Oxybutynin or venlafaxine for hot flushes in women who cannot or prefer not to use hormone replacement therapy

INTERVENTION: To compare the relative clinical and cost‐effectiveness of extended‐release oxybutynin compared to low‐dose modified‐release venlafaxine in controlling VMS after 3 months of treatment, separately, in two populations of women with menopausal VMS: (a) those that are unable to take HRT, and (b) those who prefer not to use HRT. Participants will be recruited from secondary care clinics (which include gynaecology, specialist menopause, oncology), social media and GP/hospital database searches, throughout the UK. During the recruitment process, eligibility will be checked, and consent will be obtained (either electronically or face to face). As part of the eligibility checks, participants will self‐complete a hot flush diary, and report the number and severity of hot flushes every day, for 7 days, and only those with a mean of = 5 moderate/severe hot flushes per day will be eligible to take part. Baseline data will be recorded, which will include demographics, body mass index, when hot flushes started, history of hysterectomy, reason for contraindication to HRT (Group A), lifestyle factors, use of medication, complementary and supplements. Participants will also be sent baseline questionnaires to self‐complete about their quality of life, hot flushes, overall health and wellbeing, urinary symptoms, sleep, and work productivity. Eligible participants who consent will be individually randomised on a 1:1 ratio, separately for the two participant groups, using an online randomisation system, minimised in a secure online algorithm by recruitment site, body mass index, and use of anti‐oestrogens (group A) or recent hormone (HRT) use (group B), and retaining a random element. Investigators and participants will not be blinded. CONDITION: Women experiencing menopausal and peri menopausal hot flushes ; Urological and Genital Diseases PRIMARY OUTCOME: The average Hot Flush (HF) score (frequency x severity) over one week, at week 12 SECONDARY OUTCOME: ; All measured at baseline, week 12, and 6 and 12 months and additional stated timepoints:; 1. Average HF score (also in weeks 4 and 8); 2. Frequency and severity (individually) of hot flushes/night sweats (also in weeks 4 and 8); 3. Individual domains and total score of MENQOL‐I (also at week 4); 4. Hot Flush Related Daily Interference Scale (HFRDIS) (also at week 4); 5. Health related quality of life (EQ‐5D‐5L) and capability‐wellbeing (ICECAP‐A); 6. Participant acceptability and satisfaction with treatment (also at week 4); 7. Participant‐reported global impression of change on VMS and overall wellbeing; 8. Urinary urgency, frequency and incontinence (ICIQ‐OAB); 9. Sleep quality (PSQI); 10. Work Productivity and Activity Impairment Questionnaire‐ general (WPAI); 11. Pregnancy and pregnancy outcomes (participant reported and/or patient records); 12. Common known side‐effects of each treatment (participant reported via questionnaires); 13. Change or cessation of treatment, and for breast cancer population, continuation of endocrine therapy (participant reported via questionnaires); 14. Resource Use (participant reported via questionnaires ); INCLUSION CRITERIA: Group A (HRT contraindicated) 1. Women for whom HRT is contraindicated, e.g. women with breast cancer treated with adjuvant endocrine therapy. 2. =5 moderate/ severe menopausal hot flushes daily average, collected over a week, prior to randomisation. 3. Written/electronic informed consent. Group B (prefer not to use HRT) 1. Diagnosis of menopause or perimenopause 2. Age > 45 years 3. =5 moderate/ severe menopausal hot flushes daily average, collected over a week, prior to randomisation. 4. Not intending to use HRT within 12 months. 5. Written/electronic informed consent.