Survival of UK women following hormone replacement therapy

Hormone replacement therapy (HRT) reduces women's risk of an early death—according to new research from the University of East Anglia. 

A new in-depth study found that for healthy women taking combined HRT, the overall risk of death from all causes is reduced by an average nine percent.

For healthy women taking estrogen-only therapy, the risk of death from all causes remains neutral.

HRT replaces the hormones lost when a woman goes through the menopause, and it can relieve symptoms such as hot flushes, night sweats and depression.

The study, commissioned by the Institute and Faculty of Actuaries (IFoA), is the first to look at the impact of HRT on overall life expectancy using UK primary care data.

It comes as Labour MP Carolyn Harris is introducing a private member's bill to change legislation so that women in England would not have to pay for HRT. The bill is due to receive its second reading on October 29.

Prof Nick Steel, from UEA's Norwich Medical School, said: "HRT use has been controversial for many years, as it offers symptomatic relief to many women but there have been conflicting reports about the long-term risk of breast cancer, as well as possible benefits to cardiovascular health."

The study followed 105,199 healthy women aged between 46 and 65 at first HRT prescription over up to 32 years with an average follow-up of 13 years. It compared their outcomes with 224,643 non-users of the same age and GP practice.

Most previous studies adjusted for demographic and/or lifestyle factors only. The UEA research went much further, also adjusting for type 2 diabetes, hypertension and its treatments, coronary heart disease and oophorectomy/hysterectomy status, as well as body mass index, smoking and deprivation status.

Prof Steel said: "It's exciting that this new research found that combined HRT use was linked to an overall lower risk of death, and that estrogen-only HRT was not linked to an increased risk of death.

"UK primary care data has now enabled long term follow-up of thousands of women in the UK, comparing the overall risk of death over many years for those using HRT with those not using it."

Prof Elena Kulinskaya, from UEA's School of Computing Sciences, said: "Despite the effectiveness of HRT in relieving menopausal symptoms, many symptomatic women are not willing to receive HRT because of the controversial results on its risks and benefits.

"The untreated menopausal symptoms eventually increase the risks of other health conditions, such as osteoporosis and cardiovascular disease, and incur additional costs to the healthcare systems.

"All-cause mortality is the crucial endpoint that essentially summarizes the net effect of HRT but was rarely analyzed in the past. "

Postgraduate researcher Nurunnahar Akter, also from UEA's School of Computing Sciences, said: "Our new findings that estrogen-only HRT has no impact on all-cause mortality and combined HRT reduces the risk, confirm that the overall benefits of HRT outweigh the harms and should be provided to women and to clinical decision makers when they are deciding whether to start or continue HRT."

Louise Pryor, IFoA President, said: "This study supports the emerging consensus that, for most women, the benefits of HRT outweighs the harm. We hope this research will help to inform the debate as the private member's bill is considered in Parliament and also, support women deciding whether to start or continue with HRT. 

Abstract

Objective

To estimate the effect of estrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46–65 at first prescription.

Design

Matched cohort study.

Setting

Electronic primary care records from The Health Improvement Network (THIN) database, UK (1984−2017).

Population

105 199 HRT users (cases) and 224 643 non-users (controls) matched on age and general practice.

Methods

Weibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status.

Main outcome measures

All-cause mortality.

Results

A total of 21 751 women died over an average of 13.5 years follow-up per participant, of whom 6329 were users and 15 422 non-users. The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95% CI 0.88−0.94), and in estrogen-only users was 0.99 (0.93−1.07), compared with non-users. Age-specific adjusted HRs for participants aged 46–50, 51–55, 56–60 and 61–65 years at first treatment were 0.98 (0.92−1.04), 0.87 (0.82−0.92), 0.88 (0.82−0.93) and 0.92 (0.85−0.98) for combined HRT users compared with non-users, and 1.01 (0.84−1.21), 1.03 (0.89−1.18), 0.98 (0.86−1.12) and 0.93 (0.81−1.07) for estrogen-only users, respectively.

Conclusions

Combined HRT was associated with a 9% lower risk of all-cause mortality and estrogen-only formulation was not associated with any significant changes.

Reference

N Akter, E Kulinskaya, N Steel, I Bakbergenuly. The effect of hormone replacement therapy on the survival of UK women: a retrospective cohort study 1984−2017, (2021).BJOG 2021 Nov 12. doi: 10.1111/1471-0528.17008. Online ahead of print.