The Menopause and HRT

1. The Menopause and HRT

2. Aims • Gain an understanding of what is meant by “menopause”, and how it is diagnosed • Gain an understanding of the treatment options • Think about the risks and benefits of HRT

3. Objectives • The menopause • What is it? • What are the symptoms? • How should it be investigated? • HRT • Indications • Choice • Risks • Side effects • Alternatives to HRT

4. The Menopause

5. The menopause – what is it? From the British Menopause Society: • Permanent cessation of menstruation • Only diagnosed after 12 months spontaneous amenorrhoea – a retrospective diagnosis • Climacteric/perimenopause – period of change leading up to the menopause

6. The menopause – why does it happen? • Women are born with around 1.5m oocytes • 1/3 are lost by the time of menarche. • Most women menstruate about 400 times, and 20-30 follicles start to develop each time. • Eventually the supply of responsive oocytes in the ovaries runs out

7. The menopause – hormonal changes • Ovarian follicular activity begins to fail as responsive oocytes run out • Leads to reduction in oestrogen and progesterone levels • Low level of oestrogen causes disruption of cycle and menopausal symptoms • -ve feedback loop causes rise in levels of luteinising hormone and follicle stimulating hormone

8. Epidemiology – UK • Final menstrual period usually occurs between the ages of 40 and 58, with an average age of 511 • Final menstrual period below the age of 40 is considered to be premature menopause1 • Evidence suggests that in the average woman symptoms start to increase from 2 years before the last menstrual period, reach a peak at 1 year following it, and have resolved by 8 years2 1) Nelson H; Lancet, 2008 Mar 2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med. 2008 Sep

9. How common are symptoms? • 80% of women experience menopausal symptoms1 • 45% of these find the symptoms distressing1 • Most women manage the symptoms themselves – 10% seek medical advice for their symptoms2 1) RCPE, 2003 2) Roberts; BMJ, 2007

10. Symptoms • Menstrual irregularity • Hot flushes/sweats • Urinary/vaginal symptoms • Sleep disturbance • Mood changes • Loss of libido • Others

11. Menstrual irregularity • Cycle may lengthen to months, or shorten to weeks1 • Increase in blood loss is common1 • Majority of women experience irregularities, but 10% have a sudden cessation of menstruation2 1) Nelson H; Lancet, 2008 Mar 2) “Menopause”; Clinical Knowledge Summaries

12. Hot flushes/sweats • Common 70-80% of peri-menopausal women1 • Tend to affect head, neck, face and chest. • Usually last for a few minutes but can happen multiple times during the day and night. • Most common in the first year after the last menstrual period2 1) RCPE 2003 2) “Menopause” Clinical Knowledge Summaries

13. Urinary/vaginal symptoms • Dyspareunia • Vaginal discomfort/dryness • Recurrent UTI • Urinary incontinence • Occur in 30% in early post-menopausal period, rising to 47% later in life1 1) Grady; NEJM, 2006

14. Sleep disturbance and mood change • Sleep disturbance – commonly reported symptom, probably related to mood changes – anxiety, depression, memory loss, poor concentration1 • Development of psychological symptoms has been linked to high BMI, and low amounts of physical activity2 1)Young T et al;. Sleep, 2003, Sep 2) Di Donato P et al;. Maturitis, 2005, Nov

15. Loss of libido/other changes • Loss of libido may be related to hormonal changes, but also psychological factors, vaginal dryness, partner • Others (probably due to low oestrogen): • Brittle nails • Thinning of skin • Hair loss • Generalised aches and pains

16. Investigations Generally not required, but blood tests include: • TFT • FBC • ?FSH • LH, oestrogen and progesterone levels not normally helpful

17. FSH1 • Only needed if doubt about diagnosis – eg. in premature menopause • Can be very variable during peri-menopause – single measures are unreliable, and levels should be checked when women are not using any oestrogen containing medications (including COCP) • FSH > 30 is generally taken as post-menopausal range. 1) “Menopause” Clinical Knowledge Summaries

18. Associated problems1 • Increased risk of cardiovascular disease + stroke • Increased risk of osteoporosis • Redistribution of body fat • ?Alzheimer’s Disease – more common in women so may be hormonal link, but no evidence HRT reduces risk 1) British Menopause Society

19. Treatment - HRT

20. HRT • Effective treatment for menopausal symptoms • Previously used widely and for prolonged periods • However: • Women’s health initiative (2002) – increased risk of coronary heart disease, stroke, breast cancer, PE • Million women study (2003) – increased risk breast and ovarian cancer

21. Indications for HRT1 • Treatment of menopausal symptoms where the risk benefit ratio is favourable, in fully informed women, in the lowest possible dose needed to control symptoms and for the shortest possible time • In women with premature menopause until the age of natural menopause (50) • For prevention of osteoporosis in women unable to use other medications • 1) “Menopause” Clinical Knowledge Summaries

22. Choice • Oestrogen + progestogen • Oestrogen alone • Tibolone

23. Routes of delivery • Oral tablets • Patches • Creams/gels • Nasal sprays • IUS • Oestrogen releasing vaginal ring • S/C implants

24. Which preparation? Questions: • Does the women have an intact uterus? • Are symptoms primarily vaso-motor or urogenital? • Systemic or local treatment? • Combined or oestrogen only? • Cyclical (oestrogen with progestogen from day 12-14) or continuous?

25. She has a uterus • Symptoms mainly vasomotor: • Perimenopausal – Systemic cyclical combined HRT • Postmenopausal – Systemic continuous combined HRT • Symptoms mainly urogenital: • Perimenopausal – local oestrogen OR systemic cyclical combined HRT • Post menopausal – local oestrogen OR systemic continuous combined HRT

26. She has no uterus • Symptoms mainly vasomotor – systemic oestrogen only HRT • Symptoms mainly urogenital – local oestrogen OR systemic oestrogen only HRT

27. Tibolone • Selective oestrogen receptor modulator • Oestrogenic, progestogenic and androgenic properties • Can be used if intact uterus and no bleeding for >1yr • Evidence for improvement in sexual function and vasomotor symptoms1 • Increased risk of stroke and breast cancer, especially in over 60s2 • Less risk with DVT and IHD • 1) Al-Azzawi et al; Obstet Gynecol 1999 Feb • 2) Kenemans P et al; Lancet Oncol 2009 Feb

28. HRT Snap!

29. Contraindications to HRT1 • Pregnancy and breast-feeding • Undiagnosed vaginal bleeding • VTE • Active/recent angina or MI • Suspected, current, or past breast Ca • Endometrial Ca • Active liver disease with abnormal LFTs 1) “Menopause”; Clinical Knowledge Summaries

30. What are the risks? • Venous thromboembolism • Coronary heart disease • Stroke • Breast cancer • Endometrial cancer • Ovarian cancer

31. What are the risks? Venous thrombo-embolism • Increased risk of DVT and PE; highest risk in the first year of use. • Number of women having VTE/1000 over 5 years (figures from BNF):

32. What are the risks? Coronary heart disease • Evidence for protection from CHD is lacking • Increased risk of heart disease for women starting combined HRT more than 10 years after the menopause (extra 15 cases/1000 women over 5 years)1 Rossouw JE et al; JAMA 2007, Apr

33. What are the risks? Stroke • Small increased risk of stroke for younger women on HRT, rising in older women • Number of women having stroke/1000 over 5 years (figures from BNF):

34. What are the risks? Breast cancer • Increased risk is proportional to the duration of treatment • Risk returns to untreated levels after 5 years • Number of women having breast cancer/1000 over 5 and 10 years (figures from BNF):

35. What are the risks? Endometrial cancer • Substantial increased risk with oestrogen only HRT • Use of progestogen eliminates risk, but needs to be weighed against increased risk of breast cancer • Number of women having endometrial cancer/1000 over 5 and 10 years (figures from BNF):

36. What are the risks? Ovarian cancer • Small increased risk of ovarian cancer, rises with duration of use • Number of women having ovarian cancer/1000 over 5 and 10 years (figures from BNF)

37. Follow-up1 • Initial follow up after 3 months • Thereafter, a minimum of annual checks • Check effectiveness • Side-effects • BP + weight • Breast examination – if appropriate • Pelvic examination – if appropriate • Review of risks/benefits 1) “Menopause”, Clinical Knowledge Summaries

38. Follow-up Effectiveness – if symptom control not good consider: • Poor absorption – eg. Bowel problem • Drug interaction – eg. Carbemazepine, phenytoin • Incorrect diagnosis – eg. Hypothyroidism, diabetes • Patient expectations Consider – increasing oestrogen dose, altering brand, changing delivery method

39. What are the side-effects? Oestrogen: Breast tenderness Leg cramps Bloating Nausea Headaches Bleeding – cyclical preparations produce regular and predictable bleeds, usually towards the end of the progestogen phase Progestogen: Breast tenderness Backache Depression Pelvic pain

40. Oestrogen related side-effects • More likely to occur and be problematic when there has been a longer duration of ovarian failure • Often resolve with continued use • Consider – • Breast tenderness – low fat, high carbohydrate diet • Leg cramps – exercise and calf stretches • Nausea, bloating – adjust timing of dose, take with food • Headaches – try patches (may produce more stable oestrogen levels)

41. Progestogen related side-effects • May be more problematic; may be connected to type, dose and duration of progestogen • Consider – • Changing progestogen type • Reducing dose • Altering route to something other than oral • “Long-cycle” HRT – (progestogen for 14 days every 3 months – only suitable if periods have stopped). • Continuous combined therapy or tibolone (if post-menopausal)

42. Managing bleeding • Heavy/prolonged bleeding – increase dose or duration of progestogen ?IUS • Bleeding early in progestogen phase – increase dose, change type of progestogen • Painful bleeding – change type of progestogen • Irregular bleeding – increase progestogen • No bleeding – may occur in 5% due to atropic endometrium; confirm compliance and remember to exclude pregnancy!

43. Bleeding – when to refer? • Perimenopausal woman with intact uterus • Change in pattern of withdrawal bleeds • Breakthrough bleeding persisting for more than 6 months, or does not reduce on “long-cycle” HRT • Persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks

44. Bleeding – when to refer? • Postmenopausal women with an intact uterus • Breakthrough bleeding persists for more than 6 months after starting HRT • Bleeding occurs after amenorrhoea • Persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks

45. But before changing treatment! • Pelvic examination – including visualising cervix • Confirm smears up to date • TV USS

46. And don’t forget contraception! • HRT does not suppress ovulation – contraception is still needed • If an intact uterus: • >50 – for one year after LMP • <50 – for two years after LMP

47. HRT Snap!

48. Treatment - Alternatives

49. Lifestyle measures1 • Regular aerobic exercise • Avoid triggers – caffeine, alcohol, smoking, spicy food • Wear light clothing • Good sleep hygiene • Weight loss 1) Alternatives to HRT for management of symptoms of menopause; ROCG (2006)

50. Medications1 • SSRIs/SNRIs – fluoxetine, paroxetine, citalopram and venlafaxine have been shown to reduce symptoms; unlicensed for this use • Clonidine – evidence of efficacy in treating hot flushes, but high frequency of side-effects • Gabapentin – evidence of efficacy for treating hot flushes; for specialist use 1) Nelson HD et al; JAMA, 2006 May