Hormone Replacement Therapy

Hormone Replacement Therapy GPNG , Tuesday 25th September 2012

Dr Samantha L. Whiteside • BSc(Med Sci), MB ChB, MRCGP, DFFP, DRCOG • Loc SDI • Certificate in Menopause Care in conjunction with British Menopause Society & Faculty of Sexual & Reproductive Healthcare • Part of a Multidisciplinary Expert Group updating the UK Guidelines for the Subdermal Contraceptives for the Faculty of Sexual & Reproductive Healthcare • P/T GP at Kincorth&Cove Medical Practice

Agenda “The committee decided they would like you to cover” :- • HRT - Yes or NO ?? • Changes in thinking over time , why was it discouraged ? • Why is it now encouraged? • Who is it for ? • Types of HRT.

What is the menopause? • Natural menopause; ovaries produce less & less oestrogen and progesterone. Fail to produce oestrogen and progesterone when they have few remaining egg cells. • Surgical/medical menopause; ovaries are damaged by specific treatment such as chemotherapy or radiotherapy, or when the ovaries are removed, often at the time of a hysterectomy.

Average age of natural menopause in UK is 51yrs of age • Menopause occurring before aged 45 is early menopause • Menopause before age of 40 is premature menopause • Average life expectancy for a female in the UK is 82yrs

The Menopause • Hot flushes/sweats • Period disturbance • Sleep problems/feeling tired • Memory problems/poor concentration • Irritability • Emotional lability/crying more than usual • Muscle/joint aches • Reduced/absent libido • Painful sex • Urinary symptoms

At age 51 many women have teenage children, still work, socialise ………..

Exercise more Reduce alcohol intake Stop smoking Increase phytoestrogens in the diet Various herbal medications Prescribable non-HRT Acupuncture Alexander Technique Aromatherapy Homeopathy Hypnosis Magnetic therapy Reflexology Yoga Variety of options

HRT YES or NO ?

Womens’ Health Initiative • Million Women Study

Womens’ Health Initiative Study • 15-year research program to address the common causes of death, disability and poor quality of life in postmenopausal women. • WHI was launched in 1991 and consisted of a set of clinical trials and an observational study, which together involved 161,808 ‘generally healthy’ postmenopausal women. • The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium & vitamin D supplements on cardiovascular disease,breast & colorectal cancer, and osteoporosis. • The hormone trial had two studies: the oestrogen-plus-progestogen study and the oestrogen-alone study.In both studies, women were randomly assigned to either hormone medication or placebo.

The findings Compared withplacebo, oestrogen plus progestogen resulted in: • Increased risk of heart attack; 7 additional per 10,000 women • Increased risk of stroke; 8 additional per 10,000 women • Increased risk of DVT/PE ; 18 additional per 10,000 women • Increased risk f breast cancer; 8 additional cases per 10,000 women • Reduced risk of colorectal cancer; 6 less women per 10,000 • Reduced risk of fractures; 44 fewer fractures per 10,000 women Compared with placebo, oestrogen alone resulted in: • Reduced risk of heart attack; 5 fewer per 10,000 women • Increased risk of stroke; 12 additional per 10,000 women • Reduced risk of breast cancer; 7 fewer per 10,000 women • Increased risk of DVT/PE; 7 additional per 10,000 women • Reduced risk of fracture; 56 fewer fractures per 10,000 women • No effect on colorectal cancer

Womens’ Health Initiative - WHI • Restoring the balance ten years on

10yrs on…… • Many of the risks occurred because the dose of HRT was too high for and the study was based on over weight North American women in their mid-60’s. Average BMI was 28.5 and that is already a recognised risk factor for heart disease and certain cancers such as breast cancer. • They only used one dose and type of combined HRT or oestrogen only HRT. • Very important that the findings aren’t extrapolated to a younger population of women going through the menopause in their late 40’s and 50’s and certainly not women who go through a premature menopause. • The premature way in which the WHI data were initially released caused subsequent harm to many women.

Million Women Study • Set up to investigate the effects of specific types of HRT on incident and fatal breast cancer. • 1,084,110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death.

Findings from MWS Oestrogen –only HRT causes a small increase in the risk of breast cancer Oestrogen-only HRT causes a small increase in the risk of endometrial cancer Combined HRT increases the risk of breast cancer more than oestrogen only The longer the HRT is used, the higher the risk of breast cancer The risk declines as soon as HRT is stopped

Criticisms • Not an RCT, women were self-selecting and self reporting • They were women attending for mammogram so they may already be at higher risk for breast cancer eg already suspect a lump • Investigators underestimated duration of HRT use because HRT use was only documented at study entry and they didn’t know whether women continued/stopped/restarted HRT • The follow-up was done by reports from National Cancer Registries, not by subsequent questionnaires, so changes in HRT use after initial registration were not recorded • No information on HRT switching or previous use of HRT

Risks • Increased risk of breast cancer (with >5yrs use of combined HRT over the age of 50 – additional 3-4cases per 1,000 women), the risk decreases after HRT is discontinued. Mortality from the breast cancer is not increased. Oestrogen only HRT for 7yrs did not increase breast cancer risk in the WHI trial. • Oestrogen only and combined HRT increases the risk of DVT/PE; 2-3times the background risk which is 1.7 per 1000women aged over 50. Greatest risk is in the first 12months, risk is less with non-oral route. • Cardiovascular disease increased only when combined HRT is started in women aged over 60, or with pre-existing CHD. The first ten years after the menopause = the cardiovascular window of opportunity. • Stroke risk increased when HRT started in women aged over 60yrs. For most women, the benefits outweigh the risks and remember all drugs have risks

Breast cancer HRT risk in context You have more chance of getting breast cancer if • you are obese postmenopausally or drink more than 2units of alcohol daily postmenopausally and don’t take HRT • than if you are normal weight, drink sensibly and take HRT You are also more at risk of breast cancer if • menarche was at age <11 • menopause was at age >55 • aged >35 at first pregnancy

HRT – YES or NO? The two current licensed indications for prescribing HRT are: • Relief of menopausal symptoms • Prevention / treatment of osteoporosis • HRT can be very effective in relieving symptoms such as hot flushes, sweats, mood swings, irritability, insomnia, palpitations, joint aches, vaginal dryness and discomfort and urinary frequency and is still the most effective treatment • Other possible benefits of HRT include reduction in risk of cancer of the colon, and reduced risk of coronary heart disease and Alzheimers. These possible benefits are not currently regarded as indications for HRT.

Contraindications for HRT Undiagnosed abnormal vaginal bleeding Active or recent blood clot Active or recent myocardial infarction Suspected or active breast cancer Suspected or active endometrial cancer Active liver disease with abnormal liver function tests Porphyria cutaneatarda

HRT is not contraindicated in • Controlled hypertension • Abnormal cervical cytology • Treated ovarian cancer • Benign breast disease • Varicose veins

HRT and pre-existing conditions • Breast cancer; vaginal oestrogens not contraindicated. • Diabetes; HRT may alter insulin resistance. Non-oral route preferred as more favourable effect on triglycerides • Fibroids; may worsen • Endometriosis; may worsen • Gallstones; increased risk of gallbladder disease, non-oral route preferred • Crohns/coeliac disease; can help reduce their risk of osteoporosis, non-oral route preferred to maximise absorption • Migraine; not contraindicated, non-oral route preferred

Forms of HRT • Tablet egElleste/Premique • Patch egEstradot • GelegSandrena • IUS Mirena • Ring Estring • PessariesegVagifem Most often, HRT is started in tablet form.

Systemic HRT treatment NO UTERUS UTERUS Perimenopausal; need sequential/cyclical O+P Postmenopausal or aged over 54 on cyclical; can use CC O+P or tibolone • Oestrogen only

Tibolone • Oestrogenic, progestogenic and androgenic effects • Controls symptoms and protects bones • Can help libido and low mood • Similar risk of breast cancer as oestrogen only

Indications for non-tablet route • Individual preference. • Urogenital symptoms only. • Poor symptom control with tablet HRT. • Side effects with tablet. • Bowel disorder which may affect absorption of tablet therapy. • History of migraine • Lactose sensitivity • History of gallstones. • Current use of medications such as anti-epileptic medication which may interfere with the break-down of tablet HRT. • Variable blood pressure. • High triglyceride levels. • Diabetes • Risk factors, family history or past history of deep vein thrombosis or pulmonary embolus, after full discussion.

Overview • Systemic hormone therapy is an acceptable option for relatively young (up to age 59 or within 10yrs of menopause) and healthy women who are bothered by moderate to severe menopausal symptoms • Individualisation is the key • QOL, age, time since menopause, risk of blood clots, heart disease, stroke and breast cancer. • Lowest dose for the shortest duration. Fewer than five years ideally recommended for O+P therapy, duration should be individualised. • For oestrogen therapy alone, more flexibility in duration of therapy may be possible. • There is almost no woman who should be told that she can never take HRT

Where can patients get help • Discuss with nurses/GP’s other health professionals • www.menopausematters.co.uk • www.thebms.org.uk • Referral to ARI Menopause Clinic • Private Menopause Clinic at Albyn Dr Jane Johnston Thursdays 9am-6pm

Agenda - summary “The committee decided they would like you to cover” :- • HRT - Yes or NO ?? • Changes in thinking over time , why was it discouraged ? • Why is it now encouraged? • Who is it for ? • Types of HRT.

Any Questions?

Hormone Replacement Therapy