Understanding Menopause and Hormone Replacement Therapy (HRT)

1. The Menopause and HRT

2. Learning objectives • Be aware of how women may present • Discuss some of the management options • Consider contraception at the menopause • Demystify some of the preconceptions re condition and treatment • Have some idea of the choices available • Are any HRT preps better : which ones when?

3. Menopause • How might it present? • How do you diagnose it?

5. Symptoms/Problems • Physical • Vasomotor flushing • Less skin collagen • Vaginal dryness • Urinary tract prolapse • Reduced Bone mineral density • Increased CVS risk • Psychological • Insomnia • Reduced concentration • Anxiety • Lethargy • Reduced libido

6. Menopause • Average age 51 • 80% post menopausal by 54 • By 1y flushes have stopped in 70%......30% still have them at 5y • Decreased no. of follicles, ovaries fail and don’t respond to pituitary hormones

7. ‘’I think I may be menopausal’’ • Why do they come?

8. ‘’I think I may be menopausal’’ • Women often come to check/for reassurance (similar to ‘I’m pregnant consultation) • 80% do not want HRT • They want advice and info • Less than 50% of women prescribed hrt are using it at 1 year • Websites of use http://www.cks.library.nhs.uk/menopause • http://www.womens-health-concern.org/help/factsheets/fs_hrtrisksbenefits.html

9. What could you discuss in a consultation?

10. Consultation ideas Peri or post menopausal? Is it surgical/chemo related? Promote health Diet, exercise, breast awareness, mammograms, stop smoking, BP ?lipids, ?depression screening, ?urinary symptoms screening Assess osteoporotic risk Contraception ? Tests…FSH/LH, No point if >45 (levels fluctuate massively) If <45 +no periods can indicate premature menopause ?Another reason for symptoms FSH/LH>15 + oestradiol <70pmol/l 2 FSH >30iu/l 6 wks apart If taking FSH in menstruating women day 2-3 of menses

11. Case 1 • 44 yr woman • Had menopause 7 years ago, her HRT was stopped after 5 years • Flushing is now ‘ruining her life’ • Thoughts? Votes for action?

12. Early menopause • In women with a natural or surgical menopause before age 45yrs HRT may be used until the approx age of natural menopause with no theoretical risk above and beyond baseline • The increase in bone density outweighs the risk of CVD and breast cancer

13. What types of HRT are there?

14. What types of HRT are there? • Are they the same?

15. Class Actions Oestrogen Progesterone Endometrial Protection ……….breast tissue • Vasomotor Symptoms • Bone Protection • Urogenital Tract

16. Sequential Continuous combined Amenorrhoea 90% Less blood loss/anaemia Better endometrial protection ?less ovarian cancer Better compliance Cheaper (initial irreg btb) • Reg controlled bleeds • Pt preference • (cyclical Symptoms) • (Double charge)

17. Example preparations • Continuous combined • Ellest duet conti • E.g premique • Oestrogen only • Elleste Solo • Patches/gels/implants • Cyclical HRT • Elleste-Duet • Premique calender pack 14 white (oest) and then 14 green (oest+prog) • Prempak-C

18. Progestogens • C19 derivatives • Norethisterone • Levonorgestorel More androgenic More likely to cause side effects • C21 derivatives • Medroxyprogestogen acetate • Dydrogesterone • Less androgenic • Drospirone (spironolactone deriv)

19. Tibolone • Tibolone increases risk of breast cancer (less than combined HRT) • Tibolone- combines oestrogenic and progestogenic activity with androgenic activity (if poor libido/post endometriosis surgery)… reduces TG : good for Type 2 DM/oophorectomy

20. Side Effects • Oestrogenic • Fluid retention • Bloating • Breast tenderness • Nausea • Headache • Dyspepsia (take with food) • Consider changing dose, changing oestrogen or changing delivery • Progestogenic • (In a cyclical pattern) • Fluid retention • Breast tenderness • Mood swings • Depression • Acne • Backache • Reduce progestogen duration to 10 days per cycle, change progestogen c19/21 derivatives, delivery

21. Side effects • Most side effects disappear if the woman persists beyond 12 weeks with the preparation

22. What to expect • Cyclical HRT causes a regular withdrawal bleed near the end of the progestogen phase • The aim of continuous combined HRT is to avoid bleeding but irreg bleeding may occur during early treatment-if this continues > 6m an endometrial assessment is required

23. Monitoring • Review after 3 months and then annually • Discuss bleeding pattern • Weight and BP (6/12-annually)

24. HRT • BNF states, HRT is suitable for relieving vaginal atrophy or vasomotor symptoms, not 1st line for osteoporosis … • National Osteoporosis Society 2011 now say if in 50s and Sx + bone loss: first line… • If Sx are local only: most effective Rx is Topical… • Ovestin or Vagifem every night 2/52, then 2-3 per week, repeat as necessary

25. Ovestin

26. Vagifem

27. Are there any alternatives?

28. Alternatives to HRT for flushes • Some Evidence • Red Clover (isoflavones) 6/52< • Sage • Clonidine • Phytooestrogens (soya beans, chickpeas, cereals) • SSRIs • Venlafaxine+Gabapentin • Black cohosh • Exercise • No Evidence • Vitamin E • St Johns Wort • Evening primrose

29. Why do people want alternatives?

30. Risks: suggested by WHI and MWS • Increased risk of VTE and CVA • Increased risk of endometrial cancer (if oestrogen alone) • Increased risk of breast cancer (related to duration of use, combined only, dissipates within 5yrs of stopping) • Doesn’t prevent CHD/reduce cognitive decline.. But may if younger… • CSM advise minimum effective dose for shortest duration • Problems with trials….

31. HRT and breast cancer: initial findings • Hrt increases the risk of breast cancer starting from the end of the 3rd year, risk reverts to normal 1 yr after stopping • Risk increases with duration of use • Breast cancers in women on HRT are larger and more advanced than those in women on placebo • Data from Women’s Health Initiative

32. Risks: suggested by WHI and MWSLater analysis • 50-59 or within 10y of onset of menopause • CVD: trend for reduction • Breast Ca : combined only-not sign if confounding factors taken into account. Sign reduced if oestrogen alone. • Ovarian Ca: MWS only, only seen on Oestrogen alone (ie hysterectomised) ? Sign • Endometrial Ca: unopposed oestrogen. If C/C no risk • CVA: starting <60 no incr v non users • Osteoporosis : only validated treatment for younger women-combined hrt reduces risk of hip fractures 0.66 (0.45-0.98) NNT 200 for 1 year

33. Breast cancer • 14/1000 women aged 50-64 are diagnosed with breast cancer each year • 15.5/1000 women aged 50-64 on oestrogen only HRT dx breast cancer/year • 20/1000 women aged 50-64 on combined HRT are diagnosed with breast cancer/year • 31/1000 women aged 50-79 are diagnosed with breast cancer each year • 31/1000 women aged 50-79 on oestrogen only HRT are dx with breast cancer each year • 35/1000 women aged 50-79 on combined HRT are diagnosed with breast cancer/year

34. Harms • Cardiovascular disease – combined hrt RR1.29 coronary heart disease, RR1.41 stroke (50-79) • Breast cancer as described • Endometrial cancer sequential combined hrt increases risk by 2 cases per 1000 women over 10yrs (unopposed oestrogen 5) continuous combined : reverses hyperplasia_ no increase • Venous thromboembolism, hazard ratio 2.1 (extra 4 cases per 1000 women on hrt for 5yrs)

35. Contraindications • Pregnancy/Breastfeeding • Oestrogen depdt cancer • Angina/MI • VTE • Liver disease • Untreated endometrial hyperplasia • Undiagnosed vaginal bleeding

36. Special Cases • Migraine : fluctuating levels can trigger • Valvular heart disease on warfarin: may incr bleeding • Endometriosis (may worsen) • Hyperlipidaemia: ok with statins: choose lipid friendly (C21) • Hypertension: equine can occ trigger incr BP • Epilepsy: may alter doses needed: transdermal prob better

37. When would you stop HRT? • Immediate stop? • Other reasons to stop?

38. Stop if • Sudden onset severe chest pain • Sudden SOB • Leg pain and ?DVT • Severe headache • Hepatitis/Jaundice • BP > 160/100 • Prolonged immobility • Stop HRT 4-6 wks before major surgery

39. Case 2 • Clara is 52, she has been on HRT for 5 months • She cant bear the bleeding and comes in teary as doesn’t want flushes to return • What do you want to know? • What could you do or consider?

40. Bleeding on HRT • If on a cyclical combined HRt check when the bleeding is (should be regular and predictable at end of prog phase) • Check – compliance • ?Interactions • Try a stop in HRT • ?Other reasons • If bleeding stops try changing progestogen • Refer 2 week rule if bleeding continues after HRT has been stopped for 4 wks

41. Bleeding on HRT • Refer non urgently if change in pattern of withdrawal bleeds and breakthrough bleeding persisting more than 3/12 • On continuous combined there is a 40% risk of bleeding in the 1st 4/12 • Check that they were 1 yr post bleed before commencing • ~If continues >6/12 then investigate • If bleeding commences after ammenorrhea on the prep then investigate

42. Stopping HRT • Stop gradually wean off over 6/12 • Half dose for 2-3 months • ¼ dose for 3/12 then stop • Patches may be cut to achieve this • Don’t reduce the progestogen if on a cyclical regime • If continuous reduce both simultaneously • Review after 1 month if symptoms have recurred consider restarting at lowest dose • If only vaginal symptoms then topical oestrogen's

43. Consider contraception? • HRT is not contraception • When is it safe to assume contraception no longer needed?

44. Pat • Pat is 43, she’s been on depo for 6 years and loves it, • What should you consider/advise?

45. June • June is 48, She has a mirena in, shes amenorrhoeic and having lots of hot flushes. She wants to know about HRT and whether she is ‘going through the change’

46. Contraception • HRT is not contraception • If LMP >2yrs ago and <50 yrs is prob ok • If LMP >1yr ago and >50 is prob ok • FSH raise does not guarantee

47. Jan • Jan is 50, She has a mirena (for 2 years) • She hasn’t had any periods since the first 3 months, she wants to know if she still needs it.

48. Mirena • Mirena +oestrogen • Mirena is now licensed for endometrial protection as the progestogenic part of HRT combined with a small amount of oestrogen may control hot flushes • (4yrs)

49. Other Questions?