Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hormone Replacement Therapy – what is the evidence? Dr Vikram T alaulikar MD FRCOG PhD Associate Specialist, ReLondon Hospitalcine Unit, University College Hon. Associate Professor in Women’s Health, University College London BMS certified Menopause Specialist Principal trainer for FSRH Menopause SSM Trainer for BMS principles and practice of menopause care Menopausal healthcare • Issue that affects about 50% of the population • Almost one third of women presenting to healthcare are between 40 and 60 • Another third are rapidly catching up! • Globally +/- 657 million women are 45-59 and 70-80% symptomatic • Women now spend a third of their life in menopausal phase! THIS IS NOT A MINORITY ISSUE!Timing of menopause • Median age 51 (46 in India) • 10% before 45 Age of onset of Menopause • 1% of women < 40 25 20 • 0.1% of women < 30 n 15 r p 10 Coulam Obstet Gynecol 1986 5 0 0 10 20 30 40 50 60 Stages during the journey towards menopause • Pre-menopause – before hormonal changes start • Peri-menopause – hormonal fluctuations (Usually for 2-5 years between 45-50) • Menopause – periods stop Symptoms (always retrospective diagnosis 1 year present after the last menstrual period) • Post-menopause – 1 year since periods have stopped and thereafter Management of menopause Addressing symptoms and long-term health through • Lifestyle modification • Changes at workplace TWO AIMS 1. Improve • Nutritional/self-help interventions quality of • Alternative therapies life and 2. Long-term • Non-HRT medications or health • Menopausal HRT What is HRT • Replacement of oestrogen, progesterone (and testosterone* to improve libido - off license) • Local or systemic • Not everyone needs or wishes to take HRT, but it should not be denied where it can help! • Systemic oestrogen replacement therapy is the most effective treatment for menopausal symptoms (the indication) Choice of HRT • Choice of different hormones – 17 beta oestradiol preferred oestrogen • Natural progesterone and dydrogesterone are better tolerated than norethisterone, MPA or levonorgestrel because they are less androgenic (less thrombosis and impact on risk of breast cancer)• Transdermal oestrogen preparations (gel, spray or patches) may be preferred if - • The woman is taking a hepatic enzyme–inducing drug (for example an anticonvulsant drug). • The woman has a severe liver disorder • The woman has a bowel disorder which may affect absorption of oral treatment. • The woman has a history of migraine (when steadier hormone levels may be beneficial). The woman has lactose sensitivity (most HRT tablets contain lactose). • BMI>30, Age >60 • Low-dose vaginal oestrogen (tablet, cream, pessary, or vaginal ring) can be used for urogenital symptoms alone and can be used in conjunction with systemic HRT Contraindications and caution • Do not prescribe HRT in women with: • Current, past, or suspected breast cancer • Known or suspected oestrogen-dependent cancer • Undiagnosed vaginal bleeding • Untreated endometrial hyperplasia • Previous idiopathic or current venous thromboembolism (deep vein thrombosis or pulmonary embolism), unless the woman is already on anticoagulant treatment • Active or recent arterial thromboembolic disease (for example angina or myocardial infarction) • Active liver disease with abnormal liver function tests • Pregnancy • Prescribe HRT with caution in women with: • Porphyria cutanea tarda • Diabetes, factors predisposing to venous thromboembolism, history of endometrial hyperplasia • Migraine and migraine-like headaches • Increased risk of breast cancer this is not an exhaustive list, please refer to SmPC for full information Bleed or bleed-free HRT • Cyclical HRT which causes bleeds – for women who are perimenopausal or who have just experienced menopause • Bleed free continuous HRT - for women who are post- menopausal for at least a year or more • Women with POI – prefer cyclical (especially if desiring fertility) Vaginal oestrogens • Very effective for vaginal dryness and painful sex • In suitable women, can be used as long as required and have little/no absorption into the body Other treatments for GSM • 6.5 mg a pessary containing DHEA delivered vaginally daily • Converted into oestrogens and androgens by enzymes within the epithelial cells of the vagina but not the endometrium and • Ospemifene is a selective oestrogen receptor modulator (SERM), administered orally in a dose of 60mg once daily Body-identical and Bio-identical HRT • Body-identical – oestrogen and progesterone that are similar to their biological equivalents (WELL STUDIED AND REGULATED) • Bio-identical (compounded) – custom made preparation by clinics using plant-based hormones etc. (NOT WELL REGULATED SO SAFETY AND EFFICACY CANNOT BE GUARANTEED!) Hormone Replacement Therapy (HRT) – a guide for cliniciansSupport • HRT can be commenced for vasomotor as well as other symptoms during women to perimenopause or menopause choose when to stop • There should be no arbitrary limits for duration of use of HRT and previously held HRT and views that HRT should be stopped after 2 arbitrary to 5 years or at the age of 60 are not limits should backed up - Individualise benefits versus not be risks imposed • Women with POI – at least until 50 (natural age of menopause) Coming off HRT • When women do decide to have a trial of cessation of HRT, there is no strong evidence for recommending stopping suddenly or gradually (makes no difference to whether symptoms will return) • In my own experience – reducing the dose gradually (using low dose or ultra low dose preparations or reducing the dose of patches or gel for 3-6 months) works better • HRT reduces the risk of both spine and hip as well as other osteoporotic fractures • Oestrogen remains the treatment of choice for osteoporosis* prevention in those with Other premature ovarian insufficiency benefits of • Oestrogen influences CVD risk factors, HRT especially if initiated in women below age 60 (bones/heart/ years or within 10 years of onset of menopause cognitive • Women with a premature menopause should function) take oestrogen to reduce the risk of CHD • Evidence is emerging about the role of oestrogen in relation to cognitive function and risk of dementia – watch this space! Side effects of HRT – Breakthrough bleeding • common in first 3-6 months üreassure (unless concerning features e.g. post- coital) • breakthrough on HRT ücheck compliance ü? change dose/type of progestogen ü scan if persists > 6 months Chance of finding endometrial pathology lower when bleeding on HRT (unlike PMB)Other common side-effects on starting HRT • breast tenderness • bloating • nausea • headaches tend to wear off dose-dependent, consider reducing oestrogen and building up graduallyT estosterone – levels decline in the menopause - Healthy young women produce approximately 100 – 400 mcg per day - Three to four times the amount of oestrogen produced by the ovaries - Important for libido, muscle/bone health, energy levels - Both ovaries and adrenals contribute - Levels drop during menopause - Profound loss after iatrogenic menopauseOptions • Gels, creams and implants (aim - 5 mg daily) • Free androgen index or total testosterone useful for monitoring • Remember main indication is low libido!Side effects - uncommon • Increased body hair • Generalised Hirsutism (uncommon) • Male pattern hair loss (uncommon) • Acne and greasy skin (uncommon) • Deepening of voice (rare) • Enlarged clitoris (rare)Risks of testosterone • Randomised controlled trials have not shown an increased risk of cardiovascular disease or breast cancer although longer term trials would be desirableNICE conclusions on HRT & breast cancer risk ØOestrogen alone is associated with little or no change in the risk of breast cancer ØOestrogen plus progestogen can be associated with an increase in the risk of breast cancer ØThe risk of breast cancer is related to treatment duration and reduces after stopping HRT NICE GUIDELINE 2015Pictorial explanation of risk Climent-Palmer Post-Reproductive Health 2019; 25:175-8 based on Lancet 2019; 394:1159-68VTE risk with HRT in healthy women Type of HRT odds ratio (95% CI) 26770 cases, 82672 controls. UK general practices. BMJ 2019;364:k4810 HRT & coronary heart disease ØNot increased when HRT started in women < 60 ØMay be associated with a more favourable benefit risk profile if started under the age of 60 or within 10 years of the menopause ØCardiovascular risk factors (BP, DM) are not a contraindication if optimally managed NICE GUIDELINE 2015HRT & stroke ØThe absolute risk is very small in women < 60 ØTaking oral oestrogen is associated with a small increase in the risk of stroke * ØTransdermal oestrogen is not associated with risk increase NICE 2015 *MHRA estimate from 4 to 5 cases per 1000 women over 5 years• Since publication of the WHI study results and Million Women’s study results around 2003 – a lot has changed! • Every woman’s experience of menopause is unique – and individualising HRT recommendations is important • Thank you