THE MYSTERIES OF THE MENOPAUSE AND HRT

1. THE MYSTERIES OF THE MENOPAUSE AND HRT Dr Zoe McElhinney GP Registrar Taymount Surgery Perth

2. Some definitions MENOPAUSE � cessation of menstruation, retrospective diagnosis, made after 12 months amenorrhoea. CLIMACTERIC- transitional phase of reducing ovarian function leading up to the menopause and ovarian failure.

3. Menopause facts UK average age 51 Average UK woman spends 38% of her life after the menopause In the UK post-menopausal women comprise 18% f the total population Implication of short and long term problems associated with the menopause for health care/ economics

4. Physiology Increasing resistance of ovarian follicles to stimulation by gonadotrophins As oestrogen output decreases levels of LH/FSH rise Anovulation becomes more common leading to progesterone deficiency and with resulting prolonged or irregular vaginal bleeding

5. Symptoms of the menopause acute symptoms- often early climacteric, menstruation may be continuing. May persist for many years .Effects on sleep/mood/working life/relationships. ? Causes Oestradiol receptors in CNS/ 2ndry to sleep deprivation due to sweats? 75% climacteric experience vasomotor symptoms.- Intermediate symptoms � increase in frequency with time from menopause? Effect on collagen- skin thinning, joint pain,Dysuria/urethral syndrome, dyspareunia. Osteoporosis-accelerated bone loss after menopause. Type 1 osteoporosis, typically crush fractures age 55-65 yrs.Type ( 2 senile) last 1/3 life, typically hip fractres. Caucasian western female lifetime risk osteoporotic frac = 30%. acute symptoms- often early climacteric, menstruation may be continuing. May persist for many years .Effects on sleep/mood/working life/relationships. ? Causes Oestradiol receptors in CNS/ 2ndry to sleep deprivation due to sweats? 75% climacteric experience vasomotor symptoms.- Intermediate symptoms � increase in frequency with time from menopause? Effect on collagen- skin thinning, joint pain,Dysuria/urethral syndrome, dyspareunia. Osteoporosis-accelerated bone loss after menopause. Type 1 osteoporosis, typically crush fractures age 55-65 yrs.Type ( 2 senile) last 1/3 life, typically hip fractres. Caucasian western female lifetime risk osteoporotic frac = 30%.

6. Diagnosis Mainly guided by symptoms. In younger women can measure FSH and LH+/- oestradiol Oestradiol<70pmol/l and FSH/LH > 15iu/l are found in menopausal women Consider other diagnoses eg thyroid disease, psychiatric illness, rarely phaeochromocytoma, carcinoid

7. Discussing HRT BENEFITS Symptom control Bone protection Protection against colorectal Ca RISKS Breast cancer Stroke PE Ovarian Ca Endometrial Ca

8. Evidence from randomised trials on the long term effects of HRT Lancet September 2002

9. Excess incidence/1000 HRT users over 5 years

10. Reduction in incidence per 1000 HRT users over 5 year period

11. Women�s Health initiative study JAMA July 2002

12. Findings Trial for CCT stopped early as health risks exceeded health benefits over average follow up period of 5.2 years. This only looked at Prempro ( 0.625mg CEE and 2.5 mg MPA) � not available in UK.

13. Conclusions �Overall health risks exceeded benefits from use of combined E/P for an average 5.2 year follow up among healthy postmenopausal US women. All cause mortality was not affected during the trial. The risk benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regime should not be initiated for primary prevention of CHD.�

14. The menopausal HRT and Risk of ovarian cancer study Found increased risk of ovarian Ca in women who used ERT and HRT from 1979 to 1998 Increased risk with increasing duration of use In US lifetime risk is 1.7% , HRT increases lifetime risk to 3 for less than 10 yrs use

15. Endometrial Ca riskBeresford et al. Lancet 1997 Paper show prolonged use of sequential HRT can increase risk of endometrial cancer. RR rose from 1.3 to 2.9 for 5 year use. For CCT RR fell to 0.2.

16. Million Women StudyLancet, July 2003 Looked at the effects of different types of HRT on risk of Ca breast in UK women Showed that combined, oestrogen only, and tibolone therapies all caused an increase in Ca breast The risk increased with duration of use In all cases the risk of breast Ca begins to decline when HRT is stopped, and by 5 yrs reaches the same level as women who have never taken HRT

17. The effect of oestrogen only and combined HRT on the cumulative incidence of breast and endometrial cancer

18. What points should we take from these studies? HRT should not be prescribed for primary prevention of CHD The increased risk of breast cancer with all types of HRT is confirmed, this risk is dependent on duration of use and begins to decline on cessation of therapy, reaching that of non HRT users after 5 years There is a slight increase in the risk of ovarian cancer with oestrogen only and combined therapy. The increased risk in endometrial cancer is significantly higher with cyclical HRT vs. CCT.

19. CONTRAINDICATIONS TO HRT ABSOLUTE Oestrogen dependant cancer Pregnancy Undiagnosed PV bleeding Active liver disease with abnormal LFT RELATIVE Past Hx DVT/PE Rotor/Dubin- Johnson syndromes (defects in bilirubin metabolism) Cholestasis

20. DECIDING WHICH TYPE OF HRT TO USE Post hysterectomy-oestrogen only therapy Post subtotal hysterectomy- trial of sequential therapy for 3/12, if no bleeding use oestrogen only therapy Women who are less than one year since their last period should be commenced on cyclical therapy (bleeding disturbance with CCT)

21. DECIDING WHICH TYPE OF HRT TO USE Women with no periods can be started on continuous combined therapy Change from cyclical to CCT after 2 years,or at age 54 Predominantly urogenital symptoms � use vaginal oestrogen Tibolone can be used in post menopausal women. Causes amenorrhoea, treats vasomotor, psychological problems and gives bone protection

22. SERMS Selective Oestrogen Receptor Modulators Raloxifene- licensed for prevention and treatment of post-menopausal osteoporosis Reduces risk of breast and endometrial Ca Ineffective for vasomotor symptoms

23. Routes of administration Oral Trans dermal oestrogen (patches/ gel) Oestrogen implants (25mg /50mg/100mg), beware tachyphylaxis, monitor oestrogen levels if symptoms recur Vaginal ( ring/cream /pessary) Is add in progestogen required? (for 12-14 days in 28/?IUS) Tachyphylaxis � following implant insertion get rapid rise in serum levels then plateau. When levels fall towards end of implant duration may experience symptoms even though oestrogen levels are well within normal pre-menopausal range.Tachyphylaxis � following implant insertion get rapid rise in serum levels then plateau. When levels fall towards end of implant duration may experience symptoms even though oestrogen levels are well within normal pre-menopausal range.

24. Contraception HRT does not provide contraception! Contraception required for 2 years after LMP if <50 yrs, 1yr after LMP if >50. COCP- can be used for contraception and symptom relief in women under 50 with no risk factors for venous/arterial disease. Consider waning fertility when choosing method- POP/ barriers/IUCD/IUS.

25. Surgery and HRT BNF suggests stopping HRT for major surgery under GA due to risk of venous thromboembolism There may be bleeding irregularities on recommencing if patient is on CCT, as before, investigate if persists after 6/12

26. Alternatives to HRT For bone protection- raloxifene, bisphosphonates, calcitonin, adequate calcium and vitamin D intake. For vasomotor symptoms-clonidine (centrally acting antihypertensive) side effects include dry mouth, sedation, Reynaud�s, hypertensive crisis on rapid withdrawal.

27. Alternatives to HRT Psychological symptoms- SSRIs Plant oestrogens Glucosamine

28. Irregular bleeding Irregular bleeding in the peri-menopause may be due to anovulatory cycles and progesterone deficiency Other causes include endometrial Ca, Cervical Ca, Cervical Polyp, PID, atrophic vaginitis Therefore must inspect cervix and refer for USS/ endometrial biopsy

29. Bleeding problems associated with HRT CCT- bleeding/spotting for up to 6/12 to be expected. If continues-refer. With cyclical therapy, bleeding expected 2nd week of progestogen Rx to a few days after end of progestogen phase. If outside this time- check compliance, could try increased progestogen dose or duration. If continues for 3/12 refer for investigation.

30. Bleeding problems associated with HRT Heavy bleeding may be due to insufficient progestagen or too much oestrogen- try altering dose/ duration If continues for 3/12 then refer No withdrawal bleed on cyclical therapy, not uncommon. Should she be on CCT? If bleeds after period of amenorrhoea, refer

31. Case History Mrs I 50 yrs old Erratic, heavy periods, vasomotor symptoms, sleep disturbance due to sweats Hypertension-controlled on medication POP for contraception Would like to consider HRT

32. What would you do? HRT �risks/ benefits discussion. Examination- BP, speculum and VE Refer for USS and endometrial biopsy Commence on cyclical combined HRT Advise to continue POP for contraception Alternative-?clonidene

33. Case History 2 Mrs J 56 yrs old Vaginal dryness/dyspareunia LMP 2 yrs ago, no PV bleeding Generally in good health Examination- atrophic vaginitis, otherwise normal

34. Management Vaginal oestrogen pessaries for 3/12

35. Case history 3 Miss K 36 yrs old Stopped COCP last year as wishes to conceive Periods irregular, has not conceived Investigated for infertility, results reveal elevated FSH/LH ,now experiencing flushes.

36. Management Explain results and implications Discuss HRT- importance of bone protection When discussing risks/benefits remember studies have not looked at women with early menopause Consider Cyclical HRT Discuss fertility- assisted conception?

37. THE END Any Questions? (Easy ones only please!)