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Menopause & Hormone Therapy Decisions Lisa Keller, M. D.
Limited goals for the next 45 minutes: u Define the syndrome, physiology, epidemiology. u Symptoms, potential pathophysiology. At-risk groups by age, time from menopause, as well as known risk profiles. u What we know about hormone therapy, what has shifted over the past decade, and where there is consensus. u What we don’t know, what appears likely, and how to synthesize all the above into therapeutic recommendations.
Why menopause? u So there can be grandmothers. Childbearing is a huge physiological burden. u Ovarian follicles: millions as fetus, thousands in youth, none by menopause. u Also CNS aging within the hypothalamic-pituitary axis, still being defined.
Postmenopausal Women in US 100, 000 90, 000 Population 80, 000 Age 65 years 60 -64 years 55 -59 years 50 -54 years 45 -49 years 70, 000 60, 000 50, 000 40, 000 30, 000 20, 000 10, 000 0 2000 2010* 2020* 2030* 2040* Years *Projected estimate. US Census Bureau. Statistical Abstract of the United States. 2000: 15. US Census Bureau. National population projections. Available at: http: //www. census. gov/population/www/projections/natsum-T 3. html. Accessed January 3, 2002. 2050*
Perimenopausal Transition Years 100 Women (%) 75 Reproductive Years 50 Postmenopause 25 0 35 40 45 Age (years) 50 55 60
Perimenopause u Reduction in viable ovarian follicles and follicular resistance to gonadotropins u Erratic hormonal milieu, erratic symptomatology u Although cycle length begins to shorten, potential for ovulation and pregnancy is preserved for a number of years
Menstrual Cycle Changes u Usually shorter cycle length (eg, by 2 to 7 days) u Longer or irregular later in transition u Changes in quality u Lighter volume. If heavier, more likely due to myomata or hyperplasia u Spotting prior to menses is common
Menopause-Related Changes Vasomotor symptoms u Sleep quality u Mood changes u Urogenital symptoms u Sexual well-being u Skin changes u Bone loss u Coronary heart disease (CHD) risk increases u Eye dryness u Joint inflammation u
Hormone Deficiency Effects Last period Vasomotor symptoms Sexual complaints Urogenital atrophy and symptoms Vascular and heart disease Bone loss/osteopenia 40 45 50 55 Osteoporosis 60 65 70 Age (year) 75 80 85 90+
Hot Flushes May Continue Years After Menopause Ages 29 to 82 Years Number of years women report having hot flushes as estimated by a survey of 501 untreated women who experienced hot flushes 0 2 4 6 8 10 12 14 16 18 20 22 24 28 30 Mean age of natural menopause was 49. 5 years; mean age of surgical menopause was 43. 7 years. Kronenberg F. Ann N Y Acad Sci. 1990; 592: 52 -86. Used with permission. 36 41
Non-hormonal Therapies u Herbal therapy — black cohosh, St. John’s wort u Biologically based substances — phytoestrogens: isoflavones from soy protein or red clover (unknown breast effects) u Lifestyle modifications — relaxation, paced respiration, moderate physical activity, modulation of responsibilities, sleep time
Treatment of moderate to severe vasomotor symptoms u Prescription systemic hormone therapy, either as combined estrogen-progestogen therapy (EPT) or estrogen (ET), remains the gold standard for treatment in women without contraindications u Oral contraceptives are an option for perimenopausal women, especially those needing contraception
Genitourinary Symptoms Associated With Menopause Genital Irritation, burning, pruritus Leukorrhea Dyspareunia Decreased vaginal secretions Shortening/lessening of vaginal distensibility Urinary Frequency, urgency Dysuria Nocturia Incontinence* *Controversial.
Vaginal Cytology Premenopause Postmenopause
Risks and Benefits of HT It is known with good certainty that u Changes in the urogenital tract are among the most consistent hypoestrogenic features of the climacteric u HT administered vaginally or systemically provides effective relief from atrophic vaginitis, including reduction in vaginal dryness, irritation, pruritus, and dyspareunia ACOG Task Force on HT. Obstet Gynecol. 2004; 104 (suppl 4): 56 s-61 s.
Effect of Delayed Initiation of HT on Bone Loss Metacarpal Bone Mineral Content (mg/mm) 44 At Oophorectomy 3 Years After Oophorectomy 6 Years After Oophorectomy 42 40 38 36 34 0 2 4 6 8 10 12 14 16 Years Blue area represents placebo-treated population of oophorectomized women. Lindsay R, et al. Lancet. 1976; 1: 1038 -41.
WHI: Reduction in Fracture Risk With E+P and E Alone Hip Vertebral Lower Arm/ Wrist CEE/MPA (95% n. CI) CEE alone (95% n. CI) All Fractures 0. 5 1. 0 Hazard Ratio 2. 0
WHI Fracture Results: Clinical Implications u Women treated with E alone or E+P for menopausal symptoms do not need another antiresorptive agent u HT is the only therapy that has been demonstrated to prevent fractures in a population of postmenopausal women at relatively low risk of fracture ACOG Task Force on HT. Obstet Gynecol. 2004; 104(suppl 4): 66 s-76 s. AACE Osteoporosis Task Force. Endocrine Pract. 2003; 9: 544 -64.
Menopause, HT, & Depression u Several observational studies report increased risk for onset of major depression during perimenopause u Perimenopause seems associated with increased risk of clinically significant depressive illness for subgroup of women u Some prospective studies, although not all, have demonstrated improvements of ~ 80% in newly depressed perimenopausal women started on HT (placebo 20%) u Insufficient evidence to support HT use for depression treatment , but consider in new onset
Contraindications To HT u Estrogen-dependent neoplasms (endometrial carcinoma, hyperplasia, breast cancer), venous or arterial thrombosis, high risk of cardiovascular disease, and/or liver disorders. u Oral conjugated equine estrogen (CEE) significantly increases triglyceride levels. So, oral estrogen therapy is not optimal for women with elevated triglycerides. But these patients may benefit from transdermal estriadol therapy. u Oral estrogen is not recommended for heavy smokers.
Consistent Terminology Urged u ET — Estrogen therapy u EPT — Combined estrogen-progestogen therapy u HT — Hormone therapy (encompassing both ET and EPT) u CC-EPT — Continuous-combined estrogenprogestogen therapy (daily administration of both estrogen and progestogen) u CS-EPT — Continuous-sequential estrogenprogestogen therapy (estrogen daily, with progestogen added on set sequence) u Progestogen — Both progesterone and progestin
Observational Trial Results u 1976: Lowers risk of osteoporosis u 1981: CHD benefit, inconclusive for stroke u 1988: Reduction in mortality u 1994: Reduction in Alzheimer’s risk u Accelerated use of hormone therapy
Women’s Health Initiative (WHI) Clinical Trials of HT u >27, 000 postmenopausal women randomized and enrolled from 1993 to 1998 u Mean age at baseline, ~63 years u Women with vasomotor symptoms discouraged from participating u Primary outcomes: CHD, breast cancer u E+P trial stopped in July 2002 – Breast cancer crossed monitoring boundary u E alone trial stopped February 2004 – Trend toward increased stroke
WHI Limitations u Only one estrogen was used (CEE, alone and with MPA) and only one progestogen (MPA) u Only one route of administration was used (oral) and only one dosage (0. 625 mg/2. 5 mg) u Subjects were: § Older (mean age, 63 years) § Most more than 10 years beyond menopause § Had more risk factors than younger women who typically use HT for menopausal symptoms § Largely asymptomatic
WHI E+P: Absolute Risks & Benefits No Significant Difference in # of Cases Number per Year per 10, 000 Women CEE/MPA Placebo More Cases in E+P Group CHD* Stroke Breast Cancer VTE Fewer Cases in E+P Group PE Endometrial Total Colorectal Hip Cancer Deaths Cancer Fractures
WHI E Alone: Absolute Risks & Benefits Number per Year per 10, 000 Women CEE Placebo More Cases in E Group Strokes Fewer Cases in E Group No Significant Difference in # of Cases VTE CHD Breast Cancer PE Colorectal Cancer Total Deaths Hip Fractures
More Recent WHI Analyses of Younger Women (50 -59 years) u 7% decrease in CHD with ET or EPT (2 fewer cases per 10, 000 per year of use) u 24% increase in breast cancer with EPT (9 more cases per 10, 000 per year of use) u 20% decrease in breast cancer with ET (7 fewer cases per 10, 000 per year of use) u 30% decrease in total mortality with ET or EPT (10 fewer deaths per 10, 000 per year of use) ET = CE; EPT = CE + MPA
WHI: Effect of CEE Alone on Risk of CHD by Age Group Age 50– 59 y 0. 63 0. 94 60– 69 y 1. 11 70– 79 y 0. 0 0. 5 1. 0 1. 5 Dotted vertical line represents the HR for CHD in the overall cohort (0. 95; 95% CI = 0. 79 -1. 16) P =. 07 for interaction with age Hsia J, et al. Arch Intern Med. 2006; 166: 357 -65. 2. 0
Effect of E+P on CHD in Postmenopausal Women Hazard Ratio for CHD Age (years) 0. 0 0. 5 1. 0 1. 5 2. 0 2. 5 3. 0 1. 27 50– 59 1. 05 60– 69 1. 44 70– 79 Years Since Menopause <10 10– 19 >20 Manson JE, et al. N Engl J Med. 2003; 349: 523 -34. Hazard Ratio for CHD 0. 0 0. 5 1. 0 1. 5 2. 0 0. 89 1. 22 1. 71 2. 5 3. 0
WHI Cardiovascular Summary Effects per 10, 000 women/year of ET use (50 -59 yrs) u 10 fewer deaths u 10 fewer CHD events u 2 fewer strokes u 4 additional VTE Effects per 10, 000 women/year of EPT use (<10 years postmenopause) u 6 fewer deaths u 4 fewer CHD events u 5 more strokes u 11 additional VTE
Risks and Benefits of HT It is known with good certainty that u HT does not increase CHD risk in women who initiate therapy close to the onset of menopause (within ~ 9 years of last menses) u HT does not prevent and may increase the risk of CHD in women who initiate therapy years after menopause
WHI HT Trials: Increased Risk of Venous Thromboembolism HR (95% CI) E+P 1 E alone 2 2. 06 (1. 57, 2. 70) 1. 33 (0. 99, 1. 79) 0. 5 1. 0 2. 0 Hazard Ratio 1 Cushman M, et al. JAMA. 2004; 292: 1573 -80. 2 Women's Health Initiative Steering Committee. JAMA. 2004; 291: 1701 -12. 5. 0
Risks and Benefits of HT Additional research of HT on risk of stroke is needed to clarify the effect u Meta-analyses find a small increased risk of stroke in postmenopausal women taking HT u Whether this increased risk is modified by hormone preparation, dose, or route of administration has not been established by randomized controlled trials u The risk of stroke for women taking HT increases with age, but the risk for younger women does not appear to be insignificant (still “rare” by WHO criterion) ACOG Task Force on HT. Obstet Gynecol. 2004; 104(suppl 4): 97 s-105 s.
HT and Venous Thromboembolism u Significant increase in VTE risk in postmenopausal women using systemic HT u Risk increased with both EPT and ET u VTE risk appears during first 1 -2 years after therapy initiation and decreases over time u Transdermal 17ß-estradiol and oral therapies may have different risk u Lower doses of oral estrogens may be safer than higher doses
WHI and Breast Cancer Risk With EPT use u Relative risk = 1. 24 (24% increased risk) u Absolute risk = 9 more cancers per 10, 000 women per year of EPT use With ET use u Relative risk = 0. 80 (20% decreased risk) u Absolute risk = 7 fewer cancers per 10, 000 women per year of ET use u 33% statistically significant decreased risk when adherent to treatment (i. e. , used ET 80% of the time)
Million Women Study: Breast Cancer Relative Risks Mortality 1. 22 Current use 1. 66 Implanted estrogen 1. 65 Transdermal estrogen 1. 24 Oral estrogen 1. 32 Tibolone 1. 45 2 E + P 1. 3 Estrogen only 1 Lancet. 2003; 362: 419 -427. 1. 5 2
European Trials — HT after BCA u One (HABITS) with continuous E+P showed ^ BCA recurrence risk u Other (Scandinavian trial) with ET and only intermittent P, showed 18% < BCA recurrence risk
Risks and Benefits of HT It is known with good certainty that u E+P use >5 years is associated with an increased risk of breast cancer 1, 2 – Absolute risk is small; about 2 additional cases per 1000 women using E+P for 5 years 1 u Use of unopposed E does not increase breast cancer risk in women with previous hysterectomy 3 1 ACOG Task Force on HT. Obstet Gynecol. 2004; 104(suppl 4): 11 s-6 s.
Risks and Benefits of HT Research is ongoing to determine the effects of HT on cognitive function and dementia u Like CHD, findings from observational studies and the WHI do not agree. Stratification by age and the “healthy cell bias” may explain discrepancy u HT initiation in older postmenopausal women appears to increase risk of dementia
HT in the Woman With Premature Ovarian Failure (POF) u POF is associated with premature osteoporosis and increased CV morbidity and mortality u Effective management involves early identification of POF, use of HT to relieve symptoms and prevent osteoporosis, and regular monitoring for associated conditions Nelson LM, et al. Fertil Steril. 2005; 83: 1327 -32.
Conclusions u Extrapolate with caution WHI date when considering risks of HT during or soon after the menopausal transition u Future research is critical to clarify optimal timing and duration of HT u WHI data do not address benefits and risks in women with premature menopause ACOG Task Force on HT. Obstet Gynecol. 2004; 104(suppl 4): 1 s-4 s. North American Menopause Society (NAMS). Menopause. 2003; 10: 497 -506.
Progestins Natural Steroids Found in Nature Laboratory Synthesized Structurally Related to Progesterone Native Synthetic • Progesterone Pregnane Derivatives • MPA • Megestrol acetate • Cyproterone acetate • Chlormadinone acetate • Medrogestone • Dydrogesteron e Synthetic 19 -Norpregnane Derivatives • Nomegestrol acetate • Demegestone • Trimegestone • Promegestone • Nesterone Stanczyk FZ. Rev Endocr Metab Disord. 2002; 3: 211 -24. Ethinylated • Norethindrone • Norethynodrel • Lynestrenol • Norethindrone acetate (NETA) • Tibolone • Ethynodiol acetate • Levonorgestrel • Desogestrel • Norgestimate • Gestodene Structurally Related to Testosterone Non-ethinylated • Dienogest • Drospirenone
EPIC RR [95% CI] Estrogen alone RR = 1. 1 [0. 8 -1. 6] TRANSDERMAL ESTROGENS With micronized progesterone RR = 0. 9 [0. 7 -1. 2] cases = 55 With oral synthetic progestins RR = 1. 4 [1. 2 -1. 7] cases =187 ORAL ESTROGENS With oral synthetic progestins Fournier et al, Int J Cancer, 2004. RR = 1. 5 [1. 1 -1. 9] cases = 80 RR = 1. 5 [1. 1 -1. 9] cases
Medroxyprogesterone Acetate u Most common progestin used in USA u Most intensely studied progestin u Only progestin with substantial data proving ability to prevent endometrial cancer long term u Challenges regarding cardiac, thrombotic and breast effects Gradyan D, Obstet Gynecol. 1995 Feb; 85(2): 304 -13.
Norethindrone Acetate Synthetic, patented in 1950 u Pro-drug, rapidly converted to norethindrone u NETA long half life Most common progestin in EU u NETA converts to ethinyl estradiol u In high dose, 0. 7 - 1% u 6 micrograms EE/1 milligram NETA O O OCCH 2 C CH
Natural Progesterone u Bioidentical u Several formulations u Short half life u No long term safety outcomes CH 3 C O O
Primary Prevention of Coronary Atherosclerosis with CEE and MPA vs Estradiol and Progesterone 0. 3 Coronary Plaque Size (mm 2) 0. 3 0. 2 0. 1 0 No TX CEE + MPA Adams et al. Arterioscler Thromb Vasc Biol. 1997; 17: 217 Adams et al. Arteriosclerosis. 1990; 10: 1051. 0. 2 0. 1 0 No TX E 2 + P
Coronary Artery Vasospasm in Monkeys Treated With E 2 and Progesterone or MPA Parameter E 2 + Progesterone E 2 + MPA Number of vasospasms 0/6 6/6 . 37 ±. 02 . 15 ±. 04 Minimum coronary artery diameter Miyagawa et al. Nature Med. 1997; 3: 324.
Alternative Progestins Brand Name Progestational agent Available doses Dose for Sequential Ovrette® Norgestrel 0. 075 mg 0. 075 - 0. 150 mg 0. 035 mg Micronor® Nor-QD® Norethindrone 0. 35 mg 0. 70 mg 0. 35 mg (0. 25 mg – 1 mg) Climara Pro Levonorgestrel 0. 045 e/ 0. 015 mg day, transdermal NA 0. 045 e/ 0. 015 mg day, transdermal Crinone or Prochieve Progesterone vaginal cream 0. 4 and 0. 8% daily x 10 days 1 applicator (45 mg or 90 mg q 3 -5 days) Prometrium Micronized natural progesterone 100 mg, 200 mg 200 mg/d x 10 d 100 mg N/A ™ Mirena IUC Levonorgesterol 20 mcg/day (5 yrs) Dose for Continuous
Breast vs Endometrial Risk Million Women, Lancet 2005; 365: 1543– 51
Commentary If endometrial and breast cancer are regarded as equally bad events, limiting short-term (3 -5 years) hormone therapy for menopausal management to use of estrogen alone even in women with an intact uterus makes considerable sense. If breast cancer is regarded as clinically more serious than endometrial cancer, this conclusion only becomes stronger. Diana Petitti, MD MPH Kaiser Permanente Southern California, Pasadena, CA, USA This conclusion will generate great controversy and discussion Million Women, Lancet 2005; 365:
Off-Label EPT Uses u Insufficient endometrial safety evidence to recommend off-label use of: § Long-cycle progestogen (ie, progestogen every 3 -6 mo for 12 -14 days) § Vaginal administration of progesterone § The contraceptive levonorgestrel-releasing intrauterine system § Low-dose estrogen without progestogen § Micronized oral progesterone (transdermal noted to not absorb well, not advised) u Close endometrial surveillance recommended with these approaches
Conclusions While implications of recent studies suggest that estrogen alone may be safer than E+P, standard of care remains combined therapy It is also unclear if CCHT or SCHT offers a higher degree of safety Role of progestins in breast cancer is unsettled, but in endometrial cancer its role is crystal clear u Is there such a thing as a good cancer?
Conclusions (cont. ) MPA is the only progestin in the USA with data on long term endometrial safety u Micronized progesterone may offer some superior QOL attributes and cardiovascular protection u Micronized progesterone long term EM safety is not substantiated Newer progestins may offer metabolic profile of micronized progesterone with the potency of MPA
International Prescribing Patterns Products Containing 17 -Estradiol % of Total Rx Products Containing CEE IMS Database.
Rationale for 17 -Estradiol u Biologic effects in reproductive-age women predominantly due to 17 estradiol u Plant sterol derived synthetic mimic of naturally occurring hormone u Extensive international experience u Therapeutic efficacy comparable to other estrogens
Dose and Risk of VTE Birth control pills u 80 mcg > 50 mcg > 35 mcg u Insufficient data on 20 mcg or less u Is the curve linear at the lower end HT u Higher doses appear to carry higher risk u Lowest threshold for risk unknown Interaction with thrombophilias
Transdermal Delivery Systems Avoid liver first pass • Patches Assumptions about TD route being safer than oral delivery • Gels • Creams • Sprays Evamist
Transdermal Estrogen Benefit u Circumventing first-pass metabolism u Non-elevation of triglycerides or high-density lipoproteins u Stable levels of circulating estrogen u Comparable efficacy at lower concentrations u Reduced frequency of dosing u Suitable alternative for women who chose not to use oral medication u Evidence of less thrombogenic potential
HT Therapy and Lipid Levels Oral E+P Transdermal E E+P Total cholesterol LDL-cholesterol HDL-cholesterol ( ) Triglycerides ( ) E+P is estrogen + progestin combination. Parentheses indicate blunted effect relative to unopposed estrogen.
Lipid Profile and ET * CEE 0. 625 mg/d (n=1513) * Oral estradiol 1 mg/d (n=94) * Transdermal estradiol 0. 05 mg/d (n=267) * * * * Total cholesterol * LDL cholesterol HDL cholesterol Triglycerides *P<0. 05 vs. baseline. †Analysis of 248 studies of postmenopausal women. LDL = low-density lipoprotein; HDL = high-density lipoprotein Godsland IF. Fertil Steril. 2001; 75: 898 -915.
Route of Administration u 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 u Possible lower risk of deep venous thrombosis (DVT) with non-oral route u Similar breast cancer risks with oral and transdermal estrogens per large observational study
Testosterone Treatment u Indicated for diminished libido and sexual response in postmenopausal women on ET u Politically charged. No FDA approval yet. u Estra. Test in 2 dosages, is oral Estrone and Methyltestosterone, FDA approved for hot flashes not responsive to ET alone u Particularly helpful in oovariectomized women
Management Recommendations: Before initiating testosterone treatment: u Establish baseline profiles for serum lipids and liver function tests, blood pressure u Consider retesting at 3 months u If stable, annual testing is advised
Management Recommendations: During Testosterone Treatment Testosterone therapy should be administered at the lowest dose for the shortest time that meets treatment goals
Compounded Testosterone Products u Use with caution. Understand transdermal dosage adjustments (2% = 20 mg/gm = 10 x recommended female dosage). Know your pharmacist. u Dosing may be more inconsistent vs. government-approved products
Long-Term Use of Testosterone u Due to insufficient data, conclusions cannot be made regarding the efficacy and safety of testosterone therapy exceeding 6 months u Therapeutic monitoring should include subjective assessments of: § sexual response, desire, and satisfaction and § evaluation for potential adverse effects
Testosterone Contraindications u Similar to those associated with estrogen therapy u Do not initiate testosterone therapy in postmenopausal women with: § Breast or uterine cancer § Cardiovascular disease § Liver disease
Custom-Compounded HT? u Lack of controlled clinical trials of safety and efficacy – No evidence that they are safer – Clinical trials unlikely to be performed because of high cost and lack of patent protection u Compounding is allowable for individual patients unable to tolerate FDA-approved products u Mass production and marketing beyond state lines does not meet federal guidelines u Prescribers are responsible for risk/benefit education Boothby LA, et al. Menopause. 2004; 11: 356 -67.
Saliva and Hair Tests for Hormones u No reference standards available u Lack of correlation with serum levels Data from saliva does not tell you what is going on in the target tissue u u No way to determine appropriate dosing through these tests u Inter- and intrapatient variability u In reality, dosage adjustments based on symptomatology u No evidence to suggest that “individualized estrogen or progesterone regimens” based on these tests increase efficacy or improve safety
Duration of HT Use FDA 20031 u Recommends shortest duration and lowest dose consistent with treatment goals ACOG 20042 u The lowest effective estrogen dose should be used for the shortest possible time to alleviate symptoms NAMS 20043 u Recommends duration and dose consistent with treatment goals
Optimal Dose of Estradiol Optimal dose for vasomotor symptoms u at serum level of 60 pg/ml 50%, 120 pg/ml 100% Optimal dose for bone is the highest dose u 0. 5 mg arrest losses in 60%, while 1 -2 mg superior efficacy Optimal dose for endometrium, breast, triglyceride and coagulation u lowest
Estradiol Therapeutic Range 0 25 50 75 100 125 150 175 Optimal 40 -80 pg/ml Acceptable 35 -125 pg/ml
If you must use Prem. Pro: Standard dose = 0. 625/2. 5 Newer options = 0. 45/1. 5 and 0. 30/1. 5 Less is probably better
Lowest effective dose has yet to be determined for most products CEE 0. 3 mg ♦ 0. 15 mg appears ineffective Oral estradiol 0. 5 mg ♦ 0. 25 mg appears ineffective TD estradiol 25 mcg ♦ 20 mcg in trials
Indications for Extended Use of HT ♦ After informed discussion and with ongoing supervision – For the woman for whom, in her opinion, benefits of symptom relief outweigh risks, notably after failing an attempt to withdraw from HT – For women with moderate-to-severe menopausal symptoms and at high risk for osteoporotic fracture – For prevention of osteoporosis in a high-risk woman when alternate therapies are not appropriate North American Menopause Society. Menopause. 2003; 10: 497 -506.
Discontinuing HT Use ♦ Symptoms have ~50% chance of recurring when HT is discontinued, independent of age and duration of HT use ♦ The decision to continue HT should be individualized, based on severity of symptoms, current risk-benefit ratio considerations, and when the woman in consultation with her healthcare provider believes that continuation is warranted
HT-Related Breakthrough Bleeding u All available continuous-combined E+P regimens are associated with breakthrough bleeding u Less breakthrough bleeding with lower doses u Most postmenopausal women will experience amenorrhea within 1 year of initiating therapy u All bleeding other than withdrawal bleeding should be investigated – Workup can include vaginal sonogram and endometrial biopsy or both – Endometrial sonogram showing 5 mm or more endometrial thickness should be followed by a biopsy
Pretreatment Evaluation u Complete health evaluation including history, lipids u Mammography as per national guidelines and age, preferably within 12 months of therapy u Other specific examinations, (eg, bone densitometry) on a case-by-case basis
Shared Decision-Making on HT u No universal recommendation for all women regarding the use of HT u The decision to use (or not use) HT is a personal one that should be made in consultation with a woman’s health care provider u The decision should be based on a woman’s individual health needs, concerns, and risk factors, taking into account menopauseassociated symptoms and their effect on quality of life
Summary u The benefits of using E+P therapy in healthy early postmenopausal women with symptoms outweigh the risks u Women using E-only have fewer risks than those shown in the E+P arm of the WHI u Alternate estrogens and progestins appear to carry less risk than oral CEE/MPA. Studies ongoing re: formulations, delivery route. u Postmenopausal HT should be prescribed at the lowest dose for the shortest amount of time, consistent with treatment goals
More Info on the Web www. hormonecme. org www. hormone. org www. familydoctor. org www. menopause. org (North American Menopause Society NAMS) www. afwh. org (Alexander Foundation for Women’s Health)