Menopause is associated with postprandial metabolism, metabolic health and lifestyle: The ZOE PREDICT study.

BACKGROUND: The menopause transition is associated with unfavourable alterations in health. However, postprandial metabolic changes and their mediating factors are poorly understood. METHODS: The PREDICT 1 UK cohort (n=1002; pre- n=366, peri- n=55, and post-menopausal females n=206) assessed phenotypic characteristics, anthropometric, diet and gut microbiome data, and fasting and postprandial (0-6 h) cardiometabolic blood measurements, including continuous glucose monitoring (CGM) data. Differences between menopausal groups were assessed in the cohort and in an age-matched subgroup, adjusting for age, BMI, menopausal hormone therapy (MHT) use, and smoking status. FINDINGS: Post-menopausal females had higher fasting blood measures (glucose, HbA1c and inflammation (GlycA), 6%, 5% and 4% respectively), sugar intakes (12%) and poorer sleep (12%) compared with pre-menopausal females (p<0.05 for all). Postprandial metabolic responses for glucose2hiauc and insulin2hiauc were higher (42% and 4% respectively) and CGM measures (glycaemic variability and time in range) were unfavourable post- versus pre-menopause (p<0.05 for all). In age-matched subgroups (n=150), postprandial glucose responses remained higher post-menopause (peak0-2h 4%). MHT was associated with favourable visceral fat, fasting (glucose and insulin) and postprandial (triglyceride6hiauc) measures. Mediation analysis showed that associations between menopause and metabolic health indicators (visceral fat, GlycA360mins and glycaemia (peak0-2h)) were in part mediated by diet and gut bacterial species. INTERPRETATION: Findings from this large scale, in-depth nutrition metabolic study of menopause, support the importance of monitoring risk factors for type-2 diabetes and cardiovascular disease in mid-life to older women to reduce morbidity and mortality associated with oestrogen decline. FUNDING: Zoe Ltd.

Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells.

Gender-bias in COVID-19 severity has been suggested by clinical data. Experimental data in cell and animal models have demonstrated the role of sex hormones, particularly estrogens, in viral infections such as in COVID-19. SARS-CoV-2 uses ACE2 as a receptor to recognize host cells, and the protease TMPRSS2 for priming the Spike protein, facilitating virus entry into cells. However, the involvement of estrogenic receptors in SARS-CoV-2 infection are still being explored. Thus, in order to investigate the role of estrogen and its receptors in COVID-19, the estrogen receptors ERα, ERß and GPER1 were overexpressed in bronchial BEAS-2B cell, and then infected with SARS-CoV-2. Interestingly, the levels of ACE2 and TMPRSS2 mRNA were higher in SARS-CoV-2-infected cells, but no difference was observed in cells with estrogen receptors overexpression. GPER1 can be involved in virus infection or replication, since its higher levels reduces SARS-CoV-2 load. On the other hand, pharmacological antagonism of GPER1 enhanced viral load. Those data suggest that GPER1 has an important role in SARS-CoV-2 infection.

Individual Benefits and Risks of Intravaginal Estrogen and Systemic Testosterone in the Management of Women in the Menopause, With a Discussion of Any Associated Risks for Cancer Development.

ABSTRACT: Several formulations of intravaginal oestrogen are available for the treatment of genitourinary syndrome of menopause (GSM). These are safe and effective treatments for the symptoms of GSM. Licensed doses of intravaginal oestrogen do not elevate systemic estradiol levels above the normal postmenopausal range with long term use and there is no evidence of an increased risk of coronary heart disease, stroke, thromboembolism, colorectal cancer, endometrial cancer, breast cancer or breast cancer recurrence with their use. This should reassure both women and their healthcare professionals and should lead to more women receiving these localised, vaginally administered hormonal treatments. Available evidence also suggests a positive safety profile for transdermal testosterone treatment when delivered at physiological concentrations.

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study.

It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.

Menopause and cardiovascular disease.

Cardiovascular disease is very common in women. It is still under diagnosed and under treated. Many women are not having their risk factors for cardiovascular disease properly addressed. Many healthcare professionals are uncertain about the role of hormones in cardiovascular disease. This article gives an overview of the most important risk factors for cardiovascular disease and how to manage those risk factors appropriately, based on the available evidence.