Managing menopause: a review of the biomedical evidence: summary

Managing MenopauseA Review of theBio-Medical EvidenceSummary2008

Managing MenopauseA Review of theBio-Medical EvidenceSummary2008

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryThe Women’s Health CouncilThe Women’s Health Council is a statutory body established in 1997 to advisethe Minister for Health and Children on all aspects of women’s health.The mission of the Women’s Health Council is to inform and influencethe development of health policy to ensure the maximum health andsocial gain for women in Ireland. Its membership is representative of a widerange of expertise and interest in women’s health.The Women’s Health Council has five functions detailed in its StatutoryInstruments:1. Advising the Minister for Health and Children on all aspects of women’shealth.2. Assisting the development of national and regional policies and strategiesdesigned to increase health gain and social gain for women.3. Developing expertise on women’s health within the health services.4. Liaising with other relevant international bodies which have similar functionsas the Council.5. Advising other Government Ministers at their request.The work of the Women’s Health Council is guided by three principles:• Equity based on diversity – the need to develop flexible and accessibleservices which respond equitably to the diverse needs and situations ofwomen.• Quality in the provision and delivery of health services to all womenthroughout their lives.• Relevance to women’s health needs.2The Women’s Health Council

Managing Menopause – A Review of the Bio-Medical Evidence – Summary4The Women’s Health Council

Background information on the menopauseEarly symptoms of the menopause include:Physical/Sexual symptoms• Hot flushes & night sweats• Heart palpitations• Shortness of breath• Chest tightness• Headaches• Joint aches• Dizziness• Decreased sex drivePsychological symptoms• Mood swings• Irritability• Insomnia• Anxiety• Poor sleep pattern• Difficulty concentrating• ForgetfulnessAs time goes on, other symptoms may occur, these include:• Increased frequency of passing urine• Discomfort when passing urine• Urine infections• Urinary incontinence• Vaginal dryness, discomfort, burning and itching• Dry skin and hair, and brittle nails• Loss of bone densityPsychological symptoms such as depression, mood swings, irritability, anxiety,forgetfulness and poor concentration may emerge due to hormone changes oras a result of having to cope with the physical symptoms describes above.Long term health impacts of menopauseOver time, the changes in hormone production affect various parts of thebody, in particular the bones, the cardiovascular system and the urogenitalsystem. Although, many women will not experience the symptoms describedbelow, the risk of developing these symptoms increases significantly due tothe fall in oestrogen levels.OsteoporosisOsteoporosis meaning “porosity of the bones” is a skeletal diseasecharacterized by low bone mass and deterioration of bone tissue. Thisincreases the risk of bone fractures. Oestrogen is important in slowing downthe rate of bone breakdown. Both men and women start to loose calciumThe Women’s Health Council9

Managing Menopause – A Review of the Bio-Medical Evidence – Summaryfrom their bones as they get older. However, women are much more at risk offracture than men due to three main reasons:1. Their peak bone mass is less than that in men2. They live, on average, longer than men and so have a longer period ofbone loss3. Most significantly, their rate of bone loss exceeds that in men once themenopause is reached and oestrogen levels diminish.Women may not experience any signs or symptoms of bone loss until theyhave had a fracture resulting from a simple fall or knock. Estimates from theWorld Health Organization and the International Osteoporosis Foundation(Melton et al., 1992; Kanis et al., 2000) suggest that one in three women overthe age of fifty have osteoporosis of the hip, spine or wrist. If this estimate isapplied to the Irish population, osteoporosis may affect over 190,000 womenaged over fifty, or approximately 9% of the total population (CSO, 2006).Cardiovascular diseaseCardiovascular disease (CVD) refers to diseases affecting the heart or bloodvessels, for example, Stroke and Coronary Heart Disease (CHD). In Ireland,between 2002 and 2006, an average of 2,382 women died each year fromischaemic heart disease (CSO, 2007). CHD is uncommon in women beforethe menopause, especially non-smokers. The loss of ovarian function anddrop in oestrogen levels is associated with an increased CHD risk (Stevenson,2004). Oestrogen helps to reduce cholesterol in the bloodstream and reducesthe risk of hardening and clogging of the coronary arteries, and is thereforeassociated with reduced risk of heart disease in women.Urogenital symptomsThe drop in oestrogen levels that occurs during menopause results in agradual deterioration of tissues of the urinary tract and vagina. Symptomshowever, do not appear until some years after the menopause, although theycan be particularly distressing and impair a woman’s quality of life. Womenmay experience frequent passing of water during the day or night, or stressincontinence (the involuntary leakage of urine during exercise, coughing,laughing or sneezing).10The Women’s Health Council

Managing menopausal symptoms3. Managing menopausalsymptomsThere are many different types of treatment available to relieve menopausalsymptoms. For the purpose of this review the treatments are categorised into:(i)(ii)(iii)Lifestyle modificationsPrescription therapies (hormonal and non-hormonal)Non-prescription therapies(i) Lifestyle modificationsLifestyle modifications such as having a healthy diet, exercising regularly,maintaining a healthy body weight, limiting alcohol consumption and notsmoking may be useful in relieving mild menopausal symptoms. The evidenceto support these lifestyle changes is presented below.Table 1 Summary of evidence for effectiveness of lifestyle modificationsLifestylemodificationHealthy dietRegular exerciseHealthy weightAlcoholSmokingSummary of evidenceRisk of osteoporosis & heart disease ↑ in postmenopausalwomen, therefore a healthy diet is important. In particular,adequate calcium and vitamin D, and low salt are recommended.Although thought to be beneficial, there is no evidence thatvitamin E is effective in relieving menopausal symptoms.Intensive, vigorous exercise may make hot flushes worse.Regular, moderate exercise may be beneficial for relievingmenopausal symptoms but further good quality trials arerequired to support this.Normal healthy weight women have ↓ hot flushes comparedwith overweight women.Moderate alcohol consumption seems to have no effect onhot flushes.Drinking more than 3 units of alcohol a day, or 14 units perweek is likely to ↑ hot flushes.Active smoking is thought to ↑ the likelihood of hot flushes,although 1 large study found no ↑. Passive smoke exposureis thought to ↑ likelihood of hot flushes.The Women’s Health Council11

Managing Menopause – A Review of the Bio-Medical Evidence – Summary(ii) Prescription therapies (hormonal andnon-hormonal)A description of the types of hormonal therapies available and a briefdescription of the therapies examined in this review is provided along withevidence of their effectiveness of relieving menopausal symptoms. Followingthis, the additional risks and benefits of oral oestrogen only therapy andcombined oestrogen and progesterone therapy are discussed.Hormone Replacement Therapy (HRT) useA survey of women across Ireland, aged 40 and over, was conducted inJanuary 2008. Of the 475 women surveyed, half claimed they haveexperienced or are currently experiencing the menopause. Of these women,5% were currently taking HRT, and 14% had previously taken HRT. The surveyalso showed that the majority of women (55%) used HRT for between oneand three and a half years (WHC, 2008c). Therefore, the issue of taking HRT isrelevant to a relatively small sub-section of the menopausal women.Types of HRTThere are a wide range of HRT preparations available which allow the clinicianto customize the type, dose and delivery route of the HRT to suit the needs ofeach woman. The two main types of HRT are oestrogen on its own andoestrogen combined with a second hormone, progestogen (similar toprogesterone). The oestrogen component of HRT replaces the oestrogen lostat the menopause and relieves menopausal symptoms. Oestrogen on its ownis given to women who have had a hysterectomy (women with theiruterus/womb removed). Women with an intact uterus are given acombination of oestrogen & progestogen HRT. Progestogen is necessary toprevent endometrial hyperplasia (thickening of the uterus) (Grady, et al., 1995).HRT can be taken by various delivery routes. The oral route is usually the firstchoice mainly as it is simple, economical and, in the long-term, can provideeffective protection for the cardiovascular system and bones. Women whocannot, or prefer not to use oral HRT, can use take HRT via transdermal routes(through the skin) such as patches, gels, nasal spray, vaginal formulations orimplants.Various HRT regimens can also be used to suit women at different stages ofthe menopausal process. Combined oestrogen & progestogen can be taken asa sequential, cyclical, long-cycle or continuous regimen. Perimenopausalwomen (having a period within the past 12 months) can use sequentialregimens (oestrogen everyday and progesterone for the last 10-14 days ofcycle), cyclical regimens (oestrogen from day 1-25 and progestin for 10-14days each month) or long-cycle regimens (oestrogen for 3 months andprogesterone in the 2nd half of the third month). These regimens will cause a12The Women’s Health Council

Managing menopausal symptomsmonthly bleed. Postmenopausal women (having last period over 12 monthsago) have the option of sequential, cyclical, long cycle or continuouscombined regimes, but most choose the “no bleed” (continuous combined)regimen with a daily dose of both hormones. Figure 2 summarises theregimens of HRT. The synthetic steroid Tibolone is only suitable for olderwomen, over 54 years, who have had no period for at least 12 months. AsTibolone does not stimulate the uterine lining, it can be used withoutprogesterone.There are no clear guidelines on the best way to stop using HRT. Bothimmediate cessation (“cold turkey”) and gradual tapering of the dose (bylowering the dose and/or skipping progressively more days between doses)have been suggested (NAMS, 2004). The gradual discontinuation of HRTallows the individual to lower the dose until symptoms reappear, thereforeidentifying the smallest dose required for the control of menopausalsymptoms.Figure 2:Choice of HRT Regimens(adapted from RCN, 2005)Indication for HRTIntact uterus/wombHad hysterectomyLess than 1 yearsince LMP*More than 1 yearsince LMP*Oestrogen & Progestogen HRTSequential regimenorCyclical regimenorLong-cycle regimenContinuouscombinedregimenTiboloneOestrogen only+/-AndrogenLast Menstrual Period*The Women’s Health Council13

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryOestrogen only therapyOestrogen only therapy is suitable for women without a uterus. In Europe,the most widely prescribe oestrogen is pure estradiol synthesised from soyabeans and yams. In North America, conjugated (or blended) estrogensobtained from pregnant horses’ urine are most commonly used. Oraloestrogen can provide relief from both vasomotor symptoms and vaginalatrophy (such as vaginal dryness, irritation and itching, or pain duringintercourse) however, if relief is only required from vaginal atrophy, thenoestrogen can be applied locally to the vagina to relieve symptoms (NAMS,2007). The methods of administering vaginal oestrogen include intra-vaginalcream, a vaginal ring placed high up inside the vagina, or vaginal tablet placedin the vagina.There is good evidence that shows oral oestrogen HRT to be very effective inrelieving vasomotor symptoms in menopausal women (MacLennan et al.,2004). It is well established that oestrogen therapy is also effective in relievingurogenital symptoms (such as vaginal dryness and painful intercourse), sleepdisturbances and improving quality of life (NIH, 2005). Evidence also showsoral and transdermal oestrogen have consistent and similar effects on relievinghot flushes and may have similar adverse effects (Nelson, 2004).Local vaginal oestrogen is effective at relieving urogenital symptoms. There iscurrently inadequate data to determine whether women need to takeprogesterone along with locally applied vaginal oestrogen to provideprotection from endometrial cancer, although as a precaution, progesterone isoften prescribed along with oestrogen (Sucking et al., 2006).Combined oestrogen & progestogen therapyBecause of the increased risk of endometrial cancer with oestrogen onlytherapy, all women with an intact uterus should receive combined oestrogenand progestogen HRT. Progestogen protects against the development ofendometrial cancer.It is well established that combined oestrogen and progestin HRT is effective inrelieving hot flushes. A significant reduction of 75% in the weekly frequencyof hot flushes was found for women taking HRT compared to those taking aplacebo (MacLennan et al., 2004). A review of the evidence suggests thatcombined oestrogen and progesterone HRT might be more effective inrelieving hot flushes due to the additional beneficial effects of progesterone,although this is not conclusive (MacLennan et al., 2004).14The Women’s Health Council

Managing menopausal symptomsThere is no evidence to indicate whether one HRT product or regime issuperior to another for relieving menopausal symptoms (ICSI, 2006; NAMS,2004). In clinical practice, each woman absorbs oral oestrogen differently(Helton, 1977). Therefore, it is important to find the most suitable HRT doseand regimen for each individual woman so that there is a balance betweenrelief from menopausal symptoms and any oestrogenic side effects(MacLennan et al., 2004). In general, women are recommended to use thelowest HRT dose for the shortest time necessary to control menopausalsymptoms (MHRA, 2007a; ICSI, 2006; AACE, 2006).Progesterone only therapyAlthough progesterone is primarily used in combination with oestrogen toprovide protection against endometrial cancer, progesterone used alone canprovide relief from hot flushes if the benefit-risk profile is acceptable to thewoman. There is good evidence to show that progesterone only therapy iseffective in relieving hot flushes (NAMS, 2004). However, concerns haverecently arisen over whether progestogen only therapy can increase the risk ofbreast cancer (RCOG, 2006). Considering this, it is probably inappropriate totreat women who have an increased risk of breast cancer with progestogens(RCOG, 2006). In Ireland, progesterone only therapy is not generallyprescribed to treat menopausal symptoms.Tibolone (“Livial”)Livial tablets contain the active ingredient tibolone, which is a synthetic steroidthat has some oestrogen-, progesterone- and testosterone-like effects. It hasbeen extensively researched and is licensed in Europe for the relief ofmenopausal symptoms, including hot flashes, vaginal atrophy and reducedlibido. Tibolone, like HRT, prevents bone loss in postmenopausal women withand without osteoporosis (Sturdee, 2004). It was one of the first “no period”regimens developed and is most suited to post menopausal women (Lumsden,2004; Sturdee, 2004).The effectiveness and safety of tibolone is comparable to HRT. As tiboloneseems not to stimulate the breast, it may potentially be useful in treatingmenopausal symptoms in woman with breast cancer (MacLennan, 2007).However, there is currently insufficient evidence to make any firm conclusionson the risk of tibolone to the breast. Tibolone is only suitable for olderwomen over 54 years who have had no period for at least 12 months(Lumsden, 2004; Sturdee, 2004).The Women’s Health Council15

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryOral contraceptives (OCs)Women who need contraception as well as hormone therapy to relieve hotflashes (such as women with premature ovarian failure and experiencingpremature menopause) may be prescribed the combined oestrogen andprogesterone OC pill (BMS, 2007). Premature menopause affects about 1%of women (RCN, 2005). All women with a premature menopause shouldnormally be offered HRT until the average age of menopause.There is a lack of studies conducted on the effectiveness of oral contraceptivesfor relieving menopausal symptoms in women with premature menopause.The oestrogen and progesterone found in OCs is generally stronger whencompared to HRT (NAMS, 2004). This is likely to increase the effectiveness ofOCs in relieving menopausal symptoms.Additional benefits & associated risks of HRTMenopausal symptoms do not last forever, and treatment for 2-4 years isnormally sufficient (Sturdee, 2004). Some women need to use HRT for longerto relieve menopausal symptoms and take advantage of the benefits of HRT.The safety of HRT largely depends on the age of the women. TheInternational Menopausal Society states that women younger than 60 yearsold should not be concerned about the safety profile of HRT (IMS, 2007).HRT has received widespread media attention over the last few years, much ofit negative criticism. This led to many women avoiding HRT. The initialfindings published from the large Women’s Health Initiative (WHI) studiesreported that combined HRT increased the risk of CHD, stroke, blood clots andbreast cancer. Findings published from the large Million Women Study (MWS)reported that HRT increased the risk of breast cancer and ovarian cancer.However, some limitations of the methods and analyses used in these studieshave been identified. For example, the WHI studies involved mainly olderwomen, many of whom were currently taking or had previously taken HRT.The findings, therefore, are not applicable to younger women who have neverhad HRT.To summarise, the benefits of HRT include protection from osteoporoticfracture and colon cancer, as well as providing effective relief frommenopausal symptoms. The evidence suggests using HRT increases the risk ofbreast cancer, ovarian cancer, blood clot and stroke. The effect of HRT onCHD is currently unclear, although it seems that the risk of CHD is reduced inyounger women (less than 60 years) and women beginning HRT nearmenopause (within 10 years).16The Women’s Health Council

Managing menopausal symptomsThe safety of HRT largely depends on the age of the women. Evidence for therisks of HRT in women who have premature menopause is limited, althoughaverage (baseline) risk of adverse events in these younger women is very lowand the balance of benefits and risks may therefore be more favourable thanin older women (MHRA, 2007a).Data from new research and further analyses of data obtained in previousstudies show that, for most women, the potential benefits far outweigh therisks when HRT is initiated within a few years of the menopause. Two clinicaltrials currently ongoing, KEEPS (Kronos Early Estrogen Prevention Study)(KEEPS, 2007) and ELITE (Early versus Late Intervention Trial with Estradiol)(ELITE, 2007) will, in a few years time, provide valuable evidence regarding therisks and benefits of using oral or transdermal HRT, and the age of initiatingHRT.The Medicines and Healthcare products Regulatory Agency (MHRA) conducteda comprehensive review on medicines for women’s health at their meeting inJuly 2007 and published updated safety advice on HRT after considering themost recent evidence (MHRA, 2007b). A summary of the estimated risks andbenefits, using the data provided by the MHRA, are shown in Table 2a-c.The Women’s Health Council17

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryTable 2a Summary of risks and benefits of HRT: cancer risk(adapted from MHRA, 2007b)Age range(years)Time(years)Number of womenper 1000 expectedto develop cancer*Number of women per1000 using HRT expected todevelop cancer †Further explanationOestrogenonly HRTOestrogen &progestogenHRTBreast cancer50-5960-6950-5960-695 10 12 165 15 18 2410 20 26 4410 30 39 66Risk is lower with oestrogen only HRT and whenHRT is used for around 5 years or less. The riskof breast cancer approximately doubles withlong-term use of combined HRT.Endometrial cancer50-5960-6950-5960-695 2 6 25 3 9 310 4 26 410 6 54 6Women with a uterus use combined HRT asprogesterone greatly reduces risk. The number ofcases of endometrial cancer increases approximately3 times when using oestrogen only HRT for 5 yearsand 9 times when used for 10 years.Ovarian cancer50-5960-6950-5960-695 2 2 25 3 3 310 4 5 510 6 8 8The increased risk associated with HRT is verysmall, even with long-term HRT use theincreased risk is relatively small.* Background incidence from ‘never users’ in the Million Women Study for breast cancer, and the International Agency for Research on Cancer (IARC) for ovarian & endometrial cancer.† Best estimate based on relative risk derived from meta-analyses of RCTs and observational studies for endometrial and ovarian cancer, and meta-analyses of RCTs and observational studies in Europe forbreast cancer.18The Women’s Health Council

Managing menopausal symptomsTable 2b Summary of risks and benefits of HRT: cardiovascular effect(adapted from MHRA, 2007b)Age range(years)Time(years)Number of womenper 1000 expectedto experiencecardiovasculareffect*Number of women per 1000using HRT expected toexperience cardiovascular effect †Oestrogenonly HRTOestrogen &progestogenHRTFurther explanationVenousthromboembolism(VTE)50-5960-695 5 7 125 8 10 18The risk is highest with combined HRT. Theincreased risk when using combined HRT is justover double of that compared with not using HRT.Stroke50-5960-695 4 5 55 9 12 12The increased risk of stroke is relatively small. Theincreased risk is similar for women of all agebetween 50 and 69 years, although the expectednumber of women experiencing stroke increaseswith age.Coronary heartdisease (CHD) O OP 50-5960-6970-795 14 9 14 95 31 18 31 185 44 29 44 44Younger women, and women who start HRTaround the time of menopause may have areduced risk of CHD. Women aged over 70 whotake combined HRT have a 50% increased risk ofCHD.* Background incidence from Hospital Admissions in England (HES) for VTE & stroke and the Women’s Health Initiative (WHI) for CHD.† Best estimate based on relative risk derived from meta-analyses of RCTs and observational studies for VTE, meta-analyses of RCTs for stroke, and the WHI trial for CHD. Estimates from placebo groups from the conjugated equine oestrogens (CEE) and CEE + medroxyprogesterone placebo arms of WHI trial.O=oestrogen, OP=oestrogen and progestogen.The Women’s Health Council19

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryTable 2c Summary of risks and benefits of HRT: benefits**(adapted from MHRA, 2007b)Age range(years)Time(years)Number of womenper 1000 expectedto experiencecolorectal cancerNumber of women per 1000using HRT expected toexperience colorectal canceror femur fracture or femur fracture Oestrogenonly HRTColorectal cancer O OP50-595 6 3 6 360-695 10 8 10 8Oestrogen &progestogenHRTFracture of femur O OP50-595 0.5 1.5 0.6 1.560-695 5.5 5.5 3.5 5.5**Menopausal symptom relief is not included in this table, but is a key benefit of HRT and will play a major part in the decision to prescribe HRT. Incidence estimated from placebo groups from the conjugated equine oestrogens (CEE) and CEE + medroxyprogesterone placebo arms of WHI trial.O=oestrogen, OP=oestrogen and progestogen.Further explanationEvidence suggests combined HRT has a protectiveeffect against colorectal cancer. It is estimated toreduce risk by 10%, although in terms of numberof cases per 1000, this reduction is negligible.Both oestrogen only HRT and combined HRTreduce the risk of osteoporotic fracture. A 30-40% reduction of fracture is estimated fromtaking HRT.20The Women’s Health Council

Managing menopausal symptomsPrescription therapies (non-hormonal)For women suffering from hot flashes who do not want to use HRT, or whoare advised not to use HRT (women who have breast cancer or at high risk ofgynaecological cancers), non-hormonal prescription drugs may provide aneffective option.Some prescription anti-depressants and the anti-convulsant drug, gabapentin,may provide some relief from hot flashes. While these may be prescribed inother countries for relieving menopausal symptoms, they are currently notlicensed in Ireland for this purpose.Clonidine is an anti-hypertensive drug that may also be used to relieve hotflushes. Clonidine causes blood vessels to widen increasing blood flow. InIreland, clonidine is available as “Dixarit” tables. Dixarit is prescribed primarilyto treat attacks of migraine and similar types of headache, although it is alsolicensed for the treatment of menopausal hot flushes. Dixarit may initiallycause tiredness or a dry mouth, and other side effects such as dizziness,feeling sick and restlessness at night have also been reported (Nelson et al.,2006). The evidence suggests that although clonidine is effective in relievinghot flushes (Pandya et al., 2000), the effect may only be moderate (Goldberget al., 1994).Table 3Summary of evidence on prescription therapiesHot flushesVaginal atrophyOestrogen only therapy✓✓Combined oestrogenand progesterone therapyProgesterone only therapy✓✓✓✗Tibolone✓✓Oral contraceptivesClonidine✓✓✓✗✓✗Good scientific evidence of a beneficialeffect for menopausal womenNo evidence of a beneficial effect formenopausal women21The Women’s Health Council

Managing Menopause – A Review of the Bio-Medical Evidence – Summary(iii) Non-prescription therapiesThe non-prescription therapies examined in this review include herbal therapies,phytoestrogens and complementary therapies. A description of these therapies isprovided below, followed by a summary of the evidence on their effectiveness onrelieving menopausal symptoms.Herbal therapiesAlthough herbal medicine has been used for centuries to relieve a wide range ofailments, there remains very little scientific evidence of their efficacy, safety and littleproof to support the claims made for these remedies. Like all medicines, herbaltherapies may cause side effects, and there is also some concern over the interactionof some herbal remedies with other treatments. A summary of herbal therapiescommonly used to relieve menopausal symptoms is presented in the table below.Table 4: Description of herbal therapiesHerbal therapy Possible side effects Notes Commonly used for:Black CohoshVery few reported.Avoid if have liver disease, oruse alcohol heavily. Caution iftaking blood pressuretreatment.Hot flushesSleep disturbancesVaginal drynessDepressionAnxietyDong QuaiCan make skin sensitiveto the sun & cause rash.Avoid combining with bloodthinning drugs (for e.g.Warfarin, Asprin).Hot flushesEvening primroseoilVery few reported.Contains gamma-linolenicacid, an essential fatty acid.Breast painVaginal drynessGinsengGenerally well tolerated.Most common sideeffect is inability tosleep.May lower blood sugar levels,so caution advised if diabetic.Avoid with blood thinning orclotting medication.ConcentrationDepressionLibidoSense of well-beingGinkgoVery few reported.Avoid combining with bloodthinning drugs (for e.g.Warfarin, Asprin)DepressionFatigueMemoryValerianVery rare, but womenwho use it for longperiods may developheadaches, insomnia oragitationMay have interactions withalcohol & some prescriptionmedicines. Should not bestopped suddenlyAnxietyMood swingsSleep problemsWild YamGenerally well tolerated.Very rare allergicreactions can occur.No interactions with other Increasing energyprescription drugs have been Libidoreported.Menopausal arthritisOsteoporosis VaginaldrynessThe Women’s Health Council22The Women’s Health Council

Managing menopausal symptomsPhytoestrogensPhytoestrogens are naturally occurring oestrogen-like compounds obtainedfrom plants. One of the main dietary groups of phytoestrogens is isoflavones,which are found in beans, pulses, lentils, chickpeas, tofu and soy-basedproducts. The Japanese diet contains a high level of phytoestrogens. It isthought that this is why very few Japanese women suffer from hot flushesduring the menopause. Two common sources of isoflavones are red cloverand soy.There is a lack of evidence showing red clover to have an effect in relievinghot flushes and the evidence on the effectiveness of dietary soy and soyextracts is inconclusive. Soy foods have been consumed for centuries and areconsidered safe, however, soy extracts in tablets or capsules, and foodsfortified with isoflavones may contain high levels of isolated isoflavones, thelong-term effects of which are not known (NAMS, 2004).Complementary therapiesA wide range of complementary therapies can be used to relieve short-termmenopausal symptoms. The therapies examined in this review wereacupuncture, homeopathy, reflexology and aromatherapy. Othercomplementary therapies may also be used, although there is a lack ofscientific evidence on their benefit to women suffering from menopausalsymptoms.The Women’s Health Council23

Managing Menopause – A Review of the Bio-Medical Evidence – SummaryTable 5Summary of evidence on non-prescription therapiesHot flushesMood (anxiety/depression)MemoryBlack cohosh✗✓✗Ginseng✗✓✗Ginkgo✗✗✓Dong quai✗✗✗Evening primrose oil✗✗✗Valerian✗✗✗Wild yam✗✗✗Red clover isoflavones?✗✗Soy isoflavones?✗✗AcupunctureHomeopathy??✗✗✗✗✓Some scientific evidence of a beneficial effectfor menopausal women (the evidence isgenerally quite weak & of low quality)ReflexologyAromatherapy✗✗✗✗✗✗✗?No evidence of a beneficial effect formenopausal womenInconclusive evidence24The Women’s Health Council

Conclusions4. ConclusionsScientific knowledge and evidence in this field is constantly evolving. Theevidence summarised in this review presents the current consensus. Allinterventions to relieve menopausal symptoms should be individually tailored tothe specific needs and concerns of each woman, and designed to provide anoptimal quality of life.Lifestyle modifications should be considered as the first step in menopausalsymptom relief and disease prevention. All women should be encouraged tohave a healthy lifestyle as this is important for general health and well-being aswell as beneficial to women suffering from mild menopausal symptoms.The menopause is a natural event in every woman’s life and many womenexperience very few or mild symptoms. For women who do experienceadverse health effects during the menopause, only a small proportion will useHRT. For relief of hot flushes and vaginal dryness, HRT remains the mosteffective pharmacologic intervention. As well as providing effective relief frommenopausal symptoms, the benefits of HRT include protection fromosteoporotic fracture and colon cancer. The evidence suggests using HRTincreases the risk of breast cancer, ovarian cancer, blood clot and CVD.Current evidence suggests that the risk of CHD is reduced in younger women(less than 60 years) and women beginning HRT near menopause (within 10years). Ongoing trials will, in a few years time, provide valuable evidenceregarding the risks and benefits of using oral or transdermal HRT, and the ageof initiating HRT.An individual risk profile should be conducted for every woman consideringHRT. The decision to use HRT should be a joint one between a woman andher doctor, with consideration to her need for treatment, her age, history, riskfactors and personal preferences. For all women, the lowest effective doseshould be used for the shortest time. The need to continue HRT should bereviewed every 6 to 12 months taking into consideration the change inbalance of risks and benefits.For women who cannot, or prefer not to use HRT, there are variousalternatives to consider. The evidence suggests that these alternatives provide,at best, moderate relief from menopausal symptoms. The evidence does notsupport the use of complementary therapies in relieving menopausalsymptoms. However, as complementary therapies generally work holistically,they may benefit the general health and well-being of some women.The increasing volume of evidence and choice of treatments for relievingmenopausal symptoms makes the decision over treatment choice morechallenging for women. Clear, up-to-date and easily accessible information isvital to enable women to make informed choices on menopausal treatments.The Women’s Health Council25

Managing Menopause – A Review of the Bio-Medical Evidence – Summary5. ReferencesAACE Menopause Guidelines Revision Task Force (2006). "AmericanAssociation of Clinical Endocrinologists medical guidelines for clinical practicefor the diagnosis and treatment of menopause." Endocrine Practice 12(3):315-37.British Menopause Society (2007). Premature Menopause: British MenopauseSociety Council Consensus Statement. Buckinghamshire, British MenopauseSociety. From: http://www.thebms.org.uk/statementcontent.php?id=3.Central Statistics Office (2006). Vital Statistics: Fourth quarterly and yearlysummary. Dublin, Central Statistics Office.Central Statistics Office (2007). "Central Statistics Office Website."January 28, 2007. From: http://www.cso.ie/.RetrievedELITE (2007). "Early versus Late Intervention Trial with Estridiol." From:http://www.usc.edu/schools/medicine/research/centers_programs/aru/elite.html.Goldberg, R. M., C. L. Loprinzi, et al. (1994). "Transdermal clonidine forameliorating tamoxifen-induced hot flashes." J Clin Oncol 12(1): 155-8.Grady, D., T. Gebrretsadik, et al. (1995). "HRT and endometrial cancer risk: Ameta-analysis." Obstetric Gynaecology 85(2): 304-13.Helton, E. D. and J. W. Goldzieher (1977). "The pharmacokinetics of ethynylestrogens: A review." Contraception 15(3): 255-84.Institute for Clinical Systems Improvement (2006). Menopause and HormoneTherapy (HT): Collaborative decision-making and management. Bloomington,Minnesota, ICSI. From:http://www.icsi.org/guidelines_and_more/guidelines__order_sets___protocols/womens_health/.Kanis, J. A., O. Johnell, et al. (2000). "Long-term risk of osteoporotic fracturein Mälmo." Osteoporosis Int 11(8): 669-74.KEEPS (2007) "Kronos Early Estrogen Prevention Study." From:http://www.keepstudy.org/5/18/contact_us.html.26The Women’s Health Council

ReferencesLumsden, M. A. (2004). “Hormone Replacement Therapy: Regimen and routesof administration”. In: Critchley, H., A. Gebbie. and V. Beral. Menopause andHormone Replacement. London, Royal College of Obstetricians andGynaecologists.MacLennan, A. H., J. L. Broadbent, et al. (2004). "Oral oestrogen andcombined oestrogen/progestogen therapy versus placebo for hot flushes."Cochrane Database of Systematic Reviews (Issue 4).MacLennan, A. H. and D. W. Sturdee (2007). "Long-term trials of HRT forcardioprotection: Is this as good as it gets?" Climacteric 10: 1-4.Medicines & Healthcare products Regulatory Agency (MHRA) (2007a).Hormone-replacement therapy: Safety update. UK Public Assessment Report.London, MHRA. From:http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=230.Medicines & Healthcare products Regulatory Agency (MHRA). (2007b)."Hormone-replacement therapy: Updated advice." Drug Safety Update 1(2):2-4.Melton, L. J., E. A. Chrischilles, et al. (1992). "Perspective: How many womenhave osteoporosis?" J Bone Miner Res 7(9): 1005-10.NAMS (2007). "The role of local vaginal estrogen for treatment of vaginalatrophy in postmenopausal women: 2007 position statement of The NorthAmerican Menopause Society." Menopause 14(3): 357-69.NAMS (2004). "Treatment of menopause-associated vasomotor symptoms:Position statement of The North American Menopause Society." Menopause11(1): 11-33.Nelson, H. D. (2004). "Commonly used types of postmenopausal estrogen fortreatment of hot flashes." JAMA 291(13): 1610-20.Nelson, H. D., K. K. Vesco, et al. (2006). "Nonhormonal therapies formenopausal hot flashes." JAMA 295(17): 2057-71.NIH State-of-the-Science Panel (2005). National Institutes of Health State-ofthe-ScienceConference Statement on management of menopause-relatedsymptoms. 22: 1-38. From: http://consensus.nih.gov/2005/2005MenopausalSymptomsSOS025PDF .pdf.The Women’s Health Council27

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