HRT use tied to reduced COVID-19 death risk

The use of hormonal replacement therapy (HRT) among postmenopausal women may be associated with a reduced risk of mortality after a COVID-19 diagnosis, according to a retrospective study from Sweden.

“The major finding of this nationwide registry-based study is that pharmaceutical augmentation of oestrogen levels is associated with decreased odds of death due to COVID-19 in postmenopausal women,” the researchers said.

The researchers used national health registries to identify 14,685 postmenopausal women aged 50–80 years with a documented diagnosis of COVID-19 between February 1 and September 14, 2020, in Sweden. The women were grouped into three categories (women with reduced systemic oestrogen levels [previously diagnosed with breast cancer who were receiving endocrine therapy; n=227; mean age 64.4 years], women with increased systemic oestrogen levels [on HRT]; n=2,535; mean age 60.9 years], and a control group comprising women with postmenopausal oestrogen levels and no diagnosis of breast cancer or HRT prescription between 2019 and 2020 [n=11,923; mean age 61.2 years]).

The risk of death following COVID-19 was significantly reduced among women on HRT compared with women in the control group (adjusted odds ratio [adjOR], 0.47, 95 percent confidence interval [CI], 0.34–0.63). [BMJ Open 2022;12:e053032]

The absolute risk of death was greatest among women on endocrine therapy (10.1 percent), followed by women in the control group (4.6 percent) and those on HRT (2.1 percent).

Increasing age was associated with an increased risk of post–COVID-19 death (OR, 1.15, 95 percent CI, 1.14–1.17 per 1-year increase in age), as was lower annual income category (OR, 2.79, 95 percent CI, 1.96–3.97; OR, 2.43, 95 percent CI, 1.71–3.46; and OR, 1.64, 95 percent CI, 1.11–2.41 for poorest, poor, and middle income categories, respectively). Weighted Charlson Comorbidity Index (wCCI; OR, 1.13, 95 percent CI, 1.10–1.16 per increase in wCCI) was also tied to an increased risk of COVID-19 death, as was having only primary education (OR, 1.4, 95 percent CI, 1.07–1.81).

The persistent association of increased oestrogen on decreased COVID-19 mortality following adjustment for factors known to influence COVID-19 outcomes (eg, income level) “support[s] the protective role of oestrogen in women,” the researchers said.

The risk of COVID-19 death was increased among women on endocrine therapy compared with controls (OR, 2.35), but was not statistically significant after adjusting for confounders. As such, this finding needs further assessment in a larger population of patients with breast cancer on endocrine therapy, the researchers said.

“[T]his study cannot exclude an increased risk of death from COVID-19 if systemic oestrogen levels are pharmaceutically decreased,” the researchers cautioned.

Limitations of the study included the small number of patients with breast cancer on endocrine therapy, and lack of information on duration of HRT use, compliance to oestrogen modulation therapy, and certain potential confounding factors such as body mass index and smoking.

“This study shows an association between oestrogen levels and COVID-19 death. Consequently, drugs increasing oestrogen levels may have a role in therapeutic efforts to alleviate COVID-19 severity in postmenopausal women,” the researchers said, suggesting that this could present an avenue for study in randomized trials.