone therapy on heart disease risk.”