HRT.

1. HRT. Dr Lisa Pickles. GP Brig Royd, Ripponden. September 2013.

2. Plan for this afternoon. • ‘I’d like to go on HRT.’ The initial and FU consultations. • Key messages. • Other snippets. • References/things to look up.

3. The initial HRT consultation. How to structure this. Where to start? What areas need to be covered and in what order?

4. Consultation contd: Take history in order to work out: • Indication vasomotor symptoms esp. flushes. (depression, osteoporosis maybe - not cycle control). • Patient expectations.

5. Consultation contd: Contraindications. • Pregnancy and BF. • Abnormal vaginal bleeding. • DVT. • Active or recent angina/MI. • Ca breast – suspected, current or past. • Ca endometrium or other oestrogen dependent cancer. • Active liver disease with abnormal LFTs.

6. Consultation contd: Side effects. What would you mention?

7. Consultation contd: I mention: • Sore breasts. • Leg cramps. • Bloating, mood/PMS sx (progesterone SE) (NOT weight gain, but CARE – most women put weight on because of the menopause itself. Not due to HRT). Ask patient to read the PIL that you will supply for more information.

8. Consultation contd: Risks. Mention: • Ca breast (E only has less risk than combined). • DVT . • Stroke. • Endometrial ca , only if unopposed with uterus.

9. Consultation contd: Risks. Show: • NPC patient decision aid. (note: data is based on WHI and MWS – probably over-estimates risk)

10. PDA – imagine 1000 women aged 50-59 who take combined HRT for 5 years.

11. PDA – contd:

12. Consultation contd: Risks – current thinking/research. • Heart disease. Early cohort studies – HRT reduces heart disease risk. WHI – ‘early harm’ but given to women >60yrs and relative overdoses of oral E. Danish osteoporosis trial (recent) – if HRT started within 10 years of LMP, CHD halved. ‘window of opportunity’ for primary prevention.

13. Consultation contd: • Risks – current thinking/research. 2. Breast cancer. MWS and WHI (E+P) – small increase risk of breast ca after 5 years. WHI (E) – small decrease in risk of breast ca. Recent critique of MWS and WHI illustrated key flaws which limit the ability of the trials to establish a causal association between HRT and breast ca.

14. Consultation contd: • Risks – current thinking/research. 3. Bone density. HRT now shown to reduce the risk of fracture ( as well as preserving bone density). BMS suggests HRT as 1st line therapeutic intervention for prevention and treatment of osteoporosis in menopausal women <60 ( esp. if menopausal with symptoms). Some studies suggest HRT use around the menopause may provide a long term protective effect many years after stopping (though protection declines).

15. Consultation contd: • Risks – current thinking/research. 4. VTE - oral HRT increases risk 2-4x. - probably less risk with transdermal , but no good RCT data. - MPA may have more risk than dydrogesterone. - recommend transdermal in women >60 (age increases DVT risk)

16. Consultation contd: • Risks – current thinking/research. 5. Stroke. WHI showed increased risk – but older patients studied. Re-analysis – lower risk in younger patients. Recommend transdermal route if risk factors for stroke or if >60.

17. Consultation contd: Benefits. • Improved vasomotor and urogenital symptoms. • Better sleep and mood, probably consequent upon night sweats reduction (but recent observational data suggest HRT may improve mood in the menopausal transition). • Prevention of osteoporosis. • Reduced colorectal cancer.

18. Consultation contd: Examine. • BP. • PV – only if indicated by eg abnormal bleeding. • Encourage ‘breast aware’ /mammograms and up to date smears. (I don’t weigh patients. Guidance suggests that we should).

19. Consultation contd: • Prescribe CSM statement 2003 ‘minimum effective dose should be used for the shortest time’ BMS recommendations 2013 ‘the optimum dose and duration should be decided according to the severity of a woman’s symptoms and her response to therapy’ ‘arbitrary limits should not be placed on the duration of usage of HRT’

20. Consultation contd: Prescribe. Consider: • Start low and build up as necessary. • Oral v patches (or gel) . oral cheaper, usually 1st line (unless >60 – transdermal) • Systemic or local (cream, pessary or ring). • Choice of oestrogen. conjugated E (premarin) v oestradiol. (tibolone, see end.)

21. Consultation contd: Prescribe. • Strength of oestrogen. 1mg oestradiol< or = 0.625mcg conjgd E < 2mg oestradiol < 1.25mcg conjgd E. (tibolone probably the ‘weakest’ in effect). note patches: 0.5mg oestradiol patch ~/= 2mg oral oestradiol. 0.25mg oestradiol patch ~/= 1mg oral oestradiol.

22. Consultation contd: Prescribe. • Unopposed(E only). If patient has had hysterectomy. • Combined (E + P). Has uterus. -Cyclical v continuous. (can use latter if amenorrhoeic for > 1 year ( unless POI >2 years) or if has been on cyclical HRT for 1 year.

23. Consultation contd: Prescribe. • Tibolone. Is a Selective Estrogen Receptor Modulator (SERM). Has oestrogenic, progestogenic and androgenic properties, so consider as continuous, combined preparation. Is a fairly ‘weak’ oestrogen. Less ca breast risk than combined (slightly more than E only), BUT increased ca endometrium risk and stroke risk. Not to use in > 60 years old due to CVA risk.

24. Consultation contd: Prescribe. • Possible indications for tibolone. - ‘hormone’ SE on other HRT. - if libido a problem? - if risk factors or concern re ca breast? • Testosterone – may help libido, but no licensed preparations. Would need specialist referral to consider gels. Patches recently withdrawn due to commercial, not safety reasons (were only licensed for use post surgical menopause anyway) • Choose preparation as per Formulary. www. formulary.cht.nhs.uk

25. Consultation contd: Prescribe. • Supply. 3 months supply. Then annually if all well. • Duration . Discuss? 2 yearly with HCP. Trials of stop/reduce if wished. If symptoms persist, the benefits of HRT usually outweigh the risks (BMS 2013) If premature ovarian insufficiency, usually till 51 (see next slide). • Prescription charge. Double if sequential combined.

26. Consultation contd: • Premature Ovarian Insufficiency The WHI findings do not apply to this young group. HRT in POI – simply replaces ovarian hormones that should normally be produced at this age (inform patient of this) - should generally continue till average age of menopause (51) Note: COC can be used as an alternative for symptoms (but little data on long term osteoporosis and CV disease prevention).

27. Prescribing Quiz

28. Consultation contd: Follow up. • Inform re arrangements. At Brig Royd, see GP for 1st consultation and rx. If all well, can see nurse at 3months and annually. Back to GP every 2 years. Adv to see GP if any problems. Note: BMS suggests annual review to discuss pros and cons of continuation.

29. Consultation contd: Issue Leaflet. • NPC patient decision aid re risks and benefits. • PIL of your own choice eg CKS, patient.co.uk, webmentor.

30. Consultation contd: Summary of 1st consultation. a. Discuss. • Indication • Expectations • CI • SE • Risks/benefits. b. Examine. • BP and weight. c.Prescribe. • Combined/unopposed. Tablets/patches. • Formulary. • 3 months supply. • ? Start low and increase dose if necessary. d.Follow up. • Arrange. e.Issue leaflet. Due to time limits, ? carry out a. + b. + e., then return for prescription and further explanation at a 2nd appointment.

32. Follow up consultations. At review: • Ask re SE, bleeding. • Check re planned duration of use. Consider whether to stop (usually reducing plan. CKS can be helpful here). Or can the strength be reduced? Offer restart if symptoms recur and appropriate. • Can cyclical combined be changed to continuous? ( yes if has taken for 1 year) • Revisit risk/benefit ratio and provide with up to date information. • Check BP and up to date w smear and mammogram. • Provide 12 month supply and arrange FU.

33. Follow up consultations: Dealing with problems. – ‘hormone’ SE: change of preparation. Often P effect (fluid retention/ PMS like)– dydrogesterone better. tolerated than MPA. Reduce E if sore breasts. - if poor symptom control. Increase E, change route, add vaginal E (if vag dryness) ?expectation, check patches stick.

34. FU Consultation contd: • Dealing with problems. - bleeding. • Heavy or erratic bleeding on cyclical combined – dose of progesterone should be doubled or increased duration to 21 days (consider hysteroscopy/scan if persists> 6m). • After switch to continuous combined – if BTB persists beyond 6m, then change back to cyclical for at least another year.

35. Key messages. • Tailor dose and duration to the patient. • Risk/benefit ratio – use NPCi patient decision aid and other PIL. • HRT <60 years old has favourable risk/benefit profile. • Weight is not a SE (but menopause causes weight gain). • Check BP. • Opposed oestrogen if has uterus (carries greater ca breast risk than unopposed). • Prescribe as per formulary. Tablets first line (preferably patches >60/low dose HRT).

36. Other snippets: • Endometrial cancer risk is greatly reduced with cyclical combined HRT and abolished with continuous combined HRT. • Mirena (IUS) can be used as progesterone component of HRT, licensed for 4 years for this use (5 years for contraception). • HRT is not contraceptive. It can be used with the POP. COC can be used till age 50 and may have HRT like effects till then. • Remember that tibolone is unsuitable for women> 60 years in view of stroke risk.

37. Other snippets: • Younger women with surgical menopause tend to need higher doses of HRT. Abrupt cessation of ovarian function rather than gradual failing at natural menopause. Start low and work up. • Note BMS 2013 advice that HRT can be used 1st line in management and prevention of osteoporosis (change in thinking)

38. Other snippets: • Million Women Study (looked at almost 1,000,000 women who were attending for mammograms and who also took HRT. Questionnaire study. On varied regimes) and Womens Health Initiative Study(USA. Criticised as average age studied was 63. Much older than most of our patients) were landmark studies responsible for the ‘HRT scare’. Looked at risks. 2002/2003. • A new analysis was published in Journal of FSRH early 2012 looking at MWS, WHI and Collaborative Analysis 1997. Concluded that these studies can only suggest that there may or may not be a link between HRT and Ca breast. Further research is suggested. See BMS 2013.

39. Other snippets: • Lift study. More recent. Found increased risk of CVA with tibolone compared other HRT especially if > 60y RR 2.2. (combined HRT RR 1.3). • MWS found ca breast risk: E only RR 1.3 Tibolone RR 1.5 Combined RR 2.0

40. Other snippets: • MHRA Sept 07, risks and benefits of E only and combined HRT is key document. • HRT can be given if raised BP is found so long as BP is treated and controlled 1st. • ‘Natural remedies’ – phytoestrogens (eg red clover, soy): some data. Some benefits for symptoms and on skeleton and CV system. Efficacy less than HRT . No hard data on outcome measures eg. CHD and fractures. • Give lifestyle advice. Healthy diet, exercise, reduce alcohol.

41. Other snippets: • HRT increases the risk of gallbladder disease (cholecystitis). This may be reduced by using transdermal rather than oral HRT. Caution if high risk gallbladder disease. • Migraine is not a CI, but low dose transdermal preparations may be preferable. • Cessation of HRT causes recurrent symptoms in 50%. (CKS has useful advice re reduction/stoppin)

42. Other snippets: • Pharmacological alternatives : • SSRIs eg. venlafaxine (SNRI) 37.5mg bd, fluoxetine, citalopram, paroxetine.(but avoid paroxetine and fluoxetine in those on tamoxifen – interacts) • Gabapentin can be as effective as low dose oestrogen. • Could try clonidine. A few patients benefit. Trial data suggests marginal. Non hormonal.

43. HRT cases Quiz.

44. References and things to look up. • British Menopause Societywww.thebms.org.uk • Womens Health Initiative Trial. JAMA 2002. • Million Women Study. Lancet 2003. • www.mhra.gov.uk. Drug safety update vol 1 issue 2 september 2007. • CKS (Clinical Knowledge Summaries) -menopause. • www.npci.org.uk - <60 minute workshop. - patient decision aid HRT (combined and oestrogen only). • MeRec bulletin March 2005. • BNF. • MIMs table of HRT preparations. • www.menopausematters.co.uk. Useful website for patients. • www.formulary.cht.nhs.uk. Google South West Yorkshire area prescribing committee if problems finding this website. • www.pennine-gp-training.co.uk . Abnormal vaginal bleeding guidelines (in clinical section under women’s health) and this presentation. • www.fsrh.org.uk .Contraception for women aged over 40 years. • BMJ 25/2/12. Practice. Hormone Replacement Therapy. • National Osteoporosis Society. www.nos.org.uk