1. Joanna Swallow Mary Valentine
HRT
Joanna Swallow
Mary Valentine

2. Learning objectives Which preparation in which women at which stage
Hazards to avoid
Risk/Benefit ratios
Big Studies/Evidence
Switching/Swapping/Stopping

3. Menopause Average age 51 80% post menopausal by 54
Climacteric precedes menopause
Decreased no. of follicles, ovaries fail and don’t respond to pituitary hormones

4. What symptoms do women suffer?

5. Symptoms 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. ‘’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

7. Consultation ideas?

8. Consultation ideas Promote health
Diet, exercise, breast awareness, mammograms, stop smoking, BP ?lipids, ?depression screening, ?urinary symptoms screening
Assess osteoporotic risk
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

9. HRT
BNF states, HRt is suitable for relieving vaginal atrophy or vasomotor symptoms, not 1st line for osteoporosis
Topical vaginal oestrogen rptd prn
local oestrogen pessarys 1 nocte 2/52, then 2-3 per week
British menopause society states that it is safe to continue indefinitely (not premarin cream as systemic absorption)

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

11. Risks Increased risk of VTE and CVA
Increased risk of endometrial cancer (if oestrogen alone)
Increased risk of breast cancer (related to duration of use, prep, dissipates within 5yrs of stopping
Doesn’t prevent CHD/reduce cognitive decline
CSM advise minimum effective dose for shortest duration

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

13. 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

14. HRT and breast cancer
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

15. Benefits Symptom relief
Osteoporosis- combined hrt reduces risk of hip fractures 0.66 ( )
NNT 200 for 1 year
Colonic cancer, relative risk 0.80 ( ) risk reduced 20%

16. 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?

17. 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

18. Harms
Cardiovascular disease – combined hrt RR1.29 coronary heart disease, RR1.41 stroke
Breast cancer as described
Endometrial cancer combined hrt increases risk by 2 cases per 1000 women over 10yrs (unopposed oestrogen 5)
Venous thromboembolism, hazard ratio 2.1 (extra 4 cases per 1000 women on hrt for 5yrs)

19. Tibolone
Tibolone increases risk of breast cancer (less than combined HRT)
??Duration
Tibolone- combines oestrogenic and progestogenic activity with androgenic activity taken continuously and alone
(?libido/post endometriosis surgery)

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

21. Caution Migraine FHx Breast cancer Endometriosis (may worsen)
VTE risk factors
Hypertension

22. When would you stop HRT?
Immediate stop?
Other reasons to stop?

23. 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

24. Which Type? No Uterus Intact Uterus Oestrogen only HRT
(may still wish to combine if hx of endometriosis)
Intact Uterus
Oestrogen + Cyclical progestogen for the last days
If no period for >12 months then Continuous combined Oestrogen/Progestogen or tibolone

25. Starting HRT
Begin HRT at the lowest possible dose and increase at 3/12 intervals if reqd
Record that the risks of HRT have been explained and that an informed decision has been taken by the patient
HRT patches last ¾ days or 7 days and are placed below waist and sites rotated

26. What to expect
Cyclical HRT causes a regular withdrawal bleed near the end of the progestogen phase (Note the pt on cyclical HRT has to pay 2 prescription charges)
The aim of continuous combined HRt is to avoid bleeding but irreg bleeding may occur during early treatment-if this continues an endometrial assessment is required

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

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

29. 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

30. Progestogens C19 derivatives E.g Norethisterone C21 derivatives
Levonorgestorel
More androgenic
More likely to cause side effects
C21 derivatives
E.g Medroxyprogestogen acetate
Dydrogesterone
Less androgenic

31. 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?

32. 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

33. 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

34. 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

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

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

37. 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’

38. 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

39. 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.

40. 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)

41. Other Questions?