HRT Joanna Swallow Mary Valentine Learning objectives Which

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 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: //hcd 2. 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 <70 pmol/l 2 FSH >30 iu/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 1 st 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 5 yrs 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 3 rd 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

$Benefits ► Symptom relief ► Osteoporosis- combined hrt reduces risk of hip fractures 0.$

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 45 yrs 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 RR 1. 29 coronary heart disease, RR 1. 41 stroke ► Breast cancer as described ► Endometrial cancer combined hrt increases risk by 2 cases per 1000 women over 10 yrs (unopposed oestrogen 5) ► Venous thromboembolism, hazard ratio 2. 1 (extra 4 cases per 1000 women on hrt for 5 yrs)

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 c 19/21 derivatives, delivery

Progestogens ► C 19 ► E. g derivatives Norethisterone § Levonorgestorel § More androgenic § More likely to cause side effects ► C 21 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 1 st 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 >2 yrs ago and <50 yrs is prob ok ► If LMP >1 yr 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 ► (4 yrs)