PROPHECY

PROPHECY (Predicting the Risks of Oestrogen-related Pathologies on Health Erosion to Conserve Healthy Years) is a cutting-edge project conducted in collaboration with Cardiff and Swansea Universities. Its aim is to investigate the impact of lifetime oestrogen exposure and menopausal symptoms on health, longevity, and psychological wellbeing. We use the following databanks to conduct our novel and pioneering research:

• SAIL (Secure Anonymised Information Linkage) Databank: This is a highly trusted resource including primary and secondary care data from 1996 to the present, involving 86% of the Welsh population.
• UK Biobank: This includes health data from 500,000 participants aged between 40 and 69 and is one of the most comprehensive and widely used datasets of its kind. Studying this information can help us to better understand how to prevent, diagnose and treat hormonal symptoms and health conditions.
• Health & Her: Since 2020 we have been co-ordinating web and app data from over 500,000 (anonymised) women experiencing menopausal symptoms to provide us with our own evidence and information.
  
  

Current findings from PROPHECY

The Role of Menopausal Symptoms on Future Health and Longevity: A Systematic Scoping Review

Published in Maturitas, a journal dedicated to exploring midlife health, our systematic review[i] revealed that menopausal symptoms are strongly linked to an increased risk of cardiovascular disease, psychiatric disorders, diabetes, and reduced bone mineral density. It also showed that psychological and cognitive symptoms usually improve after the menopause (with the exception of women from poorer socioeconomic backgrounds). We hope to build on this research going forwards and study whether improving menopausal symptoms can, in turn, help to reduce future health problems.

Hormone Replacement Therapy Uptake and Discontinuation Trends from 1996-2023: an Observational Study of the Welsh Population

Our study[ii] analysed HRT prescribing trends from 1996 to 2023 revealing an exponential growth in transdermal HRT (that is, delivered through the skin in patch or gel form) after 2021 and a decline in oral prescriptions post-2002. Discontinuation was highest amongst women aged 40 to 43 and those in their mid-50s and over. Using transdermal HRT was associated with higher discontinuation rates than using oral formats (the oestrogen-only or combined pills). A notable reduction in HRT prescriptions overall was attributed to socio-economic deprivation, despite the fact that prescriptions have been free in Wales since 2007.

SAIL Menopause e-Cohort (SAIL-MENO)

We developed the SAIL-MENO , a virtual cohort linking data collected digitally through online platforms. Menopause research was collected from 1996 to 2023 using linked primary care, hospital, mortality, and demographic information involving women aged between 18 and 65. Comparisons with UK Biobank showed comparable patterns – including similar prevalence rates for reporting bilateral oophorectomy (the removal of both ovaries from a woman’s body), hot flushes, premature menopause and HRT use, but a 25% lower menopause prevalence in SAIL overall, suggesting women were either under-represented in the examined data or had minimal symptoms. We have also created a code which generates SAIL-MENO publicly on our GitHub repository [iii] to support other researchers interested in exploring menopause in electronic health record data.

Menopausal Symptom Variances According to Medical Profiles

Using Health & Her data collected from 210,489 peri-menopausal and post-menopausal women between 2020 and 2024 [iv], we examined the impact of medical diagnoses and gynaecological procedures on menopausal symptoms. We found that being diagnosed with depression and anxiety had the strongest impact on increasing other symptoms, especially weight gain, low libido, vasomotor symptoms (hot flushes and night sweats) and aching joints. Undergoing gynaecological surgeries significantly increased vasomotor symptoms. Premature ovarian insufficiency (when a woman’s ovaries stop working before the age 40) was strongly associated with low libido and urogenital symptoms. Autoimmune diseases significantly contributed to increased joint aches plus low libido and sleep symptoms. Endocrine conditions such as PCOS, adenomyosis (a condition that causes endometrial tissue in the lining of the uterus to grow into the wall of the uterus), and PMDD  (a severe form of PMS) were linked to a reduction in vasomotor symptoms. Women who had undergone cancer treatment reported less weight gain and fewer psychological and physical symptoms. However, cancer treatment and breast and gynaecological cancers were associated with an increased risk of low libido, vasomotor and urogenital symptoms.

Upcoming studies

The Role of Menopause in Psychiatric Diagnoses, Self-Harm, and Suicide

In this study we use the SAIL databank and our bespoke SAIL-MENO e-cohort to explore whether women are at increased risks of psychiatric illnesses, self-harm, and suicide around the time of menopause. We will compare whether going through a surgical or premature menopause poses more risks compared to spontaneous menopause and are evaluating how menopausal symptoms and HRT could contribute to psychiatric illness.

The Role of Hormones in Midlife Men

Whilst the idea of a ‘male menopause’ remains contentious, we are also looking at how midlife hormones affect men - employing a male age-matched control group - to examine whether, or how, this is a time of increased hormonal vulnerability for both sexes.

HRT Prescribing Trends after Cancer Treatment

This study also uses SAIL data and is exploring whether women with a past cancer diagnosis for a non oestrogenic positive cancer are less likely to be prescribed HRT during menopause. We are also assessing whether women who use HRT after cancer have an increased risk of cancer recurrence or mortality.

The Links Between Cognitive Decline During Menopause and Dementia

Here we are using UK Biobank data to examine whether the menopause transition can influence declines in cognition, and whether these are associated with an increased risk of dementia. This piece of research investigates the variations between women who have gone through a surgical menopause, or a premature menopause, as well as the role of HRT and lifetime oestrogen exposure on brain health. Another key focus of this study is to evaluate whether modifying health and lifestyle factors such as BMI, diet, using supplements, drinking alcohol, and smoking could potentially improve dementia outcomes.