hormone replacement therapy (HRT); estrogen replacement therapy; postmenopausal hormone replacement therapy
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Introduction
Replacement of estrogen in postmenopausal women. (also see estrogen)
Indications
- menopause (see Women's Health Initiative)
- vasomotor symptoms, hot flashes
- 2-3 years duration[17]
- menopausal hormone replacement therapy lowers risk of psychosis relapse in midlife women with schizophrenia or schizoaffective disorder 16%[138]
- osteoporosis*
- for women who cannot tolerate bisphosphonate or raloxifene[17][89]
- USPSTF recommends against estrogen or raloxifene for osteoporosis[79]
- increases bone mineral density[18]
- reduces risk of fracture[18]
- cessation of HRT associated with
- decreased bone mineral density[67]
- increased risk of hip fracture (HR=1.5 after 2 years)
- may prevent age-related hyperkyphosis[120]
- for women who cannot tolerate bisphosphonate or raloxifene[17][89]
- atrophic vaginitis
- low-dose vaginal estrogen[115]
- oral therapy for failure of topical estrogen[17]
- hypogonadism & primary ovarian failure
- premature menopause
- chemotherapy-induced premature ovarian failure[79]
- depression#[5]
- HRT may lower risk for depression in perimenopausal women[119]
- may reduce risk of colon cancer$
- but cancers more advanced at presentation[32]
- no effect on mortality from colon cancer
- may reduce risk of diabetes mellitus[22] {HERS}
- may reduce risk of knee osteoarthritis[123]
- diminished mortality (estrogen alone)[44]
- among women with BSO at hysterectomy, estrogen-only HRT appears to diminish all-cause mortality with long-term follow-up[128]
- hormone replacement therapy treatment with estrogen alone probably slightly improves the sexual function, uncertain whether estrogen combined with progestogens improves sexual function[135]
* estrogen-progestin therapy reduces risks for diabetes mellitus & fractures (hip fracture & vertebral fractures)[70]
* estrogen alone lowers risks for fractures, invasive breast cancer, & mortality mortality[70]
* has NOT been demonstrated to reduce risk of fractures in women > 60 years of age[6]
# effect of different estrogens & of progestins is not clear
$ relative risk 0.63[16]; see Women's Health Initiative[32] Prempro doubles risk of dementia in women > 65[23] (see Womens Health Initiative (WHI) memory study)
May diminish physical function & feeling of well-being in elderly.[11]
Contraindications
- pregnancy, vaginal bleeding, liver disease, coronary artery disease, stroke history of venous thromboembolism, breast cancer, endometrial cancer[79]
- chemotherapy-induced premature menopause is not a contraindication[79]
- estrogen receptor-positive breast cancer*
- HRT after successful treatment for breast cancer is controversial[4] see HABITS trial;
- in women treated for breast cancer, menopausal hormone replacement therapy is not associated with increased risk for either breast cancer recurrence or mortality[133]
- treatment with tamoxifen or aromatase inhibitor
- concurrent vaginal estrogen for atrophic vaginitis[59]
- USPSTF recommends against HRT to prevent chronic disease[72][78][114]
- NOT currently indicated for prevention or treatment of Alzheimer's disease or other dementias[2][23][34][35][52][89]
- may lower risk of Alzheimer's disease if started within 5 years of menopause[73]
- reduces risk for Alzheimer's disease only after 10 years of self-reported use[112]
- NOT beneficial for cardiovascular disease[15][26][30][89]
- may actually increase risk of myocardial infarction#
- does not attenuate progression of coronary artery disease[93]
- 4 years of HRT do not affect carotid intima-media thickness or coronary calcium scores[94]
- HRT slows atherosclerosis (assesed by carotid intima- media thickness) in recently menopausal women but not in those > 10 years past menopause onset[103]
- if 10 year cardiovascular risk is > 10% do NOT prescribe HRT[79]
- women > 60 years of age, unless previous HRT & menopause at median age[79] - may increase cardiovascular risk
- HRT past age 65 is acceptable provided the woman has been advised of increased risks after age 60, she continues to have bothersome symptoms or is unable to use any other appropriate medication, & her clinician has determined that benefits outweigh risks[99]
- does NOT reduce frequency of urinary tract infection[9]
- does NOT help & may worsen urinary incontinence[39]
- any reduced risk for endometrial cancer outweighed by increased risk of breast cancer (see Million Women Study)
- BRAC1 mutation apparently not contraindication[54]
- concurrent statin use not a contraindication[98][136]
- not recommended for prevention of diabetes mellitus
- not beneficial for prevention of sarcopenia[127]
- not recommended for treatment of osteopenia or osteoporosis[79]
* obtain mammogram prior to initiation of therapy[8]
# may diminish risk of acute coronary syndrome in women who begin HRT within a few years of menopause[45] apparent] after 6 years[61];
- risk of adverse coronary events increases with age of starting HRT[50]
Benefit/risk
- no benefit for primary or secondary prevention of cardiovascular events[97]
- number need to harm
- 100 for deep vein thrombosis or pulmonary embolism
- 200 for stroke
- 250 for MI[97]
- symptomatic benefits most likely to outweigh risks when begun <= 60 years of age, or within 10 years of menopause onset[115]
- longer duration of estrogen exposure (endoenous or exogenous) associated with prevention of cognitive impairment[129]
- HRT begun within 5 years of menopause onset associated with better late-life cognitive function vs delayed initiation of HRT[129]
- HRT begun within 3 years of menopause onset not associated with long-term cognitive impairment or benefit[139]
Dosage
- unopposed low-dose oral estrogen if woman has had hysterectomy*
- otherwise estrogen + progestin
- transdermal estradiol is probably treatment of choice
- Premarin 0.625 mg PO QD
- transdermal estradiol modestly improves sexual function in early menopause[117]
- conjugated estrogens do not[117]
- cyclic therapy results in resumption of menses
- continuous therapy
- Provera only in women unable to tolerate estrogens
- larger & smaller doses of estrogen & progesterone are used in special circumstances
- lower dosages may become the standard of treatment[2]
- Premarin 0.3 mg plus Provera 1.5 mg PO QD
- Provera may potentiate benefits of Premarin
- unopposed transdermal estrogen 0.014 mg QD increases bone mineral density 2.1% at lumbar spine after 2 years[37]
- transdermal estrogen with vaginal progesterone may have better safety profile than oral HRT[56][116]
- transdermal estradiol* plus a levonorgestrel-releasing IUD may improve hot flashes, sleep quality, daytime fatigue, & depression[102]
- daily oral conjugated estrogens (0.45 mg) or transdermal estradiol (50 ug) with micronized oral progesterone (200 mg for 12 days each month) effective for hot flashes & night sweats[113]
- disontinuation:
- duration of HTR > 5 years associated with increased risk of breast cancer
- individualized risk assessment for HRT > 5 years[79]
- tapering upon discontinuation
- of no benefit[46][60][83]
- does NOT affect recurrence of menopausal symptoms
- may lessen recurrence of menopausal symptoms[84]
- of no benefit[46][60][83]
- 25% of women report difficulty discontinuing HRT due to withdrawal symptoms[86]
- paraxetine, pregabalin, venlafaxine or clonidine may diminish hot flashes during tapering of HRT[109]
- duration of HTR > 5 years associated with increased risk of breast cancer
* transdermal estradiol 75 mg daily
* estradiol alone in women with prior hysterectomy doubles risk of ovarian cancer & increases mortality in postmenopausal women[137]
Adverse effects
- estrogen-progestin therapy increases risk for
- breast cancer[132]
- invasive breast cancer (> 5 years of HRT)
- all types of HRT except vaginal estrogen associated with increased risk for breast cancer
- stroke
- venous thromboembolism (VTE)
- statins may reduce risk[95]; no plausible mechanism
- oral HRT but not transdermal estrogen increases risk of VTE[124]
- lung cancer mortality[88]
- gallbladder disease
- dementia
- urinary incontinence[70]
- risk of fatal & nonfatal malignancies persists 3 years after cessation of HRT[87]
- conjugated equine estrogens plus medroxyprogesterone does not increase ovarian cancer or endometrial cancer mortality at 20 years[137]
- breast cancer[132]
- increased growth of estrogen-dependent breast cancer*
- 3-fold increased risk of lobular breast cancer[12]
- NO increased risk of breast cancer if < 5 years of HRT[13]
- risk increases with duration of HRT[66]
- increased risk of breast cancer if > 4 years of HRT[14]
- relative risk of breast cancer 1.66, women age 50-64[28]
- all types of estrogens & progestins increase risk of breast cancer[29] identified[58]
- risk greatest with estrogen-progestin combinations[66]
- increased mortality associated with combined use of estrogen plus progestin (HR = 2.0)[63][64]
- estrogen-progestin hormone therapy close to the time of menopause is associated with highest breast cancer risk[74]
- relative risk of breast cancer = 1.42 after 20 years of unapposed estrogen in women s/p hysterectomy[25], relative risk 0.8 in another study, although node+ cancers were increased & need for mammography increased
- a window of time after menopause during which HRT can confidently be considered to be free of risk has not been
- risk declines after cessation of HRT; returns to baseline in 3 years[66]
- black women, obese women, & women with less dense breast may be at less risk of developing breast cancer associated with HRT[76]
- estrogen alone increases risks for
- stroke
- deep vein thrombosis
- gallbladder disease
- urinary incontinence[70]
- endometrial cancer[85]
- ovarian cancer in women with prior hysterectomy (2-fold risk)[137]
- mortality in postmenopausal women with prior hysterectomy[137]
- breast tenderness (40% 1st year, 13% 4th year of HRT)
- interference with mammograms
- continuous Progestin increases breast tissue radiographic density interfering with sensitivity of mammography for detecting breast cancer[25]
- increased false positive mammograms regardless of estrogen alone or estrogen + progestin[36]
- increased risk of ovarian cancer[47][57][96]
- excess risk 0.1%[96]
- increased risk for serous or endometrioid ovarian carcinoma[104]
- does not decrease survival among women receiving treatment for nonserous ovarian carcinoma[104]
- vaginal bleeding
- increased risk of thromboembolism
- transdermal estrogen not associated with increased risk[124]
- increased mortality in non-small cell lung cancer
- increased cardiovascular risk seems linked to progestin
- increased risk of thrombosis, myocardial infarction* & stroke* within 1st 2 years of use, even in women without heart disease[14][51]
- platelet polymorphisms in platelet glycoproteins may predict risk[49]
- conjugated equine estrogens associated with a higher risk of venous thrombosis & possibly MI than estradiol[77]
- increased risk of stroke (relative risk: 1.41)[50]
- neither benefit or harm of HRT after myocardial infarction[68]
- in early menopause, 10 years of hormone therapy might lower risk for cardiac events without raising risk for cancer, thrombosis, or stroke[71]
- transdermal estrogen lower risks for cardiovascular disease[90]
- low-dose conjugated equine estrogens lowers risk of cardiovascular disease & cardiovascular mortality[90]
- oral estradiol lowers risk for stroke[90]
- stopping HRT increases cardiovascular risk[100]
- no increase in overall mortality (+/- hysterectomy)[118]
- increased risk of gall bladder disease (cholecystitis)[18][38]
- increased risk or urinary incontinence[17][23][43]
- lupus flares ?[41]
- increased risk of GERD[53]
- increased risk of acute pancreatitis (RR=1.9)[80]
- cognitive impairment
- cognitive decline may be associated with HRT-related decreases in hippocampal & frontal lobe volumes[55]
- HRT in midlife may decrease risk for dementia, but HRT in later life increases risk of dementia[65]
- HRT at age 50-55 years is not associated with increased risk of cognitive impairment[75]
- whether initiated early or late after menopause, hormone replacement therapy does not affect cognition[111]
- HRT may be associated with a slight increase in risk for Alzheimer disease (18.6% vs 17.0%)[125]
- HRT increases risk of dementia 20 vs 16 cases per 1000 womeen within 12 years[134]
* absolute risks are small; 7 more MI, 8 more strokes & 8 more <A13981>breast cancers</A13981> per 10,000 women per year;only continuous, combined (estrogen + progestin) found associated with breast cancer[20]
* from the Women's Health Initiative[31]
- women taking Prempro have a high risk of heart disease, breast cancer, stroke & dementia[31]
- premarin alone does NOT increase the risk of heart disease or breast cancer, but does increase the risk of stroke[31][33]
Drug interactions
- check thyroid function studies in patients receiving synthroid (T4) 12 weeks after initiating HRT#[1]
- estrogen may be synergistic with bisphosphonates in increasing bone density[3]
- statins may diminish risk of venous thromboembolism[136]
# estrogen increases serum thyroxine-binding globulin (TBG)
Laboratory
- serum estradiol not routine
Mechanism of action
- benefits on bone density
- still observed if started in women > 60 years of age[10]
- 6% gain after 3 years at spine[19]
- 4% gain after 3 years at femoral neck (hip)[19]
- 2/3 of gain at spine & femoral neck lost after 2 years off HRT
- diminished risk of hip fracture (estrogen only[33])
- estrogen therapy improves insulin-stimulated glucose uptake among women in early menopause but impairs this in women > 10 years past menopause
- diminished mortality[44]
- 56.4 per 1000 person-years among nonusers, 52.8 among all users, 50.4 among those who used estrogen for 15 years or longer
- HRT slows atherosclerotic plaque progression in recently menopausal women but has neutral or adverse effects in women >= 10 years post menopause[122]
- favorable vascular effects of estradiol appear limited to women without atherosclerosis at menopause[122]
Notes
- cessation of HRT
- 2-3 years after stopping HRT, relative risks compared with women who did not use HRT
- mortality same
- breast cancer same
- cardiovascular risk same
- fractures same
- deep vein thrombosis same[17]
- use of HRT in Norway declined abruptly following publication of the WHI results in 2002, & rates have remained low[91]
- HRT use in France in higher than Norway[91]
- only markedly supraphysiologic testosterone levels enhance sexuality, lean body mass, & muscle strength in women receiving HRT[92]
More general terms
More specific terms
Additional terms
- Heart & Estrogen/Progestin Replacement Study (HERS)
- menopause
- Million Women Study
- Study of Osteoporotic Fractures (SOF)
References
- ↑ 1.0 1.1 Journal Watch 21(13):106, 2001 Arafah BM et al Increased need for thyroxine in women with hypothyroidism during estrogen therapy N Engl J Med 344:1743, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11396440
- ↑ 2.0 2.1 2.2 Journal Watch 21(13):106, 2001 Archer DF et al Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil Steril 75:1080 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11384630
Utian WH et al Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 75:1065 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11384629 - ↑ 3.0 3.1 Journal Watch 21(13):107, 2001 Harris ST et al Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol 86:1890, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11344179
- ↑ 4.0 4.1 Journal Watch 21(13):107, 2001 O'Meara ES et al Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst 93:754, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11353785
- ↑ 5.0 5.1 Journal Watch 21(15):125, 2001 Soares CM et al Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 58:529, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11386980
- ↑ 6.0 6.1 Journal Watch 21(14):112, 2001 Torgerson DJ & Bell-Syer SE Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 285:2891, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11401611
- ↑ Grady D & Cummings SR Postmenopausal hormone therapy for prevention of fractures: how good is the evidence? JAMA 285:2909, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11401615
- ↑ 8.0 8.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 9.0 9.1 Journal Watch 22(2):18, 2002 Brown JS et al Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol 98:1045, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11755552
- ↑ 10.0 10.1 Journal Watch 22(3):222, 2002 Cauley JA et al Timing of estrogen replacement therapy for optimal osteoporosis prevention. J Clin Endocrinol Metab 86:5700, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11739424
- ↑ 11.0 11.1 Journal Watch 22(6):49, 2002 Hlatky MA et al Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA 287:591, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11829697
Rexrode LM & Manson JE Postmenopausal hormone therapy and quality of life: no cause for celebration. JAMA 287:641, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11829704 - ↑ 12.0 12.1 Journal Watch 22(7):53, 2002 Chen CL et al Hormone replacement therapy in relation to breast cancer. JAMA 287:734, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11851540
- ↑ 13.0 13.1 Prescriber's Letter 9(6):35 2002
- ↑ 14.0 14.1 14.2 Prescriber's Letter 9(8):43 2002
- ↑ 15.0 15.1 Journal Watch 22(16):123, 2002 Grady D et al Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:49, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12090862
Hulley S et al Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:58, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12090863 - ↑ 16.0 16.1 Journal Watch 22(16):123, 2002 Rossouw JE for the Writing Group for the Women's Health Initiative Investigators Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288:321, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12117397
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004; 7th edition 2010
- ↑ 18.0 18.1 18.2 18.3 Journal Watch 22(24):182, 2002 US Preventive Services Task Force Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med 137:834, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12435221
Nelson HD et al Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002 Sep 17;137(6):529-41. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12230356 <Internet> http://www.ahrq.gov/clinic/3rduspstf/hrt/hrtsum1.htm - ↑ 19.0 19.1 19.2 Journal Watch 23(1):10, 2003 Gallagher JC et al Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab 87:4914, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12414850
- ↑ 20.0 20.1 Journal Watch 23(3):27, 2003 Weiss LK et al Hormone replacement therapy regimens and breast cancer risk(1). Obstet Gynecol 100:1148, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12468157
- ↑ Journal Watch 23(3):28, 2003 Barnabei VM et al Menopausal symptoms in older women and the effects of treatment with hormone therapy. Obstet Gynecol 100:1209, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12468165
- ↑ 22.0 22.1 Journal Watch 23(4):34, 2003 Kanaya AM et al Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 138:1, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12513038
- ↑ 23.0 23.1 23.2 23.3 Prescriber's Letter 10(6):33 2003 Journal Watch 23(13):101, 2003 Shumaker SA et al Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2651, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12771112
Rapp SR et al Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2663, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12771113
Wassertheil-Smoller S et al Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 289:2673, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12771114
Yaffe K Hormone therapy and the brain: deja vu all over again? JAMA 289:2717, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12771119 - ↑ Journal Watch 23(11):85, 2003 Grady D et al Postmenopausal hormones--therapy for symptoms only. N Engl J Med 348(19):1835, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12642636
- ↑ 25.0 25.1 25.2 Prescriber's Letter 10(8):47 2003
- ↑ 26.0 26.1 Journal Watch 23(17):133, 2003 Hodis HN et al Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med 349:535, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12904518
- ↑ Journal Watch 23(17):133, 2003 Manson JE et al Estrogen plus progestin and the risk of coronary heart disease N Engl J Med 349:523, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12904517
- ↑ 28.0 28.1 Journal Watch 23(19):149, 2003 Massachussetss Medical Society http://www.jwatch.org
- ↑ 29.0 29.1 Journal Watch 24(1):4-5, 2004 Beral V et al for the Million Women Study Collaborators Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362:419, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12927427
- ↑ 30.0 30.1 Prescriber's Letter 11(3):16 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200315&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 31.0 31.1 31.2 31.3 What Should I Do About My Hormone Therapy? Prescriber's Letter 11(4):23 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200413&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 32.0 32.1 32.2 Journal Watch 24(7):58-59, 2004 Chlebowski RT et al Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 350:991, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14999111
- ↑ 33.0 33.1 33.2 Journal Watch 24(10):77, 2004 Anderson GL, Limacher M, Assaf AR et al for the Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15082697
- ↑ 34.0 34.1 Estrogen-Alone Hormone Therapy Could Increase Risk of Dementia in Older Women (ADEAR News release) http://www.alzheimers.org/nianews/nianews66.html
Prescriber's Letter 11(8): 2004 Estrogen-alone Hormone Therapy Could Increase Risk of Dementia in Older Women Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200811&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 35.0 35.1 Journal Watch 24(15):118, 2004 Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogan PE, Wallace R, Dailey M, Freeman R, Hays J; Women's Health Initiative Memory Study. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):2959-68. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15213207
Shumaker SA et al Women's Health Initiative Memory Study. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):2947-58. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15213206
Schneider LS. Estrogen and dementia: insights from the Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):3005-7. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15213214 - ↑ 36.0 36.1 Journal Watch 24(16):130, 2004 Banks E, Reeves G, Beral V, Bull D, Crossley B, Simmonds M, Hilton E, Bailey S, Barrett N, Briers P, English R, Jackson A, Kutt E, Lavelle J, Rockall L, Wallis MG, Wilson M, Patnick J. Impact of use of hormone replacement therapy on false positive recall in the NHS breast screening programme: results from the Million Women Study. BMJ. 2004 May 29;328(7451):1291-2. No abstract available. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15166064 <Internet> http://bmj.bmjjournals.com/cgi/content/full/328/7451/1291
- ↑ 37.0 37.1 Journal Watch 24(22):161, 2004 Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, Vittinghoff E, Grady D. Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial. Obstet Gynecol. 2004 Sep;104(3):443-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15339752
- ↑ 38.0 38.1 Journal Watch 25(4):29, 2005 Cirillo DJ et al Effect of estrogen therapy on gallbladder disease. JAMA. 2005 Jan 19;293(3):330-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15657326
- ↑ 39.0 39.1 Prescriber's Letter 12(4): 2005 Hormone Therapy for Urinary Incontinence Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210412&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Journal Watch 25(13):104, 2005 U.S. Preventive Services Task Force. Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. Ann Intern Med. 2005 May 17;142(10):855-60. Summary for patients in: Ann Intern Med. 2005 May 17;142(10):I59. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15897536 <Internet> http://www.ahrq.gov/clinic/uspstf05/ht/htpostmenrs.htm http://www.ahrq.gov/clinic/3rduspstf/hrt/hrtsum1.htm Corresponding NGC guideline withdrawn Jan 2013
[No authors listed] Free Full Text Summaries for patients. Hormone therapy to prevent chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. Ann Intern Med. 2005 May 17;142(10):I59. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15897529 - ↑ 41.0 41.1 Journal Watch 25(16):131, 2005 Buyon JP, Petri MA, Kim MY, Kalunian KC, Grossman J, Hahn BH, Merrill JT, Sammaritano L, Lockshin M, Alarcon GS, Manzi S, Belmont HM, Askanase AD, Sigler L, Dooley MA, Von Feldt J, McCune WJ, Friedman A, Wachs J, Cronin M, Hearth-Holmes M, Tan M, Licciardi F. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):953-62. Summary for patients in: Ann Intern Med. 2005 Jun 21; 142(12 Pt 1):I22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15968009
- ↑ Brunner RL et al; Women's Health Initiative Investigators. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial. Arch Intern Med. 2005 Sep 26;165(17):1976-86. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16186467
- ↑ 43.0 43.1 Steinauer JE et al Postmenopausal hormone therapy: does it cause incontinence? Obstet Gynecol. 2005 Nov;106(5):940-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16260510
- ↑ 44.0 44.1 44.2 Paganini-Hill A et al Menstrual and reproductive factors and fracture risk: the Leisure World Cohort Study. J Womens Health (Larchmt). 2005 Nov;14(9):808-19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16313208
- ↑ 45.0 45.1 Hsia J et al Conjugated Equine Estrogens and Coronary Heart Disease: The Women's Health Initiative. Arch Intern Med. 2006 Feb 13;166(3):357-65. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16476878
Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt). 2006 Jan-Feb;15(1):35-44. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16417416
Mikkola TS, Clarkson TB. Coronary heart disease and postmenopausal hormone therapy: conundrum explained by timing? J Womens Health (Larchmt). 2006 Jan-Feb;15(1):51-3. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16417418 - ↑ 46.0 46.1 Haimov-Kochman R et al, Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: A randomized prospective study. Menopause 2006; 13:370 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16735933
- ↑ 47.0 47.1 Lacey JV Jr et al, Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 2006, 98:1397 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17018786
- ↑ Menopausal Hormone Therapy Update: The bioidentical hormone controversy and new products Elestrin and Angeliq Prescriber's Letter 14(2): 2007 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230211&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 49.0 49.1 Bray PF et al, Effect of genetic variations in platelet glycoproteins Ib-alpha and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy. Blood 2007, 109:1862 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17105818
- ↑ 50.0 50.1 50.2 Roussouw JE et al, Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007, 297:1465 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17405972
- ↑ 51.0 51.1 Vickers MR et al; WISDOM group. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ. 2007 Aug 4;335(7613):239. Epub 2007 Jul 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17626056
- ↑ 52.0 52.1 Petitti DB et al, Incidence of dementia in long-term hormone users. Am J Epidemiol 2008, 167:692 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18218608
- ↑ 53.0 53.1 Jacobson BC et al. Postmenopausal hormone use and symptoms of gastroesophageal reflux. Arch Intern Med 2008 Sep 8; 168:1798. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18779468
- ↑ 54.0 54.1 Eisen A et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst 2008 Oct 1; 100:1361. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18812548
- ↑ 55.0 55.1 Coker LH et al Postmenopausal hormone therapy and subclinical cerebrovascular disease. The WHIMS-MRI study. Neurology 2009 Jan 13; 72:125. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19139363
Resnick SM et al. Postmenopausal hormone therapy and regional brain volumes. The WHIMS-MRI study. Neurology 2009 Jan 13; 72:135. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19139364 - ↑ 56.0 56.1 Langrish JP et al Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Hypertension 2009 May; 53:805. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19332659
Canonico M et al Hormone therapy and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration and progestogens: The ESTHER study. Circulation 2007 Feb 20; 115:840-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17309934 - ↑ 57.0 57.1 Morch LS Hormone Therapy and Ovarian Cancer JAMA. 2009;302(3):298-305. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19602689 <Internet> http://jama.ama-assn.org/cgi/content/short/302/3/298?home
- ↑ 58.0 58.1 The Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA 2004 Apr 14; 291:1701. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15082697
Rossouw JE et al Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007 Apr 4; 297:1465. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17405972
Manson JE and Bassuk SS. Invited commentary: Hormone therapy and risk of coronary heart disease - Why renew the focus on the early years of menopause? Am J Epidemiol 2007 Sep 1; 166:511. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17646204
Barrett-Connor E. Hormones and heart disease in women: The timing hypothesis. Am J Epidemiol 2007 Sep 1; 166:506. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17849510
Prentice RL et al Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 2009 Jul 1; 170:12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19468079
Banks E and Canfell K. Invited commentary: Hormone therapy risks and benefits - The Women's Health Initiative findings and the postmenopausal estrogen timing hypothesis. Am J Epidemiol 2009 Jul 1; 170:24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19468078 - ↑ 59.0 59.1 Chlebowski RT et al Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): A post-hoc analysis of a randomised controlled trial. Lancet 2009 Oct 10; 374:1243. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19767090
- ↑ 60.0 60.1 Lindh-Astrand L et al. A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms. Menopause 2010 Jan/Feb; 17:72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19675505
- ↑ 61.0 61.1 Toh S et al. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: Does the increased risk ever disappear? A randomized trial. Ann Intern Med 2010 Feb 16; 152:211. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20157135
- ↑ Prescriber's Letter 17(6): 2010 COMMENTARY: Postmenopausal Hormone Therapy and Cancer Risk CHART: Postmenopausal Hormone Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260609&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 63.0 63.1 The NNT: Hormone Replacement Therapy (HRT) and Relation to Risk of Breast Cancer. http://www.thennt.com/nnt/hormone-replacement-therapy-and-breast-cancer-risk/
Chlebowski RT et al Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women JAMA. 2010;304(15):1684-1692. doi:10.1001/jama.2010.1500 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20959578 <Internet> http://jama.ama-assn.org/cgi/content/short/304/15/1684 - ↑ 64.0 64.1 Prescriber's Letter 17(12): 2010 COMMENTARY: Postmenopausal Hormone Therapy and Cancer Risk CHART: Postmenopausal Hormone Therapy PATIENT HANDOUT: What Should I Do About My Hormone Therapy? Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=261206&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 65.0 65.1 Whitmer RA et al. Timing of hormone therapy and dementia: The critical window theory revisited. Ann Neurol 2010 Nov 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21077179
- ↑ 66.0 66.1 66.2 66.3 Beral V et al Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy J Natl Cancer Inst 2011;103:296-305 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21278356 <Internet> http://www.oxfordjournals.org/our_journals/jnci/press_releases/beraldjq527.pdf
Chlebowski RT and Anderson GL The Influence of Time From Menopause and Mammography on Hormone Therapy-Related Breast Cancer Risk Assessment J Natl Cancer Inst 2011; Jan 28 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21278357 <Internet> http://jnci.oxfordjournals.org/content/early/2011/01/28/jnci.djq561.full.pdf+html - ↑ 67.0 67.1 Karim R et al. Hip fracture in postmenopausal women after cessation of hormone therapy: Results from a prospective study in a large health management organization. Menopause 2011 Nov; 18:1172. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21775911
- ↑ 68.0 68.1 Bretler D-M et al. Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events: Nationwide cohort study. BMJ 2012 Mar 27; 344:e1802 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22453184
- ↑ Prescriber's Letter 19(5): 2012 Postmenopausal Hormone Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280506&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 70.0 70.1 70.2 70.3 70.4 Nelson HD et al Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendations Annals of Internal Medicine, May 28, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22641231 <Internet> http://www.annals.org/content/early/2012/05/23/0003-4819-157-2-201207170-00466.full
- ↑ 71.0 71.1 Schierbeck LL et al Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial BMJ 2012;345:e6409 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23048011 <Internet> http://www.bmj.com/content/345/bmj.e6409
- ↑ 72.0 72.1 Moyer VA et al Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: U.S. Preventive Services Task Force Recommendation Statement Ann Intern Med. 23 October 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23090711 <Internet> http://annals.org/article.aspx?articleid=1384872
- ↑ 73.0 73.1 Shao H et al Hormone therapy and Alzheimer disease dementia New findings from the Cache County Study PMID: https://www.ncbi.nlm.nih.gov/pubmed/23100399 Neurology, Oct 24 2012 http://www.neurology.org/content/early/2012/10/24/WNL.0b013e318271f823.abstract
Henderson VW and Rocca WA Estrogens and Alzheimer disease risk: Is there a window of opportunity? Neurology, October 24, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23100400 <Internet> http://www.neurology.org/content/early/2012/10/24/WNL.0b013e318271f88f.excerpt - ↑ 74.0 74.1 Chlebowski RT et al. Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative observational study. J Natl Cancer Inst 2013 Apr 17; 105:526 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23543779
- ↑ 75.0 75.1 Espeland MA et al Long-Term Effects on Cognitive Function of Postmenopausal Hormone Therapy Prescribed to Women Aged 50 to 55 Years. JAMA Intern Med. 2013;():1-8 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23797469 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1700432
- ↑ 76.0 76.1 Hou N et al Hormone Replacement Therapy and Breast Cancer: Heterogeneous Risks by Race, Weight, and Breast Density. JNCI J Natl Cancer Inst (2013) Sept 3 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24003037 <Internet> http://jnci.oxfordjournals.org/content/early/2013/08/26/jnci.djt207.abstract
Terry MB and Tehranifar P Hormone Replacement Therapy and Breast Cancer Risk: More Evidence for Risk Stratification? JNCI J Natl Cancer Inst (2013) Sept 3 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24003038 <Internet> http://jnci.oxfordjournals.org/content/early/2013/08/26/jnci.djt239.extract - ↑ 77.0 77.1 Smith NL et al Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens. JAMA Intern Med. Published online September 30, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24081194 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1741892
- ↑ 78.0 78.1 Manson JE et al Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women's Health Initiative Randomized Trials. JAMA. 2013;310(13):1353-1368 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2408492 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1745676
Nabel EG The Women's Health Initiative - A Victory for Women and Their Health. JAMA. 2013;310(13):1349-1350 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24084919 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1745653 - ↑ 79.0 79.1 79.2 79.3 79.4 79.5 79.6 79.7 79.8 Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19 American College of Physicians, Philadelphia 2012, 2015, 2021
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 80.0 80.1 Oskarsson V et al Postmenopausal hormone replacement therapy and risk of acute pancreatitis: a prospective cohort study. CMAJ January 27, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24468693 <Internet> http://www.cmaj.ca/content/early/2014/01/27/cmaj.131064.full.pdf+html
- ↑ Prescriber's Letter 21(3): 2014 Postmenopausal Hormone Therapy CHART: Postmenopausal Hormone Therapy COMMENTARY: Nonhormonal Therapy for Hot Flashes COMMENTARY: New Drug: Osphena (Ospemifene) SPECIAL REPORT: Natural Medicines in the Clinical Management of Menopausal Symptoms Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300310&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Santen RJ, Allred DC, Ardoin SP et al Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab. 2010 Jul;95(7 Suppl 1):s1-s66. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20566620
- ↑ 83.0 83.1 Aslan E, Bagis T, Kilicdag EB, Tarim E, Erkanli S, Kuscu E. How best is to discontinue postmenopausal hormone therapy: immediate or tapered? Maturitas. 2007 Jan 20;56(1):78-83. Epub 2006 Oct 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17046182
- ↑ 84.0 84.1 Haskell SG, Bean-Mayberry B, Gordon K. Discontinuing postmenopausal hormone therapy: an observational study of tapering versus quitting cold turkey: is there a difference in recurrence of menopausal symptoms? Menopause. 2009 May-Jun;16(3):494-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19182695
- ↑ 85.0 85.1 Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005 Apr 30-May 6;365(9470):1543-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15866308
- ↑ 86.0 86.1 Grady D, Ettinger B, Tosteson AN Predictors of difficulty when discontinuing postmenopausal hormone therapy. Obstet Gynecol. 2003 Dec;102(6):1233-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14662209
- ↑ 87.0 87.1 Heiss G, Wallace R, Anderson GL Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008 Mar 5;299(9):1036-45. doi:http://dx.doi.org/ 10.1001/jama.299.9.1036. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18319414
- ↑ 88.0 88.1 Chlebowski RT1, Schwartz AG, Wakelee H Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009 Oct 10;374(9697):1243-51 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19767090
- ↑ 89.0 89.1 89.2 89.3 Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012 Jul 11;7:CD004143 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22786488
Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Trial does not change the conclusions of Cochrane review of long term hormone therapy for perimenopausal and postmenopausal women. BMJ. 2012 Dec 3;345:e8141; author reply e8164. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23208255 - ↑ 90.0 90.1 90.2 90.3 Shufelt CL et al. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: Findings from the Women's Health Initiative Observational Study. Menopause 2014 Mar; 21:260. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24045672
- ↑ 91.0 91.1 91.2 Espen Gjelsvik B, Straand J, Hunskaar S, Dalen I, Rosvold EO. Use and discontinued use of menopausal hormone therapy by healthy women in Norway: The Hordaland Women's Cohort study. Menopause 2014 May; 21:459 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23982111 <Internet> http://journals.lww.com/menopausejournal/pages/articleviewer.aspx?year=2014&issue=05000&article=00006&type=abstract
- ↑ 92.0 92.1 Huang G et al. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: Effects on sexual function, body composition, muscle performance and physical function in a randomized trial. Menopause 2014 Jun; 21:612. PMID:24281237
- ↑ 93.0 93.1 Harman SM et al Arterial Imaging Outcomes and Cardiovascular Risk Factors in Recently Menopausal Women: A Randomized Trial. Ann Intern Med. Published online 29 July 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25069991 <Internet> http://annals.org/article.aspx?articleid=1891628
- ↑ 94.0 94.1 Harman SM et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: A randomized trial. Ann Intern Med 2014 Aug 19; 161:249. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25069991
- ↑ 95.0 95.1 Fournier JP et al. Concurrent use of statins and hormone therapy and risk of venous thromboembolism in postmenopausal women: a population-based case-control study. Menopause 2014 Sep; 21:1023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24937027
- ↑ 96.0 96.1 96.2 Collaborative Group on Epidemiological Studies of Ovarian Cancer Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. The Lancet. February 12, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25684585 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961687-1/abstract
- ↑ 97.0 97.1 97.2 The NNT: Hormone Replacement Therapy for Cardiovascular Prevention of a First Heart Attack or Stroke. http://www.thennt.com/nnt/hormone-replacement-therapy-for-cardiovascular-prevention-of-a-first-heart-attack-or-stroke/
The NNT: Hormone Replacement Therapy For Cardiovascular Prevention (After Prior Heart Attack or Stroke) http://www.thennt.com/nnt/hormone-replacement-therapy-for-cardiovascular-prevention-after-prior-heart-attack-or-stroke/
Main C, Knight B, Moxham T et al Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2013 Apr 30;4:CD002229 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23633307 - ↑ 98.0 98.1 Berglind IA et al. Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins. Menopause 2015 Apr; 22:369. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25335101
Hodis HN and Mack WJ. Hormone therapy and risk of all-cause mortality in women treated with statins. Menopause 2015 Apr; 22:363 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25756694 - ↑ 99.0 99.1 North American Menopause Society. The North American Menopause Society statement on continuing use of systemic hormone therapy after age 65. Menopause 2015 Jul; 22:693. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26035150
Gass ML, Maki PM, Shifren JL et al. NAMS supports judicious use of systemic hormone therapy for women aged 65 years and older. Menopause 2015 Jul; 22:685-686. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26035151 - ↑ 100.0 100.1 100.2 Mikkola TS et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab 2015 Sep 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26414962
- ↑ Pereira RI, Casey BA, Swibas TA et al Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action. J Clin Endocrinol Metab. 2015 Dec;100(12):4456-62. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26425886
- ↑ 102.0 102.1 Santoro N, Teal S, Gavito C et al Use of a levonorgestrel-containing intrauterine system with supplemental estrogen improves symptoms in perimenopausal women: a pilot study. Menopause. 2015 Dec;22(12):1301-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26575111
- ↑ 103.0 103.1 Hodis HN, Mack WJ, Henderson VW et al Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med 2016; 374:1221-1231. March 31, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27028912 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1505241
Keaney JF Jr, Solomon CG Postmenopausal Hormone Therapy and Atherosclerosis - Time Is of the Essence. N Engl J Med 2016; 374:1279-1280. March 31, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27028919 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1602846 - ↑ 104.0 104.1 104.2 Lee AW, Ness RB, Roman LD et al Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk. Obstet Gynecol. 2016 May;127(5):828-36. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27054934
Power L, Lefas G, Lambert P et al Hormone Use After Nonserous Epithelial Ovarian Cancer: Overall and Disease-Free Survival. Obstet Gynecol. 2016 May;127(5):837-47. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27054933 - ↑ Manson JE. Current recommendations: what is the clinician to do? Fertil Steril. 2014 Apr;101(4):916-21. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24680650
- ↑ Manson JE, Chlebowski RT, Stefanick ML et al Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013 Oct 2;310(13):1353-68. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24084921 Free PMC Article
- ↑ North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012 Mar;19(3):257-71 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22367731 (corresponding NGC guideline withdrawn Feb 2018)
- ↑ Sweetland S, Beral V, Balkwill A et al Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost. 2012 Nov;10(11):2277-86. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22963114 Free Article
- ↑ 109.0 109.1 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
- ↑ Cunha EP, Azevedo LH, Pompei LM et al Effect of abrupt discontinuation versus gradual dose reduction of postmenopausal hormone therapy on hot flushes. Climacteric. 2010 Aug;13(4):362-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20151792
- ↑ 111.0 111.1 Henderson VW et al. Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology 2016 Jul 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27421538
- ↑ 112.0 112.1 Imtiaz B, Tuppurainen M, Rikkonen T et al. Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study. Neurology 2017 Feb 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28202700 <Internet> http://www.neurology.org/content/early/2017/02/15/WNL.0000000000003696
- ↑ 113.0 113.1 Santoro N et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: The Kronos Early Estrogen Prevention Study. Menopause 2017 Mar; 24:238. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27779568 <Internet> http://insights.ovid.com/crossref?an=00042192-201703000-00003
- ↑ 114.0 114.1 USPSTF Draft Recommendation Statement May 2017 Menopausal Hormone Therapy: Primary Prevention of Chronic Conditions. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/menopausal-hormone-therapy-preventive-medication1
US Preventive Services Task Force Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women. US Preventive Services Task Force Recommendation Statement. JAMA. 2017;318(22):2224-2233 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29234814 https://jamanetwork.com/journals/jama/fullarticle/2665782
Gartlehner G, Patel SV, Feltner C et al Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal WomenEvidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2017;318(22):2234-2249 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29234813 https://jamanetwork.com/journals/jama/fullarticle/2665781
Lewis CE, Wellons MF Menopausal Hormone Therapy for Primary Prevention of Chronic Disease. JAMA. 2017;318(22):2187-2189 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29234792 https://jamanetwork.com/journals/jama/fullarticle/2665758
Grady D Evidence for Postmenopausal Hormone Therapy to Prevent Chronic Conditions. Success, Failure, and Lessons Learned. JAMA Intern Med. Published online Dec 12, 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29234779 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2665666
Wenger NK Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions. Unfulfilled Expectations. JAMA Cardiol. Published online December 12, 2017. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29234780 https://jamanetwork.com/journals/jamacardiology/fullarticle/2665996
US Preventive Services Task Force Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons. US Preventive Services Task Force Recommendation Statement. JAMA. 2022;328(17):1740-1746 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36318127 https://jamanetwork.com/journals/jama/fullarticle/2797867
Gartlehner G et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2022 Nov 1; 328:1747-1765. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36318128 https://jamanetwork.com/journals/jama/fullarticle/2797868 - ↑ 115.0 115.1 115.2 115.3 North American Menopause Society The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28650869 <Internet> http://www.menopause.org/docs/default-source/2017/nams-2017-hormone-therapy-position-statement.pdf
- ↑ 116.0 116.1 Anello J, Feinberg B, Heinegg J et al Menopause Guidelines on treatment of menopause by the American Association of Clinical Endocrinologists and the American College of Endocrinology. Medscape: New Guidelines and Recommendations, August 2017. http://reference.medscape.com/viewarticle/884517
- ↑ 117.0 117.1 117.2 Taylor HS, Tal A, Pal L et al Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early PostmenopauseAncillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. Published online August 28, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28846767 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2652573
- ↑ 118.0 118.1 Manson JE, Aragaki AK, Rossouw JE et al Menopausal Hormone Therapy and Long-term All-Cause and Cause- Specific Mortality. The Women's Health Initiative Randomized Trials. JAMA. 2017;318(10):927-938 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28898378 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2653735
McNeil M Menopausal Hormone TherapyUnderstanding Long-term Risks and Benefits. JAMA. 2017;318(10):911-913. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28898364 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2653719 - ↑ 119.0 119.1 Gordon JL, Rubinow DR, Eisenlohr-Moul TA et al Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition. A Randomized Clinical Trial JAMA Psychiatry. Published online January 10, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29322164 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2668205
Joffe H, Hickey M. Should Hormone Therapy Be Used to Prevent Depressive Symptoms During the Menopause Transition? JAMA Psychiatry. Published online January 10, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29322180 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2668201 - ↑ 120.0 120.1 Woods GN, Huang MH, Cawthon PM et al. Patterns of menopausal hormone therapy use and hyperkyphosis in older women. Menopause. 2018 Jul;25(7):738-743. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29462096 https://insights.ovid.com/crossref?an=00042192-201807000-00006
- ↑ Hodis HN, Mack WJ, Henderson VW et al Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016 Mar 31;374(13):1221-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27028912 Free PMC Article
- ↑ 122.0 122.1 122.2 Sriprasert I, Hodis HN, Karim R et al. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early versus late postmenopause. J Clin Endocrinol Metab. 2019 Feb 1;104(2):293-300. ePub: Sep 28, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30272234
- ↑ 123.0 123.1 Jung JH, Bang, CH, Song, GG et al Knee osteoarthritis and menopausal hormone therapy in postmenopausal women. A nationwide cross-sectional study. Menopause: 2019 Jun; 26:598 ePub: December 21, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30586007 https://journals.lww.com/menopausejournal/Abstract/publishahead/Knee_osteoarthritis_and_menopausal_hormone_therapy.97442.aspx
- ↑ 124.0 124.1 124.2 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019;364:k4810 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30626577 https://www.bmj.com/content/364/bmj.k4810
- ↑ 125.0 125.1 Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti R et al Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study. BMJ 2019;364:l665 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30842086 Free full text https://www.bmj.com/content/364/bmj.l665
Maki M et al Menopausal hormone therapy and cognition. BMJ 2019;364:l877. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30842090 https://www.bmj.com/content/364/bmj.l877 - ↑ Collaborative Group on Hormonal Factors in Breast Cancer Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. Aug 29, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31474332 Free Article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X/fulltext
- ↑ 127.0 127.1 Javed AA, Mayhew AJ, Shea AK, Raina P. Association between hormone therapy and muscle mass in postmenopausal women: A systematic review and meta-analysis. JAMA Netw Open 2019 Aug; 2:e1910154 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31461147 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2749051
- ↑ 128.0 128.1 Manson JE, Aragaki AK, Bassuk SS et al. Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy: A randomized trial. Ann Intern Med 2019 Sep 10; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31499528 https://annals.org/aim/article-abstract/2749725/menopausal-estrogen-alone-therapy-health-outcomes-women-without-bilateral-oophorectomy
- ↑ 129.0 129.1 129.2 Matyi JM, Rattinger GB, Schwartz S, Buhusi M, Tschanz JT. Lifetime estrogen exposure and cognition in late life: The Cache County Study. Menopause 2019 Dec; 26:1366. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31613825 https://insights.ovid.com/crossref?an=00042192-201912000-00005
Liu JH. Does estrogen provide "neuroprotection" for postmenopausal women? Menopause 2019 Dec; 26:1361 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31663985 https://insights.ovid.com/crossref?an=00042192-201912000-00003 - ↑ Rothaus C Hormone Therapy for Postmenopausal Women. NEKM Resident 360. Jan 29, 2020 https://resident360.nejm.org/clinical-pearls/hormone-therapy-for-postmenopausal-women
- ↑ 131.0 131.1 Sriprasert I et al. Factors associated with serum estradiol levels among postmenopausal women using hormone therapy. Obstet Gynecol 2020 Sep 10; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32925623 PMCID: PMC7529896 https://journals.lww.com/greenjournal/Abstract/2020/10000/Factors_Associated_With_Serum_Estradiol_Levels.7.aspx
- ↑ 132.0 132.1 Vinogradova Y et al Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases BMJ 2020;371:m3873 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33115755 https://www.bmj.com/content/371/bmj.m3873
- ↑ 133.0 133.1 133.2 Cold S et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst 2022 Jul 20; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35854422 https://academic.oup.com/jnci/article/114/10/1347/6645744
Cathcart-Rake EJ, Ruddy KJ. Vaginal estrogen therapy for the genitourinary symptoms of menopause: Caution or reassurance? J Natl Cancer Inst 2022 Jul 20; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/35854417 https://academic.oup.com/jnci/article/114/10/1315/6645745 - ↑ 134.0 134.1 Sung YF et al. Use of hormone replacement therapy and risk of dementia: A nationwide cohort study. Neurology 2022 Oct 25; 99:e1835 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36240091 https://n.neurology.org/content/99/17/e1835
- ↑ 135.0 135.1 Lara LA, Cartagena-Ramos D, Figueiredo JB et al Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2023 Aug 24;8(8):CD009672. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37619252 PMCID: PMC10449239 (available on 2024-08-24) Review.
- ↑ 136.0 136.1 136.2 Davis JW, Weller SC, Porterfield L et al Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy. JAMA Netw Open. 2023;6(12):e2348213 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38100102 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812959
- ↑ 137.0 137.1 137.2 137.3 137.4 Smith J Ovarian Cancer Risk Doubled by Estrogen-Only HRT Medscape. June 13, 2024 https://www.medscape.com/s/viewarticle/ovarian-cancer-risk-doubled-estrogen-only-hrt-2024a1000b2p
Chlebowski RT, Aragaki AK, Pan K, et al. Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women`s Health Initiative Randomized Trials. J Clin Oncol. 2024 Aug 22:JCO2301918. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39173088 - ↑ 138.0 138.1 Brand BA, Sommer IE, Gangadin SS Real-World Effectiveness of Menopausal Hormone Therapy in Preventing Relapse in Women With Schizophrenia or Schizoaffective Disorder. Am J Psychiatry. 2024 Oct 1;181(10):893-900. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39262210
- ↑ 139.0 139.1 Gleason CE, Dowling NM, Kara F et al Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study. PLoS Med. 2024 Nov 21;21(11):e1004435. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39570992 Clinical Trial.