2. HORMONE REPLACEMENT, AN OVERVIEW DR SARAH WHITFIELD

3. Aims To increase confidence in dealing with menopausal symptoms in women. To increase knowledge with regards counselling a woman about HRT and prescribing it. Objectives Look at who HRT can be prescribed for Contra-indications to HRT Benfits versus risks Types of HRT How long? When to stop Alternatives to HRT Case Studies to apply what we have learnt

4. WHO NEEDS HRT? Women with Premature ovarian failure. Age <45 Treated up till age 51 [treat symptoms and prevent osteoporosis, CVD and dementia] Peri and postmenopausal women who have vasomotor and UG symptoms, short term low dose. [ 2-3 years but may need longer]

5. QUESTIONS TO ASK 1/ Are they having menopausal symptoms? 2/ Impact on their life 3/ Their ideas about treatment options

6. DEFINITIONS Premature menopause/ premature ovarian failure =menopause below the age of 45 years. Perimenopause = from the time the clinical features of the menopause start to 12 months after the last menstrual period. [women who are experiencing symptoms due to decreasing oestrogen levels]. Postmenopausal = when she has not had a period for 12 months [menstruation ceases permanently due to the loss of ovarian follicular activity]

7. SYMPTOMS AND DIAGNOSIS OF MENOPAUSE The diagnosis of menopause should be based on history, symptoms, and age of the woman, without relying on laboratory investigations. An examination may rule out other causes.history, symptoms, and age of the woman, without relying on laboratory investigations. An examination may rule out other causes. What are the symptoms of the menopause? The perimenopause usually begins with a change to the menstrual pattern.perimenopause usually begins with a change to the menstrual pattern. In western societies, the most common symptoms are hot flushes, night sweats (the. night-time manifestation of a hot flush), vaginal dryness, and sleep disturbance. Vasomotor symptoms Urogential Sleep disturbances

8. DURATION OF SYMPTOMS How long are menopausal symptoms likely to last? Without treatment: Menopausal symptoms are usually self limiting (2–5 years), although some women may experience symptoms for many years [RCPE, 2003].RCPE, 2003]. Hot flushes are usually present for less than 5 years; however, some women may continue to flush beyond the age of 60 years [Rees et al, 2009].Rees et al, 2009]. Vaginal symptoms (including dryness, discomfort, itching, and dyspareunia) generally persist or worsen with ageing [Grady, 2006Grady, 2006

9. FURTHER EVALUATION 1/Fulfil criteria for HRT? [POF, peri/postmenopausal] 2/ Any C.I? 3/ Benefits versus risks 4/ Uterus or not? 5/ Peri or postmenopausal 6/ Type of HRT, regimen

10. CONTRA-INDICATIONS Current, past, or suspected breast cancer. Known or suspected oestrogen-sensitive cancer. Undiagnosed genital bleeding. Untreated endometrial hyperplasia. Previous idiopathic or current venous thromboembolism (deep vein thrombosis or pulmonary embolism). Active or recent arterial thromboembolic disease (for example angina or myocardial infarction). Untreated hypertension. Active liver disease. Porphyria cutanea tarda (absolute contraindication).

11. BENEFITS Improvement in symptoms [vasomotor, UG, sleep, mood] Osteoporosis HRT is effective in; preserving bone density preventing osteoporosis in both spine and hip, reducing the risk of osteoporosis-related fractures. Reduction bowel cancer

12. RISKS CVD. RC data from Danish osteoporosis trial, reduced incidence CHD by 50% if commenced within 10 year of menopause. [window of opportunity for primary prevention]. BUT WHI RCT, small increase incidence CHD first 12 months. In women > 60 and large dose Cognition Obervational data, improvement if HRT started early in menopause, possibly reduces long term risk Alzheimers but further trials needed Evidence form well designed studies e.g WHI, no significant improvement in memory or cognitive function with HRT in older PM women Increases risk dementia in women 65-79

13. RISKS CONTINUED Breast cancer WHI small increased risk, MWS raised concerns Recent critique of both, number of key flaws on both which limit the ability of the trials to establish a causal association Ovarian Cancer Conflicting data Endometrial cancer Unopposed E therapy increases but largely neutralised with use progesterone Sequential combined HRT may be associated with small increase Continuous combined significant reduction Colorectal cancer Reduction [no data on transdermal]

14. WOMENS AGE AND RISK Up to age 50 No risk 50-60 Benefits outweigh risks 60-70 Benefits = Risks [over 60 swap to transdermal route] >70 Risks outweigh benefits

15. OESTROGEN ONLY HRT Women without a uterus Oral tablet (daily). Transdermal patch (once weekly or twice weekly) or gel (daily). Vaginal ring (Estring ® ), creams, and pessaries. Non oral oestrogen avoids first pass effect through liver, doesnt increase risk VTE Conjugated [equine] or estradiol, both deemed natural. Synthetic oestrogens e.g ethinyloestradiol not suitable

16. OESTEROGEN/PROGESTERONE HRT Perimenopausal women Need to be on combined cyclical preparations. Progesterone is needed for some part of the cycle as endometrial protection from the uterus. It is easiest to prescribe in a one tablet preparation. There are 2 types; 1/ Monthly cyclical regimen; oestrogen is in every daily tablet, progesterone is in 10-14 tablets at the end of each cycle. Expect monthly withdrawal bleed after progesterone finished. This is the usual regimen. 2/ 3 monthly cyclical regimen, oestrogen daily, progesterone for 14/7 every 13 weeks. Only one available is Tridestra Norethisterone and levonogestrel [norgestrel]; more androgenic [patches container either of these, no other progesterones] Dydrogesterone and medroxyprogesterone; less androgenic and often better tolerated Drospirenone; less androgenic, may be useful in women who c/o fluid retention in progesterone phase

17. OESTROGEN/PROGESTERONE COMBINED HRT Postmenopausal Women Can be switched from cyclical to continous combined preparations [no bleed except poss irreg first 6 months, refer if spotting after 6 month]. May be difficult to decide when they become postmenopausal [1 year after amenorrhoea] 54 years [80% women postmenopausal] Previous amenorrhoea or raised FSH and been on HRT for several years likely postmenopausal. Oral tablet (daily). Transdermal patch (once weekly or twice weekly): In transdermal combined hormone replacement therapy (cyclical or continuous) the progestogen is either combined into the patch or given separately as a tablet.

18. HOW LONG? WHEN TO STOP POF, up to age 51-52 then discuss further risks benefits For peri/postmenopausal, advised for some time in view of WHI and MWS is smallest dose, shortest period of time. Very recently, thinking up to age 60 probably benefits outweigh risks. 60-70 benefits equal risks, and over 70 no place for HRT. How to stop? Abrupt or reduced dose over 2-3 months

19. LIFESTYLE ADVICE FOR MENOPAUSAL SYMPTOMS Hot flushes and night sweats: Taking regular exercise and losing weight (if applicable) may reduce the severity and frequency of flushes. Wearing lighter clothing, sleeping in a cooler room, reducing stress, and avoiding possible triggers (such as spicy foods, caffeine, smoking, and alcohol) may also be helpful in reducing these symptoms. Sleep disturbances: Avoiding exercise late in the day and maintaining a regular bedtime can improve sleep. Mood and anxiety disturbances: Adequate sleep, regular physical activity, and relaxation exercises may help. Cognitive symptoms: Exercise and good sleep hygiene may improve subjective cognitive symptoms.

20. ALTERNATIVES TO HRT Clonidine marginal benefit of clonidine over placebo SSRIs A significant amount of evidence exists for the efficacy of SSRIs such as fluoxetine and paroxetine in treating vasomotor symptoms; Gabapentin, hot flushs use is limited by side effects such as drowsiness Tibolone. synthetic steroid hormone oest, prog and androgen properties] CVA increased 2.2 fold [risks outweigh benefits age > 60]Increase risk endometrial Ca [increased risk with duration of use, may causes spotting first 6 months] Increase risk breast ca

21. OTHER ALTERNATIVES Red clover Black cohosh Phytoestrogens

22. LETS LOOK AT SOME CASES!

23. SUMMARY HRT prescribed before the age of 60 has a favourable benefit/risk profile. It is imperative that women with POF are encouraged to use HRT at least until the average age of the menopause. If HRT is to be used in women over 60 years of age, lower doses should be started, preferably with a transdermal route of administration