The main highlight of our study is that MHT in postmenopausal women seems to be related with a quicker recovery from COVID-19, proved by a lower rate of hospital admission and a shorter follow up length. To our best knowledge, this is the first study that evaluates MHT and COVID-19 related aspects. HBP and respiratory disorders were related as independent factors for greater risk of hospital admission due to COVID-19. MHT was linked with a fewer rate of hospital admission; although was not found as an independent factor in the multivariate analysis.
Epidemiological studies in the general population have focused in factors associated with a poor clinical outcome of COVID-19 (10, 11). In a systematic review including 207 studies and more than 75.000 patients from twelve countries, in consistency with our data, found that factors as age, HBP, and chronic respiratory conditions were related with higher disease severity and worst clinical outcome of COVID-19 (12). Epidemiological studies usually do not consider factors as depression or fibromyalgia, even when those are highly prevalent among postmenopausal women, making them a relevant target to correlate with disease progression (13–15). According to our results, both fibromyalgia and depression are related with a more severe infection and extended follow up, although only fibromyalgia proved to be an independent factor for domiciliary isolation. Taking that into account, we strongly believe that those are important factors to be included and evaluated in postmenopausal women with COVID-19.
Several studies have shown greater disease severity in men compared with women, pointing to a possible protective role of estrogens. (2, 5, 16–18). Even between pre and postmenopausal women, there are differences in prognosis regardless of age. (19). Seeland et al, in a wide epidemiological study found that postmenopausal women above 50 years old under MHT with COVID-19, had a reduction greater than 50% in mortality, driven by estrogens levels (1). Recently, another important epidemiological study using the COVID Symptom Study Smartphone Application in the United Kingdom, including around 18.000 women with COVID-19 under MHT, found that hospital admission was not greater in this group of patients, although they exhibit a higher and broader spectrum of symptoms. Only age, mass body index and smoking habit were assessed as confounding variables, nevertheless, diagnosis was made based on symptoms and prediction models and not in molecular tests, which potentially limits extrapolation of results (20).
Medical sick leave and domiciliary isolation, have deleterious implications at the social, family and working levels, without mentioning at the economical sphere. The deleterious cognitive and emotional consequences of this highly restrictive measurement, due to the physical distancing from the usual environment and dimensions in which patients have to reside during days or weeks, has been studied (21). Besides, working cessation in women who work as independents, posed great drawbacks in income (22). Lastly, it has been noted that prolonged domiciliary isolation has a negative impact in quality of life related to menopause, measured with specific quality of life instruments for menopause (23).
Because of everything mentioned above, a prompt recovery and a shorter isolation period is crucial to the wellbeing of menopausal women in all means. In our study, postmenopausal women under MHT finished their isolation and returned to daily life faster. It is possible that estrogens as a protective factor played an important role in this scenario, especially in the early stages of the infection. In addition, alleviation of climacteric symptoms by MHT could also improve patient wellbeing and avoid COVID-19 symptoms masking. For this reason, unlike some recommendations given in the early phases of the coronavirus pandemic, it does not seem reasonable to suspend MHT in symptomatic postmenopausal women with non-serious infection (24).
We believe that these results will contribute to the scaring literature regarding the management of postmenopausal COVID-19 patients and could be used as a reference for future research involved in the establishment of the the relationship between exogenous estrogens intake and viral infections outcomes. Nevertheless, the results of this work should be taken cautiously, as we are aware of the several limitations of this study. Limited number of patients presented, especially in the MHT group, impossibility to perform a comparison regarding administration route, composition or doses of MHT and a potentially source of bias arising from the analysis based on their employment status. This last one is minimized given the fact that the health care professional in charge of the follow up, was required to specify the end of follow up in an epidemiological survey.