Menopausal hormone therapy for women with obesity in the era of COVID-19

Obesity represents the condition of excessive body fat accumulation. According to the World Health Organization (WHO), obesity rates have almost been tripled since the 1970s. It is estimated that over 1.9 billion adults (39%) worldwide are overweight, of whom 650 million are obese (13%) [1]. The problem is especially important in the western world and affects particularly postmenopausal women. Indeed, approximately 50% of the latter are overweight, of whom 25% are obese [2–4]. Obesity often leads to other morbidities, such as type 2 diabetes mellitus (T2DM), dyslipidaemia, and hypertension; additionally, it increases the risk of gynaecological malignancies, cardiovascular disease (CVD), thrombosis, osteoarthritis and musculoskeletal disease [1–4]. Vasomotor symptoms (VMS) are generally more common in obese women than in normal-weight women. In the Study of Women's Health Across the Nation (SWAN), the likelihood of increased flushing was 1.27 times higher for any standard deviation (SD) increase in body fat percentage [5]. The women who gain weight during the transition to menopause are prone to develop VMS [2–5]. Menopausal hormone therapy (MHT), including tibolone and the combination of conjugated equine estrogens and bazedoxifene (CE/BZA), is the most effective treatment for VMS associated with menopause at any age. However, benefits are more likely to outweigh risks if the treatment is initiated for symptomatic women before the age of 60 years or within 10 years after menopause [6]. Specific caution is required for obese women because of their increased risk of thromboembolic disease. Obese women in the placebo arm of the Women's Health Initiative (WHI) study presented a 2.9-fold greater risk of venous thrombosis compared with normal-weight women [7]. This risk increases with age, body mass index (BMI) and the presence of thrombotic mutations [2–4]. In the era of COVID-19, the illness that is caused by the infection with the new coronavirus SARS-CoV-2, a new thrombotic risk factor has been added to this list. COVID-19 is associated with a systemic inflammatory response, often accompanied by activation of coagulation, especially in those with clinical disease. This favours the appearance of thrombotic events and may produce various coagulopathies [8]. Globally, the proportion of men andwomenwho have tested positive for SARS-CoV-2 is comparable. However, men are about 60% more likely to develop severe illness or die from complications. It is not clear whether this is due to biological differences between the two genders, differences in behavioural habits, or differences in the rates of comorbidities [9]. People with obesity have low-grade