The Menopause and HRT

Learning objectives Be aware of how women may present Discuss some of the management options Consider contraception at the menopause Demystify some of the preconceptions re condition and treatment Have some idea of the choices available Are any HRT preps better : which ones when?

Menopause How might it present? How do you diagnose it? Consider pre/peri/post menopausal. Surgical/acute

Symptoms/Problems 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

Menopause Average age 51 80% post menopausal by 54 By 1y flushes have stopped in 70%......30% still have them at 5y Decreased no. of follicles, ovaries fail and don’t respond to pituitary hormones

‘’I think I may be menopausal’’ Why do they come?

‘’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://www.womens-health-concern.org/help/factsheets/fs_hrtrisksbenefits.html

What could you discuss in a consultation?

Consultation ideas Peri or post menopausal? Is it surgical/chemo related? Promote health Diet, exercise, breast awareness, mammograms, stop smoking, BP ?lipids, ?depression screening, ?urinary symptoms screening Assess osteoporotic risk Contraception ? Tests…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

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

What types of HRT are there?

What types of HRT are there? Are they the same?

Class Actions Oestrogen Progesterone Vasomotor Symptoms Bone Protection Urogenital Tract Endometrial Protection ……….breast tissue

Sequential Continuous combined Reg controlled bleeds Pt preference (cyclical Symptoms) (Double charge) Amenorrhoea 90% Less blood loss/anaemia Better endometrial protection ?less ovarian cancer Better compliance Cheaper (initial irreg btb)

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

Progestogens C19 derivatives C21 derivatives Less androgenic Norethisterone Levonorgestorel More androgenic More likely to cause side effects C21 derivatives Medroxyprogestogen acetate Dydrogesterone Less androgenic Drospirone (spironolactone deriv)

Tibolone Tibolone increases risk of breast cancer (less than combined HRT) Tibolone- combines oestrogenic and progestogenic activity with androgenic activity (if poor libido/post endometriosis surgery)… reduces TG : good for Type 2 DM/oophorectomy

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

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

What to expect Cyclical HRT causes a regular withdrawal bleed near the end of the progestogen phase The aim of continuous combined HRT is to avoid bleeding but irreg bleeding may occur during early treatment-if this continues > 6m an endometrial assessment is required

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

HRT BNF states, HRT is suitable for relieving vaginal atrophy or vasomotor symptoms, not 1st line for osteoporosis … National Osteoporosis Society 2011 now say if in 50s and Sx + bone loss: first line… If Sx are local only: most effective Rx is Topical… Ovestin or Vagifem every night 2/52, then 2-3 per week, repeat as necessary

Ovestin

Vagifem

Are there any alternatives? Symptomatic measures

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

Why do people want alternatives?

Risks: suggested by WHI and MWS Increased risk of VTE and CVA Increased risk of endometrial cancer (if oestrogen alone) Increased risk of breast cancer (related to duration of use, combined only, dissipates within 5yrs of stopping) Doesn’t prevent CHD/reduce cognitive decline.. But may if younger… CSM advise minimum effective dose for shortest duration Problems with trials….

HRT and breast cancer: initial findings 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

Risks: suggested by WHI and MWS Later analysis 50-59 or within 10y of onset of menopause CVD: trend for reduction Breast Ca : combined only-not sign if confounding factors taken into account. Sign reduced if oestrogen alone. Ovarian Ca: MWS only, only seen on Oestrogen alone (ie hysterectomised) ? Sign Endometrial Ca: unopposed oestrogen. If C/C no risk CVA: starting <60 no incr v non users Osteoporosis : only validated treatment for younger women-combined hrt reduces risk of hip fractures 0.66 (0.45-0.98) NNT 200 for 1 year

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

Harms Cardiovascular disease – combined hrt RR1.29 coronary heart disease, RR1.41 stroke (50-79) Breast cancer as described Endometrial cancer sequential combined hrt increases risk by 2 cases per 1000 women over 10yrs (unopposed oestrogen 5) continuous combined : reverses hyperplasia_ no increase Venous thromboembolism, hazard ratio 2.1 (extra 4 cases per 1000 women on hrt for 5yrs)

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

Special Cases Migraine : fluctuating levels can trigger Valvular heart disease on warfarin: may incr bleeding Endometriosis (may worsen) Hyperlipidaemia: ok with statins: choose lipid friendly (C21) Hypertension: equine can occ trigger incr BP Epilepsy: may alter doses needed: transdermal prob better

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

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?