An update on hormone therapy in postmenopausal women: Mini-review for the basic scientist

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 313, Issue 5, 2017, Pages H1013-H1021

  Miller, Virginia M ^a   Mitchell Harman, S ^b  

^a MAYO CLINIC   (United States)

^b Kronos Longevity Research Institute   (United States)

Author keywords

17 estradiol; Conjugated equine estrogen; Early versus late intervention trial; Kronos early estrogen prevention study; Timing hypothesis; Women s health initiative

Indexed keywords

CONJUGATED ESTROGEN; EQUILIN; ESTRADIOL; ESTROGEN; ESTRONE; GESTAGEN; PROGESTERONE; SEX HORMONE;

CARDIOVASCULAR EFFECT; HEALTH CARE; HORMONAL THERAPY; HUMAN; OUTCOME ASSESSMENT; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; SCIENTIST; WOMEN'S HEALTH; AGE; ANIMAL; COMORBIDITY; DRUG ADMINISTRATION; DRUG FORMULATION; ESTROGEN THERAPY; EVIDENCE BASED MEDICINE; FEMALE; MEDICAL RESEARCH; PATIENT SAFETY; PRACTICE GUIDELINE; PROCEDURES; RISK FACTOR; STANDARDS; TREATMENT OUTCOME;

AGE FACTORS; ANIMALS; BIOMEDICAL RESEARCH; COMORBIDITY; DRUG ADMINISTRATION SCHEDULE; DRUG COMPOUNDING; ESTROGEN REPLACEMENT THERAPY; ESTROGENS; EVIDENCE-BASED MEDICINE; FEMALE; HUMANS; PATIENT SAFETY; POSTMENOPAUSE; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS; TREATMENT OUTCOME;

EID: 85032972475     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00383.2017     Document Type: Review

References (64)

1. Adams MR, Clarkson TB, Kaplan JR, Koritnik DR. Experimental evidence in monkeys for beneficial effects of estrogen on coronary artery atherosclerosis. Transplant Proc 21: 3662–3664, 1989.
2. Adams MR, Kaplan JR, Manuck SB, Koritnik DR, Parks JS, Wolfe MS, Clarkson TB. Inhibition of coronary artery atherosclerosis by 17-β estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. Arteriosclerosis 10: 1051–1057, 1990. doi:10.1161/01.ATV.10.6.1051.
3. Anderson G, Cummings S, Freedman LS, Furberg C, Henderson M, Johnson SR, Kuller L, Manson J, Oberman A, Prentice RL, Rossouw JE; The Women’s Health Initiative Study Group. Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19: 61–109, 1998. doi:10.1016/S0197-2456(97)00078-0.
4. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; 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 291: 1701–1712, 2004. doi:10.1001/jama.291.14.1701.
5. Baber RJ, Panay N, Fenton A; IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric 19: 109–150, 2016. doi:10.3109/13697137.2015.1129166.
6. Biglia N, Cagnacci A, Gambacciani M, Lello S, Maffei S, Nappi RE. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 20: 306–312, 2017. doi:10.1080/13697137.2017.1315089.
7. Boardman HM, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, Gabriel Sanchez R, Knight B. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015: CD002229, 2015.
8. Bray PF, Larson JC, Lacroix AZ, Manson J, Limacher MC, Rossouw JE, Lasser NL, Lawson WE, Stefanick ML, Langer RD, Margolis KL; Women’s Health Initiative Investigators. Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events. Am J Cardiol 101: 1599–1605, 2008. doi:10.1016/j.amjcard.2008.01.043.
9. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 75: 1102–1109, 1987. doi:10.1161/01.CIR.75.6.1102.
10. Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Lévesque H, Trillot N, Barrellier MT, Wahl D, Emmerich J, Scarabin PY; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 115: 840–845, 2007. doi:10.1161/CIRCULATIONAHA.106.642280.
11. Clarkson TB, Meléndez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause 20: 342–353, 2013. doi:10.1097/GME.0b013e3182843aad.
12. Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates. JAMA 271: 289–294, 1994.
13. Criqui MH, Suarez L, Barrett-Connor E, McPhillips J, Wingard DL, Garland C. Postmenopausal estrogen use and mortality. Results from a prospective study in a defined, homogeneous community. Am J Epidemiol 128: 606–614, 1988. doi:10.1093/oxfordjournals.aje.a115008.
14. Faigle JW, Schenkel L. Pharmacokinetics of Estrogens and Progestogens. London: Churchill Livingston, 1998, p. 273–294.
15. Falkeborn M, Persson I, Adami HO, Bergström R, Eaker E, Lithell H, Mohsen R, Naessén T. The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. Br J Obstet Gynaecol 99: 821–828, 1992. doi:10.1111/j.1471-0528.1992.tb14414.x.
16. Farr JN, Khosla S, Miyabara Y, Miller VM, Kearns AE. Effects of estrogen with micronized progesterone on cortical and trabecular bone mass and microstructure in recently postmenopausal women. J Clin Endocrinol Metab 98: E249–E257, 2013. doi:10.1210/jc.2012-3406.
17. Garcia M, Miller VM, Gulati M, Hayes SN, Manson JE, Wenger NK, Bairey Merz CN, Mankad R, Pollak AW, Mieres J, Kling J, Mulvagh SL. Focused cardiovascular care for women: the need and role in clinical practice. Mayo Clin Proc 91: 226–240, 2016. doi:10.1016/j.mayocp.2015.11.001.
18. Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 133: 933–941, 2000. doi:10.7326/0003-4819-133-12-200012190-00008.
19. Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, Hopkins PN, Lobo RA, Manson JEM, Merriam GR, Miller VM, Neal-Perry G, Santoro N, Taylor HS, Vittinghoff E, Yan M, Hodis HN. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med 161: 249–260, 2014. doi:10.7326/M14-0353.
20. Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: the Kronos Early Estrogen Prevention Study. Climacteric 8: 3–12, 2005. doi:10.1080/13697130500042417.
21. Harman SM, Vittinghoff E, Brinton EA, Budoff MJ, Cedars MI, Lobo RA, Merriam GR, Miller VM, Naftolin F, Pal L, Santoro N, Taylor HS, Black DM. Timing and duration of menopausal hormone treatment may affect cardiovascular outcomes. Am J Med 124: 199–205, 2011. doi:10.1016/j.amjmed.2010.09.021.
22. Henderson BE, Paganini-Hill A, Ross RK. Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynecol 159: 312–317, 1988. doi:10.1016/S0002-9378(88)80074-7.
23. Herrington DM, Fong J, Sempos CT, Black DM, Schrott HG, Rautaharju P, Bachorik PS, Blumenthal R, Khan S, Wenger NK. Comparison of the heart and estrogen/progestin replacement study (HERS) cohort with women with coronary disease from the National Health and Nutrition Examination Survey III (NHANES III). Am Heart J 136: 115–124, 1998. doi:10.1016/S0002-8703(98)70191-7.
24. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, Selzer RH, Liu CR, Liu Ch CH, Azen SP; Estrogen in the Prevention of Atherosclerosis Trial Research Group. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 135: 939–953, 2001. doi:10.7326/0003-4819-135-11-200112040-00005.
25. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, Li Y, Feng M, Dustin L, Kono N, Stanczyk FZ, Selzer RH, Azen SP; ELITE Research Group. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med 374: 1221–1231, 2016. doi:10.1056/NEJMoa1505241.
26. Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, Azen SP. The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 128: 262–269, 1998. doi:10.7326/0003-4819-128-4-199802150-00002.
27. Hodis HN, Mack WJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, Budoff MJ, Henderson VW. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause 22: 391– 401, 2015. doi:10.1097/GME.0000000000000343.
28. Hsia J, Langer RD, Manson JE, Kuller L, Johnson KC, Hendrix SL, Pettinger M, Heckbert SR, Greep N, Crawford S, Eaton CB, Kostis JB, Caralis P, Prentice R; Women’s Health Initiative Investigators. Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative. Arch Intern Med 166: 357–365, 2006. doi:10.1001/archinte.166.3.357.
29. Lacut K, Oger E, Le Gal G, Blouch MT, Abgrall JF, Kerlan V, Scarabin PY, Mottier D; SARAH Investigators. Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein. Thromb Haemost 90: 124–131, 2003.
30. Langer RD. The evidence base for HRT: what can we believe? Climacteric 20: 91–96, 2017. doi:10.1080/13697137.2017.1280251.
31. Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, Kuller LH, Cochrane BB, Hunt JR, Ludlam SE, Pettinger MB, Gass M, Margolis KL, Nathan L, Ockene JK, Prentice RL, Robbins J, Stefanick ML; WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med 356: 2591–2602, 2007. doi:10.1056/NEJMoa071513.
32. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wong ND, Crouse JR, Stein E, Cushman M; Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 349: 523–534, 2003. doi:10.1056/NEJMoa030808.
33. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med 340: 1801–1811, 1999. doi:10.1056/NEJM199906103402306.
34. Miller VM, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Naftolin F, Santoro N, Taylor HS, Harman SM. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Transl Res 2: 228–239, 2009. doi:10.1007/s12265-009-9104-y.
35. Miller VM, Duckles SP. Vascular actions of estrogens: functional implications. Pharmacol Rev 60: 210–241, 2008. doi:10.1124/pr.107.08002.
36. Miller VM, Jenkins GD, Biernacka JM, Heit JA, Huggins GS, Hodis HN, Budoff MJ, Lobo RA, Taylor HS, Manson JE, Black DM, Naftolin F, Harman SM, de Andrade M. Pharmacogenomics of estrogens on changes in carotid artery intima-medial thickness and coronary arterial calcification: Kronos Early Estrogen Prevention Study. Physiol Genomics 48: 33–41, 2016. doi:10.1152/physiolgenomics.00029.2015.
37. Miller VM, Petterson TM, Jeavons EN, Lnu AS, Rider DN, Heit JA, Cunningham JM, Huggins GS, Hodis HN, Budoff MJ, Santoro N, Hopkins PN, Lobo RA, Manson JE, Naftolin F, Taylor HS, Harman SM, de Andrade M. Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study. Physiol Genomics 45: 79–88, 2013. doi:10.1152/physiolgenomics.00114.2012.
38. Miller VT, Larosa J, Barnabei V, Kessler C, Levin G, Smithroth A, Griffin M, Stoy DB, Bush T, Zacur H, Foster D, Anderson J, McKenzie A, Miller S, Wood PD, Stefanick ML, Marcus R, Akana A, Heinrichs L, Kirchner C, Ohanlan K, Ruyle M, Sheehan M, Judd HL, Greendale G, Bayalos R, Lozano K, Kawakami K, Barrettconnor E, Langer R, Kritzsilverstein D, Carrionpetersen ML, Cavero C, Schrott HG, Johnson SR, Feddersen DA, Krutzfeldt DL, Benda JA, Pauerstein C, Trabal J, Schenken R, Stern MP, Rodriguezsifuentes M, Easton C, Wells HB, Espeland M, Howard G, Byington R, Legault C, Shumaker S, Hogan P, Hire D, Wasilauskas C, James M, Lane K, Terrell T, Reece S, Pierce J, Snow M, Anthony S, Mebanesims IL, Einhorn P, Hunsberger S, Waclawiw M, Lippel K, Lucas D, Verter J, Jackson S, Kelaghan J, Perlman J, Wolf P, McGowan J, Gordon S, Heyse S, Fradkin J, Sherman S, Page L, Sorenson A, Hulka B, Brody B, Burkman R, Heaney R, Krauss R, Roberts H, Wittes J, Riggs L, Moss R, Albers J, Marcovina S, Fineberg SE, Tracy RP, Merino M, Scully R, Livolsi V, Kessler G; The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Proges-tin Interventions (PEPI) Trial. JAMA 273: 199–208, 1995. doi:10.1001/jama.1995.03520270033028.
39. Moyer AM, de Andrade M, Weinshilboum RM, Miller VM. Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women. Menopause 23: 863–869, 2016. doi:10.1097/GME.0000000000000648.
40. Moyer AM, Miller VM, Faubion SS. Could personalized management of menopause based on genomics become a reality? Pharmacogenomics 17: 659–662, 2016. doi:10.2217/pgs.16.17.
41. Nair GV, Herrington DM. The ERA trial: findings and implications for the future. Climacteric 3: 227–232, 2000. doi:10.1080/13697130008500132.
42. 42a. North American Menopause Society. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause 24: 728-753, 2017.
43. Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and mortality: long-term follow-up of women in the Walnut Creek Study. Obstet Gynecol 70: 289–293, 1987.
44. Rivera CM, Grossardt BR, Rhodes DJ, Brown RD Jr, Roger VL, Melton LJ 3rd, Rocca WA. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 16: 15–23, 2009. doi:10.1097/gme.0b013e31818888f7.
45. Rocca WA, Gazzuola-Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, Kirkland JL, Stewart EA, Miller VM. Accelerated accumulation of multimorbidity after bilateral oophorectomy: a populationbased cohort Study. Mayo Clin Proc 91: 1577–1589, 2016. doi:10.1016/j.mayocp.2016.08.002.
46. Rocca WA, Gazzuola Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, Kirkland JL, Stewart EA, Miller VM. Bilateral oophorectomy and accelerated aging: cause or effect? J Gerontol A Biol Sci Med Sci 72: 1213–1217, 2017. doi:10.1093/gerona/glx026.
47. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 297: 1465–1477, 2007. doi:10.1001/jama.297.13.1465.
48. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; 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: 321–333, 2002. doi:10.1001/jama.288.3.321.
49. Santoro N, Allshouse A, Neal-Perry G, Pal L, Lobo RA, Naftolin F, Black DM, Brinton EA, Budoff MJ, Cedars MI, Dowling NM, Dunn M, Gleason CE, Hodis HN, Isaac B, Magnani M, Manson JE, Miller VM, Taylor HS, Wharton W, Wolff E, Zepeda V, Harman SM. 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 24: 238–246, 2017. doi:10.1097/GME.0000000000000756.
50. Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 17: 3071–3078, 1997. doi:10.1161/01.ATV.17.11.3071.
51. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Køber L, Jensen JE. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 345, oct09 2: e6409, 2012. doi:10.1136/bmj.e6409.
52. Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol 54: 1561–1575, 2009. doi:10.1016/j.jacc.2009.04.098.
53. Shufelt CL, Merz CN, Prentice RL, Pettinger MB, Rossouw JE, Aroda VR, Kaunitz AM, Lakshminarayan K, Martin LW, Phillips LS, Manson JE. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: findings from the Women’s Health Initiative Observational Study. Menopause 21: 260–266, 2014. doi:10.1097/GME.0b013e31829a64f9.
54. Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: long-term health consequences. Maturitas 65: 161–166, 2010. doi:10.1016/j.maturitas.2009.08.003.
55. Sowers MR, Wilson AL, Karvonen-Gutierrez CA, Kardia SR. Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the Study of Women’s Health Across the Nation (SWAN). Am J Med 119, Suppl 1: S103–S110, 2006. doi:10.1016/j.amjmed.2006.07.012.
56. Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 313: 1044–1049, 1985. doi:10.1056/NEJM198510243131703.
57. Stefanick ML, Cochrane BB, Hsia J, Barad DH, Liu JH, Johnson SR. The Women’s Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. Ann Epidemiol 13, Suppl: S78–S86, 2003. doi:10.1016/S1047-2797(03)00045-0.
58. Tanz LJ, Stuart JJ, Williams PL, Rimm EB, Missmer SA, Rexrode KM, Mukamal KJ, Rich-Edwards JW. Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women. Circulation 135: 578–589, 2017. doi:10.1161/CIRCULATIONAHA.116.025954.
59. Tepper PG, Brooks MM, Randolph JF Jr, Crawford SL, El Khoudary SR, Gold EB, Lasley BL, Jones B, Joffe H, Hess R, Avis NE, Harlow S, McConnell DS, Bromberger JT, Zheng H, Ruppert K, Thurston RC. Characterizing the trajectories of vasomotor symptoms across the menopausal transition. Menopause 23: 1067–1074, 2016. doi:10.1097/GME.0000000000000676.
60. Thurston RC, Chang Y, Barinas-Mitchell E, Jennings JR, von Känel R, Landsittel DP, Matthews KA. Physiologically assessed hot flashes and endothelial function among midlife women. Menopause 24: 886–893, 2017. doi:10.1097/GME.0000000000000857.
61. Valdiviezo C, Garovic VD, Ouyang P. Preeclampsia and hypertensive disease in pregnancy: their contributions to cardiovascular risk. Clin Cardiol 35: 160–165, 2012. doi:10.1002/clc.21965.
62. Wild RA, Wu C, Curb JD, Martin LW, Phillips L, Stefanick M, Trevisan M, Manson JE. Coronary heart disease events in the Women’s Health Initiative hormone trials: effect modification by metabolic syndrome: a nested case-control study within the Women’s Health Initiative randomized clinical trials. Menopause 20: 254–260, 2013. doi:10.1097/GME.0b013e31826f80e0.
63. Winham SJ, de Andrade M, Miller VM. Genetics of cardiovascular disease: importance of sex and ethnicity. Atherosclerosis 241: 219–228, 2015. doi:10.1016/j.atherosclerosis.2015.03.021.
64. Wolf PH, Madans JH, Finucane FF, Higgins M, Kleinman JC. Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort. Am J Obstet Gynecol 164: 489–494, 1991. doi:10.1016/S0002-9378(11)80006-2.