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HRT Joanna Swallow Mary Valentine Learning objectives ► Which preparation in which women at which stage ► Hazards to avoid ► Risk/Benefit ratios ► Big Studies/Evidence ► Switching/Swapping/Stopping 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 What symptoms do women suffer? Symptoms ► Physical ► Psychological ► Vasomotor ► Insomnia flushing ► Less skin collagen ► Vaginal dryness ► Urinary tract prolapse ► Reduced Bone mineral density ► Increased CVS risk ► Reduced concentration ► Anxiety ► Lethargy ► Reduced libido ‘’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://hcd2.bupa.co.uk/fact_sheets/html/menopau se.html ► Consultation ideas? 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 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) 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 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 Monitoring ► Review after 3 months and then annually ► Discuss bleeding pattern ► Weight and BP (6/12-annually) 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 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 Benefits ► Symptom relief ► Osteoporosis- combined hrt reduces risk of hip fractures 0.66 (0.45-0.98) ► NNT 200 for 1 year ► Colonic cancer, relative risk 0.80 (0.74-0.86) risk reduced 20% 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? 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 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) 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) Contraindications ► Pregnancy/Breastfeeding ► Oestrogen depdt cancer ► Angina/MI ► VTE ► Liver disease ► Untreated endometrial hyperplasia ► Undiagnosed vaginal bleeding Caution ► Migraine ► FHx Breast cancer ► Endometriosis (may worsen) ► VTE risk factors ► Hypertension When would you stop HRT? ► Immediate stop? ► Other reasons to stop? 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 Which Type? ► ► ► ► No Uterus ► Oestrogen only HRT Intact Uterus Oestrogen + Cyclical progestogen for the last 12-14 days If no period for >12 months then Continuous combined Oestrogen/Progestogen or tibolone (may still wish to combine if hx of endometriosis) 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 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 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 Side effects ► Most side effects disappear if the woman persists beyond 12 weeks with the preparation 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 ► ► Progestogens ► C19 ► E.g derivatives Norethisterone Levonorgestorel More androgenic More likely to cause side effects ► C21 derivatives ► E.g Medroxyprogestogen acetate ► Dydrogesterone ► Less androgenic 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? 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 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 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 Consider contraception? ► HRT is not contraception ► When is it safe to assume contraception no longer needed? Pat ► Pat is 43, she’s been on depo for 6 years and loves it, ► What should you consider/advise? 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’ 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 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. 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) Other Questions?