Study finds MHT not linked to increased risk of death

A decades-long study of almost 900,000 women has concluded that menopausal hormone therapy (MHT) is not associated with an increased risk of death.
 
However, the study has already drawn concerns from leading experts, who say key characteristics, such as a patient’s weight and smoking status, were not considered. 
 
Published in the BMJ on Thursday, the research includes 876,805 Danish women who were tracked after their 45th birthday for around 14 years.
 
While initial data suggests the risk of death was higher for women who used MHT, ‘when influential factors were taken into account, no meaningful difference in risk of death was found’, the authors write.
 
They found the duration of MHT use led to no increased risk of death, even after 10 or more years of use.
 
And MHT in a transdermal form had a slightly lower risk of death compared to no treatment, although the authors stress this ‘should be interpreted with caution and await scrutiny in future studies’.
 
However, Professor Susan Davis, an endocrinologist and head of Monash University’s Women’s Health Research Program, said observational studies, such as the Danish research, have a ‘healthy user bias’.
 
‘Major factors that impact life expectancy, namely smoking and overweight/obesity, were not even considered or even mentioned as a study limitation,’ Professor Davis said.
 
‘While the authors adjusted their analyses for a large number of characteristics, these critical factors that influence life expectancy were not included.
 
‘So, while this is a nice paper, the limitations are those of all observational studies, especially amplified in the post-Women’s Health Initiative years when people thought MHT caused breast cancer and heart disease.’
 
The research also found that women who had undergone bilateral oophorectomy aged 45–54 for non-cancerous reasons experienced a significant survival benefit when using MHT, leading to an up to 34% lower risk of death.
 
But Professor Davis said this is the finding she feels ‘most cautious about’.
 
‘What I cannot reconcile with these data is that the average life expectancy for women born in Denmark in 1950 was 71 years, and longer for each later year of birth,’ she explained.
 
‘I really would not expect women who had their ovaries out for reasons other than cancer to have a life expectancy that is 10–13 years younger than the general population.
 
‘So, why were the women in the study who had ovaries removed (cancer excluded) dying so young?’
 
The research comes after three new MHTs were added to the Pharmaceutical Benefits Scheme in March last year – Estrogel, Estrogel Pro, and Prometrium.
 
Since then, more than 363,000 women have been written 1.5 million scripts for the treatments.
 
Dr Amy Dwyer, National Breast Cancer Foundation research fellow, said the Danish study provides ‘reassuring real-world evidence’, but urged the importance of nuance during treatment.
 
‘For women with significant menopausal symptoms, especially those who lose ovarian function early through surgery, the balance of evidence suggests that hormone therapy can be both safe and beneficial,’ she said.

‘Population-level studies like this are essential, but we also need mechanistic insight to understand which formulations are safest for the breast.
 
‘The key message is nuance: hormone therapy is not one uniform entity, and individual risk depends on timing, indication, and the specific hormones used.’
 
Backing up this call for nuance, research released last year, authored by Professor Davis, also highlights the need for an individualised approach to MHT, as well as the need for shared decision-making between healthcare professionals and patients.
 
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menopausal hormone therapy menopause MHT women’s health