Joanna Swallow Mary Valentine 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 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

‘’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/menopause.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 Intact Uterus Oestrogen only HRT (may still wish to combine if hx of endometriosis) Intact Uterus Oestrogen + Cyclical progestogen for the last 12-14 days If no period for >12 months then Continuous combined Oestrogen/Progestogen or tibolone

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 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

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

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?