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Hormone replacement therapy use linked to lower mortality risk from COVID-19

7th June 2022

Use of hormone replacement therapy within 6 months of an infection with COVID-19 is associated with a reduced mortality risk

The use of hormone replacement therapy (HRT) by women within 6 months of developing an infection with COVID-19 has been found to be linked with a significantly reduced risk of subsequent death, according to a retrospective analysis by a group of UK researchers.

Deaths from COVID-19 have shown a male bias with one estimate suggesting that men are 1.7-times more likely to die than women. However, this observation is not new and similar findings were observed with severe acute respiratory syndrome, where the mortality rate was 21.9% for men but only 13.2% for women.

The reasons behind these apparent sex-related differences are unclear but attention has focused on a potentially protective effect of oestrogens.

Data from the COVID symptom study found that women using the combined oral contraceptive pill had a lower rate of predicted infection with COVID-19 although the relationship with the use of hormone replacement therapy was less clear.

To date, only one retrospective analysis of women using hormone replacement therapy has been undertaken and suggested that the fatality risk for women over 50 years of age and in receipt of oestradiol therapy was reduced by more than 50%.

In an effort to better understand the relationship between HRT use and mortality after infection with COVID-19, the UK team retrospectively examined information held in the Oxford-Royal College of General Practitioners Research and Surveillance Central database. They identified a cohort of women with a PCR confirmed COVID-19 infection and who had been prescribed HRT within 6 months of their date of infection.

The researchers set the study’s primary outcome as all-cause mortality during the follow-up period (January 2020 to June 2020) and also extracted included age, ethnicity and co-morbidities which were adjusted for in their regression analysis.

HRT use and all-cause mortality

A total of 5451 women with a mean age of 59 years were included and followed for a mean of 164.9 days and of whom 4.3% were prescribed HRT.

As in other studies, the risk of death was higher among women who were older, underweight and with co-morbidities such as hypertension and the use of immunosuppressants.

During the follow-up period, a total of 664 women (12.2%) died and the risk of all-cause mortality was significantly less likely in those using HRT (odds ratio, OR = 0.22, 95% 0.05 – 0.94, p = 0.041).

Interestingly, women prescribed HRT and asthma, had a much lower risk of mortality (OR = 0.58, 95% CI 0.42 – 0.81, p = 0.001) and the authors suggested that since these women were also likely to be prescribed steroids, this could have produced an added protective effect.

The authors concluded that women should be reassured that there was no reason to stop using HRT because of the pandemic and called for future studies to examine the effect of different doses and formulations and how these might impact on COVID-19 outcomes.

Dambha-Miller H et al. Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study Fam Pract 2022

HRT use increases risk of disease recurrence in breast cancer survivors

18th November 2021

Meta-analysis shows HRT use among women who have survived breast cancer is associated with a significant increased risk of disease recurrence.

Hormone replacement therapy (HRT) use for the management of menopausal symptoms in women with a history of breast cancer is associated with a significant increase in the risk of disease recurrence according to a meta-analysis by researchers from Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Although there have been major advances in the treatment of breast cancer, the blocking of oestrogen is associated with several adverse effects which negatively impact on a patient’s quality of life. HRT use is the most effective treatment for symptoms related to a reduction in the level of oestrogen although its use in breast cancer survivors is generally avoided. Among healthy women, the use of oestrogen only HRT leads to a reduced risk of breast cancer but when oestrogen is combined medroxyprogesterone, the risk is increased. Though it is generally advised that the use of HRT is avoided in patients with a history of breast cancer it has been suggested that there is insufficient evidence to contra-indicate HRT in breast cancer survivors.

With some uncertainty over whether HRT increases the risk in breast cancer survivors who experience oestrogen depletion-related symptoms, the Italian team decided to perform a systematic review and meta-analysis to assess the overall safety of systemic HRT use and its impact on disease recurrence in breast cancer survivors. They searched all of the main databases but restricted their search to articles published in English, randomised, placebo-controlled trials with breast cancer survivors and any studies reporting on the recurrence of breast cancer.


The literature search identified 12 studies of which, only 4 were included in the final analysis examining the effect of HRT on 4050 breast cancer survivors. All trials had randomised patients to either HRT or placebo with a total of 2022 patients randomised to HRT, either oestrogen/progestogen combinations or tibolone.

There was a low degree of heterogeneity in studies and compared to the placebo group, the use of HRT significantly increased the risk of breast cancer recurrence (hazard ratio, HR = 1.46, 95% CI 1.12 – 1.91, p = 0.006). In subgroup analysis, among patients with hormone receptor-positive tumours, the risk of disease recurrence was also significantly increased in those using hormonal therapy (HR = 1.80, 95% CI 1.15 – 2.82, p = 0.010). In contrast, in patients with hormone receptor-negative disease, there was no significant increase in risk (HR = 1.19, 95% CI 0.80 – 1.77, p = 0.39). In a further analysis, the risk of breast cancer recurrence was no different between combined HRT and tibolone (HR = 1.51 95% CI 0.84 – 2.72).

Based on these findings, the authors concluded that future research should focus on finding alternatives to hormone replacement therapy for women who have survived breast cancer yet experience symptoms related to oestrogen deficiency.


Poggio F et al. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat 2021