Age Management Medicine News: November/December 2021 – #2

Combined HRT Could Reduce All-Cause Mortality by 9%, Study Results Show

Julia Robinson

Nov. 10, 2021 ( — Combined hormone replacement therapy (HRT) is associated with a 9% lower risk of all-cause mortality in healthy women, results from a large retrospective cohort study have suggested.

The study, which is yet to be peer-reviewed, examined electronic primary care records from The Health Improvement Network database, gathered between 1984 and 2017.

The researchers followed 105,199 healthy women aged 46–65 years at first HRT prescription over a time period of up to 32 years, with an average follow-up of 13.5 years, and compared their outcomes with 224,643 non-users of the same age and GP practice.

After adjusting for various factors, including hypertension and its treatments, body mass index and deprivation status, the researchers found that, over an average of 13.5 years follow-up per participant, a total of 21,751 women died, of whom 6,329 were users of combined HRT and 15,422 were not.

They calculated that, compared to non-users, the adjusted hazard ratio of overall all-cause mortality in combined HRT users was 0.91 (95% confidence interval [CI] 0.88-0.94), and 0.99 in oestrogen-only users (95% CI 0.93-1.07).

“This research strengthens the emerging consensus that for most women the benefits of long-term HRT outweigh the harms, but every woman’s situation is different and the risk and benefits from different conditions should be considered individually,” the authors concluded.

One of the authors of the paper, Nick Steel, clinical professor in public health at Norwich Medical School, described the research as “exciting”.

“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,” he said.

“UK primary care data [have] 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.”

Nuttan Tanna, pharmacist consultant in women’s health and osteoporosis at London North West University Healthcare NHS Trust, said the study findings were “important” as the patient data were adjusted for comorbidities that can affect the risk-benefit evaluation of HRT for complex patients.

“It is interesting to note the risk reduction for death for users of combined HRT. If the data stand up to peer review then the findings are significant, given the number of menopausal women population wide,” she added.

Current clinical guidelines from the National Institute for Health and Care Excellence (NICE) recommend offering combined HRT to symptomatic women with a uterus, and oestrogen-only HRT to women without a uterus, after discussing the benefits and risks.

According to NICE, the benefits of HRT include prevention of osteoporotic fractures, colorectal cancer and cardiovascular disease if the therapy is started before the age of 60 years. All-cause mortality studies were not reviewed by NICE as part of its guideline development.

Patients in England currently pay £9.35 for each prescription item, including for HRT; however, a private members’ bill — the Menopause (Support and Services) Bill — could mean patients in England would be entitled to free HRT prescriptions, in line with Scotland and Wales, where all prescriptions are free to everyone.

In the second reading of the bill, on 29 October 2021, the government said that it would look to implement longer prescribing cycles, in line with NICE guidelines, so that women receive fewer prescriptions, reducing the need to pay frequent prescription charges.

This could mean women would only have to pay one charge for up to a 12-month supply of HRT, saving up to £205 per year as a result.

To further improve access to HRT prescriptions, the government also committed to looking into combining two hormone treatments into one prescription, which affects approximately 10% of women accessing HRT.


The Pharmaceutical Journal, PJ, November 2021, Vol 307, No 7955;307(7955)::DOI:10.1211/PJ.2021.1.115109

 © 2021 Royal Pharmaceutical Society