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EVERYTHING YOU NEED TO KNOW ABOUT HRT Urvi Vyas MENOPAUSE The last menstrual period >12 months amennorhoea with no other cause in women >50 years Occurs earlier in smokers High production of FSH and LH as the negative feedback from oestrogen diminishes CLINICAL FEATURES Vasomotor- hot flushes Urogenital- vaginal dryness and atrophy, recurrent UTI’s and incontinence Psychological- irritability, confusion, loss of libido, depression CVS- increased risk of ischaemic heart disease Osteoporosis- decreased bone density MANAGEMENT Oral tablets- oestrogen only, opposed oestrogen, continuous combined oestrogen and progesterone therapy Patches Creams implants INDICATIONS FOR HRT Early menopause, continue until age 50 Hysterectomy before the menopause, even if the ovaries are conserved Relief of symptoms during the menopause 2nd line treatment of osteoporosis for women >51 years CHOICE OF PREPARATION For women without a uterus i.e had hysterectomy- give oestrogen alone Premarin, Progynova, Harmogen For women with an intact uterus- progesterone is required for the last 12-14 days of the cycle to prevent endometrial proliferation Prempack, Nuvelle, Trisequens Continuous combined oestrogen and progesterone therapyKliofem, Premique, Climesse CONTRAINDICATIONS Oestrogen-dependent cancer i.e. endometrial cancer History of breast cancer Active or recent arterial thromboembolic disease (angina or MI) VTE Liver disease Dubin-Johnson and Rotor syndromes EVIDENCE REGARDING RISKS The womens health initiative (WHI) (JAMA 2002;288;321) RCT of 16000 asymptomatic post menopausal women aged 50-79, randomised to continuous combined HRT or placebo. A small increase in the rates of breast cancer (from 30 to 38) coronary heart disease (from 30 to 37) stroke (from 21 to 29) VTE (from 16 to 34) A decrease in colorectal cancer (from 16 to 10) hip fractures (from 15 to 10) Overall global risk was 15% higher in the HRT group Compounding factors were that the average age was 63, older than the UK average, and continuous combined HRT rather than cyclical HRT was used THE MILLION WOMEN STUDY Epidemiological cohort study looking at women’s HRT use when invited for breast screening, and then followed up to look at breast cancer development (Lancet 2003;362:419) All women on HRT had a higher breast cancer risk than never users The risk was highest with combined preparations The absolute risk remains small eg for 1 000 women taking combined HRT for 5 years there would be 6 extra cases of breast cancer Oestrogen-only HRT and tibolone are associated with small increases in endometrial cancer Combined HRT decreases endometrial cancer risk But combined HRT is associated with a greater increase in breast cancer risk than oestrogenonly or tibolone Because breast cancer is more common, overall there is greater overall risk of cancer with combined HRT HRT AND BREAST CANCER RISK Your pt aged 50, has a 6.1% risk of getting breast cancer in the next 30 year. If she takes combined HRT for 3 years the risk rises to 6.41% For 5 years, to 6.7% For 10 years, to 7.69% With oestrogen only HRT, after 5 year the risk is 6.28% (BMJ 2005:331:347) The risk/benefit ratio is favourable to treat menopausal symptoms, in fully-informed women, using the lowest possible doses for the shortest possible time WHEN LONG TERM HRT NEEDED Long term combined preparations are less safe than oestrogen alone Consider using oestrogen alone with an IUS Consider Tibolone TIBOLONE 1st line treatment for menopausal sx 2nd line therapy for prevention of osteoporosis 2.2 times inc risk of stroke Inc risk of endometrial cancer, risk increases with duration of use Increased risk of having breast cancer diagnosed, lower than for combined HRT, risk returned to baseline within a few years of stopping treatment Decreases HDL TOPICAL CREAMS Deliver oestrogen locally to vaginal tissues: pessaries, creams, rings No progesterone is needed but use is limited to 3 months if uterus is present ALTERNATIVES Clonidine may reduce flushing symptoms but has many side effects Beta-blockers may be used for palpitations and tachycardia Antidepressants and sedatives can be used if symptoms persist Calcium, vitamin D, Bisphosphonates for osteoporosis COMPLEMENTARY TREATMENTS Black cohosh-seems to ease hot flushes but long term effects are unknown Red Clover-conflicting evidence, some species contain coumarins so unsuitable for women who take anticoagulants such as warfarin Dong quai, evening primrose oil, vitamin E and ginseng are no better than placebo Kava has been linked to cases of serious liver damage and so should be avoided