Menopause: Hormone Therapy Does Not Slow Atherosclerosis

Hormone Replacement Therapy (HRT) in newly menopausal women controls vasomotor symptoms, including hot flushes, and improves some markers of cardiovascular disease (CVD), according to a recent study [Kronos Early Oestrogen Prevention Study (KEEPS)]. However, HRT has no effect on the progression of atherosclerosis.

  • No change in atherosclerosis progression
  • Improved lipid profile
  • Improved insulin resistance
  • Improved vasomotor symptoms and quality of life
  • No effect on Blood pressure
  • Increase vaginal bleeding

Earlier research has suggested a decrease in progression of atherosclerosis progression with oestrogen.
Imaging at baseline and 4 years showed HRT had no effect on atherosclerosis progression. It did however improve Cardiovascular Disease factors such as lipid profile and insulin resistance, as well as vasomotor symptoms as well as the quality of life. 
The authors state “Hormone therapy initiated early in menopause appears to have a favourable balance of risks and benefits with a substantial improvement in vasomotor symptoms and quality of life and improvement in a number of biomarkers.”
Therapy type affected different markers, with oral oestrogen improving cholesterol and transdermal oestrogen improving insulin sensitivity. “That would suggest that for a woman who has risk factors for diabetes and metabolic syndrome, transdermal might be a better choice than oral,” 
Because oral ooestrogen has been found to have a prothrombotic effect, transdermal delivery may also be better for women with existing risk CVD risk factors.
No effect on blood pressure was noted (lower dose used) in contrast to the Women’s Health Initiative in 2002, which showed modest increases in systolic blood pressure with higher-dose therapy in older women.
The study however lacks the power to provide conclusive evidence on long-term adverse clinical events such as stroke, thromboembolism, myocardial infarction, breast cancer, and all-cause mortality.

Atherosclerosis Progression 
The primary outcome was annual change in carotid artery intima-media thickness.
Secondary endpoints included changes in markers of CVD risk. No changes in blood pressure were observed. Insulin resistance decreased with transdermal oestrogen, whereas oral oestrogen improved both low- and high-lipoprotein cholesterol levels. Oral therapy also increased levels of CVD markers such as C-reactive protein and sex-hormone-binding globulin, but not interleukin 6.
Adverse events such as rashes, fractures, headaches, and genitourinary problems were similar in all 3 groups, whereas vaginal bleeding was significantly more common in the treated groups.
The authors concede that in referencing a population of healthy younger menopausal women, KEEPS results might not be generalizable to women at greater CVD risk, and that higher doses of oestrogen might have a greater effect on endothelial health.

“To the extent that these imaging methods predict CVD events, our findings suggest that HRT neither is a risk nor is protective in the population studied,” the authors write. Noting that the long-term effects of low-dose HRT remain uncertain, they call for further studies to clarify the relevance of the 2 oestrogen routes to CVD pathogenesis.

Get more information about Hormone Replacement Therapy.


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Naylin Appanna
Womens Health Centre
Waikato U21’s