Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Nov 27;11(11):CD004143.
doi: 10.1002/14651858.CD004143.pub6.

Long-term hormone therapy for perimenopausal and postmenopausal women

Magdalena Bofill Rodriguez  1 , Li Ning Yong  2 , Sanja Mirkov  3   4 , Christine Bekos  5 , Anne Lethaby  1 , Cindy Farquhar  1
Affiliations

Long-term hormone therapy for perimenopausal and postmenopausal women

Magdalena Bofill Rodriguez et al. Cochrane Database Syst Rev. .

Abstract

Background: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005.

Objectives: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women.

Search methods: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024.

Selection criteria: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews.

Data collection and analysis: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE.

Main results: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms.

Authors' conclusions: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Trial registration: ClinicalTrials.gov NCT05586724.

PubMed Disclaimer

Conflict of interest statement

Cindy Farquhar is an editor of the Cochrane Gynaecology and Fertility Group and declares that she has taken no part in the editorial process for this update.

Sanja Mirkov has declared two fiduciary officer roles (unpaid voluntary work) with the Society of Hospital Pharmacists of Australia. She receives royalties for her contribution to a pharmacology textbook: McKenna's Pharmacology for Nursing and Other Health Professionals 3rd edition, 2021. She has received payments for editorial work and seminars.

MB, CB, LNY and AL have no interests to declare.

Update of

References

References to studies included in this review

Barakat 2006 {published data only}
    1. Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group study. Journal of Clinical Oncology 2006;24:587-92. [DOI: 10.1200/JCO.2005.02.8464] [PMID: ] - DOI - PubMed
ELITE 2014 {published and unpublished data}
    1. Henderson VW, St John JA, Hodis HN, McCleary CA, Stanczyk FZ, Shoupe D, et al. Cognitive effects of estradiol after menopause - a randomized trial of the timing hypothesis. Neurology 2016;87(7):699-708. [DOI: 10.1212/WNL.0000000000002980] - DOI
    1. Hodis HN, Mack MJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal timing hypothesis. Menopause (New York, N.Y.) 2015;22(4):391-401. [DOI: 10.1097/GME.0000000000000343] [PMID: ] - DOI - PMC - PubMed
    1. Hodis HN, Mack MJ, Shoupe D, Azen SP, Stanczyk FZ, et al. Testing the menopausal hormone therapy timing hypothesis: the Early versus Late Intervention Trial with Estradiol. Circulation 2014;130:[no pagination].
    1. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-leving J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. New England Journal of Medicine 2016;374(13):1221-31. [DOI: 10.1056/NEJMoa1505241] [PMID: ] - DOI - PMC - PubMed
    1. Mack WJ, Hodis HN, St John JA, McCleary CA, Stanczyk FZ, Shoupe D, et al. Cognitive outcomes from the early versus late intervention trial with estradiol: a test of the critical window hypothesis. Menopause (New York, N.Y.) 2014;21(12):1330.
EPAT 2001 {published data only}
    1. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, et al. Estrogen in the prevention of atherosclerosis: a randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine 2001;135:939-53. [DOI: 10.7326/0003-4819-135-11-200112040-00005] [PMID: ] - DOI - PubMed
    1. Karim R, Mack WJ, Lobo RA, Hwang J, Liu C, Liu C. Determinants of the effect of estrogen on the progression of subclinical atherosclerosis: Estrogen in the Prevention of Atheroscerosis Trial. Menopause (New York, N.Y.) 2005;12(4):366-73. [DOI: 10.1097/01.GME.0000153934.76086.A4] - DOI
EPHT 2006 {published data only}
    1. Veerus P, Fischer K, Hovi SL, Karro H, Rahu M, Hemminki E. Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial. BMC Women's Health 2010;8:5. [DOI: 10.1186/1472-6874-8-5] [PMID: ] - DOI - PMC - PubMed
    1. Veerus P, Hovi S, Fischer K, Rahu M, Hakama M, Hemminki E. Results from the Estonian postmenopausal hormone therapy trial (IRSRCTN35338757). Maturitas 2006;55:162-73. [DOI: 10.1016/j.maturitas.2006.01.012] [PMID: ] - DOI - PubMed
    1. Vorobjov S, Hovi S, Veerus P, Pisarev H, Rahu M, Hemminki E. Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial (ISRCTN35339757). Maturitas 2005;52:286-95. [DOI: 10.1016/j.maturitas.2005.05.001] [PMID: ] - DOI - PubMed
ERA 2000 {published data only}
    1. Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, et al. Effects of oestrogen replacement on the progression of coronary artery atherosclerosis. New England Journal of Medicine 2000;343:522-9. [DOI: 10.1056/NEJM200008243430801] [PMID: ] - DOI - PubMed
    1. Herrington DM, Reboussin DM, Potvin Klein K, Sharp PC, Shumaker SA, Snyder TE, et al. The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort. Controlled Clinical Trials 2000;21:257-85. [DOI: 10.1016/s0197-2456(00)00054-4] [PMID: ] - DOI - PubMed
    1. Nair GV, Herrington DM. The ERA trial: findings and implications for the future. Climacteric 2000;3:227-32. [DOI: 10.1080/13697130008500132] [PMID: ] - DOI - PubMed
ESPRIT 2002 {published data only}
    1. Cherry N, McNamee R, Heagerty A, Kitchener H, Hannaford P. Long-term safety of unopposed estrogen used by women surviving myocardial infarction: 14-year follow-up of the ESPRIT randomised controlled trial. British Journal of Obstetrics and Gynaecology 2014;121:700-5. [DOI: 10.1111/1471-0528.12598] - DOI
    1. The Esprit Team. Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial. Lancet 2002;360:2001-8. [DOI: 10.1016/s0140-6736(02)12001-0] - DOI
EVTET 2000 {published data only}
    1. Hoibraaten E, Mowinckel MC, Ronde H, Bertina RG, Sandset PM. Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial. British Journal of Haematology 2001;115:415-20. [DOI: 10.1046/j.1365-2141.2001.03111.x] [PMID: ] - DOI - PubMed
    1. Hoibraaten E, Qvigstad E, Andersen IO, Mowinckel MC, Sandset PM. The effects of hormone replacement therapy (HRT) on hemostatic variables in women with previous venous thromboembolism - Results from a randomized, double-blind, clinical trial. Thrombosis and Haemostasis 2001;85:775-81. [DOI: 10.1055/s-0037-1615717] [PMID: ] - DOI - PubMed
    1. Hoibraaten E, Qvigstad E, Andersen TO, Mowinckel MC, Sandset PM. Increased risk of recurrent venous thromboembolism during hormone replacement therapy. Thrombosis and Haemostasis 2000;84:961-7. [PMID: ] - PubMed
Ferenczy 2002 {published data only}
    1. Ferenczy A, Gelfand MM, Van de Weijer PH, Rioux JE. Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17 beta-estradiol combined with sequential 5-20 mg dydrogesterone. Climacteric 2002;5:26-35. [DOI: 10.1080/cmt.5.1.26.35] [PMID: ] - DOI - PubMed
Greenspan 2005 {published data only}
    1. Greenspan SL, Resnick NM, Parker RA. The effect of hormone replacement on physical performance in community-dwelling elderly women. American Journal of Medicine 2005;118:1232-9. [DOI: 10.1016/j.amjmed.2005.03.004] [PMID: ] - DOI - PubMed
HERS 1998 {published data only}
    1. Bibbins-Domingo K, Lin F, Vittinghoff E, Barrett-Connor E, Hulley SB, Grady D. Effect of hormone therapy among women with heart failure and coronary artery disease. American Journal of Cardiology 2005;95(2):289-91. [DOI: 10.1016/j.amjcard.2004.09.021] [PMID: ] - DOI - PubMed
    1. Byington RP, Furberg CD, Herrington DM, Herd JA, Hunninghake D, Lowery M, et al. Effect of oestrogen plus progestin on progression of carotid atherosclerosis in postmenopausal women with heart disease. Arteriosclerosis, Thrombosis, and Vascular Biology 2002;22:1692-7. [DOI: 10.1161/01.ATV.0000033514.79653.04] [PMID: ] - DOI - PubMed
    1. Grady D, Applegate W, Bush T, Furberg C, Riggs B, Hulley SB. Heart and Estrogen/progestin Replacement Study (HERS): design, methods and baseline characteristics. Controlled Clinical Trials 1998;19:314-35. [DOI: 10.1016/s0197-2456(98)00010-5] [PMID: ] - DOI - PubMed
    1. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy. Journal of the American Medical Association 2002;288(1):49-57. [DOI: 10.1001/jama.288.1.49] [PMID: ] - DOI - PubMed
    1. Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. Annals of Internal Medicine 2000;132(9):689-96. [DOI: 10.7326/0003-4819-132-9-200005020-00002] [PMID: ] - DOI - PubMed
KEEPS 2012 {published and unpublished data}
    1. Asthana S, Gleason CE, Wharton W, Dowling MN, Carlsson CM, et al. The Kronos Early Estrogen Prevention Study: results of the cognitive and affective substudy (KEEPS-Cog). In: Menopause: 23rd Annual Meeting of North American Menopause Society, 2012 October 3-6; Orlando (FL). Vol. 19. 2012:1365-404. [DOI: 10.1097/gme.0b013e3182739e2f] - DOI
    1. FIles JA, Miller VM, Cha S, Pruthi S. Effects of different hormone therapies on breast pain in recently postmenopausal women: findings from the Mayo Clinic KEEPS Breast Pain Ancillary Study. Journal of Womens Health 2014;23(10):801-5. [DOI: 10.1089/jwh.2014.4871] [PMID: ] - DOI - PMC - PubMed
    1. Gleason C, Wharton W, Dowling M, Brinton E, Santoro N, et al. The Kronos Early Estrogen Prevention Study - Cognitive and Affective Sub-study (KEEPS-CA): menopausal hormone therapy effects on mood, quality of life and memory complaints. In: Menopause: 23rd Annual Meeting of North American Menopause Society, 2012 Oct 3-6; Orlando (FL). Vol. 19. 2012:1402 (P-89). [DOI: 10.1097/gme.0b013e3182739e2f] - DOI
    1. Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-cognitive and affective study [KEEPS]. PLoS Medicine 2015;12(6):e1001833. [DOI: 10.1371/journal.pmed.1001833] - DOI
    1. Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized controlled KEEPS-Cognitive and Affective Study. PLoS Medicine 2015;12(6):e1001833. [DOI: 10.1371/journal.pmed.1001833] [PMID: ] - DOI - PMC - PubMed
Mulnard 2000 {published data only}
    1. Mulnard R, Cotman C, Kawas C, Van Dyck C, Sano M, Doody R, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 2000;283(8):1007-15. [DOI: 10.1001/jama.283.8.1007] [PMID: ] - DOI - PubMed
Nachtigall 1979 {published data only}
    1. Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstetrics and Gynecology 1979;54(1):74-9. [DOI: 10.1097/00006250-197907000-00017] [PMID: ] - DOI - PubMed
Notelovitz 2002 {published data only}
    1. Notelovitz M, John VA, Good WR. Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in health, postmenopausal women. Menopause (New York, N.Y.) 2002;9(5):343-53. [DOI: 10.1097/00042192-200209000-00007] [PMID: ] - DOI - PubMed
Obel 1993 {published and unpublished data}
    1. Bech P, Munk-Jensen N, Obel EB, Ulrich LG, Eiken P, Pors Nielsen SP. Combined versus sequential hormonal replacement therapy: a double blind placebo-controlled study on quality of life-related measures. Psychotherapy and Psychosomatics 1998;67:259-65. [DOI: 10.1159/000012289] [PMID: ] - DOI - PubMed
    1. Bech P. Personal communication with J. Marjoribanks. December 2003.
    1. Obel EB, Munk-Jensen N, Svenstrup B, Bennett P, Micic S, Henrik-Nielsen R, et al. A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. Maturitas 1993;16:13-21. [DOI: 10.1016/0378-5122(93)90129-6] [PMID: ] - DOI - PubMed
PEPI 1995 {published data only}
    1. Barrett-Connor E, Slone S, Greendale G, Kritz-Silverstein D, Espeland M, Johnson SR, et al. The postmenopausal estrogen/progestin interventions study: primary outcomes in adherent women. Maturitas 1997;27:261-74.
    1. Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins. Circulation 1999;100:717-22.
    1. Espeland MA, Bush TL, Mebane-Sims I, Stefanick ML, Johnson S, Sherwin R, et al. Rationale, design and conduct of the PEPI trial. Controlled Clinical Trials 1995;16:3S-19S.
    1. Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G. Postmenopausal hormone therapy and change in mammographic density. Journal of the National Cancer Institute 2003;951(1):30-7.
    1. Miller VT, Byington RL, Espeland MA, Langer R, Marcus R, Shumaker S, et al. Baseline characteristics of the PEPI particpants. Controlled Clinical Trials 1995;16:54S-65S.
Ran 2017 {published data only}
    1. Ran SY, Yu Q, Chen Y, Lin SQ. Prevention of postmenopausal osteoporosis in Chinese women: a 5-year, double-blind, randomized, parallel placebo-controlled study. Climateric 2017;20(4):391-6. [DOI: 10.1080/13697137.2017.1325459] - DOI
    1. Yu, Q, Ran, S, Chen, Y, et al. Prevention of postmenopausal osteoporosis in Chinese women: a 5-year double-blind, randomized, parallel placebo control study. Maturitas 2017;100:193-4. [DOI: 10.1016/j.maturitas.2017.03.248] - DOI
REPLENISH 2018 {published data only}
    1. Archer DF, Graham S, Gasper G, Constantine G, Bernick B, Mirkin S. Replenish trial: combination capsule of estradiol/progesterone (TX-001HR) for treating hot flushes. Obstetrics and Gynecology 2017;129(5):133S. [DOI: 10.1097/01.AOG.0000514678.75674.b8] - DOI
    1. Archer DF, Lobo RA, Kagan R, Constantine GD, Pickar JH, Gasper G, et al. Replenish trial: endometrial safety with a 173-estradiol and progesterone combination (TX-001HR) in postmenopausal women with vasomotor symptoms. Endocrine Reviews 2017;38(3):[no pagination]. [URL: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01399904/...]
    1. Kaunitz AM, Constantine G, Bernick B, Mirkin S. 17beta-estradiol/progesterone in a single, oral, softgel capsule (TX-001HR) significantly increased the number of symptom-free days in the replenish trial. Menopause (New York, N.Y.) 2020;27(12):1382-7. [10.1097/GME.0000000000001615]
    1. Liu JH, Black DR, Larkin L, Graham S, Bernick B, Mirkin S. Breast effects of oral, combined 17β-estradiol, and progesterone capsules in menopausal women: a randomized controlled trial. Menopause (New York, N.Y.) 2020;27(12):1388-95. [DOI: 10.1097/GME.0000000000001631] [PMID: ] - DOI - PMC - PubMed
    1. Liu L, Klein L, Eaton C, Panjrath G, Martin LW, Chae CU, et al. Menopausal hormone therapy and risks of first hospitalized heart failure and its subtypes during the intervention and extended postintervention follow-up of the Women's Health Initiative randomized trials. Journal of Cardiac Failure 2020;26(1):2-12. [DOI: 10.1016/j.cardfail.2019.09.006] - DOI
Tierney 2009 {published data only}
    1. Tierney MC, Oh P, Moineddin R, Greenblatt EM, Snow WG, Fisher RH, et al. A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women. Psychoneuroendocrinology 2009;34(7):1065-74.
WAVE 2002 {published data only}
    1. Bittner V, Tripputi M, Hsia J, Gupta H, Steffes M. Remnant-like lipoproteins, hormone therapy and angiographic and clinical outcomes: the Women's Angiographic Vitamin and Estrogen trial. American Heart Journal 2004;147:293-9.
    1. Hsia J, Alderman EL, Verter JI, Rogers WJ, Thompson P, Howard BV, et al. Women's angiographic vitamin and estrogen trial: design and methods. Controlled Clinical Trials 2002;23:708-27.
    1. Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women. JAMA 2002;288(19):2432-40.
WEST 2001 {published data only}
    1. Kernan WN, Brass LM, Viscoli CM, Sarrel PM, Makuch R, Horowitz RI. Estrogen after ischemic stroke: clinical basis and design of the Women's Estrogen for Stroke Trial. Journal of Stroke and Cardiovascular Diseases 1998;7(1):85-95.
    1. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horowitz RI. A clinical trial of estrogen-replacement therapy after ischemic stroke. New England Journal of Medicine 2001;345(17):1243-9.
    1. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horowitz RI. Estrogen therapy and risk of cognitive decline: results from the Women's Estrogen for Stroke Trial (WEST). American Journal of Obstetrics and Gynecology 2004;192:387-93.
WHI 1998 {published data only}
    1. Anderson GL, Chlebowski RT, Aragaki AK, Kuller LH, Manson JE, Gass M, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet 2012;13:476-86.
    1. Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, et al. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006;55:103-15.
    1. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. Journal of the American Medical Association 2003;290(13):1739-48.
    1. Armstrong NM, Espeland MA, Chen JC, Masaki K, Wactawski-Wende J, Li W, et al. Associations of hearing loss and menopausal hormone therapy with change in global cognition and incident cognitive impairment among postmenopausal women. Journals of Gerontology 2020;75(3):537-44. [DOI: 10.1093/gerona/glz208] - DOI
    1. Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Willliams RS, McGovernn PG, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstetrics and Gynecology 2005;105(5 Part 1):1063-73.
WISDOM 2007 {published data only}
    1. Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, et al. 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. British Medical Journal Online First 2007;335:239. [DOI: 10.1136/bmj.39266.425069.AD] - DOI
    1. Vickers MR, Martin J, Meade TW, WISDOM Study Team. The women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial. BMC Women's Health 2007;7(2):1-17. [DOI: 10.1186/1472-6874-7-2] - DOI
    1. Welton AJ, Vickers MR, Kim J, Ford D, Lawton BA, MacLennan AH, et al, Wisdom Team. Health related quality of life after combined hormone replacement therapy: randomised controlled trial. BMJ 2008;337(212):a1190. [DOI: 10.1136/bmj.a1190] - DOI
Yaffe 2006 {published data only}
    1. Yaffe K, Vittinghoff E, Ensrud KE, Johnson KC, Diem S, Hanes V, et al. Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life. Archives of Neurology 2006;63:945-50. [DOI: 10.1001/archneur.63.7.945] - DOI

References to studies excluded from this review

AHT 2015 {published and unpublished data}71318684
    1. Eeles RA, Morden JP, Gore M, Mansi J, Glees J, Wenzel M, et al. Adjuvant hormone therapy may improve survival in epithelial ovarian cancer: results of the AHT randomized trial. Journal of Clinical Oncology 2015;33(35):4138-44.
Aitken 1971 {published data only}
    1. Aitken JM, Lorimer AR, McKay Hart D, Lawrie TD, Smith DA. The effects of oophorectomy and long-term mestranol therapy therapy on the serum lipids of middle-aged women. Clinical Science 1971;41:597-603.
    1. Aitken JM, McKay Hart D. Oestrogen in oophorectomized women. British Medical Journal 1971;2(5758):400-1.
Aitken 1973 {published data only}
    1. Aitken JM, Hart DM, Lindsay R, Anderson JB, Smith DA, Wilson GM. Prevention of bone loss following oophorectomy in premenopausal women: a retrospective assessment of the effects of oophorectomy and a prospective controlled trial of the effects of mestranol therapy. Israel Journal of Medical Sciences 1976;12(7):607-14.
    1. Aitken JM, Lindsay R, Hart DM. Long-term oestrogens for the prevention of post-menopausal osteoporosis. Postgraduate Medical Journal 1976;52 Suppl 6:18-25.
    1. Aitken M, Hart DM, Lindsay R. Oestrogen replacement therapy for prevention of osteoporosis after oophorectomy. British Medical Journal 1973;3:515-8.
    1. Lindsay R, Aitken JM, Anderson JB, Hart DM, MacDonald EB, Clarke AC. Long-term prevention of postmenopausal osteoporosis by oestrogen. Lancet 1976;1(7968):1038-40.
Angerer 2001 {published data only}
    1. Angerer P, Stork S, Kothny W, Schmitt P, Schacky C. Effect of oral postmenopausal hormone replacement on progression of atherosclerosis: a randomised controlled trial. Arteriosclerosis, Thrombosis and Vascular Biology 2001;21(2):262-8.
Bloch Thomsen 2002 {published data only}
    1. Bloch Thomsen A, Silvestri S, Haarbo J, Christiansen C, Bjarnason N. Association between target organ responses during hormone replacement therapy. Abstracts of Posters:10th World Congresss on Menopause, Climacteric 2002;5 Suppl 1:57.
Chen 2001 {published data only}
    1. Chen FP, Lee N, Soong YK, Huang KE. Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on cardiovascular risk factors. Menopause: The Journal of the North American Menopause Society 2001;8(5):347-52.
Christiansen 1981 {published data only}
    1. Christiansen C, Christensen MS, Jensen J, Hagen C, Stocklund K, Transbol I. Effects of natural oestogen/gestagen and thiazide on coronary risk factors in normal postmenopausal women: a 2 year double-blind placebo study [Naturlig ostrogen/gestagen og tiazids virkning pa kardiovaskulaere risikofaktorer hos postmenopausale kvinder]. Ugeskrift for Laeger 1981;143:2230-4.
Corrado 2002 {published data only}
    1. Corrado F, Altavilla D, D'Anna R, Cancellieri F, Cannata ML. Effects of the phytoestrogen genistein and hormone replacement therapy on bone mineral density and metabolism in early post-menopausal women: a randomised double blind placebo-controlled study. Abstracts of Posters: 10th World Congress on Menopause: Climacteric 2002;5 (Suppl 1):173.
Corson 1999 {published data only}
    1. Corson SL, Richart RM, Caubel P, Lim P. Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17-Beta estradiol and norgestimate on endometrial histology. International Journal of Fertility 1999;44(6):279-85.
De Roo 1999 {published data only}
    1. De Valk-de Roo GW, Stehouwer CD, Meijer P, Mijatovic V, Kluft C, Kenemans P, et al. Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: a 2-year placebo-controlled study. Arteriosclerosis, Thrombosis and Vascular Biology 1999;19:2993-3000.
    1. Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJ, Pines A, et al. Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in health postmenopausal women: two randomized, placebo-controlled, 2-year studies. American Journal of Obstetrics and Gynecology 2002;186:729-36.
Dowling 2017 {published data only}
    1. Dowling M, Miller VM, Gunter JL, Shuster LT, Zuk SM, Bailey KR, et al. The role of cardiovascular health in moderating the effects of postmenopausal hormone therapy on neuroimaging outcomes. Alzheimer's & Dementia: the Journal of the Alzheimer's Association 2017;13(P3: Poster Presentations):937-8.
Eiken 1996 {published data only}
    1. Eiken P, Kolthoff N, Pors Nielsen SP. Effect of 10 years' hormone replacement therapy on bone mineral content in postmenopausal women. Bone 1996;5 Suppl:191S-3S.
ESTRATAB 1997 {published data only}
    1. Genant HK, Lucas J, Weiss S, Akin M, Emkey R, McNaney-Flint H, et al. Low-dose esterified estrogen therapy. Archives of Internal Medicine 1997;157:2609-15.
    1. Trabal JF, Lenihan JP, Melchione TE, Stoltz RR, Khairi S, Yang HN, et al. Low-dose unopposed estrogens: preliminary findings on the frequency and duration of vaginal bleeding in postmenopausal women receiving esterified estrogens over a two-year period. Menopause: The Journal of the North American Menopause Society 1997;4(3):130-8.
    1. Watts NB, Nolan JC, Brennan JJ, Yang HM, ESTRATAB/Osteoporosis Study Group. Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two year study. Menopause (New York, N.Y.) 2000;7(6):375-82.
EWA 2000 {published data only}
    1. Os I, Hofstad AE, Brekke M, Abdelnoor M, Nesheim BI, Jacobsen AF, et al. The EWA (Estrogen in Women with Atheroscelerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. Journal of Internal Medicine 2000;247:433-41.
Genant 1990 {published data only}
    1. Genant HK, Baylink DJ, Gallagher JC, Harris ST, Steiger P, Herber M. Effect of estrone sulfate on postmenopausal bone loss. Obstetrics and Gynecology 1990;76(4):579-84.
Gordon 2018 {published data only}
    1. Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: A randomized clinical trial. JAMA Psychiatry 2018;75(2):149-57. [DOI: 10.1001/jamapsychiatry.2017.3998] - DOI
Graser 2001 {published data only}
    1. Graser T, Muller A, Druckman R, Oettel M. Effects of a combination of 2 mg estradiol valerate and 3 mg dienogest on coagulation, lipid profile and glucose metabolism in postmenopausal women. Drugs of Today (Barcelona, Spain: 1998) 2001;37 Suppl:87-99.
HABITS 2004 {published data only}
    1. Holmberg L, Anderson H, for the HABITS Steering, Data Monitoring Committees. HABITS (hormonal replacement therapy after breast cancer - is it safe?) A randomised comparison: trial stopped. Lancet 2004;363(9407):453-5.
Haines 2003 {published data only}
    1. Haines CJ, Fan Yim S, Chung TK, Lan CW, Lau EW, Ng MH, et al. A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being and quality of life in postmenopausal Chinsese women. Maturitas 2003;44:207-14.
Hall 1998 {published data only}
    1. Hall G, Pripp U, Schenck-Gustafsson K, Landgren B-M. Longterm effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease. Maturitas 1998;28:235-42.
Jensen 1985 {published data only}
    1. Jensen J, Christiansen C, Rodbro P. Cigarette smoking, serum estrogens and bone loss during hormone-replacement therapy early after menopause. New England Journal of Medicine 1985;313:973-5.
Komulainen 1998 {published data only}
    1. Komulainen MH, Kroger H, Tuppurainen MY, Heikkinen A-M, Alhava E, Honkanen R, et al. HRT and vit D in prevention of non-vertebral fractures in postmenopausal women: a 5 year randomized trial. Maturitas 1998;31:45-54.
Lufkin 1992 {published data only}
    1. Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Annals of Internal Medicine 1992;117(1):1-9.
Maki 2004 {published data only}
    1. Maki PM, Resnick SM, Brandt J, Dobs AR, Durso SC, McCrae RR. Changes in self-reported personality coincident with declines in cognition: results from parallel hormone therapy trials in elderly men and women. Neurobiology of Aging 2004;25 Suppl 2:106.
Mirkin 2016 {published and unpublished data}
    1. Mirkin S, Pinkerton JV, Kagan R, Thompson JR, Pan K, Pickar JH, et al. Gynaecologic safety of conjugated estrogens plus bazedoxifene: pooled analysis of five phase 3 trials. Journal of Women's Health 2016;25(5):431-9.
Mizunuma 2010 {published data only}
    1. Mizunuma H, Taketani Y, Ohta H, Honjo H, Gorai I, Itabashi A, et al. Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis. Climacteric 2010;13:72-83.
NCT00006399 {unpublished data only}
    1. NCT00006399. Effects of estrogen on memory in post-menopausal women and patients with Alzheimer disease [Estrogen modulation effects on cholinergic function in normal post-menopausal women and patients with Alzheimer's disease]. https://clinicaltrials.gov/study/NCT00006399 (first posted 21 August 2000).
Ng 1992 {published data only}
    1. Ng HT, Chang SP, Yanfg TZ, Cho MP, Wei TC. Estradiol administered in a percutaneous gel for the prevention of postmenopausal bone loss. Asia-Oceania Journal of Obstetrics and Gynaecology 1993;19(2):115-9.
Nielsen 2006 {published data only}
    1. Nielsen T, Ravn P, Pitkin J, Christiansen C. Pulsed estrogen therapy improves postmenopausal quality of life: a 2-year placebo-controlled study. Maturitas 2006;53(2):184-90.
    1. Nielsen TF, Ravn P, Bagger YZ, Warming L, Christiansen C. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study. Osteoporosis International 2004;15(2):168-74.
Ory 1998 {published data only}
    1. Ory SJ, Field CS, Herrmann RR, Zinsmeister AR, Riggs BL. Effects of long-term transdermal administration of estradiol on serum lipids. Mayo Clinic Proceedings 1998;73(8):735-8. [DOI: 10.4065/73.8.735] - DOI
Os 2002 {published data only}
    1. Os I, Os A, Sandset PM, Bolling S, Seljeflot I, Djurovic S, et al. Hormone replacement therapy does not affect plasma homocysteine in postmenopausal women with coronary artery disease. Cardiology 2002;98:6-12.
Paoletti 2015 {published data only}
    1. Paoletti AM, Cagnacci A, Di Carlo C, Orru MM, Neri M, D'Alterio MN, et al. Clinical effect of hormonal replacement therapy with estradiol associated with noretisterone or drosperinone. A prospective randomized placebo controlled study. Gynecological Endocrinology 2015;31(5):384-9.
Papworth 2002 {published data only}
    1. Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofield PM. A study of hormone-replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. British Journal of Obstetrics and Gynaecology 2002;109:1056-62.
Pefanco 2007 {published data only}
    1. Pefanco MA, Kenny AM, Kaplan RF, Kuchel G, Walsh S, Kleppinger A, et al. The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women. Journal of the American Geriatrics Society 2007;55(3):426-31.
Post 2001 {published data only}
    1. Post MS, Van der Mooren MJ, Van Baal WM, Neel SJ, Netelenbos JC, Kenemans P. Raloxifene reduces impedance to flow within the uterine artery in early postmenopausal women: a 2-year randomized placebo-controlled comparative study. American Journal of Obstetrics and Gynecology 2001;185:557-62.
    1. Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJ, Pines A, et al. Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women: two randomized, placebo-controlled, 2-year studies. American Journal of Obstetrics and Gynecology 2002;186:729-36.
Rasgon 2014 {published data only}
    1. Rasgon NL, Geist CL, Kenna HA, Wroolie TE, Williams KE, Silverman DH. Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia. PLoS ONE 2014;9(3):e89095.
Saitta A 2001 {published data only}
    1. Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, et al. Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin-1 levels, and endothelium-dependent vaso-dilation in postmenopausal women. Arteriosclerosis, Thrombosis and Vascular Biology 2001;21(9):1512-9.
Sanchez‐Guerrero 2007 {published data only}
    1. Sanchez-Guerrero J, Gonzalez-Perez M, Durand-Carbajal M, Lara-Reyes P, Jimenez-Santana L, Romero-Diaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis and Rheumatism 2007;56(9):3070-9.
Schierbeck 2012 {published data only}
    1. Scheirbeck LL, Rejnmakr L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345(e6409):1-11.
SMART 5 {published data only}
    1. NCT00808132. A double-blind, randomized, placebo-and active-controlled efficacy and safety study of the effects of bazedoxifene/conjugated estrogens combinations on endometrial hyperplasia and prevention of osteoporosis in postmenopausal women: SMART 5. https://clinicaltrials.gov/study/NCT00808132 (first posted 15 December 2008). [EUCTR2008-003203-32-PL]
    1. Pinkerton J, Harvey JA, Lindsay R, Pan K, on behalf of SMART-5 investigators. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. Journal of Clinical Endocrinology and Metabolism 2014;99(2):E189-198. [DOI: 10.1210/jc.2013-1707] - DOI
Steiner 2007 {published data only}
    1. Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, et al. Unopposed estradiol therapy in postmenopausal women. Obstetrics and Gynecology 2007;109:581-7.
Stevenson 2016 {published data only}
    1. Stevenson TE, Brincat MP, Pollacco J, Stevenson JC. Effect of hormone replacement therapy on intervertebral disc height. Climacteric 2023;26(2):110-3. [DOI: 10.1080/13697137.2022.2158728] - DOI
Teede 2002 {published data only}
    1. Teede HJ, Liang YL, Kotsopoulos D, Zoungas S, Craven R, McGrath BP. Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal women: effects on arterial compliance and endothelial function. Climacteric 2002;5:160-9.
ULTRA 2005 {published data only}
    1. Diem S, Grady D, Quan J, Vittinghoff E, Wallace R, Hanes V, et al. Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years. Menopause (New York, N.Y.) 2006;1:130-8.
    1. Waetjen LE, Brown JS, Vittinghoff E, Ensrud KE, Pinkerton J, Wallace R, et al. The effect of ultralow-dose transdermal estradiol on urinary incontinence in postmenopausal women. Obstetrics and Gynecology 2005;1:946-52.
Virtanen 1999 {published data only}
    1. Virtanen I, Polo-Kantola P, Erkkola R, Polo O, Ekholm E. Climacteric vasomotor symptoms do not imply autonomic dysfunction. British Journal of Obstetrics and Gynaecology 1999;106:155-64.
Wharton 2011 {published data only}
    1. Wharton W, Baker LD, Gleason CE, Dowling M, Barnet JH, Johnson S, et al. Short-term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer's disease: results of a randomized controlled trial. Journal of Alzheimer's Disease 2011;26:495-505.
Yoon 2018 {published data only}
    1. Yoon BK, Chin J, Kim JW, Shin MH, Ahn S, Lee DY, et al. Menopausal hormone therapy and mild cognitive impairment: a randomized, placebo-controlled trial. Menopause (New York, N.Y.) 2018;25(8):870-6. [DOI: 10.1097/GME.0000000000001140] - DOI

References to studies awaiting assessment

ChiCTR‐IPR‐16008754 {published data only}
    1. ChiCTR-IPR-16008754. Prevention and treatment of estrogen therapy on the perimenopausal diseases of multi-center study in China. Chinese Clinical Trial Register. [ChiCTR-IPR-16008754]
Hodis 2003 {published data only}
    1. Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. New England Journal of Medicine 2003;349(6):535-45. [DOI: 10.1056/NEJMoa030830] - DOI

References to ongoing studies

NCT04090957 {published data only}
    1. NCT04090957. Estetrol for the treatment of moderate to severe vasomotor symptoms in postmenopausal women [A randomized double-blind placebo controlled phase 3 trial to evaluate the efficacy and safety of estetrol for the treatment of moderate to severe vasomotor symptoms in postmenopausal women (E4Comfort Study II)]. https://clinicaltrials.gov/study/NCT04090957 (first posted 16 September 2019). [NCT04090957]
    1. NCT04209543. Estetrol for the treatment of moderate to severe vasomotor symptoms in postmenopausal women (e4comfort study I) [NOTE: original protocol]. Clinical trials.gov. [NCT04209543]
    1. Utian W, Lobo R, Mawet M, Taziaux M, Gaspard U, et al. A phase 3 protocol to assess the efficacy and safety of estetrol (E4), a promising new treatment for menopausal vasomotor symptoms. Menopause (New York, N.Y.) 2019;26(12):1445-81 (p73). [DOI: 10.1097/GME.0000000000001456] - DOI
NCT05586724 {published data only}
    1. NCT05586724. Micronized progesterone versus norethisterone acetate in combination with estrogen as menopausal hormone therapy [Safety of oral micronized progesterone versus norethisterone acetate in continuous combination with oral estrogen as menopausal hormone therapy - a double-blind randomized study - PROBES study (progesterone breast endometrial safety study)]. https://clinicaltrials.gov/study/NCT05586724 (first posted 19 October 2022).

Additional references

Abelin 2012
    1. Abelin AP, Nunes CM, Camazzola FE, Santos RP. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345:e6409. [DOI: 10.1136/bmj.e6409] - DOI
AMS 2016
    1. Australian Menopause Society. AMS guide to equivalent HRT/MHT doses. https://www.menopause.org.au/for-women/information-sheets/426-ams-guide-... (accessed 6 January 2017).
Anderson 2003
    1. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. JAMA 2003;290(13):1739-48. [DOI: 10.1001/jama.290.13.1739] - DOI
Anderson 2004
    1. Anderson G, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al, 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;291(14):1701-12. [DOI: 10.1001/jama.291.14.1701] - DOI
Anderson 2006
    1. Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, et al. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006;55:103-15. [DOI: 10.1016/j.maturitas.2006.05.004] - DOI
Anderson 2012
    1. Anderson GL, Chlebowski RT, Aragaki AK, Kuller LH, Manson JE, Gass M, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet 2012;13:476-86. [DOI: 10.1016/S1470-2045(12)70075-X] - DOI
Avis 2001
    1. Avis NE, Stellato R, Crawford S, Bromberger J, Ganz P, Cain V, et al. Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Social Science & Medicine 2001;52(3):345-56. [DOI: 10.1016/s0277-9536(00)00147-7. PMID: 11330770] - PubMed
Banks 2009a
    1. Banks E, Canfell K. Invited Commentary: Hormone therapy risks and benefits – The Women's Health Initiative findings and the postmenopausal estrogen timing hypothesis. American Journal of Epidemiology 2009;1:24-8. [DOI: 10.1093/aje/kwp113] - DOI
Banks 2009b
    1. Banks E, Reeves GK, Beral V, Balkwill A, Liu B, Roddam A, for the Million Women Study collaborators. Hip fracture incidence in relation to age, menopausal status, and age at menopause: prospective analysis. PLoS Medicine 2009;6(11):e1000181. [DOI: 10.1371/journal.pmed.1000181] - DOI
Barlow 1997
    1. Barlow DH. HRT and the risk of deep vein thrombosis. International Journal of Gynaecology and Obstetrics 1997;59(1):S29-33. [DOI: 10.1016/s0020-7292(97)90196-x] - DOI
Barret‐Connor 2007
    1. Barrett-Connor E. Hormones and heart disease: the timing hypothesis. American Journal of Epidemiology 2007;166(5):506-10.
Barrett‐Connor 1998
    1. Barrett-Connor E, Grady D. Hormone replacement therapy, heart disease and other considerations. Annual Review of Public Health 1998;19:55-72.
Barrett‐Connor 2001
    1. Barrett-Connor E, Stuenkel CA. Hormone replacement therapy (HRT) - risks and benefits. International Journal of Epidemiology 2001;30:423-6.
Bassuk 2016
    1. Bassuk SS, Manson JE. The timing hypothesis: do coronary risks of menopausal hormone therapy vary by age or time since menopause onset? Metabolism: Clinical and Experimental 2016;65(5):794-803. [DOI: 10.1016/j.metabol.2016.01.004] - DOI
Bath 2005
    1. Bath PM, Gray LJ. Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ 2005;330:342.
Beral 2002
    1. Beral V, Banks E, Reeves G. Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 2002;360:942-4.
Beral 2003
    1. Beral V, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419-27.
Beral 2011
    1. Beral V, Reeves G, Bull D, Green J, for the Million Women Study Collaborators. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. Journal of the National Cancer Institute 2011;103:296-305. [DOI: 10.1093/jnci/djq527] - DOI
Bhupathiraju 2017
    1. Bhupathiraju SN, Grodstein F, Rosner BA, Stampfer MJ, Hu FB, Willett WC, et al. Hormone therapy use and risk of chronic disease in the nurses' health study: a comparative analysis with the Women's Health Initiative. American Journal of Epidemiology 2017;186(6):696-708. Published correction in: American Journal of Epidemiology 2018; 187(3):636. [DOI: 10.1093/aje/kwx131] - DOI
Boardman 2015
    1. Boardman HM, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database of Systematic Reviews 2015, Issue 3. Art. No: CD002229. [DOI: 10.1002/14651858.CD002229.pub4] - DOI
Canonico 2007
    1. Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Levesque H, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007;115(7):840-5.
Cauley 2003
    1. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density. JAMA 2003;290(13):1729-38.
CGHFBC 2019
    1. 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 2019;394(10204):1159-68. [DOI: 10.1016/S0140-6736(19)31709-X] - DOI
Chakrabarti 2014
    1. Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: an overview. Canadian Journal of Cardiology 2014;30(7):705-12. [DOI: 10.1016/j.cjca.2013.08.006] - DOI
Chlebowski 2003
    1. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. JAMA 2003;289(24):3243-53.
Chlebowski 2004
    1. Chlebowski RT, Col N. Menopausal hormone therapy after breast cancer. Lancet 2004;363:410-1.
Chlebowski 2008
    1. Chlebowski RT, Anderson G, Pettinger M, Lane D, Langer RD, Gillian MA, et al, for the Women’s Health Initiative Investigators. Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Archives of Internal Medicine 2008;168(4):370-7.
Chlebowski 2009
    1. Chlebowski RT, Schwartz AG, Wakelee H, Anderson GK, Stefanick, ML, 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;374(9697):1243-51.
Chlebowski 2010a
    1. Chlebowski, Anderson G, Manson JE, Pettinger M, Yasmeen S, Lane D, et al. Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy. Journal of Clinical Oncology 2010;28:2690-7.
Chlebowski 2010b
    1. Chlebowski RT, Anderson GL, Manson JE, Schwartz AG, Wakelee H, Gass M, et al. Lung cancer among postmenopausal women treated with estrogen alone in the women's health initiative randomized trial. Journal of the National Cancer Institute 2010;102(18):1413-21.
Chlebowski 2010c
    1. Chlebowski RT, Anderson G, Gass M, Lane DS, Aragaki AK, Kuller LH, et al, Women's Health Initiative Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010;304(15):1719-20.
Chlebowski 2015a
    1. Chlebowski RT, Rohan TE, Manson JE, Aragaki AK, Kaunitz A, Stefanick ML, et al. Breast cancer after use of estrogen plus progestin and estrogen alone. JAMA 2015;1(3):296-305.
Chlebowski 2015b
    1. Chlebowski RT, Aragaki AK, Anderson GL. Menopausal hormone therapy influence on breast cancer outcomes in the Women's Health Initiative. Journal of the National Comprehensive Cancer Network 2015;13(7):917-24.
Chlebowski 2020
    1. Chlebowski RT, Anderson GL, Aragaki AK, Manson JE, Stefanick ML, Pan K, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the women's health initiative randomized clinical trials. JAMA 2020;24(4):369-80. [DOI: 10.1001/jama.2020.9482] - DOI
Cody 2009
    1. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No: CD001405. [DOI: 10.1002/14651858.CD001405.pub3] - DOI
Cody 2012
    1. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No: CD001405. [DOI: 10.1002/14651858.CD001405.pub3] - DOI
Cushman 2004
    1. Cushman M, Kuller LH, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;292(13):1573-80.
Deady 2004
    1. Deady J. Clinical monograph: hormone replacement therapy. Journal of Managed Care Specialty Pharmacy 2004;10(1):33-47. [DOI: 10.18553/jmcp.2004.10.1.33] - DOI
Douketis 2005
    1. Douketis JD, Julian JA, Kearon C, Anderson DR, Crowther MA, Bates SM, et al. Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study. Journal of Thrombosis and Haemostasis: JTH 2005;3(5):943-8. [DOI: 10.1111/j.1538-7836.2005.01268.x] - DOI
El Khoudary 2019
    1. El Khoudary SR, Greendale G, Crawford SL et al. The menopause transition and women’s health at midlife: a progress report from the Study of Women’s Health Across the Nation (SWAN). Menopause (New York, N.Y.) 2019;26(10):1-15. [DOI: 10.1097/GME.0000000000001424] - DOI
Espeland 2004
    1. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women. JAMA 2004;291(24):2959-3007.
Espeland 2013
    1. Espeland MA, Shumaker SA, Leng I, Manson JE, Brown CM. Long term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50-55 years. JAMA Internal Medicine 2013;173(15):1429-36.
Espeland 2016
    1. Espeland MA, Rapp SR, Manson JE, Goveas JS, Shumaker SA, Hayden KM, et al. Long-term effects on cognitive trajectories of postmenopausal hormone therapy in two age groups. Journals of Gerontology Series A-Biological Sciences and Medical Sciences 2016;00(00):11-8.
FDA 2021
    1. Food and Drug Administration (FDA) Center for Drug Evaluation and Research. Guidance for industry: estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms – recommendations for clinical evaluation. Available at http://www.fda.gov/cder/guidance/5412dft.doc; January 2003 (accessed 18 March 2021). [URL: http://www.fda.gov/cder/guidance/5412dft.doc]
Furness 2012
    1. Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No: CD000402. [DOI: 10.1002/14651858.CD000402.pub4] - DOI
Gaudard 2016
    1. Gaudard A, Silva de Souza S, Puga ME, Marjoribanks J, Da Silva EM, Torloni MR. Bioidentical hormones for women with vasomotor symptoms. Cochrane Database of Systematic Reviews 2016, Issue 8. Art. No: CD010407. [DOI: 10.1002/14651858.CD010407.pub2] - DOI
Gottlieb 2003
    1. Gottlieb S. FDA insists that oestrogen products for menopause carry a warning. BMJ (Clinical Research Ed.) 2003;326(7381):126. [PMID: ] - PMC - PubMed
Grady 1995
    1. Grady G, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstetrics and Gynecology 1995;85(2):304-13.
Grady 2002
    1. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 2002;288(1):49-57. [DOI: 10.1001/jama.288.1.49] - DOI
Greendale 1999
    1. Greendale GA, Lee NP, Arriola ER. The menopause. Lancet 1999;353:571-80.
Greiser 2006
    1. Greiser CM, Greiser EM, Dören M. Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis. Human Reproduction Update 2007;13(5):453-63.
Guidozzi 1999
    1. Guidozzi F, Daponte A. Estrogen replacement for ovarian cancer survivors: a randomized controlled trial. Cancer 1999;86:1013-8.
Health and Human Services 2025
    1. US Department of Health and Human Services. Fact sheet: FDA initiates removal of “black box” warnings from menopausal hormone replacement therapy products; November 2025. https://www.hhs.gov/press-room/fact-sheet-fda-initiates-removal-of-black... (accessed 24 November 2025).
Heiss 2008
    1. Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, et al. Health risks and benefit 3 years after stopping randomized treatment with estrogen and progestin. JAMA 2008;299(9):1036-45.
Hemminki 1997
    1. Hemminki E, McPherson K. Impact of post menopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. BMJ 1997;315:149-53.
Hemminki 2000a
    1. Hemminki E. Hormone replacement therapy: discrepancies between evidence and recommendations. Scandinavian Journal of Public Health 2000;28:81-3.
Hemminki 2000b
    1. Hemminki E, McPherson K. Value of drug-licensing documents in studying the effect of postmenopausal hormone therapy on cardiovascular disease. Lancet 2000;355:566-9.
Hendrix 2006
    1. Hendrix SL, Wassertheil-Smoller S, Johnson KC, Howard BV, Kooperberg C, Rossouw JE, et al. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006;113:2425-34.
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from https://www.cochrane.org/authors/handbooks-and-manuals/handbook/archive/....
Higgins 2024
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 6.5 (updated August 2024). Cochrane, 2024. Available from training.cochrane.org/handbook.
Hogervorst 2009
    1. Hogervorst E, Yaffe K, Richards M, Huppert FA. Hormone replacement therapy to maintain cognitive function in women with dementia. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No: CD003799. [DOI: 10.1002/14651858.CD003799.pub2] - DOI
Holmberg 2004
    1. Holmberg L, Anderson H, for the HABITS Steering, Data Monitoring Committees. HABITS (hormonal replacement therapy after breast cancer – is it safe?), a randomised comparison: trial stopped. Lancet 2004;363:453-5.
Holmberg 2008
    1. Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. Journal of the National Cancer Institute 2008;100(7):475-82.
Hulley 1998
    1. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;19(280):605-13. [10.1001/jama.280.7.605. PMID: 9718051] - PubMed
Hulley 2002
    1. Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, et al. Noncardiovascular disease outcomes during 6.8 years of hormone replacement. Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002;288(1):58-66. [DOI: 10.1001/jama.288.1.58] [PMID: ] - DOI - PubMed
Hulley 2004
    1. Hulley SB, Grady D. The WHI estrogen-alone trial - do things look any better? JAMA 2004;291:1769-71.
ICR 2001
    1. Institute of Cancer Research. UK randomised trial of hormone replacement therapy (HRT) in women with a history of early breast cancer. http://www.icr.ac.uk/ctsu/hrt.htm (accessed 8 March 2005).
Ismail 2010
    1. Ismail SI, Bain C, Hagen S. Oestrogens for treatment or prevention of pelvic organ prolapse in postmenopausal women. Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No: CD007063. [DOI: 10.1002/14651858.CD007063.pub2] - DOI
Jordan 2015
    1. Jordan VC. The new biology of estrogen induced apoptosis applied to treat and prevent breast cancer. Endocrine-related Cancer 2015;22(1):R1-31.
Kaplan 1985
    1. Kaplan NM. Effect on blood pressure and other cardiovascular risk factors. Journal of Reproductive Medicine 1985;30(10):802-4. [PMID: ] - PubMed
Kaunitz 2002
    1. Kaunitz AM. Use of combination hormone replacement therapy in light of recent data from the Women's Health Initiative. Mayo Clinic Proceedings 2002;77(11):1243–51. [DOI: 10.4065/77.11.1243] - DOI
Kim 2025
    1. Kim D, Jordan V, Casciola F, Ferguson M, Humphries A, Bofill Rodriguez M, et al. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia or endometrial cancer. Cochrane Database of Systematic Reviews 2025, Issue 10. Art. No: CD000402. [DOI: 10.1002/14651858.CD000402.pub5] - DOI
Knopp 1988
    1. Knopp RH. The effects of postmenopausal estrogen therapy on the incidence of arteriosclerotic vascular disease. Obstetrics and Gynaecology 1988;72(5):23-30. [PMID: ] - PubMed
Kohn 2019
    1. Kohn GE, Rodriguez KM, Hotaling J, Pastuszak AW. The history of estrogen therapy. Sexual Medicine Reviews 2019;7(3):416-21. [DOI: 10.1016/j.sxmr.2019.03.006] - DOI
Kongnyuy 1999
    1. Kongnyuy EJ, Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No: CD001018. [DOI: 10.1002/14651858.CD001018] - DOI
Kurman 1985
    1. Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer 1985;56(2):403-12.
LaCroix 2011
    1. LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, et al, WHI Investigators. Health outcomes after stopping conjugated equine esotrogens among postmenopausal women with prior hysterectomy. JAMA 2011;305(13):1305-14.
Lara 2023
    1. Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-e-Silva A, Ferriani RA, Martins WP, et al. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2023, Issue 8. Art. No: CD009672. [DOI: 10.1002/14651858.CD009672.pub3] - DOI
Lethaby 2008
    1. Lethaby A, Hogervorst E, Richards M, Yesufu A, Yaffe K. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No: CD003122. [DOI: 10.1002/14651858.CD003122.pub2] - DOI
Lethaby 2016
    1. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2016, Issue 8. Art. No: CD001500. [DOI: 10.1002/14651858.CD001500.pub3] - DOI
MacLennan 2004
    1. MacLennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No: CD002978. [DOI: 10.1002/14651858.CD002978.pub2] - DOI
Manson 2003
    1. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, et al. Estrogen plus progestin and the risk of coronary heart disease. New England Journal of Medicine 2003;349:523-34.
Manson 2013
    1. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended post-stopping phases of the Women's Health Intiative randomized trials. JAMA 2013;310(13):1353-68.
Manson 2015
    1. Manson JE. The ‘timing hypothesis’ for estrogen therapy in menopausal symptom management. Women's Health (Hillsdale, N.J.) 2015;11(4):437-40.
Manson 2020
    1. Manson JE, MD, Bassuk SS, Kaunitz AM, Pinkerton JV. The Women's Health Initiative trials of menopausal hormone therapy: lessons learned. Menopause (New York, N.Y.) 2020;27(8):918-28. [DOI: 10.1097/GME.0000000000001553] - DOI
Marjoribanks 2012
    1. 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;345:e8141.
Matthews 1997
    1. Matthews KA, Shumaker SA, Bowen DJ, Langer RD, Hunt JR, Kaplan RM, et al. Women's Health Initiative: why now? What is it? What's new? American Psychologist 1997;52(2):101-16.
McKinney 1998
    1. McKinney KA, Thompson W. A practical guide to prescribing hormone replacement therapy. Drugs 1998;56(1):49-57.
Miller 2008
    1. Miller VM, Duckles SP. Vascular actions of estrogens: functional implications. Pharmacological Reviews 2008;60:210-41.
Mittermeier 2020
    1. Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database of Systematic Reviews 2020;9:1465-858. [DOI: 10.1002/14651858.CD012658.pub2] - DOI
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:2535.
Mukherjee 2025
    1. Mukherjee A, Davis S. Update on menopause hormone therapy; current indications and unanswered questions. Clinical Endocrinology 2025 Jan 29 [Epub ahead of print]. [DOI: 10.1111/cen.15211] - DOI
NAMS 2017
    1. Hormone Therapy Position Statement Advisory Panel. The 2017 Hormone Therapy Position Statement of the North American Menopause Society. Menopause (New York, N.Y.) 2017;24(7):728-53. [DOI: 10.1097/GME.0000000000000921] - DOI
NAMS 2022
    1. North American Menopause Society (NAMS) Advisory Panel. The 2022 hormone therapy position statement of the North American Menopause Society. Menopause (New York, N.Y.) 2022;29(7):767-94. [DOI: 10.1097/GME.0000000000002028] - DOI
Nastri 2013
    1. Nastri CO, Lara LA, Ferriani RA, Rosa‐e‐Silva A, Figueiredo JB, Martins WP. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No: CD009672. [DOI: 10.1002/14651858.CD009672.pub2] - DOI
Nees 2022
    1. Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, et al. Endometrial hyperplasia as a risk factor of endometrial cancer. Archives of Gynecology and Obstetrics 2022;306(2):407-21. [DOI: 10.1007/s00404-021-06380-5] - DOI
Nelson 2008
    1. Nelson HD. Menopause. Lancet 2008;371(9614):1-7. [DOI: 10.1016/S0140-6736(08)60346-3] - DOI
NICE 2015
    1. National Institute for Health and Care Excellence. Menopause. Clinical Guideline: methods, evidence and recommendations; October 2015. https://www.nice.org.uk/guidance/ng23/evidence/full-guideline-559549261 (accessed September 2016).
NICE 2024
    1. National Institute for Health and Care Excellence. Menopause: identification and management. NG23; November 2015; last updated November 2024. https://www.nice.org.uk/guidance/ng23/chapter/recommendations (accessed prior to 7 November 2025).
Obiorah 2013
    1. Obiorah I, Jordan VC. The scientific rationale for a delay after menopause in the use of conjugated equine estrogens in postmenopausal women that causes a reduction in breast cancer incidence and mortality. Menopause (New York, N.Y.) 2013;20(4):372-82.
Oliver‐Williams 2019
    1. Oliver-Williams C, Glisic M, Shahzad S, Brown E, Pellegrino Baena C, Chadni M, et al. The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review. Human Reproduction Update 2019;25(2):257-71. [DOI: 10.1093/humupd/dmy039] - DOI
Palacios 2010
    1. Palacios S, Henderson VW, Siseles N, Tan D, Villaseca P. Age of menopause and impact of climacteric symptoms by geographical region. Climacteric 2010;13:419-28.
Pedersen 2003
    1. Pedersen AT. Issues to debate on the Women's Health Initiative (WHI) study. Epidemiology or randomized clinical trials - time out for hormone replacement therapy studies? Human Reproduction (Oxford, England) 2003;18(11):2241-4.
Prentice 2009a
    1. Prentice RL, Manson JE, Langer RD, Anderson GL, Pettinger M, Jackson RD, et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. American Journal of Epidemiology 2009;170:12-23.
Prentice 2009b
    1. Prentice RL, Pettinger M, Beresford SA, Wactawski-Wende J, Hubbell FA, Stefanick ML, et al. Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women's Health Initiative clinical trial and observational study. Cancer Epidemiology, Biomarkers and Prevention 2009;18(5):1531-7.
RANZCOG 2020
    1. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Managing menopausal symptoms; September 2020. Available at https://ranzcog.edu.au/wp-content/uploads/2022/05/Managing-menopausal-sy... 2020. [URL: https://ranzcog.edu.au/wp-content/uploads/2022/05/Managing-menopausal-sy...]
Reslan 2012
    1. Reslan OM, Khalil RA. Vascular effects of estrogenic menopausal hormone therapy. Review of Recent Clinical Trials 2012;7(1):47-70.
Resnick 2004
    1. Resnick SM, Coker LH, Maki PM, Rapp SR, Espeland MA, Shumaker SA. The Women's Health Initiative Study of Cognitive Aging (WHISCA): a randomized clinical trial of the effects of hormone therapy on age-associated cognitive decline. Clinical Trials (London, England) 2004;1:440-50.
RevMan 2025 [Computer program]
    1. Review Manager (RevMan). Version 9.9.0. The Cochrane Collaboration, 2025. Available at https://revman.cochrane.org.
Salpeter 2004
    1. Salpeter SR, Walsh JM, Greyber E, Ormiston TM, Salpeter EE. Mortality associated with hormone replacement therapy in younger and older women. Journal of General Internal Medicine 2004;19:701-04.
Scheffers 2015
    1. Scheffers CS, Armstrong S, Cantineau AE, Farquhar C, Jordan V. Dehydroepiandrosterone for women in the peri- or postmenopausal phase. Cochrane Database of Systematic Reviews 2015;1:Art. No.: CD011066. [DOI: 10.1002/14651858.CD011066.pub2] - DOI
Schroll 2012
    1. Schroll J. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345:e6409.
Schünemann 2024
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence [last updated August 2023]. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.5. Cochrane, 2024. Available from cochrane.org/handbook.
Shapiro 2003
    1. Shapiro S. Risks of estrogen plus progestin therapy: a sensitivity analysis of findings in the Women's Health Initiative randomized controlled trial. Climacteric 2003;6:302-10.
Shumaker 1998
    1. Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, et al. The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Controlled Clinical Trials 1998;19:604-21.
Shumaker 2003
    1. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, 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 2004;289(20):2651-62. [DOI: 10.1001/jama.289.20.2651] - DOI
Shumaker 2004
    1. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Fillit H, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291(24):2947-58.
Simon 2012
    1. Simon MS, Chlebowski RT, Wactawski-Wende J, Johnson KV, Muskovitz A, Kato I, et al. Estrogen plus progestin and colorectal cancer incidence and mortality. Journal of Clinical Oncology 2012;30(32):3983-90.
Sprague 2012
    1. Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstetrics and Gynecology 2012;120(3):595-603. [DOI: 10.1097/AOG.0b013e318265df42] [PMID: ] - DOI - PubMed
Stefanick 2003
    1. Stefanick ML, Cochrane BB, Hsia J, Barad D, Liu J, Johnson S. The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. Annals of Epidemiology 2003;13:S78-86.
Stefanick 2005
    1. Stefanick ML. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. American Journal of Medicine 2005;118(12 Suppl 2):64-73. [DOI: 10.1016/j.amjmed.2005.09.059] - DOI
Suckling 2006
    1. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No: CD001500. [DOI: 10.1002/14651858.CD001500.pub2] - DOI
Uhler 2000
    1. Uhler ML, Marks JW, Judd HL. Estrogen replacement therapy and gallbladder disease in postmenopausal women. Menopause (New York, N.Y.) 2000;7(3):162-7. [DOI: 10.1097/00042192] - DOI
Vaughan 2013
    1. Vaughan L, Espeland MA, Snively B, Shumaker SA, Rapp SR, Shupe R, et al. The rationale, design, and baseline characteristics of the Women's Health Initiative Memory Study of Younger Women (WHIMS-Y). Brain Research 2013;1514:3-11.
WHI 1998
    1. The Women’s Health Initiative Study Group. Design of the Women’s Health Initiative clinical trial and observational study. Controlled Clinical Trials 1998;19(1):61-109. [DOI: 10.1016/s0197-2456(97)00078-0] [PMID: ] - DOI - PubMed
WHI 2002
    1. 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 randomised controlled trial. JAMA 2002;288:321-33.
Yuk 2023
    1. Yuk JS, Kim M. Effects of menopausal hormone therapy on the risk of ovarian cancer: Health Insurance Database in South Korea–based cohort study. Menopause (New York, N.Y.) 2023;30(5):490-6. [DOI: 10.1097/GME.0000000000002176] - DOI
Zhao 2014
    1. Zhao A, Chlebowski RT, Anderson GL, Kuller LH, Manson JE, Gass M, et al. Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects. Breast Cancer Research 2014;16:R30.

References to other published versions of this review

Cochrane HRT Study Group 2003
    1. Cochrane HRT Study Group. Hormone replacement therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No: CD004143. [DOI: 10.1002/14651858.CD004143] - DOI
Farquhar 2005
    1. Farquhar C, Marjoribanks J, Lethaby A, Suckling JA, Lamberts Q. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2005, Issue 7. Art. No: CD004143. [DOI: 10.1002/14651858.CD004143.pub2] - DOI
Farquhar 2009
    1. Farquhar C, Marjoribanks J, Lethaby A, Suckling JA, Lamberts Q. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No: CD004143. [DOI: 10.1002/14651858.CD004143.pub3] - DOI
Marjoribanks 2012a
    1. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No: CD004143. [DOI: 10.1002/14651858.CD004143.pub4] - DOI
Marjoribanks 2017
    1. Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No: CD004143. [DOI: 10.1002/14651858.CD004143.pub5] - DOI

Publication types

MeSH terms

Associated data

LinkOut - more resources