Menopause management seminar

Menopause management seminar

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  Management ofManagement of MenopauseMenopause DrYusmadi Abdullah
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  Life After MenopauseLifeAfter Menopause  Age at menopause : 51.7 (average)  1900 : life expectancy at 40 years old  1950 : life expectancy at 65 years old  2000 : life expectancy at 83 years old (Malaysian women - 75.4 years)
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  “Women now live athird of their lives after menopause” 8th International Congress on Menopause, Sydney 1996
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  MenopauseMenopause  MenopauseMenopause isthe permanentis the permanent cessation of menstruation thatcessation of menstruation that results from loss of ovarian follicularresults from loss of ovarian follicular activity.activity.  Menopausal age :Menopausal age : 45 – 55 years45 – 55 years  Mean age ( M )Mean age ( M ) :: 50.7 years50.7 years  Premature menopausePremature menopause < 45< 45 yearsyears  Late menopauseLate menopause > 55 years> 55 years
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   is thecessation of menstruationis the cessation of menstruation that follows surgical removal ofthat follows surgical removal of both ovaries orboth ovaries or iatrogenic ablationiatrogenic ablation of ovarian functionof ovarian function byby chemotherapy, radiotherapy orchemotherapy, radiotherapy or treatment with GnRH analogues.treatment with GnRH analogues. Induced /surgical menopauseInduced /surgical menopause
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  PerimenopausePerimenopause  Is theperiod beginnning with the first clinical, biological and endocrinological features of the approaching menopause such as vasomotor symptoms and menstrual irregularity  Can be 1 or 2 years and for some as long as 7 to 10 year
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  DiagnosisDiagnosis  For those50 years and above :For those 50 years and above : 12 consecutive month of12 consecutive month of amenorrhoea is diagnostic.amenorrhoea is diagnostic.  For those below 50 years :For those below 50 years : ** FSHFSH > 30 IU/l> 30 IU/l
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  Consequences of menapauseConsequencesof menapause  Vasomotor symptoms  Psychological symptoms  Sexual dysfunction  Osteoporosis  Cardiovascular Disease  Urogenital Atrophy
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  Vasomotor SymptomsVasomotor Symptoms Hot flushes and night sweats are experienced by as many as 85% of women around the menopause.  Most would experience these symptoms for < 5 years, however about 25% would experience it for more than 5 years.
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  Sexual DysfunctionSexual Dysfunction The underlying problem for female sexual dysfunction are usually multifactorial.  Oestrogen deficiency can lead vaginal dryness and dyspareunia,  Non hormonal factors such as conflict between partners, insomnia, inadequate stimulation, life stresses can also lead to sexual dysfunction.
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   Depressed mood,anxiety, irritability, mood swings, lethargy and lack of energy have been associated with the menopause.  General population studies suggest that most women do not experience major mood changes during the menopause. Psychological SymptomsPsychological Symptoms
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  Prospective epidemiologicalProspective epidemiological studiesstudies ‘psychological problems experienced during the menopause are likely to be associated with past problem and current life stresses’
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  OsteoporosisOsteoporosis  Affects 1:3women.  Risk factors include family history of fracture, low BMI, early menopause, cigarette smoking, alcohol abuse, sedentary lifestyle, corticosteroids, hyperthyroidism.  Common sites for osteoporotic fracture are lower end of radius (wrist/Colles’ fracture), proximal femur (hip) and vertebrae.
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  Cardiovascular DiseaseCardiovascular Disease common cause of death in women after the age of 60 years.  Risk factors for myocardial infarction are abnormal FLP, smoking, depression and stress.  Incidence of stroke increases with age.  Risk factors are hypertension, smoking, diabetes, hyperlipidaemia, obesity.
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  Urogenital AtrophyUrogenital Atrophy Oestrogen and progestrone receptors are present in the vagina, urethra, bladder and pelvic floor musculature.  Oestrogen deficiency after menopause cause atrophic changes in the urogenital tract and is associated with urinary symptoms which may co-exist with symptoms of vaginal atrophy.
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  Treatment OptionTreatment Option Makinglifestyle changes - healthy diet, exercise and stress reduction. Hormone replacement therapy. Complementary and alternative therapies.
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  Hormone ReplacementHormone Replacement TherapyTherapy
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  How to approach?Howto approach? Counseling Health screening – history , examination and investigation Knowledge??
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  Hormone ReplacementHormone Replacement TherapyTherapy combine regime- estrogen and progestogen in women with uterus  Oestrogen /ERT only – women with no uterus
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  OestrogensOestrogens  Natural :oestradiol, oestrone and oestriol which are chemically synthesised from soya beans or yams; conjugated equine oestrogen (CEE) consisting primarily of estrone sulphate and equilin sulphate,obtained from urine of pregnant horses,  Synthetic : ethinyl oestradiol and mestranol (less suitable for HRT)
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  ProgestogensProgestogens  High androgenicpotency  marked adverse effects on lipoproteins!  negates beneficial effects of estrogen  eg. 19-nor progestogens, norgestrel, norethisterone  Moderate androgenic potency  some effects on plasma lipids  eg. Medroxyprogesterone acetate (MPA)
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  No androgenic potency no effect on blood lipids  Eg dydrogesterone (Duphaston) Eg - Femaston
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  Routes of AdministrationRoutesof Administration  Oral -most widely used -well tolerated -highly effective -rapid onset -‘first-pass’ effect (beneficial changes in HDL:LDL)  Transdermal -patches or gels -messy, time consuming -redness/itchiness -need of oral progestogen: low compliance  Intravaginal -vaginal rings, pessaries, cream -no effects on vasomotor symptoms, osteoporosis or CVD -creams or tablets:messy -need oral progestogen: poor compliance  Subcutaneous -surgically inserted pellets -hormone release varies -treatment can’t be reversed -estrogen effects persist
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  Prescribing RegimensPrescribing Regimens Estrogen therapy may be  cyclical :administered for first 21 days of the cycle)  continuous :administered throughout the cycle)  Progestogens therapy may be  sequentially :added for last 10 - 14 days of the cycle (induces a withdraw bleed)  continuously (to eliminate withdrawal bleed)
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  HRT CHARTHRT CHART link
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  Weight Gain andAndroid Fat Distribution in Menopause
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  % change frombaseline after 24 months (n=26, n=28, n=26) Hänggi W et al. Endocrinology 1998;48:691-699. Effect of HRT on Body Weight and Fat Distribution -2 0 2 4 6 Total Body Fat Mass Trunk Fat mass Total Body Weight Controls Tibolone femoston 2/10 * *p<0.05 vs. baseline * * %changefrombaseline
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  Sequential TherapySequential Therapy Mimics the menstrual cycle.  Regular, monthly periods.  Periods often lighter.  Appropriate for perimenopausal women with irregular bleed.
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  Continuous Combined RegimeContinuousCombined Regime  A continuous-combined regime is to eliminate wihdrawal bleeding.  Use should be avoided within the first 12 months after the last menstrual bleed.  Spottings may occur during the first 3 - 4 months in most women.  Appropriate for postmenopausal women who do not wish for any regular withdrawal bleed.
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  Duration of SystemicDurationof Systemic TreatmentTreatment  Vasomotor symptoms - up to 5 years and then evaluate as some women do experience symptoms for more than 5 years.  Prevention or treatment of osteoporosis - needs to be continued for life as BMD falls when treatment is stopped. However other option should be discussed as long term HRT is associated with other risk.
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   Premature menopause- usually advised to continue until the natural age of menopause ~ 51 years. There after need to reevaluate what is the endpoint of treatment.
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  Treatment of LocalTreatmentof Local SymptomsSymptoms Treatment is usually long term if not life long as symptom return on cessation of treatment. Synthetic oestrogens or CEE should be avoided as they are well absorbed from the vagina. The options available are low dose natural oestrogen e.g vaginal oestriol by cream or pessary or oestradiol by tablet or ring. With the recommended dose regimen, progestogen need not be added for endometrial protection.
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  - effective intreating hot flushes and improvement is usually seen within 4 weeks with maximum effect achieved by 3 months. - treatment should be continued for at least 1 year. Vasomotor symptomsVasomotor symptoms
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  Percentage of menopausalsymptoms in 186 women during a 52 week period of femoston® 2/10 treatment Baseline 6 weeks 52 weeks 0 10 20 30 40 50 60 70 80 Hot flushes Night sweats Sweating attacks Vaginal dryness Painful intercourse Percentageofwomen Amy JJ. Eur Menop J 1995;2 (Suppl.):16-22 Relief of Menopause Symptoms with femoston® 2/10
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  Urogenital symptoms andsexualityUrogenital symptoms and sexuality - vaginal dryness, superficial dyspareunia, urinary frequency and urgency respond well to oestrogens - urinary incontinence, however, is not improved
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  - reduces therisk of spine, hip and other osteoporotic fracture. - need lifelong treatment to be effective in preventing fracture. - not recommended as a first-line treatment as risks outweigh benefits. - standard dose for bone protection are CEE 0.625mg, oestradiol 1-2mg and transdermal 25-50µg. OsteoporosisOsteoporosis
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  Bone Mineral Density% Change Stevenson JC et al. Maturitas 2001;38:197-203. Significant increase in BMD of the lumbar vertebrae and hips 1 mg estradiol plus 5, 10 or 20 mg continuous dydrogesterone, N=177, 1 year treatment duration * p<0.01 vs. baseline 0.0% 1.0% 2.0% 3.0% 4.0% L2-4 Vertebrae Femoral Neck Ward's Triangle Trochanter 3.6%* 1.16%* 1.62%* 2.83%* %increasefrombaseline
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  Prevention and TreatmentofPrevention and Treatment of OsteoporosisOsteoporosis  Biphosphonates - shown to reduce both vertebral and non- vertebral fractures - principal side-effect : irritation of upper GIT so given weekly/monthly to reduce this. Eg - alandroanate  SERMs (Raloxifene) - shown to reduce vertebral fracture. - does not treat vasomotor symptoms, cause transient side effects such as hot flushes and leg cramps. - Has an equal propensity with HRT to cause VTE
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  Prevention and TreatmentPreventionand Treatment of Osteoporosisof Osteoporosis  Calcitriol - active metabolite of vitamin D and facilitates the intestinal absorption of calcium.  Calcium - in postmenopausal women not on HRT 1.5 gram/day and in those on HRT 1.0 gram/day of elemental calcium is needed to preserve bone health.  Vitamin D - oral supplementation of 700-800IU/day seem to reduce risk of vertebral and non-vertebral fractures in ambulatory or institutionalized elderly people.
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  Colorectal cancerColorectal cancer -reduces risk of colorectal cancer by about one-third
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  HRT AND BreastcancerHRT AND Breast cancer - risk of breast cancer is dependent on the regimen prescribed, greatest with combined oestrogen-progestrogen replacement. - Risk of breast cancer minimal after 5 years of usage - The WHI found : risk in the oestrogen- alone group was 23% lower than in the placebo group.
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  Nurses' Health Study(January 2006Nurses' Health Study (January 2006))  Data suggest that timing of hormone initiation in relation to age of onset of menopause might influence coronary risk; women beginning HT/ET near onset of menopause had a significantly reduced risk (30% less) of CHD;  no significant correlation between HT/ET and CHD risk was observed among women who initiated therapy 10 years or more after menopause. Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation.
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  Effects of unopposedestrogen and risk of invasiveEffects of unopposed estrogen and risk of invasive breast cancer (Nurses' Health Study, May 2006)breast cancer (Nurses' Health Study, May 2006)  Data indicate that use of estrogen alone did not increase the risk of invasive breast cancer until 20 years of use and beyond, and risk was increased at 15 years for estrogen receptor and progesterone receptor- positive cancers. Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006;166:1027-1032.
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  Breast DisorderBreast Disorder Benign breast disease - no convincing evidence to show that the risk of breast cancer is increased in patients with benign breast disease  Previous breast cancer - studies on systemic HRT showed contradictory results with some showing adverse outcome and some showed no further increase risk. However, low dose vaginal oestrogen are not contraindicated for vaginal symptoms.
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  HRT AND EndometrialcancerHRT AND Endometrial cancer - unopposed oestrogen therapy increased the risk of endometrial cancer and risk is still increased for 5 years or more after discontinuation of therapy. - addition of progestogen reduces this risk but not completely with sequential progestogens especially if used for more than 5 years. - no increase risk is found with combined continuous regimen.
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  HRT andHRT andVenousVenous thromboembolic diseasethromboembolic disease - highest risk occurs in the first year of use. - however, absolute risk is small as VTE occurs in 1.7 per 1000 in women older than 50 years who are not taking HRT and mortality is low (1-2%). - limited data suggest that transdermal HRT is associated with a lower risk than the oral route.
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  HRT and CANCERHRTand CANCER Cervical and ovarian cancer - not contraindicated except for endometrioid ovarian cancer where some doubt exist and progestogen addition is recommended. Endometrial cancer - need to be given with progestogen.
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  Cardiovascular DiseaseCardiovascular Disease Hypertension - no evidence shows that oestradiol- based HRT increases blood pressure or has an adverse effect in women with hypertension. Rarely CEE may cause severe hypertension which returns to normal upon stopping treatment.  Hyperlipidaemia - depends on type of HRT used.  Venous thromboembolism - relative contraindication. If still need to give as benefits outweighed risks then the transdermal route might be safer (limited evidence)  HRT and surgery - to stop 4 weeks prior to elective surgery or to continue HRT with thromboprophylaxis.
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  Endocrine DiseaseEndocrine Disease Diabetes Mellitus - HRT seems to improve the glycaemic control with varying results depending on the type and route of administion.  Thyroid disease - dose of thyroxine may need to be increased as oestrogen can can increase the concentration of thyroxine-binding globulin.
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  Non-oestrogen Based TreatmentNon-oestrogenBased Treatment  Menopausal symptoms - progestogens such as NET 5mg/day or megestrol acetate 40mg/day - Clonidine - 50-75mg bd, of limited value and effectiveness - SSRI, gabapentin  Vaginal atrophy - lubricants, moisturisers
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  What are otheroptions?What are other options? Exercise – yoga, Taichi, meditations Healthy food – increase fruits and vegetable intake Alternative – black cohosh, red clovers, etc
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  Case StudiesCase Studies
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  Case Study 1CaseStudy 1  45 year old woman, para 3, complains of:  irregular bleeding (not heavy)  vasomotor symptoms (hot flushes, night sweats) What would you advise her ?What would you advise her ?
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  Case Study 1CaseStudy 1 1.1. Health ScreenHealth Screen • Detailed history of general health status including family history • Physical examination: BP, Anemia, Thyroid, CVS, Lung, Breasts, Pelvic examination including Pap Smear. • Blood Examination: Hb, Lipid profiles, FBS, Others if indicated. • Other investigations: Mammography, BMD (Dexa) 2. Treatment … If all tests are normal the choices are: • Combined Cyclical HRT (regular-bleed)
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  Case Study 1CaseStudy 1 2. …Treatment Combined Cyclical HRT (regular-bleed) • Short-term • Pregnancy? Rees M, Purdie DW (2002), Management of the Menopause. Pg 112
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  Case Study 2CaseStudy 2 50 year old woman, posthysterectomy 3 years (ovaries not removed), has menopausal symptoms. She wants to know what are her options for:  hot flushes  night sweats  Dryness of vagina  Dyspareunia What would you advise her ?What would you advise her ?
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  Case Study 2CaseStudy 2 1.1.Health ScreenHealth Screen • Baseline workup as is case 1 2. Treatment • If normal mammogram and no contraindication, estrogen only therapy can be started • For fast relieve of vaginal symptoms, local application of vaginal cream can be used for short term
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  Case Study 2CaseStudy 2 3. Weigh the benefits and risks What are my risks ? • Cardiovascular disease − no protection − If coronary artery disease present, higher risk of mortality in the first year • Breast Cancer − Increased risk (MW study) − No increase in risk (WHI Study) − Increase mortality from breast cancer (MW Study)
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  Case Study 2CaseStudy 2 4. Alternative therapy if there are other risk factors What are my options? • Prozac/Effexor • Antihypertensives (Aldomet) • Unproven therapy − Black Cohosh − Phytoestrogens − Advise on spritual exercise yoga, taichi etc
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  Case Study 3CaseStudy 3 60 year old woman, has taken HRT for 10 years is seeking your advice whether she should stop or continue taking HRT ? What would you advise her ?What would you advise her ?
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  Counseling risk outweighbenefit Health screening Offer non pharmacological treatment now consider HT rather than HRT?
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   Nonpharmacological treatmentof postmenopausal symptoms  Article first published online: 11 JAN 2013  © 2013 Royal College of Obstetricians and Gynaecologists Issue  The Obstetrician & Gynaecologist Volume 15, Issue 1, pages 19–25, January 2013
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  Where are wenow?Where are we now?
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  ACOG: State-of-the-Art Guideto HormoneACOG: State-of-the-Art Guide to Hormone TherapyTherapy  Combined hormone therapy should not be used for prevention of diseases such as cardiovascular disease, due to the small but significant increased risk of conditions such as breast cancer, heart attack, stroke, and blood clots;  Estrogen-alone therapy, used for women who have had a hysterectomy, should also not be used for prevention of diseases, due to increased risks of blood clots and stroke. Although ET carries fewer risks than combined HT, women with a uterus should not use estrogen alone due to their increased risk of uterine cancer;
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  ACOG: State-of-the-Art GuidetoACOG: State-of-the-Art Guide to Hormone TherapyHormone Therapy  Hormone therapies are appropriate for the relief of vasomotor symptoms, so long as a woman has weighed the risks and benefits with her doctor; and  Women on combined HT or ET should take the smallest effective dose for the shortest possible time and annually review the decision to take hormones.
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  NAMS (North AmericanMenopause Society –NAMS (North American Menopause Society – Sept 2003)Sept 2003)  The primary indication for systemic hormone therapy is moderate and severe menopausal symptoms: Hot flashes, night sweats/insomnia, mood swings  When treating moderate and severe urogenital atrophy (vaginal dryness, dyspareunia, urinary frequency, and incontinence), local estrogen preparations are preferred.
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   2. HRTfor treating menopausal symptoms  Treatment is justified since the benefits outweigh the risks.  4. HRT for managing osteoporosis  Consider alternative therapies such as calcium, biphosponates and the selective estrogen receptor modulators. (SERMs)
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   3. HRTfor preventing cardiovascular diseases  3.1 Conventional HRT should not to be used for primary prevention however a low dose HRT and transdermal therapy can be considered to be used.  3.2 HRT should not be used for secondary prevention against heart disease.  3.3 Women at risk of cardiovascular disease who wish to discontinue HRT should consider dietary and lifestyle changes (weight loss, regular exercise, stop smoking) as well as the use of drugs to lower cholesterol and blood pressure.