Long COVID (postacute sequelae of SARS-CoV-2 infection, or PASC) is an emerging syndrome that affects 50% to 70% of people who survive COVID-19 for up to 3 months or longer after acute disease.1 It is a multisystem condition that causes dysfunction of respiratory, cardiac, and nervous tissue, at least in part likely due to alterations in cellular energy metabolism and reduced oxygen supply to tissue.3 Patients who have had SARS-CoV-2 infection report persistent symptoms and signs that affect their quality of life. These may include neurocognitive, cardiorespiratory, gastrointestinal, and musculoskeletal symptoms; loss of taste and smell; and constitutional symptoms.2 There is no one test to determine if symptoms are due to COVID-19.3
Acute COVID-19 mortality risk factors include increasing age, chronic comorbidities, and male sex. However, long COVID risk factors are quite different. A meta-analysis and review of 20 articles that met inclusion criteria (n = 13,340 study participants), limited by pooling of crude estimates, found that risk factors were female sex and severity of acute disease.4 A second meta-analysis of 37 studies with 1 preprint found that female sex and comorbidities such as pulmonary disease, diabetes, and obesity were risk factors for long COVID.5 Qualitative analysis of single studies (n = 18 study participants) suggested that older adults can develop more long COVID symptoms than younger adults, but this association between advancing age and long COVID was not supported when data were pooled into a meta-analysis.3 However, both single studies (n = 16 study participants) and the meta-analysis (n = 7 study participants) did support female sex as a risk factor for long COVID, along with single studies suggesting increased risk with medical comorbidities for pulmonary disease, diabetes, and organ transplantation.5 In this discussion, we focus on long COVID and its relationship with perimenopause and chronic fatigue syndrome.
Perimenopause
Perimenopause: A temporary disruption to physiologic ovarian steroid hormone production following COVID could acutely exacerbate symptoms of perimenopause and menopause.
JoAnn V. Pinkerton, MD, MSCP
The higher prevalence of long COVID in women younger than 50 years6 supports the overlap that studies have shown between symptoms of long COVID and perimenopause,7 as the median age of natural menopause is 51 years. Thus, health care providers need to differentiate between long COVID and other conditions, such as perimenopause, which share similar symptoms (FIGURE). Perimenopause might be diagnosed as long COVID, or the 2 might affect each other.
Symptoms of long COVID include fatigue, brain fog, and increased heart rate after recovering from COVID-19 and may continue or increase after an initial infection.8 Common symptoms of perimenopause and menopause, which also could be seen with long COVID, include typical menopausal symptoms such as hot flashes, night sweats, or disrupted sleep; changes in mood including dysthymia, depression, anxiety, or emotional lability; cognitive concerns such as brain fog or decreased concentration; and decreased stamina, fatigue, joint and muscle pains, or more frequent headaches. Therefore, women in their 40s or 50s with persistent symptoms after having COVID-19 without an alternative diagnosis, and who present with menstrual irregularity,9 hot flashes, or night sweats, could be having an exacerbation of perimenopausal symptoms, or they could be experiencing a combination of long COVID and perimenopausal symptoms.
- Consider long COVID, versus perimenopause, or both, in women aged younger than 50 years
- Estradiol, which has been shown to alleviate perimenopausal and menopausal symptoms, also has been shown to have beneficial effects during acute COVID-19 infection
- Hormone therapy could improve symptoms of perimenopause and long COVID if some of the symptoms are due to changes in ovary function
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