Umea, Sweden—Should hormone supplementation be part of the treatment for COVID-19 when older women become infected?

That is a question raised by a new Swedish study suggesting that higher estrogen levels in older women appear to protect against severe novel coronavirus infection and death.

In the article in BMJ Open, University of Umea–led researchers posit that it might be worth exploring supplemental hormone treatment in postmenopausal women with COVID-19.

They point out that in general, women seem to have a lower risk of severe COVID-19 infection than men, which also is true for MERS (Middle East Respiratory Syndrome).

A possibility, according to the study, is that estrogen has some protective effect. That led to the effort to determine whether augmentation of estrogen in postmenopausal women decreases the risk of death following COVID-19.

The study team performed a nationwide registry-based study in Sweden based on registries from the Swedish Public Health Agency, with a focus on all individuals who tested positive for SARS-CoV-2. Participants were 14,685 postmenopausal women between ages 50 and 80 years with verified COVID-19.

The study notes that most patients with breast cancer (BC) have estrogen receptor–positive cancer and are usually given adjuvant endocrine therapy after surgery in order to reduce the risk of cancer recurrences, leading to reduced systemic estrogen levels, adding, “On the other hand, systemic estrogen levels are augmented in women taking postmenopausal hormone therapy (HT) to relieve menopausal symptoms. In a nationwide cohort, we used the opposing effects of endocrine therapy in patients with BC and women taking postmenopausal HT in modulating systemic estrogen levels as a model to test the hypothesis that increased estrogen levels are protective towards COVID-19 death.”

For the study, pharmaceutical modulation of estrogen was defined by (1) women with previously diagnosed breast cancer and receiving endocrine therapy (decreased systemic estrogen levels); (2) women receiving hormone replacement therapy (increased systemic estrogen levels); and (3) a control group not fulfilling requirements for group 1 or 2 (postmenopausal estrogen levels).

Results indicate that unadjusted ORs for death following COVID-19 were 2.35 (95% CI 1.51 to 3.65) for group 1 and 0.45 (0.34 to 0.6) for group 2. Only the adjusted OR for death remained significant for group 2 with OR 0.47 (0.34 to 0.63). Researchers report that the absolute risk of death was 4.6% for the control group versus 10.1% and 2.1% for the decreased and increased estrogen groups, respectively.

The study determined that the risk of death due to COVID-19 was significantly associated with age, OR 1.15 (1.14 to 1.17); annual income, poorest 2.79 (1.96 to 3.97), poor 2.43 (91.71 to 3.46), and middle 1.64 (1.11 to 2.41); and education (primary 1.4 [1.07 to 1.81)] and wCCI 1.13 (1.1 to 1.16).

The researchers conclude, “This study shows an association between estrogen levels and COVID-19 death. Consequently, drugs increasing estrogen levels may have a role in therapeutic efforts to alleviate COVID-19 severity in postmenopausal women and could be studied in randomized control trials.”

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