Menopause and HRT

1. Menopause and HRT Sharan Pobbathi Alena Billingsley

2. Will cover: • What is the menopause? • Diagnosing the menopause • Management • Non-hormonal • HRT • Premature menopause

3. Programme • Patient experience • Presentation • Case Studies (CSA style) • Quiz

4. Menopause – what and when • The menopause may be • Natural or induced • Natural menopause is the permanent cessation of the menstrual cycle due to loss of ovarian follicular activity • Only known retrospectively one year after the last period • Average is 51 years

5. Induced menopause • Specific treatment e.g. chemotherapy or radiotherapy • Oophorectomy • Treatment with gonadotrophin-releasing hormone (GnRH) analogues

6. Diagnosis - symptoms • Short Term • Vasomotor • Flushes • Night sweats • Insomnia • Sexual dysfunction • Vaginal dryness • Dyspareunia • Decreased libido • Musculoskeletal • Joint aches • Fat redistribution • Psychological • Depressed mood • Anxiety • Irritability • Mood swings • Lethargy • Difficulty concentrating

7. Consequences of the menopause • Long term • Osteoporosis • 1 in 3 increase in risk of fracture • Cardiovascular disease • MI and stroke most common cause of death >60y • Oophoretomised women have 2-3 fold risk of CHD • Urogenital • Lower urinary tract and pelvic floor atrophy leading to frequency, urgency, nocturia, incontinence, recurrent infections • Vaginal atrophy

8. Investigations • FSH is only used if diagnosis is in doubt • FSH >30 iu/L • Don’t do LH, oestradiol and progesterone as not helpful • TFTs if confusion about symptoms • BMD if significant risk of osteoporosis

9. Management – Non-hormonal • Lifestyle advice • Avoid hot drinks especially caffeinated ones, and alcohol • Stop smoking • Fans and layering • Use of vaginal moisturisers e.g. Replens MD® and Sylk ® • No evidence that diet (phytoestrogens) affects symptoms

10. Management – Non-hormonal • OTC remedies • Black cohosh • Oestrogen like effect • May help with emotional symptoms • Interacts with antihypertensives and risk of liver failure • St John’s Wort • Recognised anti-depressant effects • Lots of interactions

11. Management – Non-hormonal • Licensed • Clonidine for hot flushes • SEs insomnia, dry mouth, dizziness, constipation, drowsiness • Unlicensed • SSRIs/SNRI (venlafaxine) for mood swings, vasomotor symptoms • Gabapentin for musculoskeletal; SEs dizziness, fatigue, tremor, weight gain

12. HRT • Counselling about risks and benefits • Contraindications to HRT • Different routes/types of HRT • Deciding on appropriate HRT (systemic or local) • Following up patients on HRT • Stopping HRT

13. Benefits of HRT • Proven • Relief of menopausal symptoms • Prevention/treatment of osteoporosis • Reduced risk of colorectal cancer

14. Risks of HRT • Breast cancer • Increased by 26% in ♀ > 50 years taking combined HRT for > 5 years • Returns to baseline 5 years after stopping • VTE • 2-3x with oral HRT, highest in first year • Absolute risk remains small •  risk of acute coronary events in women with pre-existing CVD in first year •  risk of CVA

15. Women’s Health Initiative • Launched in 1991 • Effect of postmenopausal HRT, diet modification, and calcium and vitamin D supplements • heart disease • Fractures • breast and colorectal cancer. • Combined HRT • ↑ MI, CVA, VTE, breast cancer • ↓ colorectal cancer and fractures • Oestrogen alone • ↔ MI, colorectal cancer • ↑ CVA, VTE • ? Breast cancer • ↓ fractures

16. Million Women Study • National study involving over a million women aged 50 and over • Main focus is effect of HRT use • Over 1 in 4 women in target age group are in study •  risk breast cancer in women using HRT, particularly with combined HRT •  risk breast if HRT peri- rather than postmenopause

17. Contraindications to HRT* specialist initiation • Hormone dependent cancer – endometrial cancer, current or past breast cancer* • Active or recent arterial thrombotic disease (CVD, CVA)* • VTE* • Otosclerosis* • Severe active liver disease (oral oestrogen) • Undiagnosed breast mass • Undiagnosed abnormal vaginal bleeding • Dubin-Johnson and Rotor syndromes

18. Relative contraindications • May require extra supervision • Uterine fibroids • Endometriosis • Hypertension • Migraine

19. HRT

21. Local symptoms • Vaginal dryness, soreness, dyspareunia, urinary frequency/urgency • Various preparations • Pessaries e.g. Ortho-Gynsest® • Creams e.g. Gynest ®, Ovestin ® • Tablets e.g. Vagifem ® • Rings e.g. Estring ® • Some damage latex condoms/diaphragms

22. Non-oral oestrogens • All estradiol 17 beta • Avoid first pass metabolism in liver • Available as • Patches • Gels (less irritating than a patch) • Implants (last resort) • Low, medium and high doses • Potentially more suitable for women: • With liver disease or gallstones • At risk of VTE • With DM and others with raised TGs • On enzyme inducers • First line for women with migraine and malabsorption

23. Oral oestrogens • Three types • Conjugate equine oestrogens (CEEs) • Estradiol 17 beta • Estradiol valerate • Low, medium, high doses • Start at low dose

24. Progestogens – three types • Testosterone analogues (C19 - androgenic SEs) • Norethisterone, levonorgestrel (Mirena®), Norgestrel • Progesterone analogues (C21) • Dydrogesterone, medroxyprogesterone acetate (MPA) • Newer (derivates of norgestrel) • Desogestrel, norgestimate, gestodene

25. Why bother about type? • Oral (combined or alone), transdermal (combined) and intrauterine • If patient gets PMS-type symptoms • Can alter progestogen to less androgenic type • Can alter route of progestogen (e.g. to IUS)

27. HRT

28. Perimenopausal • Sequential if regular period or cyclical if infrequent (Tridestra®) • Progestogen 12-14 days/month • 5% - 15% have no monthly bleed • Tridestra® gives 3 monthly bleed • Postmenopausal • Continuous (no bleed HRT) • Require investigation if persistent bleeding • > 6 months • Heavier bleeding • Bleeding after a period of amenorrhoea • Tibolone

29. Tibolone • Synthetic steroid that properties of oestrogen, progestogen & testosterone • For prevention of osteoporosis in postmenopausal women • For short term use in pre-menopausal ♀ being treated with GnRH • Increases risk of stroke in ♀ > 60 years, similar to conventional HRT in younger ♀

30. Side Effects of HRT • Nausea, vomiting, abdominal cramps, bloating • Weight changes • Breast tenderness • PMS-like syndrome • Sodium and fluid retention • Glucose intolerance • Altered blood lipids • Mood changes • Headache, migraine, dizziness • Leg cramps • And more…

31. Testosterone? • Women who have had TAH+BSO may experience testosterone deficiency (abrupt rather than gradual fall in levels) • Can offer replacement • Implants (need to monitor levels before each change) • Patches • SEs: hirsutism, deep voice, clitomegaly • Must be on oestrogen, but not CEE

32. Questions to ask… • Does patient want HRT? • Is the patient informed about risks and benefits? • Are symptom local or systemic? • Does the patient have a uterus? • Is the patient peri- or postmenopausal • Which oestrogen? • Which progestogen?

34. Premature menopause • Classification • Normal: 45 – 55 years (average 51 years) • Early: 40 – 45 years • Premature: < 40 years • Unpredictable, so need to continue contraception • Diagnosis • Minimum of two FSH >30 iu/L at least one month apart

35. Other Investigations • Pregnancy test! • TFTs • Prolactin for hyperprolactinaemia • Auto-antibodies (ovarian/thyroid/adrenal) • Karyotyping if < 30 years for mosaic Turner’s Syndrome • Baseline DEXA, then repeat every 2 - 5 years • Baseline fasting lipids (yearly, depending on RFs) • Follicle tracking on USS (fertility)

36. Risks of premature menopause • Life expectancy is reduced (2 years) • Untreated, • 50% higher risk of osteoporotic fracture between 50-70 years •  risk of CVD compared to woman of same age • 260%  risk of dementia following removal of a single ovary by age 38 •  risk Parkinson’s

37. Treating premature menopause • Oestrogen replacement with progesterone • Given most conveniently as COCP • Continue until aged 50 years

38. Follow up on HRT • Three monthly until stabilised, then yearly • At follow up, check: • Symptom control • bleeding control • Side effects • BP, BMI • Reassess risk vs. benefits • Breast awareness

39. Duration of use • Minimum dose for shortest period • Symptoms last between 2-5 years, so try stopping at 3-5 years • Woman can continue longer as counselled re risks…

40. Stopping • Ensure progestogen dose offers endometrial protection if ↓ing slowly (high dose oestrogens only) • No evidence of how best to stop i.e. gradual versus sudden • When stopping HRT, warn patient of 2-3 months rebound vasomotor symptoms

41. HRT • Sudden severe chest pain • Sudden dyspnoea • Unexplained swelling/severe calf pain • Severe stomach pain • Neurological effects • Hepatitis, jaundice, hepatomegaly • Systolic BP > 160, diastolic >95 mmHg • Prolonged immobility • Detection of RF that is contraindication • Stop 4-6 weeks before any major surgery

42. Summary • HRT is good for menopausal symptoms and osteoporosis prevention • Non-hormonal treatments can help with symptoms • HRT is not necessarily systemic • Treatment must be regularly reviewed

43. Stopping contraception around the menopause - 1 • Contraception may be stopped at 55 years • Women using hormonal contraception, and have regular bleeding at 55 years should continue with contraception • Ideally women over 50 years should switch to POP, implant, LNG-IUS or barrier method until aged 55, or until menopause confirmed

44. Stopping contraception around the menopause - 2 • FSH is not a reliable indicator of menopause in women using combined hormonal contraception • Women with premature menopause may need specialist contraceptive opinion (ovarian activity may return spontaneously)

45. Stopping contraception around the menopause - 3 • If using non-hormonal methods of contraception, • Women over 50 years can stop after 1 year of amenorrhoea • Women under 50 years can stop after 2 years • Women over 40 yeas with a copper IUD (≥ 300 mm2 copper) inserted at or over age 40 can retain the device until the menopause • FSH is best used in women aged over 50 on progestogen only methods • Need 2 x FSH ≥ 30iu/L, 6 weeks apart, and then contraception can be stopped after a year

46. HRT and Contraception • Women should not rely on HRT for contraception • POP can be used to provide contraception with combined HRT • Women using oestrogen replacement may use LVG-IUS (Mirena®) to provide endometrial protection. • When IUS is used as progestogen component, it must be changed no later than 5 years (license says 4 years)

47. Resources • eLFH learning modules • Menopause and HRT InnovAiT, Vol.2, No. 1, pp 10 – 16, 2009. • Common problems of the menopause InnovAiTfirst published online May 16, 2012 doi:10.1093/innovait/ins075 • http://www.menopausematters.co.uk/ • http://www.menopausematters.co.uk/tree.php • http://www.millionwomenstudy.org • http://www.nhlbi.nih.gov/whi/ • FSRH Guidance: Contraception for women ages over 4o years (July 2010)

48. QUIZ

49. Question 1 • Which one of the following conditions is least likely to be the cause of post menopausal bleeding? • Atrophic vaginitis • Cervical intraepithelial neoplasia (CIN) • Hormone replacement therapy • Tamoxifen therapy • Urethral caruncle

50. Question 2 • The age at which a woman reaches the menopause is related to: • Age at menarche • Ethnic group • Family tendency • Parity • Regularity of cycle