Menopause and HRT

1. Menopause and HRT DA Ganeshananthan ST3

2. Last menstrual period Primary ovarian failure and lack of oestrogen Results in increased FSH and LH Usually around 51 years old The menopause

3. gradual reduction of oestrogen and beginning of symptoms May last for several years, starting 45.5- 47.5 years May start earlier with smoking, hysterectomy, fragile X autoimmune disorders, chemotherapy Post menopausal year after last period Peri menopause

4. Menopause occurs when oocytes are no more Start with 1.5 million oocytes, 1/3 lost before menarche 20-30 start to develop each menstrual cycle, and most degenerate Menopause thought to be caused by aging, as parity and time of menarche have no influence �

5. 1.vasomotor Hot flushes occur in85% females Episodes last few mins Frequency of episodes, hourly �every few days symptoms

7. Assoc with palpitation, nausea, vomiting More common in smokers, thin individuals and lower social class Caused by fluctuation in oestrogen level , irregular ovarian function �

8. 2. insomnia- ?due to hot flushes occurring at night 3. physiological symptoms- irritability, lethargy, loss of libido, depression. ? due to lack of oestrogen or result of other symptoms, ie vasomotor

9. 4. urogenital. Occur several years after menopause Thinning of vaginal skin, redness and loss of ruggae- superficial dysparaeunia and loss of libido/avoidance of intercourse. Loss of pelvic tone may result in vaginal prolapse, cystocele, rectocele

10. Decreased urinary pH (and hence change in bact flora) results in pruritis and discharge Uterus atrophies, fibroids shrink, endometriosis and pelvic pain symptoms abate Ovaries reduce in size

11. 5.osteoporosis- due to osteoclastic action more than osteoblastic action, which is directly stimulated by oestrogen �

12. FSH >30 IU/l LH raised Low oestrodiol level If pt still having periods, may need to repeat to see if perimenopausal � investigations

13. HRT aims to replace oestrogen and reduce symptoms, If pt has uterus, will need progesterone to prevent unopposed effect of oestrogen on it � Treatment of Menopause

15. Arrest flushing, headaches and insomnia Reverses genital tract atrophy Improvement in physiological symptoms Reduces osteoporosis and fracture rate Benefits of HRT

16. Uterus - If unopposed oestrogen given, predisposes to endometrial hyperplasia, endometrial carcinoma and irreg bleeding patterns Increased risk of thrombosis with HRT Complications of HRT

18. h/o endometrial or breast cancer consider stopping HRT after cardiovascular event, previous venous thromboembolism or arterial t thromboembolic disease ie, angina or MI hepatitis or liver disease dubin Johnson and rotar syndromes � CI to HRT

19. Oral Transdermal patch Cream Subcutaneous implant Preparations of HRT

20. oral dose highest, as removed by liver, first pass metabolism � preparations Oestrogen only- Premarin, progynova, harmogen Combined oest and prog- prempak-C, Nuvelle, Trisequens progesterone given for 12 days per month, so can be relatively low dose. SE of progesterone incl irritability, breast tenderness, bloating pts get withdrawal bleed � Preparations of HRT

21. continuous prog and oestrogen- suitable for pts yr or more after menopause (Why), and who dislike withdrawal bleed- Kliofem, premique, climesse �

22. patch gives more constant rate of oestrogen implants in diff dosages testosterone implant given in some cases to increase libido

23. Local pessary, cream, ring, tablet if symptoms mainly urogenital, if used long term, may need oral progest for 10-14 days. Use lowest effective dose. Investigate spotting/ beak through bleeding

24. Following adverse publicity Pts may have CI to HRT May want �more natural� replacement May feel it is safer Complimentary Therapy

25. Phytoestrogens- found in plants, action similar to oestrogen. May be found in enriched food, soya products, or tablets Herbal preparations Black cohosh some evidence from placebo controlled studies, long term effect not known Evening primrose may help breast tenderness Dong quai Ginkgo biloba ginseng

27. Conflicting evidence In WHI oestrogen+progest Vs placebo, inc of Ca breast increased Oestrogen only arm, inc of Ba Ca decreased Advice � Females with strong family or personal h/o ca breast should not take HRT Breast Cancer and HRT

28. Before menopause risk for coronary artery disease lags behind men by 10 yrs. After menopause risk is similar for men and women. Framingham study showed the increased risk for post menopausal women. The Women�s Health initiative showed that hormone and oestrogen therapy are not indicated for prevention of CAD Cardiovascular problems and HRT

29. Use of hormone and oestrogen therapy around peri � and menopause may reduce the risk of CAD as More than 9yrs after menopause, CAD is established, and hormone/oestrogen does not help Oestrogen reduces ldl, increases hdl. Some studies show that best predictor for of CAD in women is TG, LDL, and lipoprotein a

30. 2001 meta analysis of 22 trials show 27% risk reduction in non vert fractures �(Grady and Cummings) RR for hip and wrist was 40%, increased to 55% in pts younger than 60yrs. WHI also showed decreased bone fractures for pts on HRT. Osteoporosis and HRT

31. However indication for HRT is vasomotor symptoms, not osteoporosis, other meds used to prevent fracture 2ndary to osteoporosis.

32. The WHI was launched in 1991 and consisted of a set of clinical trials and an observational study, which together involved 161,808 generally healthy postmenopausal women. The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer. The hormone trial had two studies: the estrogen-plus-progestin study of women with a uterus and the estrogen-alone study of women without a uterus. (Women with a uterus were given progestin in combination with estrogen, a practice known to prevent endometrial cancer.) In both hormone therapy studies, women were randomly assigned to either the hormone medication being studied or to placebo. Those studies have now ended. The women in these studies are now participating in a follow-up phase, which will last until 2010. Women's Health Initiative

34. Compared with the placebo, estrogen plus progestin resulted in: Increased risk of heart attack Increased risk of stroke Increased risk of blood clots Increased risk of breast cancer Reduced risk of colorectal cancer Fewer fractures No protection against mild cognitive impairment and increased risk of dementia (study included only women 65 and older) Compared with the placebo, estrogen alone resulted in: No difference in risk for heart attack Increased risk of stroke Increased risk of blood clots Uncertain effect for breast cancer No difference in risk for colorectal cancer Reduced risk of fracture

35. The Million Women Study is a national study of women�s health, involving more than one million UK women aged 50 and over. 1 in 4 women over 50 participating. The main focus of the study relates to the effects of hormone replacement therapy use, but the large size of the study means that a very broad range of health issues can be addressed. The million women study

36. The Million Women Study is investigating how various reproductive and lifestyle factors affect women�s health. In particular, the study is looking at how hormone replacement therapy affects a woman�s breasts and other aspects of her health. Other factors being investigated include diet, exercise, employment patterns, oral contraceptive use, childbirth and breastfeeding, and family history of illness, in relation to a wide range of cancers and to other conditions such as fractures, gallbladder problems and cardiovascular disease.

37. Gp notebook Emedicine British menopause society Menopause matters Womans health initiative Million woman study reference

39. Thank you