1. Hormone Replacement Therapy Dr Belinda Magnus

2. Menopause - Background  Vasomotor symptoms affect around 80% women during the menopause – severe in 20%  Median symptom duration 4 years – up to 12 years in 10%.  NB Diagnosis is usually clinical based on typical symptoms - 1yr amenorrhoea > 50yo, 2 yrs < 50yo

3. HRT – Indications for Use  For women with premature/ early menopause (<40yo or <45yo respectively) until the age of natural menopause – around 51yo  For treating menopausal symptoms where risk:benefit ratio is favourable in FULLY INFORMED women  Do not start in women over 60yo

4. Benefits of HRT  MOST EFFECTIVE RX AT REDUCING VASOMOTOR SYMPTOMS – within 4/52, maximum improvement by 3mo, improves sleep & mood  Also: Improves urogenital symptoms (sexual function/ recurrent UTIs); reduces osteoporosis risk; can reduce incidence of CHD if started within 10 years of menopause (controversial – see risks); possibly reduced risk colorectal ca with combined HRT.

5. Risks of HRT (1)  RISK-FREE until age of natural menopause  VTE: low in healthy women under 60yo. Over 60yo – risks much higher, esp if obese/ smoking/ previous VTE.  Stroke: Not increased in women under 60yo. Lower risk with transdermal oestrogens; effect may be dose-related.

6. Risks of HRT (2)  Breast cancer: still contentious  No increased risk with oestrogen-only up to 5 yrs  Combined HRT ↑ risk but greatest over 60yo  Generally, absolute risk increase is small – approx 1 extra case of breast ca per 1000 women/ annum – similar to risk with obesity/ nulliparity/ late menopause/ drinking 2-3 units of alcohol per day  Risk returns to non-user within 5 yrs of stopping  Combined HRT also increases breast density and risk of abnormal mammogram – important

7. Risks of HRT (3)  Endometrial ca: Oestrogen-only in women with uterus – so not given  Ovarian ca – conflicting evidence, possibly increased risk but the only RCT on this concluded no increased risk  CHD: Increased risk in woman starting this over 60yo

8. Contraindications to HRT  Undiagnosed abnormal vaginal bleeding  VTE  Active or recent angina/ MI  Suspected/ current/ past breast ca  Endometrial ca or other oestrogen- dependent ca  Active liver disease with abnormal LFTs  Uncontrolled HTN  Pregnancy or breastfeeding  If women want it – refer for specialist advice

9. Starting HRT (1) ↓ ↓ Uterus Hysterectomy (total) ↓ ↓ ↓ Periods? Postmenopausal? Oestrogen ↓ ↓ Cyclic HRT Continuous combined HRT

10. Starting HRT (2)  If subtotal hysterectomy – 3mo cyclic HRT + if withdrawal bleed = uterine tissue → continuous combined, if no withdrawal bleed → oestrogen alone

11. Monitoring HRT (1)  F/U 3mo initially after starting - BP, weight, symptoms, bleeding  Erratic bleeding common in first 3-6mo – if persisting afterwards, needs further inv  Monthly cyclic preparations should produce regular, predictable bleeds towards the end/ soon after progestogen phase  If bleeding heavy/ irregular on cyclic HRT, can double progesterone dose or ↑ duration to 21 days  Progesterone SE (eg: fluid retention/ weight gain/ mood swings) can halve progesterone dose or ↓ duration to 7-10 days

12. Monitoring/ Stopping HRT (2)  Reassess at least annually  Can consider FSH if previously normal if symptom-free for 1-2 years to consider stopping  If stopping – can decrease dose first if on high dose to try and minimise Sx

13. Alternative Forms of HRT  Oral most common  Non-oral (eg: patches/ gels) avoid 1 st -pass metabolism through the liver so are more suitable for eg: nausea/ liver disease/ malabsorption/ thrombosis/ enzyme-inducing drugs  HRT is NOT a contraceptive – 50yo.

14. Alternatives to HRT (1)  Vaginal atrophy/ urogenital symptoms – topical oestrogen first-line eg: tablet/ cream/ pessary/ vaginal ring  Mirena licensed as alternative for endometrial protection (4 years) with oestrogen component if get SE with other progestogens/ contraception still needed/ persistent bleeding on cyclical HRT + normal inv

15. Alternatives to HRT (2)  Tibolone: good for libido, less good than HRT for flushing; no need for cyclical progestogen; can use with uterus but only post-menopause; may increase risk breast/ endometrial ca + stroke; not to use in >60yo due to stroke risk  Clonidine: for flushing only; can cause hypotension; causes severe dry mouth; have to wean down to stop.

16. Case 1  45yo woman – early menopause  Severe flushing, not sleeping well, high- powered job in City and needs to be alert, works long hours.  Has read on internet and worried ++ about HRT risks – grandmother had breast cancer age 70yo  What do you counsel her?

17. Case 2  53yo woman – menopause started age 51  Severe flushing, night sweats, irritability.  What other questions to ask?  What decides if she can have HRT? What risks do you have to tell her about?

18. Case 3  60yo woman – been on HRT since 53yo for severe flushing + other vasomotor symptoms  ‘I can’t possibly come off HRT, my symptoms were so bad before.’  High chol, HTN (well controlled)  Taking Ellest duet Conti  How do you counsel her and what are the options?  What if her symptoms were mainly vaginal dryness during sex/ recurrent UTIs?

19. THE END Any Questions?