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Premature Menopause

Premature Menopause. Michael Savvas King’s College Hospital,London. Premature Menopause . Menopause before the age of 40 Affects 1% of women. Loss of Ovarian Function. May not be permanent Spontaneous recurrence of ovarian function and even pregnancy are possible.

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Premature Menopause

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  1. Premature Menopause Michael Savvas King’s College Hospital,London.

  2. Premature Menopause • Menopause before the age of 40 • Affects 1% of women

  3. Loss of Ovarian Function • May not be permanent • Spontaneous recurrence of ovarian function and even pregnancy are possible

  4. Six months of amenorrhoea • Less than 1% return of fertility

  5. Diagnosis • Amenorrhoea • Climacteric Symptoms • Raised FSH - Reduced Oestradiol • Biopsy unhelpful

  6. Causes of Premature Menopause • Idiopathic • Chromosomal abnormalities Turner’s syndr., X chromosome deletions • Autoimmune • Galactosaemia • Radiotherapy / Chemotherapy • Surgery – TAH, BSO, Ovarian Cystectomy • Infection - Mumps, TB.

  7. X chromosome deletionRossetti et al 2004 • Inherited deletion of X chromosome in mother and two daughters • Mother menopause at 43 years • Daughters menopause at 17 and 22 years • Role of environment

  8. POF - The role of pelvic surgery • Hysterectomy • Uterine Artery Embolisation • Ovarian surgery • Other Pelvic surgery

  9. Anastomoses in pelvic circulationRazavi et al 2004 76 patients undergoing UAE 10 (6.6%) main blood supply to the ovary was from the UA

  10. Consequences of POF • Symptoms • Infertility • Bone Loss • Heart Disease

  11. POF - Psychological Symptoms • Depression • Low levels of self esteem and Life satisfaction • Sexual Dysfunction

  12. POF-SymptomsBaber, Abdalla and Studd (1991) • Vasomotor 76% • Loss of libido 31% • sexual enjoyment reduced 37% • Most Distressing symptom Loss of fertility 54% Feeling Older 27%

  13. Premature Ovarian Failure May present with infertility

  14. POF & Subfertility • 12 women aged 35-40 with poor ovarian response to stimulation • 11 developed menopausal symptoms within 7 years • Only 4 out of 24 controls (Nikolaou et al 2002)

  15. POF- Osteoporosis • Rate of bone loss same as following natural menopause • But consequences more severe as longer life expectancy

  16. Premature menopause • Associated with significantly higher incidence of osteoporotic fractures Van Der Voort DJ et al Osteoporosis Int 2003

  17. Premature Menopause • Increased incidence of heart disease

  18. Age at menopause and heart disease • 12115 women aged 50-65 attending for breast screening • Risk of heart disease higher in women with early menopause • For each year delay in menopause mortality from heart disease decreased by 2% Van der Schouw et al Lancet 1996

  19. Premature menopause and endothelial functionKalantaridou et al 2004 • 18 women with premature menopause • Endothelial function assessed using flow mediated dilatation of the the brachial artery in response to hyperaemia of the hand • Before and after six months CEE 0.625 and cyclical MPA

  20. Endothelial function • Flow mediated dilatation lower in women with prem. Menopause. • After six months HRT flow mediated dilatation was improved and reached normal values • GTN induced (endothelial independent) dilatation no difference in two groups

  21. Premature Menopause • 19,731 post menopausal women studied • All cause mortality • Inversely related to age at menopause Jacobsen et al Am J epidemiol. 2003

  22. Premature MenopauseHRT • Need HRT at least until the age of 51 • Compliance usually very good • Results of WHI and HERS studies not applicable to this age group • But what is the most appropriate HRT?

  23. Premature MenopauseHRT • Oral • Patches, Gels • Implants • COC

  24. Choice of HRT for women with premature ovarian failure UK Soc Paediatric Endocrinology 42 questionnaires (28 responses) • COCP 18 (64%) • Oral HRT (sequential) 5 (18%) • Transdermal HRT (sequential) 3 (11%) • Ethinyloestradiol (sequential) 2 (7%)

  25. PrematureMenopause • Combined pill • Convenient • “Peer Friendly” • Free

  26. Premature Menopauseand the COC • Combined Pill v HRT • Guttman et al 2001 Clin Endocrinol • 0.625mg v 30mcg EE in 17 adult women with Turner’s Syndrome • FSH most suppressed by EE, BUT HRT was superior at minimising hyperinsulinaemia & bone turnover

  27. Hormone Implants • Higher Circulating oestradiol • More effective Symptom control • Better skeletal effects • Better effects on uterus?

  28. 1.0 0.9 0.8 0.7 spine prox femur 0.0 Pre treat Oral Implant Mean (+SEM) spine and femoral neck bone density in post menopausal women untreated and oral and implant therapy Savvas et al. 1988

  29. Percentage change in bone density on 3 different doses of hormone implants after 1 yearStudd et al BJOG (1994)

  30. Testosterone • Can improve mood and libido • Particularly helpful following oopherectomy

  31. HRT and Breast cancer • Fear of breast cancer important factor deterring women from taking HRT

  32. Incidence of Breast Cancer from 50 to 70 years of ageBeral et al 1997

  33. Women’s Health InitiatveJAMA 2002;288:321-333 • Two parallel RCT • Study 1 • 8506 women received HRT • (0.625mg CEE+2.5mg MPA) • 8102 received placebo • Study 2 • Oestrogen alone Vs placebo Women with menopausal symptoms or osteoporosis needing HRT not recruited into study.

  34. WHI E+P Study

  35. WHI StudyStudy 1 • Due to run for 8.5 years • Halted at a mean 5.2 years • Incidence of Breast cancer reached pre-specified safety limit

  36. 10,000 Women receiving HRTper year • 8 additional cases of Ca breast (RR 1.26) • 7 heart attacks (RR 1.29) • 8 strokes (RR 1.41) • 8 pulmonary embolism (RR 2.13) • 6 fewer cases of bowel cancer • 6 fewer hip fractures • overall mortality not affected

  37. Problems with WHI (E+P) study • Patients were old • Even younger women were many years past the menopause • Patients were overweight • Risks may be related to progestagens in general or specifically to MPA • Related to Continuous combined regimen

  38. WHI and Heart Disease • Backround Incidence of cardiac events in this group is 53/10 000 per year • Study thus underpowered to detect change in this group • Larger numbers in this age group may have revealed significant reduction in risk

  39. Since the WHI StudyJuly 17th 2002 • 50% of American women have stopped HRT • 30% of British women have stopped HRT

  40. WHI oestrogen alone JAMA 2004 ;291:1701-1712 • Mean age 63.6 • Study terminated at 6.8 years • Increased risk CVAs • No increased risk Breast Cancer CHD Pulmonary Embolus

  41. WHI Oestrogen alone • CVAs 12 extra cases per 10 000 woman years • Breast cancer 7 fewer cases per 1000 woman year but not statistically significant

  42. WHI oestrogen alone • Data suggest more favourable findings in 50-59–year-old women • Absolute risk small

  43. WHI oestrogen aloneBreast Cancer and age

  44. HRT and risk of breast cancer • Survey of 600 doctors in 2004 203 Gynaecologist 145 Physicians 219 GPs • Correct estimate of risk 28% • Overestimated risk 67% Gynaecologist more likely to accurately estimate risk Williams et al 2005

  45. HRT and Estimated Risk of Breast CancerCoombs et al BMJ 2005 50 yr old woman cumulative risk to 79 yrs No HRT 6.1% Oestrogen alone 6.3% Combined HRT 6.7% • Additional breast cancer risk for an individual is very small

  46. Premature Menopause • Impact of WHI and HRT in women with Premature Menopause • Ng C., Reddy N., Panay N. 2004 ESHRE Berlin • Awareness of Recent HRT Publicity 100% • 7 (16%) had stopped HRT as a result of publicity • 5 sought advice before stopping • 37% were considering stopping HRT because of breast cancer fears • Less than half realised that risks did not apply to their age group

  47. Premature ovarian failure Fertility Treatment

  48. Fertility • Spontaneous pregnancy very rare • Ovulation induction unsuccessful

  49. Oocyte Donation IVF Using donated oocytes

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