Hormone replacement therapy (HRT) and the heart
Channel: York Cardiology
Date: 22/11/2020

The arrival of menopause can be particularly distressing both mentally and physically. A number of conditions are associated with menopause. These include hot flashes, an increase in incidence of osteoporosis, alzheimer’s, vaginal atrophy and cardiovascular disease. At the beginning of the 20th century, the FDA approved an estrogen replacement medication called Premearin for the treatment of hot flashes. 
In the 1970s, it was found that unopposed estrogen therapy was associated with an increase in endometrial cancer and HRT became unfavourable. 
Subsequently however researchers found that if the dose of estrogen was reduced and combined with progesterone then the risk of endometrial cancer was reduced and once again HRT in the form of combined therapy (estrogen and progesterone) became popular again.
In 1988, the FDA approved HRT as a treatment not only for hot flashes but also for prevention of osteoporosis. As confidence and usage increased, researchers became interested in cardiovascular disease prevention.
We know that the incidence of cardiovascular events increases in post-menopausal women. This was shown nicely in the SWAN study which found that in women with hot flashes, there was a higher incidence of sub-clinical cardiovascular disease which included more calcification in the walls of the big vessels in the body (aorta) compared to women without menopausal symptoms. GIven this observation, researchers became very interested in trying to work out whether replacement of hormones by giving patients HRT could in fact prevent or arrest the sub clinical cardiovascular disease and in some way prove protective. 
A bunch of observational studies did in fact suggest that this could be the case and doctors became very interested in prescribing HRT to women to reduce the risk of heart disease. 
In 1998, a study was undertaken to better study the effects of HRT on the most common causes of mortality and morbidity in women such as cardiovascular disease, cancer and osteoporosis. This was called the Women’s health Initiative study.
16608 women with intact uteruses were given either a combination of oestrogen and progesterone or placebo and a further 10739 women without uteri were given oestrogen or placebo. The results were published after 5 years and claimed that in women with intact uteri, there was an increase in coronary disease and breast cancer but there was a reduction in osteoporotic fractures and colon cancer. On the basis of these results the trial was stopped prematurely and the message sent out was that HRT was a bad bad thing and there was a huge drop in HRT prescription.
In the group of women without uteri, they found that there was a small increased risk of strokes and there did not appear to be any benefit in terms of cardiovascular risk or breast cancer (but there was no increase risk either) but again there was a consistent beneficial effect on osteoporotic fractures and colon cancer. Nevertheless the overall message still remained that HRT was not such a great thing and it could be used maybe sparingly for osteoporosis and symptoms relief (from hot flashes) but should definitively not be used in asymptomatic women. 
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