Presentation on theme: "Back to the Future: Applying New Evidence in Menopause Management"— Presentation transcript:
1 Back to the Future: Applying New Evidence in Menopause Management Michael Policar, MD, MPH
2 Topics To Be Discussed New information from the WHI The expanding range of treatments for managing menopausal symptomsWhich treatments are available to your patient?Practice RecommendationsHow can your patient use these treatments safely, effectively, and conveniently?
3 NAMS Definitions Progestogen Progesterone or progestin (P) ET Estrogen (E) therapyEPT Combined E+P therapyHT Hormone therapy (ET and EPT)CC-EPT Continuous-combined E+P therapy- E+P given every dayCS-EPT Continuous-sequential E+P therapy- E daily with P added on set sequenceNAMS position statement. Menopause 2007.
4 The WHI Re-analyzedAct 1Let’s Get This Out of the Way….
5 Background: HRT sMenopause seen as endocrine deficiency requiring hormone replacement therapy1960s: successful oral contraceptive introduction“The Pill” freed women from fear of pregnancyHRT offered women freedom from fear of aging1972: Forever Feminine by Robert A. Wilson, MD1980s: Expanding uses of HRTInitially used to treat hot flashes, vaginal sxsLater uses…protection of bone and heart5
7 Background: Late 1980sIn 40 retrospective observational studies, both EPT and ET reduced the risk of heart attack by 50%Most studies included women in their 50sWomen were self-selected for hormone use (or not); studies were subject to selection biasConventional wisdomAll women should use HT for heart protection, unless there was a reason not to do soWomen with CVD risk factors, especially previous MI, stroke, HTN or diabetes, should use HT7
8 Background:1990s1990: Wyeth requested that FDA add labeling to HT products that included cardioprotectionFDA insisted that RCTs be performed to prove that HT improved CVD outcomes vs. placeboTwo RCTs initiated to evaluate cardioprotectionHERS: secondary prevention trialWHI: primary prevention trial
9 HERS Study: 1998 Does EPT reduce MIs in women with CHD? 2,763 women randomized to CC-EPT or placeboEntry: MI, CABG, balloon angioplasty, + angiogramMenopausal, intact uterus, years of ageAverage follow up: 4.1 yearsStudy findingsEPT had no value in reduction of MIs or CHD deathsMore deaths in year 1; neutral thru year 8Not seen in prior observational studies3-fold increased risk of VTE eventsHulley, JAMA 1998:280:6059
10 Women’s Health Initiative (WHI): 2002 : RCT with 17,000 womenPostmenopausal women years old33%: yrs old; 45%: yo; 22% yoAverage age: 64 years oldEnd pointsPrimary prevention of MI and strokeHip fracture, various cancersTreatment armsIf uterus: CC-EPT (CEE+MPA) vs. placeboIf no uterus: ET (CEE) vs. placebo10
11 WHI: EPT Arm Study Results Released July 2002: Findings after 5 WHI: EPT Arm Study Results Released July 2002: Findings after 5.2 yearsEvent RR Risk/10K/yr Benefit/10K/yrHeart attackStrokeBreast cancerTE eventColorectal CAHip fracturesDiscontinued early, as “risks greater than benefits”11
14 WHI : ET-Only Study Arm Released 2004: Findings after 7 years Outcome Change vs. PlaceboCoronary heart disease No difference in riskBreast cancer No difference in riskStroke Increased riskHip fractures Decreased riskDementia, cognitive Trend toward increasedChange (> 65 years old) risk14
15 WHI and HERS: The 2004 Take Home Message HT does not protect women from heart attacks over the long term…and actually may increase the risk of MI in the first year of HT useThe rest is “specialty-specific” perception of benefit and risk15
16 Was the WHI designed to evaluate the safety and efficacy of EPT in treating menopausal changes? The Women’s Health InitiativeWas not a menopause studyWas a drug study of the effect of hormones on CVD, cancer, fractures, and memory in older women (average 64 year old)
17 How Different Were WHI Findings Compared to Earlier Studies? Manson JE, Menopause 2006;13:139
18 WHI: HT and Risk of CV Disease by Age and Years Since Menopause Roussow JE. JAMA. 2007: Combined secondary analysisAge at HT initiationHeart attackStrokeDeath from any cause50–59 years↓ 7%↑ 13%↓ 30%60–69 years↓ 2%↑ 50%↑ 5%70–79 years↑ 26%↑ 21%↑ 14%A combined secondary analysis of WHI studies to determine if age at initiation of HT affected cardiovascular risk was published in the Journal of the American Medical Association (JAMA) in Both arms of the WHI were combined for this analysis, which allowed for evaluation of more than 26,000 women.This secondary analysis revealed that women who initiated HT closer to the age of menopause had a significantly reduced risk of death from any cause compared to women who took placebo. Additionally, risk of heart attack was reduced in women receiving HT closer to the age of menopause, but not at a significant level. On the other hand, stroke risk was elevated for all groups regardless of years since menopause.“Women who initiated HT closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion* for statistical significance.”*Statistically significant defined as p<0.01.
19 WHI (EPT arm) Re-analyses Age vs. Years Since Menopause Age (years)50–5960–6970–79Years Since Menopause<1010–19201.271.051.440.891.221.71Manson et al evaluated the risk of CHD in certain subgroups of the WHI, designated by factors such as age and years since menopause to determine whether women were at a higher or a lower risk for CHD with CEE/MPA compared with placebo,In this analysis, no significant interaction between age or years since menopause and treatment was observed (P = 0.36 for the age analysis and P = 0.33 for years-since-menopause analysis), although there was a numerical trend towards a higher risk with CEE/MPA use among those women with the longest times since menopause.While the investigators noted that the findings of the subgroup analyses should be interpreted with caution because of the small size of many of the subgroups as well as the large number of comparisons performed (approximately 36 tests were performed), these findings are consistent with accumulating data that the timing of initiation of HT in relation to the development of atherosclerosis is an important variable that may influence the potential risks and benefits of HT.Hypertension per se should not be considered contraindication to estrogen therapy since research shows that replacement doses of estrogen have little effect on blood pressure.The WHI combined estrogen-progestin trial noted only a small increase (1.5 mmHg) in systolic pressure compared with placebo.86 In the WHI trial of unopposed estrogen, a similar difference between the hormone and placebo groups of 1.1 mmHg was observed.ReferencesManson JE, et al. N Engl J Med. 2003;349:Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.Anderson, GL, Limacher, M, Assaf, AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291:1701.Hazard Ratio for CHDManson JE, et al. N Engl J Med. 2003;349:523-34Manson JE, et al. N Engl J Med. 2003;349:19
20 WHI: Estrogen and Major Health Outcomes in Women Under 60 Years of Age % difference in relative riskEvents/ 10,000 WY of CEE therapyTotal mortality-29 (-11Coronary heart disease-37 ( )Stroke-11 (-2New onset DM-12 ( )-14Fracture-30 ( )-56Breast cancer-18 ( )-8VTE+37 ( )+4Hodis HN, Mack WJ. Menopause Management 2008
21 The Unified Hypothesis 2005 WHIPhillips LS, Langer RD,Postmenopausal hormonetherapy: critical reappraisaland a unified hypothesis.Fertility and Sterility 2005;83:558-66
22 Clinical Implications: Unified Hypothesis Mild cardioprotectionWomen in their early-mid 50s, whoInitiate HT soon after menopause, withFew or no heart disease or stroke risk factorsAnd who use estrogen-only regimensIncreased heart disease riskWomen in their mid-60s or later, whoInitiate HT long after menopause, who haveHeart disease or stroke risk factorsAnd who use estrogen and progestin regimens
23 Benchmark HT Cardioprotection Studies Primary Prevention“Healthy women”Secondary PreventionWomen with known heart diseaseObservationalStudiesNurses Health StudyVarious small studiesRandomized Clinical TrialsWHIKEEPSHERS
24 Key Points: NAMS March 2007 Position Statement on Hormone Therapy The North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007Copyright 2007
25 HT and Coronary Heart Disease ET/EPT not recommended as single or primary indication for coronary protection in women of any ageData do not currently support EPT in secondary prevention of CHDNAMS position statement. Menopause 2007.
26 HT and StrokeBoth ET and EPT appear to increase the risk of ischemic stroke in postmenopausal womenNo HT regimen should be used for the primary or secondary prevention of strokeHT should be avoided for women who have elevated baseline risk of strokeNAMS position statement. Menopause 2007.
27 HT and Venous Thromboembolism Significant increase in VTE risk in postmenopausal women using systemic HTRisk increased with both EPT and ETVTE risk appears during first 1-2 years after therapy initiation and decreases over timeTransdermal 17ß-estradiol and oral therapies may have different riskLower doses of oral estrogens may be safer than higher dosesNAMS position statement. Menopause 2007.
28 EPT and Breast Cancer Risk Breast cancer risk increases with EPT use beyond 5 yearsIncreased absolute risk in WHI is viewed as rare (4-6 additional invasive cancers/10,000 women/year when use EPT used for ≥ 5 yrs)Not clear whether risk differs between CC-EPT and CS-EPTNAMS position statement. Menopause 2007.
29 ET and Breast Cancer Risk (cont’d) Women in WHI’s ET arm had 8 fewer cases of invasive breast cancer/10,000 women/yr of ET useAvailable evidence suggests ET for < 5 years has little breast cancer risk impactLimited observational data suggest ET given longer than 15 years may increase riskNAMS position statement. Menopause 2007.
32 General Health Recommendations Exercise: aerobic + strength trainingReduction in hot flashes in some womenHealthier heart; stronger bonesNational Osteoporosis Foundation (NOF) Feb 2008Adults under age 50 need, per day1,000 mg of calcium*IU of vitamin D3Adults 50 and over need, per day1,200 mg of calcium*800-1,000 IU of vitamin D3* In divided doses, preferably with meals
33 Hot Flashes: Lifestyle Changes Exercise routinely, at least 3-4 days/weekCool room temperature, especially at nightDress in layers (remove outer layers if warm)Avoid hot and spicy foodsRelaxing activitiesAvoid cigarettesMinimize alcoholA number of lifestyle and social factors may influence hot flush frequency:Warm ambient air temperatures increase a woman’s core body temperature and make her more likely to reach the sweating thresholdLess physical activity increases the relative risk of hot flushes; daily exercise is associated with an overall decreased incidenceAnecdotally, spicy foods have been reported to trigger hot flushes, though there is no clinical evidence to support this relationshipRelaxation techniques may decrease or alleviate symptomsOther lifestyle factors that affect vasomotor symptoms:Cigarette smoking (past and current) increases the relative risk of hot flushes, perhaps because of its effect on estrogen metabolismWhile low levels of alcohol consumption (< or =1 drink per day for women) do not have a measurable effect on occurrence of vasomotor symptoms, greater amounts of alcohol intake may promote such symptoms.ReferencesNorth American Menopause Society. Menopause. 2004;11:11-33.Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:Huntley AL, Ernst E. Menopause. 2003;10:Greendale GA, Gold EB. Lifestyle factors: are they related to vasomotor symptoms and do they modify the effectiveness or side-effects of hormone therapy? Am J Med Dec 19;118 Suppl 12B:North American Menopause Society. Menopause. 2004;11:11-33; Kronenberg F, Fugh-Berman A. Ann Intern Med ;137:805-13; Huntley AL, Ernst E. Menopause. 2003;10:North American Menopause Society. Menopause. 2004;11:11-33.Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:Huntley AL, Ernst E. Menopause. 2003;10:
34 Botanicals and PhytoSERMs Probably better than placeboBlack cohoshNo evidence of efficacySoy isoflavones Not better than pboRed clover isoflavones Not better than pboEvening primrose oil Not better than pboDong quai Not better (as monotx)Ginseng Not better than pboVitamin E Not better than pboChasteberry (Vitex) No studies
35 Botanicals: Black Cohosh Total of 14 trials reported, including 4 randomized trials using placebo and/or estrogen treatment arm3 of 4 RCTs found black cohosh to be beneficial12 of 14 trials reported some benefitCurrently, longest trial is 6 monthsNIH-funded, large, randomized, prospective, 2-year trial ongoingPreliminary data fail to show binding to E receptorsBinding to serotonin receptor notedFour randomized trials of black cohosh with placebo or estrogen control groups have been conducted.Tablets (40mg/d) vs placebo; duration, 2 months1—Outcomes included frequency and intensity of hot flushes; menopause symptom index (6 symptoms); global rating of health scale; follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. FINDINGS: No significant difference between groups in frequency and intensity of hot flushes (decreased in both groups); significantly greater decrease in sweating in treatment group than in placebo group (P=.04); no changes in global rating scale or FSH and LH levels; study duration was short.Liquid (40 drops twice daily) vs conjugated estrogens (0.25mg/d) vs diazepam (2mg/d); duration, 3 months2—Outcomes included Kupperman index (KI) scores (modified 5 symptoms); Hamilton Anxiety scale (HAM-A); self-assessment depression scale (SDS); clinical global impression (CGI) scale; and vaginal maturation index (VMI). FINDINGS: Kupperman index, HAM-A, SDS, and CGI showed “highly significant reductions” with all three therapies; VMI: “trend toward estrogenic stimulation” for Remifemin and estrogen; no statistical calculations were reported.Tablets (4 mg twice daily) vs conjugated estrogens (0.625 mg/d) vs placebo; duration, 3 months3—Outcomes included Kupperman index scores (9 symptoms); hot flushes; HAM-A; VMI. FINDINGS: Significant improvement in Kupperman score, HAM-A (P=<.001), and VMI (P=<.01); no change in estrogen or placebo groups; hot flushes decreased from 4.9 to 0.7/d in Remifemin group, 5.2 to 3.2 in estrogen group, and 5.1 to 3.1 in placebo group (significance not indicated); lack of effect with estrogen calls other findings into question.Tablets (4 mg of triterpine glycosides twice daily) vs estriol (1 mg/d) vs conjugated estrogen (1.25 mg/d) vs estrogen/progesterone combination; duration, 6 months4—Outcomes included Kupperman index scores (modified 17 symptoms), LH and FSH levels. FINDINGS: Kupperman scores improved in all groups (P=.01); no differences among treatment groups; no changes in LH and FSH levels.Investigators note that there is a great need for alternatives to hormone therapy for use by symptomatic menopausal women. Alternatives to estrogen can encompass lifestyle change, complementary and alternative medicine (CAM), and prescription nonhormonal therapies. The use of CAM therapies for menopausal symptoms is widespread and has been increasing. A recent study indicates that relatively low concentrations of actein or the EtOAc fraction of black cohosh can cause synergistic inhibition of human breast cancer cell proliferation when combined with different classes of chemotherapy agents.References1Jacobson JS, et al. J Clin Oncol. 2001;19:2Warnecke G. Med Welt. 1985;36:871-4.3Stoll W. Therapeutikon. 1987;1:23-31.4Lehmann-Willenbrock E, Riedel HH. Zentralbl Gynakol. 1988;110:611-8.Kessel B, Kronenberg F. Endocrinol Metab Clin North Am Dec;33(4):Einbond LS, et al. Planta Med Oct;72(13):Four randomized trials of black cohosh with placebo or estrogen control groups have been conducted.- Tablets (40 mg/d) vs placebo; duration, 2 months1—Outcomes included frequency and intensity of hot flushes; menopause symptom index (6 symptoms); global rating of health scale; follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. FINDINGS: No significant difference between groups in frequency and intensity of hot flushes (decreased in both groups); significantly greater decrease in sweating in treatment group than in placebo group (P = .04); no changes in global rating scale or FSH and LH levels; study duration was short.- Liquid (40 drops twice daily) vs conjugated estrogens (0.25 mg/d) vs diazepam (2 mg/d); duration, 3 months2—Outcomes included Kupperman index (KI) scores (modified 5 symptoms); Hamilton Anxiety scale (HAM-A); self-assessment depression scale (SDS); clinical global impression (CGI) scale; and vaginal maturation index (VMI). FINDINGS: Kupperman index, HAM-A, SDS, and CGI showed “highly significant reductions” with all three therapies; VMI: “trend toward estrogenic stimulation” for Remifemin and estrogen; no statistical calculations were reported.- Tablets (4 mg twice daily) vs conjugated estrogens (0.625 mg/d) vs placebo; duration, 3 months3—Outcomes included Kupperman index scores (9 symptoms); hot flushes; HAM-A; VMI. FINDINGS: Significant improvement in Kupperman score, HAM-A (P < .001), and VMI (P < .01); no change in estrogen or placebo groups; hot flushes decreased from 4.9 to 0.7/d in Remifemin group, 5.2 to 3.2 in estrogen group, and 5.1 to 3.1 in placebo group (significance not indicated); lack of effect with estrogen calls other findings into question- Tablets (4 mg of triterpene glycosides twice daily) vs estriol (1 mg/d) vs conjugated estrogens (1.25 mg/d) vs estrogen/progesterone combination; duration, 6 months4—Outcomes included Kupperman index scores (modified 17 symptoms), LH and FSH levels. FINDINGS: Kupperman scores improved in all groups (P = .01); no differences among treatment groups; no changes in LH and FSH levels.1Jacobson JS, et al. J Clin Oncol. 2001;19: ; 2Warnecke G. Med Welt. 1985;36: Stoll W. Therapeutikon. 1987;1: Lehmann-Willenbrock E, Riedel HH. Zentralbl Gynakol. 1988;110:611-8.
36 Botanicals: Black Cohosh Available as Remifemin, Estroven, or other single or combination productsDosage: mg dailyAdverse effects: headaches, stomach discomfort, heaviness in legsHot Flashes
37 Non-hormonal Hot Flash Therapies DrugHot Flash ReductionAntidepressantsParoxetine62-65%Venlafaxine38-60%Fluoxetine20%AnticonvulsantsGabapentin45%AntihypertensivesMethyldopa65%Clonidine38%Menopause 2004;11(1): 11-33ACOG Task Force on HTObstet Gynecol 2004; 104:106s-17s.
39 Prescription HT Options: ET and EPT OralTransdermalIntravaginalETMicronized estradiolConjugated equine estrogens (CEE)Synthetic conjugated estrogensEsterified estrogensEstropipateEstradiol acetatePatchesGelsEmulsionSprayCreamsIntravaginal tabletRingsEPTCC-EPTCS-EPTE+P (combination) patchesAs you can see there are many different options and formulations for hormone therapy. Refer to your handout for more detailed information.Med Lett Drugs Ther 2004; 46:98.39
40 HT Regimens Month 1 Month 2 Estrogen Progestin 14d Off for 14 d Continuous-sequential (CS) EPTProgestinContinuous combined (CC) EPTEstrogen Therapy (ET)3dContinuous-pulsed (CP) EPT40
41 Choice of HT Regimen If no uterus: estrogen only If uterus present Goal is to avoid vaginal bleeding entirely, or, at least, to make it predictableEndometrial activity predicts bleeding patternRecent spontaneous or induced bleedingContinuous sequentialNo bleeding for >2-3 cyclesContinuous combined41
42 ET Oral Tablets Product Brand Standard dose Low dose Estropipate Ogen Ortho-estGeneric0.625 mnoneMicronized E2Estrace1.0 mg0.5 mgEstradiol acetateFemtrace0.9 mg0.45 mg
43 ET Transdermal: Patch* Brand nameMg/24 hrUse/ wkAlora0.025, 0.05, 0.075, 0.12Esclim0.025, , 0.05, 0.075, 0.1Estraderm0.05, 0.1VivelleVivelle-DotClimara0.025, ,0.05, 0.06, 0.075, 0.11Menostar0.014 ☼* All contain 17B- estradiol only☼ Indicated only for prevention of osteoporosis
45 Choice of Estrogens Start low dose transdermal or oral estrogen If suboptimal response, modify by:Change the estrogen dose (upward)Change the estrogen preparationChange delivery systems (oral transdermal)Consider an estrogen-androgen combinationInjectable estrogen not recommendedDosage equivalencies are not knownEstrogen cannot be discontinued easily
46 Route of Administration Non-oral routes of ET/EPT administration may offer advantages and disadvantages vs oral routes, but the long-term risk-benefit ratio has not been demonstratedPossible lower risk of deep venous thrombosis (DVT) with non-oral routeSimilar increased breast cancer risks with oral and transdermal estrogens, per large observational studyNAMS position statement. Menopause 2007.
47 Oral vs. TD-E: The Risk of VTE The ESTHER StudyOR = 4.0 ( )Adjusted Odds Ratio (95% CI)In the WHI, postmenopausal women randomly assigned to oral hormone therapy had 2.1 times higher risk of venous thromboembolic events than those receiving placebo.A large case-control study of postmenopausal women was conducted in order to explore the relationship between estrogen use and venous thromboembolism (VTE) risk. A total of 155 postmenopausal women with a first documented episode of idiopathic VTE were compared with 381 control women matched for age, study center, and time of recruitment. The case subjects included 92 women with pulmonary embolism and 63 women with deep vein thrombosis.After adjusting for potential confounding factors, women taking oral estrogen therapy had 3.5 times higher risk of VTE as compared with nonusers and 4.0 times higher risk as compared to those taking transdermal estrogen. Transdermal estrogen users did not have an increased risk of either DVT or PE. These results show that oral estrogen—but not transdermal estrogen—is associated with increased risk of VTE in postmenopausal women.ReferenceScarabin P-Y, Oger E, Plu-Bureau G, et al. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003;362:Scarabin P-Y, et al. Lancet. 2003;362:
48 “First Line” Use of Transdermal Estrogen Underlying medical conditionsHistory of DVT or PTEHigh triglyceride levelsGall bladder diseaseNeed for “steady state” drug releaseDaily mood swings (especially while on oral HT)Migraine headachesInability to use oral tabletsStomach upset due to oral estrogen intakeProblems with taking a daily pill
49 Lower HT DosesProvide nearly equivalent vasomotor and genital skin symptom relief and preservation of BMD compared to standard dosesAdditional local ET may be required for persistent vaginal symptomsLower HT doses better tolerated and may have a better risk-benefit ratio than standard doses(cont’d)NAMS position statement. Menopause 2007.
50 Lower HT Doses (cont’d) Lower-than-standard ET/EPT doses should be considered, such as daily doses of0.3 mg oral conjugated estrogensmg oral micronized 17β-estradiol0.025 mg transdermal 17β-estradiol patchor the equivalentNAMS position statement. Menopause 2007.
51 Progestogen Indication Primary menopause-related indication is endometrial protection from unopposed ETAdequate progestogen (as CC-EPT or CS-EPT) recommended with intact uterusProgestogen not generally indicated with ET post-hysterectomyNAMS position statement. Menopause 2007.
55 Off-Label EPT UsesInsufficient endometrial safety evidence to recommend off-label use ofLong-cycle progestogen (ie, P every 3-6 months for days)Vaginal administration of progesteroneLevonorgestrel intrauterine system (Mirena)Low-dose estrogen without progestogenClose endometrial surveillance recommended with these approachesNAMS position statement. Menopause 2007.
56 Compounded Bioidentical Hormones “Then, suddenly, the Seven Dwarfs of Menopause arrived at my door without warning: Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and All-Dried-Up….What was it that sent those wretched dwarfs packing? Natural bioidentical hormones.”Here we have Suzanne Sommers, who is largely responsible for bringing the concept of bioidenticals into the mainstream.Somers S. The Sexy Years: Discover the Hormone Connection: The Secret to Fabulous Sex, Great Health, and Vitality for Women and Men. Front Matter Random House, Crown Publishing, NY.
57 Compounded Hormone Therapy The marketing of compounded hormonal therapyOnly bioidentical hormones are usedCombination of 2 or 3 estrogens is more “natural”Dosage is tailored to the individualMore “pure” than commercial productsSafer delivery systems (no dyes, etc)The realityThe same hormones are used in commercial and compounded 17b-E2 and progesterone
59 Compounded Hormone Therapy Compounded hormones will probably work, but…Salivary hormone levels are not usefulThe value of adding E1 + E3 has not been evaluatedProgesterone skin cream is not absorbedCompounded hormone doses are not standardizedFDA-approved HT products will offerBioidentical hormonesChoice of delivery systemsFormulary coverage/ lower out-of-pocket costs
62 Act 3Practice Guidelines How can your patient use these treatments safely, effectively, and conveniently?
63 Treatment of Hot Flashes If mild sxs, try exercise, black cohosh + phytoSERMInitiate low dose HT ifModerate or severe symptomsNon-hormonal treatments have failedNo interest in non-hormonal therapyTitrate estrogen dosage upward if neededWhen estrogen can’t be used, offerSSRI or SNRIGabapentin, clonidine, a-methyldopa,MPA or Megesterol (Megace)Attempt discontinuation after 1-2 years63
64 Treatment of Sleep/ Irritability Sxs If mild symptomsLifestyle change, black cohosh, phytoSERMsIf severe symptoms or no response to aboveLow dose HT, then titrate upwardIf mood swings, transdermal E preferredDepression component, or no response to HTSNRI or SSRI
65 HT and Vaginal AtrophyWhen HT is considered solely for this indication, local (not systemic) vaginal ET is generally recommendedProgestogen generally not indicated with low-dose, local vaginal ETVaginal lubricants often improve vaginal dryness and painful intercourseNAMS position statement. Menopause 2007.
66 Vaginal Estrogen Therapies ProductBrandDosageDoseConjugated estrogen creamPremarin cream0.625 mg/ gramDaily, then 1-3 time/wkEstradiol creamEstrace0.01%(0.1 mg/ gm)Estradiol vaginal tabletVagifem25 microgramsDaily for 2 wks, BIWEstradiol ringEstring7.5 mcg/ 24 hrsEvery 90 daysEstradiol ring*Femring0.05 mg/d0.1 mg/dEvery 3 months*Intended to be used as systemic HT
67 Vaginal ET: Endometrial Surveillance? There are insufficient data to recommend annual endometrial surveillance in asymptomatic women using low-dose, local vaginal ETCloser surveillance may be required if a woman isAt high risk for endometrial cancerUsing a greater dose of vaginal ETHaving symptoms such as spotting, breakthrough bleedingNAMS position statement. Menopause 2007.
68 HT and CognitionInitiating EPT after age 65 not recommended for primary prevention of dementia or cognitive declineInsufficient evidence to support ET/EPT for primary prevention of dementia when therapy is initiated during perimenopause or early postmenopauseET does not appear to convey direct benefit or harm for treatment of Alzheimer’s diseaseNAMS position statement. Menopause 2007.
69 HT and CognitionMany women experience worsening of short term memory with onset of menopause9 RCTs and 8 cohort studiesHT does not improve cognitive performance in women without symptomsIf symptoms, HT improved verbal memory, reasoning, and motor speed testsReasonable to provide HT to lessen cognitive changes in symptomatic menopausal women
70 Hormone Therapy and Fracture Prevention ProsGood data on fracture prevention (mainly 2o prevention)Relatively lower cost than boisphosphonatesLess concern of adverse effects with ET alone (vs EPT)ConsRequires long term use and surveillancePost-menopausal bleeding can be troublesomeIncreased risk of breast cancer after 5 years of useUtilityFracture prophylaxis if using HT for another indicationOtherwise, consider bisphosphonates as first line70
71 HT and “Quality of Life” RCTs and retrospective studies show that HT has no effect on “quality of life” measuresMany woman who wean from HT state that they “feel worse”…even after 20 years after menopause!Conventional wisdomIn women who “feel better on/ worse off” of HT, continue low dose HT if few or no risk factorsWhen (& how often) to re-attempt wean uncertainDon’t start HT for solely for improving QOL
73 Discontinuation of HTAfter 2 years, recommend a trial of HT discontinuationIs tapering from hormone therapy necessary?Grady D, Obstet Gynecol 2003;102:1233n= 377 who attempted discontinuation of HT74% successfully stopped; 26% resumed71% stopped abruptly; 29% tapered: equal success“Rebound” hot flashes occur in some women and can last up to 3 months…many experts recommend a taperTaper hormone therapy over 8-12 weeksReduce dose or extend intervals (every 2, then 3 days)Cut patches in half