On the final day of ISGE, Martin Birkhaeuser began by introducing one of his own patient cases - a 78 year old lady that first came to see him in April 2002, still working as an architect, active and independent, still suffering from severe vasomotor symptoms (VMS) but controlled by 2 x 12.5 estradiol patches/week. Then in October 2003 her GP stopped her MHT/HRT, telling her it was “criminal at this age” and it would kill her. In January 2004 she returned to Dr Birkhaeuser because she was suffering from depressive symptoms, loss of concentration, hot flushes - such severe vasomotor symptoms that she had to quit the job she loved, her quality of life suffered greatly. They made the decision to begin the transdermal estradiol again, within 4 months all her symptoms had disappeared, she once again had a good quality of life and at aged 80 she was able to return to her beloved profession, she was happy.
The study that provoked her misery? The Women’s Health Initiative (WHI) trial.
Prior to 2002 there was no discussion about whether to continue to prescribe HRT past 65, but after researchers halted the WHI study three years early due to an increased risk of breast cancer, heart disease and stroke, the press reports caused such mass fear that many doctors and their patients immediately stopped their prescription.
In recent years, reanalysis of the study results and further research mean there is a better understanding of risk. Dr Birkhaeuser is of the opinion that the only significant results from the WHI study were an increased risk of venous thromboembolism (VTE) and a reduction in fractures, and everything else was misinformation.
Let’s discuss the research…
Menopause Hormone Therapy (MHT) after 65: Potential benefits
Treatment of persisting VMS and low QOL
Around 25% of women still suffer hot flushes at the age of 65, in some women VMS may last even up to 80-90 years old (Huang et al, 2008) (Vikstrӧm et al, 2013).
A Swedish patient study found that whilst quality of life in post-menopausal women not taking MHT was scored at 87, following a patient questionnaire, those women taking HRT scored 105 - the same as pre-menopausal controls (Wiklund et al, 1993).
The WHI study had a mean age of 56, it showed reductions in both the combined arm and the single – proving that if patients begin HT at that age they then have a significantly reduced risk of fractures. Another study, carried out in Denmark, showed reduced fractures in patients taking MHT over the course of 6 years from when they began treatment (Mosekilde et al, 2000).
It’s estimated that 43,000 fractures a year are accounted for by patients stopping MHT following the WHI study (Karim et al, 2011).
Potential CVD risk
Following the WHI study women were told they were at a high risk of a heart attack if they took MHT beyond 65. However, the 27,000+ women included in the WHI study were more than 10 years post menopause when they began taking MHT. Age means they are were likely to already have or have increased risk of cardiovascular disease. Various studies since have shown that MHT use by healthy women soon after the onset of menopause is associated with a reduced risk of CHD (Grodstein et al, 2000) (Grodstein et al, 2001). Though the dose and type of hormone appears to be crucial to this reduced risk. The Framingham study and the Olmsted County study, by Rivera et al, 2009, show us that menopause alone increases the risk of cardiovascular disease.
The low risk patients showed no change in their stroke risk, only patients with high risk factors showed an increased risk of stroke upon taking MHT. Dr Birkhaeuser suggests that age is more likely responsible for the stroke numbers as well as for the DVT numbers, but to be cautious he recommends transdermal HRT.
Potential breast cancer risk
In the WHI study, the risks for breast cancer seemed to depend on the regimen - a estrogen-progestin combination therapy increased risk, whilst a estrogen-only MHT decreased risk. However, Dr Birkhaeuser evaluates that perhaps the data was over-optimistic for estrogen-only and if you look at other studies you can summarise that there’s no increased risk.
Risk of Alzheimer’s disease
There is no data on Alzheimers from WHI as they mixed up all the dementia data instead of separating it into different groups, this means no reliable conclusions can be found.
Dr Birkheiser explained that a study by Zandi et al, in JAMA showed that the risk of Alzheimers decreased with HRT, there are also hints that other forms of dementia decrease too but we need more studies on this to properly evaluate.
The total mortality data in the WHI study did not show an increase in mortality as was intimated in 2002. This was finally put to rest recently when the principal investigators followed up with the women all these years on and didn’t find they died any faster, sooner or worse deaths than those that took placebo.
Oestrogens after menopause – continuation for >10 years – So what’s the conclusion?
There are no reasons to place arbitrary limitations on the duration of MHT. The decision on whether to continue has to be based on a woman’s individual risk profile.
The lowest effective dose should be administered (Additionally, the patches can be cut in half to build up tolerance, if side-effects).
A non-oral route of administration should be preferred, oral and transdermal have the same level of efficacy (Nelson, 2004).
If needed, micronized progesterone or dydrogesterone should be preferred.