1. HRT/Contraception Joanna Swallow Mary Valentine

2. Menopause Average age 51 Average age 51 80% post menopausal by 54 80% post menopausal by 54 Climacteric precedes menopause Climacteric precedes menopause Decreased no. of follicles, ovaries fail and don’t respond to pituitary hormones Decreased no. of follicles, ovaries fail and don’t respond to pituitary hormones

3. What symptoms do women suffer?

4. Symptoms Physical Physical Vasomotor flushing Vasomotor flushing Less skin collagen Less skin collagen Vaginal dryness Vaginal dryness Urinary tract prolapse Urinary tract prolapse Reduced Bone mineral density Reduced Bone mineral density Increased CVS risk Increased CVS risk Psychological Psychological Insomnia Insomnia Reduced concentration Reduced concentration Anxiety Anxiety Lethargy Lethargy Reduced libido Reduced libido

5. ‘’I think I may be menopausal’’ Women often come to check/for reassurance (similar to ‘I’m pregnant consultation) Women often come to check/for reassurance (similar to ‘I’m pregnant consultation) 80% do not want HRT 80% do not want HRT They want advice and info They want advice and info Less than 50% of women prescribed hrt are using it at 1 year Less than 50% of women prescribed hrt are using it at 1 year Websites of use http://www.cks.library.nhs.uk/menopause Websites of use http://www.cks.library.nhs.uk/menopause http://www.cks.library.nhs.uk/menopause http://hcd2.bupa.co.uk/fact_sheets/html/menop ause.html http://hcd2.bupa.co.uk/fact_sheets/html/menop ause.html

6. 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 15 + oestradiol <70pmol/l 2 FSH >30iu/l 6 wks apart If taking FSH in menstruating women day 2-3 of menses

7. HRT BNF states, HRt is suitable for relieving vaginal atrophy or vasomotor symptoms, not 1 st line for osteoporosis BNF states, HRt is suitable for relieving vaginal atrophy or vasomotor symptoms, not 1 st line for osteoporosis Topical vaginal oestrogen rptd prn 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)

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

9. Risks Increased risk of VTE and CVA Increased risk of VTE and CVA Increased risk of endometrial cancer (if oestrogen alone) Increased risk of endometrial cancer (if oestrogen alone) Increased risk of breast cancer (related to duration of use, prep, dissipates within 5yrs of stopping Increased risk of breast cancer (related to duration of use, prep, dissipates within 5yrs of stopping Doesn’t prevent CHD/reduce cognitive decline Doesn’t prevent CHD/reduce cognitive decline CSM advise minimum effective dose for shortest duration CSM advise minimum effective dose for shortest duration

10. Breast cancer 14/1000 women aged 50-64 are diagnosed with breast cancer each year 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 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 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 are diagnosed with breast cancer each year 31/1000 women aged 50-79 on oestrogen only HRT are dx 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 35/1000 women aged 50-79 on combined HRT are diagnosed with breast cancer/year

11. 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 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 Risk increases with duration of use Breast cancers in women on HRT are larger and more advanced than those in women on placebo Breast cancers in women on HRT are larger and more advanced than those in women on placebo Data from Women’s Health Initiative Data from Women’s Health Initiative

12. Benefits Symptom relief Symptom relief Osteoporosis- combined hrt reduces risk of hip fractures 0.66 (0.45-0.98) Osteoporosis- combined hrt reduces risk of hip fractures 0.66 (0.45-0.98) NNT 200 for 1 year NNT 200 for 1 year Colonic cancer, relative risk 0.80 (0.74- 0.86) risk reduced 20% Colonic cancer, relative risk 0.80 (0.74- 0.86) risk reduced 20%

13. 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 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 The increase in bone density outweighs the risk of CVD and breast cancer

14. Harms Cardiovascular disease – combined hrt RR1.29 coronary heart disease, RR1.41 stroke Cardiovascular disease – combined hrt RR1.29 coronary heart disease, RR1.41 stroke Breast cancer as described Breast cancer as described Endometrial cancer combined hrt increases risk by 2 cases per 1000 women over 10yrs (unopposed oestrogen 5) 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) Venous thromboembolism, hazard ratio 2.1 (extra 4 cases per 1000 women on hrt for 5yrs)

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

16. Caution Migraine Migraine FHx Breast cancer FHx Breast cancer Endometriosis (may worsen) Endometriosis (may worsen) VTE risk factors VTE risk factors Hypertension Hypertension

17. Stop if Sudden onset severe chest pain Sudden onset severe chest pain Sudden SOB Sudden SOB Leg pain and ?DVT Leg pain and ?DVT Severe headache Severe headache Hepatitis/Jaundice Hepatitis/Jaundice BP > 160/100 BP > 160/100 Prolonged immobility Prolonged immobility Stop HRT 4-6 wks before major surgery Stop HRT 4-6 wks before major surgery

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

19. 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 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 HRT patches last ¾ days or 7 days and are placed below waist and sites rotated

20. 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) 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 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

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

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

23. Side Effects Oestrogenic Oestrogenic Fluid retention Fluid retention Bloating Bloating Breast tenderness Breast tenderness Nausea Nausea Headache Headache Dyspepsia (take with food) Dyspepsia (take with food) Consider changing dose, changing oestrogen or changing delivery Consider changing dose, changing oestrogen or changing delivery Progestogenic Progestogenic (In a cyclical pattern) (In a cyclical pattern) Fluid retention Fluid retention Breast tenderness Breast tenderness Mood swings Mood swings Depression Depression Acne Acne Backache Backache Reduce progestogen duration to 10 days per cycle, change progestogen c19/21 derivatives, delivery Reduce progestogen duration to 10 days per cycle, change progestogen c19/21 derivatives, delivery

24. Progestogens C19 derivatives C19 derivatives E.g Norethisterone E.g Norethisterone Levonorgestorel Levonorgestorel More androgenic More androgenic More likely to cause side effects More likely to cause side effects C21 derivatives C21 derivatives E.g Medroxyprogestogen acetate E.g Medroxyprogestogen acetate Dydrogesterone Dydrogesterone Less androgenic Less androgenic

25. Bleeding on HRT If on a cyclical combined HRt check when the bleeding is (should be regular and predictable at end of prog phase) If on a cyclical combined HRt check when the bleeding is (should be regular and predictable at end of prog phase) Check – compliance Check – compliance ?Interactions ?Interactions Try a stop in HRT Try a stop in HRT ?Other reasons ?Other reasons If bleeding stops try changing progestogen If bleeding stops try changing progestogen Refer 2 week rule if bleeding continues after HRT has been stopped for 4 wks Refer 2 week rule if bleeding continues after HRT has been stopped for 4 wks

26. Bleeding on HRT Refer non urgently if change in pattern of withdrawal bleeds and breakthrough bleeding persisting more than 3/12 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 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 Check that they were 1 yr post bleed before commencing ~If continues >6/12 then investigate ~If continues >6/12 then investigate If bleeding commences after ammenorrhea on the prep then investigate If bleeding commences after ammenorrhea on the prep then investigate

27. Stopping HRT Stop gradually wean off over 6/12 Stop gradually wean off over 6/12 Half dose for 2-3 months Half dose for 2-3 months ¼ dose for 3/12 then stop ¼ dose for 3/12 then stop Patches may be cut to achieve this Patches may be cut to achieve this Don’t reduce the progestogen if on a cyclical regime Don’t reduce the progestogen if on a cyclical regime If continuous reduce both simultaneously If continuous reduce both simultaneously Review after 1 month if symptoms have recurred consider restarting at lowest dose Review after 1 month if symptoms have recurred consider restarting at lowest dose If only vaginal symptoms then topical oestrogen's If only vaginal symptoms then topical oestrogen's

28. Contraception HRT is not contraception HRT is not contraception If LMP >2yrs ago and 2yrs ago and <50 yrs is prob ok If LMP >1yr ago and >50 is prob ok If LMP >1yr ago and >50 is prob ok FSH raise does not guarantee FSH raise does not guarantee

29. Mirena Mirena +oestrogen 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 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) (4yrs)

30. Other Questions?