MHT and CHD: Is MHT a risk for older women?

Yesterday we reported from Dr. Stevenson’s symposium session on MHT and CHD (you can catch up on what we learnt at https://womenshealthedu.com/new-blog/2017/5/22/hrt-and-chd-evidence-and-suggestions). Today he was back bright and early to kick the day off by diving deeper into the potential CHD risk MHT may pose to older women.

As we discussed previously, MHT is significantly beneficial in reducing CHD in younger women, with studies showing it can account for up to a 50% reduction in cardiovascular disease in women under the age of 60 or in those who have been initiated with MHT within 10 years of menopause onset. Not only has MHT proven effective in primary prevention but also in secondary prevention, literature shows younger women who have CHD have better survival rates taking MHT than those on placebo.

 

Since these initial benefits have been published, a number of randomised clinical trials have been conducted producing a variety of different results. The HERS trial published by Stampfer et al. demonstrated no evidence of benefit in secondary prevention, whilst the Danish Osteoporosis study published by Schierbeck et al. showed that MHT significantly reduced MCI and mortality compared to women on the placebo, those on MHT also had no additional adverse events such as stroke, VTE or breast cancer.  A WHI post market study of the CEE arm also showed benefit was apparent when MHT was initiated below the age of 60 as CT scans of study participants on MHT showed a significant reduction in coronary artery classification compared to those randomised on the placebo.

The ELITE study (Howard et al.) looked at early vs later intervention, they recruited two groups of patients; one group of women were within the first 6 years after the onset of menopause and a second group who had already passed the 10 year post onset mark. Results showed that the intermedial thickness progress significantly reduced in early starters. Data from Hodis et al. has also shown that early intervention can lead to a significant reduction in atheroma progression.

But what about women over the age of 60? Data from the Finnish National Registry study published by Tuomikoski et al. showed that whilst women who were initiated with MHT below 60 benefitted from a significant reduction in CHD there was no significant benefit in women initiated over the age of 60. This was also the case in the WHI CEE arm (Hsai et al.) which showed that MHT had no benefit in older women, however both studies confirmed that although there was no improvement in CHD in older women there was also no increase in risk. 

So why does MHT not have the same effect in women over 60? Dr. Stevenson believes this is because coagulation activation is higher in older women.  MHT can result in a dose dependent increase in MMP activity as estrogen modulates pro-MPP-2 availability; at low dose this may altenuate excess collagen deposition and more importantly at high doses this may be involved with vascular lesion formation or plaque destabilisation. Therefore oestrogen could be a contributing factor in why women don’t experience the same effects at different ages.

What is the key takeaway from all of this data? We know that age is a huge risk factor for CHD and MHT can be beneficial in prevention of coronary events in younger women with early initiation reaping the largest benefits. For older women, MHT does not pose a CHD risk and can continue to be provided, with data showing initiating a low dose can ensure cardiovascular safety in elderly women.

Do you agree? Have you seen any data out there to suggest MHT may be a risk for older women? Let us know in the comments below!

References

1.       Stampfer and Grodstein. Raven Press, 1994

2.       Schierbeck et al. BMJ 2012; 345: e64094

3.       Howard et al. N Engl J Med 2016; 374:1221-12, 31March 31, 2016

4.       Hodis et al. Ann Intern Med 2001; 135; 939-953

5.       Tuomikoski et al. Obstet Gynecol 2014; 124: 947-53

6.       Hsai et al. Arch Intern Med 2006; 166: 357-65