Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study

Abstract

Objective: Several recent observational studies have linked metabolic co-morbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection. Design: Population-based closed cohort study between 31st January 2020 and 22nd July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN). Methods: Main outcome was incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, body mass index, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS. Results: We identified 21,292 women with a coded diagnosis of PCO/PCOS and randomly selected 78,310 age and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1,000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 [95% CI 1.27-1.80], p<0.001). After adjusting for age and BMI, HR reduced to 1.36 [1.14-1.63], p=0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 [1.05-1.56], p=0.015). Conclusion: Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic.

Proxalutamide (GT0918) Reduces the Rate of Hospitalization in mild-to-moderate COVID-19 Female Patients: A Randomized Double-Blinded Placebo-Controlled Two-Arm Parallel Trial

“…[10][11][12][13][14] Although initially it has been considered that androgens would play a relevant role in COVID-19 only in males, females with hyperandrogenism, that could theoretically be under higher risk of severe COVID-19, were indeed correlated with more symptoms and more severity. [15][16][17] In accordance, preliminary observational data showed that women with hyperandrogenism that used antiandrogens not only had the increased risk mitigated, but also had fewer symptoms when compared to non-hyperandrogenic women. 18 Taken together, there is growing body of evidence to support that SARS-CoV-2 infectivity is mediated by the androgen receptor and will likely respond to drugs that reduce androgen receptor function.…”

“…Whether a potent NSAA would be effective for females was uncertain, and based on the translation between the SARS-CoV-2 large dependence on TMPRSS2, indirectly related to androgen activity (i.e., circulating androgens and sensitivity to androgens) and the presence of infection in a non-neglectable percentage of women, and on previous findings that women with hyperandrogenism experimented more symptoms than nonhyperandrogenic women, 16,17 while the chronic use of an antiandrogen (spironolactone) mitigated the overrepresentation of symptoms in women. 18,19 In terms of reduction of hospitalization rate, the efficacy of proxalutamide was demonstrated to be similar between females (86%) and males (91%) if used in the daily dose of 200mg for seven days.…”

SARS-CoV-2 Viral Entry Proteins in Hyperandrogenemic Female Mice: Implications for Women with PCOS and COVID-19

“…Moreover, a recent cross-sectional case-control study showed that COVID-19 positive outpatient women with PCOS had a higher incidence of COVID-19-associated symptoms such as low-grade fever, anosmia, ageusia, dry cough, among others, when compared with non-hyperandrogenemic COVID-19 positive women [ 23 ]. A large epidemiological study of more than 20,000 women with PCOS, matched 1:4 with control women, found a 36% increase risk for COVID-19 compared to controls after adjusting for BMI, age, and impaired glucose regulation [ 24 ]. This study further highlights the relevance to this population and the need for heightened focus.…”

Proxalutamide Reduction of Mortality Rate in Hospitalized COVID-19 Patients Depends on Treatment Duration – an Exploratory Analysis of the Proxa-Rescue AndroCoV Trial

“…2,3 Early observations in COVID-19 pandemic have identified hyperandrogenic phenotypes as independent risk factors for disease severity in both males [4][5][6] and females. [7][8][9] Antiandrogens have mechanistic plausibility to work against SARS-CoV-2, 10,11 have demonstrated pre-clinical [12][13][14] and preliminary clinical efficacy against COVID-19, both when used continuously [15][16][17] or initiated during the course of the disease 18 .…”