Menopause

1. Menopause Phil Thirkell

2. Define the menopause [2 marks] • No menstrual periods for 12 months

3. What happens at the menopause? • End of Ovulation • End of Menstrual cycle • Stabilising of hormones

5. What 3 classical symptoms are associated with the menopause? • Hot flushes • Sweats (sometimes only at night) • Vaginal dryness

6. What other symptoms are associated with the menopause? • Headaches • Migraine • Palpitations • Sleep disturbance • Cystitis • Urinary frequency • Urinary incontinence • Loss of concentration • Poor memory • Irritability • Loss of libido • Skin thinning • Hair loss • Brittle nails • Osteoporosis • Central adiposity

7. What is the average age of the menopause? • 51 years

8. What causes the onset of symptoms? • Low oestrogen? • Rising FSH? • Rising GnRH? • Fluctuating oestrogen?

9. What is osteoporosis? • Progressive disease • Decreased bone mineral density and bone mass • Increases the risk of fractures

10. How is osteoporosis diagnosed? • Dual-energy X-ray absorptiometry (DEXA) scan • Fragility fracture  DEXA • WHO definition • 2.5 standard deviations below the mean peak bone mass

11. What are the risk factors for osteoporosis? • Age (men and women) • Menopause (drop in oestrogen causes increased bone resorption) • Smoking • Malnutrition • Vitamin D deficiency • Family history • Drugs – steroids • Cushings

12. Which fractures typically occur in osteoporosis? • Wrist • Hip • Vertebral body • Rib

14. How is osteoporosis managed? • Weight-bearing exercise • Diet • Bisphosphonates • Strontium ranelate • Hormone Replacement Therapy • Teriparatide • recombinant parathyroid hormone • Monoclonal antibodies – denosumab

15. Management of Menopause • Do nothing • Hormone Replacement Therapy • Anti-depressants – flushes + mood

16. Do nothing • Symptoms bearable for many women • Will resolve themselves in time

17. Hormone Replacement Therapy • Oestrogen • ± progesterone – if they have a uterus, progesterone inhibits proliferation of endometrium and decreases risk of endometrial cancer • SERMs – selective estrogen receptor modulators • Act as a partial agonist/antagonist at different oestrogen receptors • Femarelle • Prevents hot flushes and bone mineral loss • Doesn’t increase risk of breast/uterine cancer • Doesn’t increase clots or change the lipid profile

18. Benefits of HRT • Reduces vasomotor symptoms • Improves urogenital symptoms • Reduces osteoporosis risk

19. Risks of HRT • Breast cancer • Venous thromboembolism • Stroke • Endometrial cancer • Dementia • Gall bladder disease • Lung cancer • Ovarian cancer

20. Early menopause • Before the age of 45 (or 40) • Primary ovarian failure • Secondary ovarian failure • Hormonal disorders – Addison’s, Hypothyroid, Diabetes • Chromosomal abnormalities

21. Which test can be used to identify early menopause? • Follicle stimulating hormone blood test

22. How to treat early menopause? • Treat with hormones until the average menopausal age – 51 • If a woman reaches menopause early, her bones will start to resorb and bone density will be decreased, leading to greater risk of osteoporosis/fractures • Keep hormone replacement going until 51 • Although increased risk of breast cancers etc. the woman isn’t getting extra oestrogens, just replacing what she should have had at this age

23. Untreated premature menopause causes increased risk of…? • Osteoporosis • Cardiovascular disease • Dementia • etc.

24. A patient of yours is asked if she would like to take part in a trial of a new drug for the menopause. It claims to reduce the number of hot flushes but without any of the side effects of oestrogen. She agrees and will be entered into a randomised controlled trial, comparing the new drug with existing HRT. i . Define what is meant by randomised in this context. ii. Give TWO reasons why it being randomised is an important feature of this type of trial. iii. Define what is meant by controlledin this context.

25. i. random allocation of treatment • equal chance of being assigned to either group • analogous to flipping a coin • not the choice of researchers or patient ii. To minimise bias To minimise confounding factors iii. The group receiving treatment are matched for a parallel group receiving the standard treatment/ a different treatment/ placebo/ no treatment etc.

26. Give and explain TWO ethical issues you will consider when advising the patient about this type of trial.

27. Clinical Equipoise – reasonable uncertainty about which treatment is better Scientifically robust – is the study big enough to generate useful data? Informed consent – written, informed, free to withdraw from trial etc.

28. The trial is extended nationwide and all menopausal women are invited. The incidence and prevalence of menopausal women has been calculated. Define incidenceandprevalence.

29. Incidence – the number of new cases of a condition occurring in a defined population in a set time period. Prevalence – the number of existing cases of a condition in a defined population at a specific time

30. What are the advantages of an RCT? What are the disadvantages?

31. Advantages Reduces bias Reduces confounders Can show causality Good for rare drugs/exposures Disadvantages Cost Time Limited to a few exposures/drugs