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Back to the Future: Applying New Evidence in Menopause Management Michael Policar, MD, MPHwww.PolicarLectures.com.

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Presentation on theme: "Back to the Future: Applying New Evidence in Menopause Management Michael Policar, MD, MPHwww.PolicarLectures.com."— Presentation transcript:

1 Back to the Future: Applying New Evidence in Menopause Management Michael Policar, MD, MPHwww.PolicarLectures.com

2 Topics To Be Discussed New information from the WHI New information from the WHI The expanding range of treatments for managing menopausal symptoms The expanding range of treatments for managing menopausal symptoms –Which treatments are available to your patient? Practice Recommendations Practice Recommendations –How can your patient use these treatments safely, effectively, and conveniently?

3 NAMS Definitions Progestogen Progesterone or progestin (P) Progestogen Progesterone or progestin (P) ET Estrogen (E) therapy ET Estrogen (E) therapy EPT Combined E+P therapy EPT Combined E+P therapy HT Hormone therapy (ET and EPT) HT Hormone therapy (ET and EPT) CC-EPT Continuous-combined E+P therapy CC-EPT Continuous-combined E+P therapy - E+P given every day - E+P given every day CS-EPT Continuous-sequential E+P therapy CS-EPT Continuous-sequential E+P therapy - E daily with P added on set sequence - E daily with P added on set sequence NAMS position statement. Menopause 2007.

4 Lets Get This Out of the Way…. Lets Get This Out of the Way…. Act 1 The WHI Re-analyzed

5 Background: HRT s Menopause seen as endocrine deficiency requiring hormone replacement therapy Menopause seen as endocrine deficiency requiring hormone replacement therapy 1960s: successful oral contraceptive introduction 1960s: successful oral contraceptive introduction –The Pill freed women from fear of pregnancy –HRT offered women freedom from fear of aging 1972: Forever Feminine by Robert A. Wilson, MD 1972: Forever Feminine by Robert A. Wilson, MD 1980s: Expanding uses of HRT 1980s: Expanding uses of HRT –Initially used to treat hot flashes, vaginal sxs –Later uses…protection of bone and heart

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7 Background: Late 1980s In 40 retrospective observational studies, both EPT and ET reduced the risk of heart attack by 50% In 40 retrospective observational studies, both EPT and ET reduced the risk of heart attack by 50% –Most studies included women in their 50s –Women were self-selected for hormone use (or not); studies were subject to selection bias Conventional wisdom Conventional wisdom –All women should use HT for heart protection, unless there was a reason not to do so –Women with CVD risk factors, especially previous MI, stroke, HTN or diabetes, should use HT

8 Background:1990s 1990: Wyeth requested that FDA add labeling to HT products that included cardioprotection 1990: Wyeth requested that FDA add labeling to HT products that included cardioprotection FDA insisted that RCTs be performed to prove that HT improved CVD outcomes vs. placebo FDA insisted that RCTs be performed to prove that HT improved CVD outcomes vs. placebo Two RCTs initiated to evaluate cardioprotection Two RCTs initiated to evaluate cardioprotection –HERS: secondary prevention trial –WHI: primary prevention trial

9 HERS Study: 1998 Does EPT reduce MIs in women with CHD? Does EPT reduce MIs in women with CHD? 2,763 women randomized to CC-EPT or placebo 2,763 women randomized to CC-EPT or placebo –Entry: MI, CABG, balloon angioplasty, + angiogram –Menopausal, intact uterus, years of age –Average follow up: 4.1 years Study findings Study findings –EPT had no value in reduction of MIs or CHD deaths »More deaths in year 1; neutral thru year 8 »Not seen in prior observational studies –3-fold increased risk of VTE events Hulley, JAMA 1998:280:605

10 Womens Health Initiative (WHI): : RCT with 17,000 women : RCT with 17,000 women Postmenopausal women years old Postmenopausal women years old –33%: yrs old; 45%: yo; 22% yo –Average age: 64 years old End points End points –Primary prevention of MI and stroke –Hip fracture, various cancers Treatment arms Treatment arms –If uterus: CC-EPT (CEE+MPA) vs. placebo –If no uterus: ET (CEE) vs. placebo

11 WHI: EPT Arm Study Results Released July 2002: Findings after 5.2 years EventRR Risk/10K/yr Benefit/10K/yr Heart attack1.297 Stroke1.418 Breast cancer1.268 TE event Colorectal CA0.636 Hip fractures0.665 Discontinued early, as risks greater than benefits Discontinued early, as risks greater than benefits

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14 WHI : ET-Only Study Arm Released 2004: Findings after 7 years OutcomeChange vs. Placebo Coronary heart diseaseNo difference in risk Breast cancerNo difference in risk StrokeIncreased risk Hip fracturesDecreased risk Dementia, cognitiveTrend toward increased Change (> 65 years old)risk

15 WHI and HERS: The 2004 Take Home Message HT does not protect women from heart attacks over the long term 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 use The rest is specialty-specific perception of benefit and risk The rest is specialty-specific perception of benefit and risk

16 The Womens Health Initiative Was not a menopause study Was not a menopause study Was a drug study of the effect of hormones on CVD, cancer, fractures, and memory in older women (average 64 year old) Was a drug study of the effect of hormones on CVD, cancer, fractures, and memory in older women (average 64 year old) Was the WHI designed to evaluate the safety and efficacy of EPT in treating menopausal changes?

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 analysis *Statistically significant defined as p<0.01. Age at HT initiation Heart attack Stroke Death from any cause 50–59 years 7% 7% 13% 13% 30% 30% 60–69 years 2% 2% 50% 50% 5% 5% 70–79 years 26% 26% 21% 21% 14% 14% 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.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.

19 WHI (EPT arm) Re-analyses Age vs. Years Since Menopause Manson JE, et al. N Engl J Med. 2003;349: Hazard Ratio for CHD Age (years) 50–59 60–69 70–79 Years Since Menopause <10 10–

20 % difference in relative risk Events/ 10,000 WY of CEE therapy Total mortality-29 ( Coronary heart disease -37 ( )-11 Stroke-11 ( New onset DM-12 ( )-14 Fracture-30 ( )-56 Breast cancer-18 ( )-8 VTE+37 ( )+4 WHI: Estrogen and Major Health Outcomes in Women Under 60 Years of Age in Women Under 60 Years of Age Hodis HN, Mack WJ. Menopause Management 2008

21 The Unified Hypothesis 2005 Phillips LS, Langer RD, Postmenopausal hormone therapy: critical reappraisal and a unified hypothesis. Fertility and Sterility 2005; 83: WHI

22 Clinical Implications: Unified Hypothesis Mild cardioprotection Mild cardioprotection –Women in their early-mid 50s, who –Initiate HT soon after menopause, with –Few or no heart disease or stroke risk factors –And who use estrogen-only regimens Increased heart disease risk Increased heart disease risk –Women in their mid-60s or later, who –Initiate HT long after menopause, who have –Heart disease or stroke risk factors –And who use estrogen and progestin regimens

23 Benchmark HT Cardioprotection Studies Primary Prevention Healthy women Secondary Prevention Secondary Prevention Women with known heart disease Observational Studies Nurses Health Study Various small studies Randomized Clinical Trials WHI KEEPS HERS

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 2007 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 2007 Copyright 2007

25 HT and Coronary Heart Disease ET/EPT not recommended as single or primary indication for coronary protection in women of any age ET/EPT not recommended as single or primary indication for coronary protection in women of any age Data do not currently support EPT in secondary prevention of CHD Data do not currently support EPT in secondary prevention of CHD NAMS position statement. Menopause 2007.

26 HT and Stroke Both ET and EPT appear to increase the risk of ischemic stroke in postmenopausal women Both ET and EPT appear to increase the risk of ischemic stroke in postmenopausal women No HT regimen should be used for the primary or secondary prevention of stroke No HT regimen should be used for the primary or secondary prevention of stroke HT should be avoided for women who have elevated baseline risk of stroke HT should be avoided for women who have elevated baseline risk of stroke NAMS position statement. Menopause 2007.

27 HT and Venous Thromboembolism Significant increase in VTE risk in postmenopausal women using systemic HT Significant increase in VTE risk in postmenopausal women using systemic HT Risk increased with both EPT and ET Risk increased with both EPT and ET VTE risk appears during first 1-2 years after therapy initiation and decreases over time VTE risk appears during first 1-2 years after therapy initiation and decreases over time Transdermal 17ß-estradiol and oral therapies may have different risk Transdermal 17ß-estradiol and oral therapies may have different risk Lower doses of oral estrogens may be safer than higher doses Lower doses of oral estrogens may be safer than higher doses NAMS position statement. Menopause 2007.

28 EPT and Breast Cancer Risk Breast cancer risk increases with EPT use beyond 5 years Breast cancer risk increases with EPT use beyond 5 years Increased absolute risk in WHI is viewed as rare (4-6 additional invasive cancers/10,000 women/year when use EPT used for 5 yrs) Increased 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-EPT Not clear whether risk differs between CC-EPT and CS-EPT NAMS position statement. Menopause 2007.

29 ET and Breast Cancer Risk (contd) Women in WHIs ET arm had 8 fewer cases of invasive breast cancer/10,000 women/yr of ET use Women in WHIs ET arm had 8 fewer cases of invasive breast cancer/10,000 women/yr of ET use Available evidence suggests ET for < 5 years has little breast cancer risk impact Available evidence suggests ET for < 5 years has little breast cancer risk impact Limited observational data suggest ET given longer than 15 years may increase risk Limited observational data suggest ET given longer than 15 years may increase risk NAMS position statement. Menopause 2007.

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31 Therapeutic Interventions Non-Hormonal Act 2

32 General Health Recommendations Exercise: aerobic + strength training Exercise: aerobic + strength training –Reduction in hot flashes in some women –Healthier heart; stronger bones National Osteoporosis Foundation (NOF) Feb 2008 National Osteoporosis Foundation (NOF) Feb 2008 –Adults under age 50 need, per day »1,000 mg of calcium* » IU of vitamin D 3 –Adults 50 and over need, per day »1,200 mg of calcium* »800-1,000 IU of vitamin D 3 * In divided doses, preferably with meals

33 Hot Flashes: Lifestyle Changes Exercise routinely, at least 3-4 days/week Exercise routinely, at least 3-4 days/week Cool room temperature, especially at night Cool room temperature, especially at night Dress in layers (remove outer layers if warm) Dress in layers (remove outer layers if warm) Avoid hot and spicy foods Avoid hot and spicy foods Relaxing activities Relaxing activities Avoid cigarettes Avoid cigarettes Minimize alcohol Minimize alcohol North American Menopause Society. Menopause. 2004;11:11-33; Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-13; Huntley AL, Ernst E. Menopause. 2003;10:

34 Botanicals and PhytoSERMs Probably better than placebo Black cohosh Black cohosh No evidence of efficacy Soy isoflavonesNot better than pbo Soy isoflavonesNot better than pbo Red clover isoflavonesNot better than pbo Red clover isoflavonesNot better than pbo Evening primrose oilNot better than pbo Evening primrose oilNot better than pbo Dong quaiNot better (as monotx) Dong quaiNot better (as monotx) GinsengNot better than pbo GinsengNot better than pbo Vitamin ENot better than pbo Vitamin ENot better than pbo Chasteberry (Vitex)No studies Chasteberry (Vitex)No studies

35 Botanicals: Black Cohosh Total of 14 trials reported, including 4 randomized trials using placebo and/or estrogen treatment arm Total of 14 trials reported, including 4 randomized trials using placebo and/or estrogen treatment arm –3 of 4 RCTs found black cohosh to be beneficial –12 of 14 trials reported some benefit –Currently, longest trial is 6 months NIH-funded, large, randomized, prospective, 2-year trial ongoing NIH-funded, large, randomized, prospective, 2-year trial ongoing –Preliminary data fail to show binding to E receptors –Binding to serotonin receptor noted

36 Botanicals: Black Cohosh Available as Remifemin, Estroven, or other single or combination products Available as Remifemin, Estroven, or other single or combination products Dosage: mg daily Dosage: mg daily Adverse effects: headaches, stomach discomfort, heaviness in legs Adverse effects: headaches, stomach discomfort, heaviness in legs Hot Flashes

37 Non-hormonal Hot Flash Therapies Drug Hot Flash Reduction Antidepressants Paroxetine Paroxetine62-65% Venlafaxine Venlafaxine38-60% Fluoxetine Fluoxetine20% Anticonvulsants Gabapentin Gabapentin 45% 45% Antihypertensives Methyldopa Methyldopa 65% 65% Clonidine Clonidine38% Menopause 2004; 11(1): ACOG Task Force on HT Obstet Gynecol 2004; 104:106s-17s.

38 Therapeutic Interventions: Hormonal Medications Act 2

39 Prescription HT Options: ET and EPT OralTransdermalIntravaginal ET Micronized estradiol Conjugated equine estrogens (CEE) Synthetic conjugated estrogens Esterified estrogens Estropipate Estradiol acetate Patches Gels Emulsion Spray Creams Intravaginal tablet Rings EPT CC-EPT CS-EPT E+P (combination) patches Med Lett Drugs Ther 2004; 46:98.

40 HT Regimens Month 1 Month 2 Estrogen Progestin 14d Off for 14 d Continuous-sequential (CS) EPT Estrogen Progestin Continuous combined (CC) EPT Estrogen Estrogen Therapy (ET) 3d Continuous-pulsed (CP) EPT

41 Choice of HT Regimen If no uterus: estrogen only If no uterus: estrogen only If uterus present If uterus present –Goal is to avoid vaginal bleeding entirely, or, at least, to make it predictable Endometrial activity predicts bleeding pattern Endometrial activity predicts bleeding pattern –Recent spontaneous or induced bleeding »Continuous sequential –No bleeding for >2-3 cycles »Continuous combined

42 ET Oral Tablets ProductBrand Standard dose Low dose EstropipateOgenOrtho-estGeneric m none Micronized E 2 EstraceGeneric 1.0 mg 0.5 mg Estradiol acetate Femtrace 0.9 mg 0.45 mg

43 ET Transdermal: Patch* Brand name Mg/24 hr Use/ wk Alora 0.025, 0.05, 0.075, Esclim 0.025, , 0.05, 0.075, Estraderm 0.05, Vivelle 2 Vivelle-Dot 0.025, , 0.05, 0.075, Climara 0.025, ,0.05, 0.06, 0.075, Menostar * All contain 17B- estradiol only Indicated only for prevention of osteoporosis

44 ET Transdermal: Gels, Emulsions, Sprays* Brand name Type mg/24 hr Use DivigelGel 0.25, 0.5, 1 mg/ packet 1 packet daily ElestrinGel 0.87 gm pump 1 pump daily EstroGelGel 1.25 gm pump 1 pump daily EstrasorbEmulsion 1.74 gm/ pouch 2 pouches daily EvamistSpray 1.53 mg/ spray 1 spray daily * All contain 17B- estradiol only

45 Choice of Estrogens Start low dose transdermal or oral estrogen Start low dose transdermal or oral estrogen If suboptimal response, modify by: If suboptimal response, modify by: –Change the estrogen dose (upward) –Change the estrogen preparation –Change delivery systems (oral transdermal) –Consider an estrogen-androgen combination Injectable estrogen not recommended Injectable estrogen not recommended –Dosage equivalencies are not known –Estrogen 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 demonstrated 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 demonstrated Possible lower risk of deep venous thrombosis (DVT) with non-oral route Possible lower risk of deep venous thrombosis (DVT) with non-oral route Similar increased breast cancer risks with oral and transdermal estrogens, per large observational study Similar increased breast cancer risks with oral and transdermal estrogens, per large observational study NAMS position statement. Menopause 2007.

47 Oral vs. TD-E: The Risk of VTE The ESTHER Study Scarabin P-Y, et al. Lancet. 2003;362: Adjusted Odds Ratio (95% CI) OR = 4.0 ( )

48 First Line Use of Transdermal Estrogen Underlying medical conditions Underlying medical conditions –History of DVT or PTE –High triglyceride levels –Gall bladder disease Need for steady state drug release Need for steady state drug release –Daily mood swings (especially while on oral HT) –Migraine headaches Inability to use oral tablets Inability to use oral tablets –Stomach upset due to oral estrogen intake –Problems with taking a daily pill

49 Lower HT Doses Provide nearly equivalent vasomotor and genital skin symptom relief and preservation of BMD compared to standard doses Provide nearly equivalent vasomotor and genital skin symptom relief and preservation of BMD compared to standard doses Additional local ET may be required for persistent vaginal symptoms Additional local ET may be required for persistent vaginal symptoms Lower HT doses better tolerated and may have a better risk-benefit ratio than standard doses Lower HT doses better tolerated and may have a better risk-benefit ratio than standard doses (contd) NAMS position statement. Menopause 2007.

50 Lower HT Doses (contd) Lower-than-standard ET/EPT doses should be considered, such as daily doses of Lower-than-standard ET/EPT doses should be considered, such as daily doses of –0.3 mg oral conjugated estrogens – mg oral micronized 17β-estradiol –0.025 mg transdermal 17β-estradiol patch –or the equivalent NAMS position statement. Menopause 2007.

51 Progestogen Indication Primary menopause-related indication is endometrial protection from unopposed ET Primary menopause-related indication is endometrial protection from unopposed ET Adequate progestogen (as CC-EPT or CS-EPT) recommended with intact uterus Adequate progestogen (as CC-EPT or CS-EPT) recommended with intact uterus Progestogen not generally indicated with ET post-hysterectomy Progestogen not generally indicated with ET post-hysterectomy NAMS position statement. Menopause 2007.

52 Progesterone/ Progestin Products Oral Progestin Equiv dose Available doses MPA 5-10 mg 1.2, 2.5, 5, 10 mg Micronized progesterone mg 100, 200 mg Drospirenone 0.5 mg/d Norethindrone acetate 1.0 mg/d 0.5, 1.0 mg/d Norethindrone mg/d 0.35 mg Norgestimate 0.09 mg Norgestrel 150 mcg/d

53 EPT Oral Tablets EstrogenProgestin Dosing Activella 17 -E2 1 mg NETA 0.5 mg Once daily oral Angeliq 17 -E2 1 mg Drosperinone 0.5 mg Once daily oral FemHRT EE 5 g EE 2.5 g NETA 1 mg NETA 0.5 mg Once daily oral Prefest 17 - E2 1 mg Micronized NGM 0.09 mg E (alone) 3 days E+P 3 days Premphase 14 active 14 placebo CEE mgMPA 5 mg Once daily oral (CS-EPT) Prempro 28 active CEE mg 0.45 mg 0.3 mg MPA 5.0 mg; 2.5 mg 2.5 mg 1.5 mg Once daily oral (CC-EPT)

54 EPT Transdermal Patches EstrogenProgestinDosing CombiPatch 17 -E mg NETA mg Twice weekly Climara Pro 17 -E mg LNG mg Once weekly

55 Off-Label EPT Uses Insufficient endometrial safety evidence to recommend off-label use of Insufficient endometrial safety evidence to recommend off-label use of –Long-cycle progestogen (ie, P every 3-6 months for days) –Vaginal administration of progesterone –Levonorgestrel intrauterine system (Mirena) –Low-dose estrogen without progestogen Close endometrial surveillance recommended with these approaches Close endometrial surveillance recommended with these approaches NAMS 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. 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 therapy The marketing of compounded hormonal therapy –Only bioidentical hormones are used –Combination of 2 or 3 estrogens is more natural –Dosage is tailored to the individual –More pure than commercial products –Safer delivery systems (no dyes, etc) The reality The reality –The same hormones are used in commercial and compounded 17b-E 2 and progesterone

58 Sources of Exogenous Hormones

59 Compounded Hormone Therapy Compounded hormones will probably work, but… Salivary hormone levels are not useful Salivary hormone levels are not useful The value of adding E 1 + E 3 has not been evaluated The value of adding E 1 + E 3 has not been evaluated Progesterone skin cream is not absorbed Progesterone skin cream is not absorbed Compounded hormone doses are not standardized Compounded hormone doses are not standardized FDA-approved HT products will offer FDA-approved HT products will offer –Bioidentical hormones –Choice of delivery systems –Formulary coverage/ lower out-of-pocket costs

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62 Practice Guidelines How can your patient use these treatments safely, effectively, and conveniently? Act 3

63 Treatment of Hot Flashes If mild sxs, try exercise, black cohosh + phytoSERM If mild sxs, try exercise, black cohosh + phytoSERM Initiate low dose HT if Initiate low dose HT if –Moderate or severe symptoms –Non-hormonal treatments have failed –No interest in non-hormonal therapy Titrate estrogen dosage upward if needed Titrate estrogen dosage upward if needed When estrogen cant be used, offer When estrogen cant be used, offer –SSRI or SNRI –Gabapentin, clonidine, a-methyldopa, –MPA or Megesterol (Megace) Attempt discontinuation after 1-2 years Attempt discontinuation after 1-2 years

64 Treatment of Sleep/ Irritability Sxs If mild symptoms If mild symptoms –Lifestyle change, black cohosh, phytoSERMs If severe symptoms or no response to above If severe symptoms or no response to above –Low dose HT, then titrate upward –If mood swings, transdermal E preferred Depression component, or no response to HT Depression component, or no response to HT –SNRI or SSRI

65 HT and Vaginal Atrophy When HT is considered solely for this indication, local (not systemic) vaginal ET is generally recommended When HT is considered solely for this indication, local (not systemic) vaginal ET is generally recommended Progestogen generally not indicated with low- dose, local vaginal ET Progestogen generally not indicated with low- dose, local vaginal ET Vaginal lubricants often improve vaginal dryness and painful intercourse Vaginal lubricants often improve vaginal dryness and painful intercourse NAMS position statement. Menopause 2007.

66 Vaginal Estrogen Therapies ProductBrandDosageDose Conjugated estrogen cream Premarin cream mg/ gram Daily, then 1-3 time/wk Estradiol cream Estrace0.01% (0.1 mg/ gm) Daily, then 1-3 time/wk Estradiol vaginal tablet Vagifem 25 micrograms Daily for 2 wks, BIW Estradiol ring Estring 7.5 mcg/ 24 hrs Every 90 days Estradiol ring* Femring 0.05 mg/d 0.1 mg/d Every 3 months *Intended to be used as systemic HT

67 There are insufficient data to recommend annual endometrial surveillance in asymptomatic women using low-dose, local vaginal ET There are insufficient data to recommend annual endometrial surveillance in asymptomatic women using low-dose, local vaginal ET Closer surveillance may be required if a woman is Closer surveillance may be required if a woman is – At high risk for endometrial cancer – Using a greater dose of vaginal ET – Having symptoms such as spotting, breakthrough bleeding NAMS position statement. Menopause Vaginal ET: Endometrial Surveillance?

68 HT and Cognition Initiating EPT after age 65 not recommended for primary prevention of dementia or cognitive decline Initiating EPT after age 65 not recommended for primary prevention of dementia or cognitive decline Insufficient evidence to support ET/EPT for primary prevention of dementia when therapy is initiated during perimenopause or early postmenopause Insufficient evidence to support ET/EPT for primary prevention of dementia when therapy is initiated during perimenopause or early postmenopause ET does not appear to convey direct benefit or harm for treatment of Alzheimers disease ET does not appear to convey direct benefit or harm for treatment of Alzheimers disease NAMS position statement. Menopause 2007.

69 HT and Cognition Many women experience worsening of short term memory with onset of menopause Many women experience worsening of short term memory with onset of menopause 9 RCTs and 8 cohort studies 9 RCTs and 8 cohort studies –HT does not improve cognitive performance in women without symptoms –If symptoms, HT improved verbal memory, reasoning, and motor speed tests Reasonable to provide HT to lessen cognitive changes in symptomatic menopausal women Reasonable to provide HT to lessen cognitive changes in symptomatic menopausal women

70 Hormone Therapy and Fracture Prevention Pros Good data on fracture prevention (mainly 2 o prevention) Good data on fracture prevention (mainly 2 o prevention) Relatively lower cost than boisphosphonates Relatively lower cost than boisphosphonates Less concern of adverse effects with ET alone (vs EPT) Less concern of adverse effects with ET alone (vs EPT)Cons Requires long term use and surveillance Requires long term use and surveillance Post-menopausal bleeding can be troublesome Post-menopausal bleeding can be troublesome Increased risk of breast cancer after 5 years of use Increased risk of breast cancer after 5 years of useUtility Fracture prophylaxis if using HT for another indication Fracture prophylaxis if using HT for another indication Otherwise, consider bisphosphonates as first line Otherwise, consider bisphosphonates as first line

71 HT and Quality of Life RCTs and retrospective studies show that HT has no effect on quality of life measures RCTs and retrospective studies show that HT has no effect on quality of life measures Many woman who wean from HT state that they feel worse…even after 20 years after menopause! Many woman who wean from HT state that they feel worse…even after 20 years after menopause! Conventional wisdom Conventional wisdom –In women who feel better on/ worse off of HT, continue low dose HT if few or no risk factors –When (& how often) to re-attempt wean uncertain –Dont start HT for solely for improving QOL

72 The Finale Act 4

73 Discontinuation of HT After 2 years, recommend a trial of HT discontinuation After 2 years, recommend a trial of HT discontinuation Is tapering from hormone therapy necessary? Is tapering from hormone therapy necessary? –Grady D, Obstet Gynecol 2003;102:1233 –n= 377 who attempted discontinuation of HT –74% successfully stopped; 26% resumed –71% stopped abruptly; 29% tapered: equal success Rebound hot flashes occur in some women and can last up to 3 months…many experts recommend a taper Rebound hot flashes occur in some women and can last up to 3 months…many experts recommend a taper Taper hormone therapy over 8-12 weeks Taper hormone therapy over 8-12 weeks –Reduce dose or extend intervals (every 2, then 3 days) –Cut patches in half

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75 If what I just said sounded unusually clear, then you must have misunderstood me Alan Greenspan


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