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?
Consider pre/peri/post menopausal. Surgical/acute

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% % 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

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 Vasomotor Symptoms
Bone Protection
Urogenital Tract
Endometrial Protection
……….breast tissue

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

17. Example preparations Continuous combined Oestrogen only Cyclical HRT
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 C21 derivatives Less androgenic
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 Progestogenic (In a cyclical pattern) Fluid retention
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?
Symptomatic measures

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 MWS Later 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 ( ) NNT 200 for 1 year

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