Skip to main content
SpringerLink
Log in

Hormone Therapy in Menopause

  • Chapter
  • First Online:
Hormonal Pathology of the Uterus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1242))

Abstract

As longevity expands, women are spending a third of their existence in menopause and beyond. The vast majority suffer from symptoms that negatively impact their quality of life. Systemic vasomotor symptoms (VMS) are the classic cluster affecting 80% of peri- and post-menopausal women. Once thought to be relatively brief, they sometimes persist more than 10 years. Compelling, yet enigmatic, is the recent finding that women with bothersome and long VMS compared with age-matched peers often have worst underlying preclinical markers of cardiovascular disease (CVD).

Local vulvovaginal and urinary symptoms, now termed genitourinary syndrome of menopause (GSM), are seen in 50% of postmenopausal women, and it negatively impacts quality of life. Estrogen remains the most effective treatment for both VMS and GSM, for osteoporosis prevention, and for symptom relief as well as chronic disease prevention in women who experience premature menopause whether from primary ovarian insufficiency (POI) or iatrogenic etiologies. For women who have contraindications to estrogen therapy or who personally object, a panoply of nonhormonal modalities can be offered to treat both systemic and local menopausal symptoms. A historical review of estrogen studies reveals why its persona has vacillated from hero to villain (after the WHI) and back to hero. The “timing hypothesis” and its underlying mechanism shed light on the pleiotropic nature of estrogen. Finally reviewed is the compelling argument from notable thought-leaders that estrogen, in those without contraindications, should be considered for primary prevention of cardiovascular disease as well as the prevention of chronic disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Carotid ultrasound measurement of carotid artery intimal media thickness (CIMT), also used in the KRONOS and KEEPS studies to test the timing hypothesis, is an accepted surrogate for measurement of CVD risk.

  2. 2.

    FMD is performed by first measuring the resting diameter of the brachial artery with ultrasound, then distally placing a blood pressure cuff and stressing the artery by inflating it 40 mm above the systolic BP for 4 min, then deflating the cuff and, 2 min later, measuring the final brachial artery diameter. The calculation formula is FMD = 100 × peak diameter after cuff deflation minus resting diameter divided by resting diameter) is an accepted surrogate marker for endothelial dysfunction.

References

  1. Menopause practice: a clinician’s guide. North American Menopause Society; 2014.

    Google Scholar 

  2. Murphy SL, Xu J, Kockanek KD. Deaths: final data for 2010. Natl Vital Stat Rep. 2013;61(4):1–117.

    PubMed  Google Scholar 

  3. Pinkerton JV, Aguirre FS, Blake J, Hodis H, et al. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause. 24(7):728–53.

    Google Scholar 

  4. Stuenkel C, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice guideline. J Clin Endocrinol Metab. 2015;100:3975–4011.

    Article  CAS  PubMed  Google Scholar 

  5. Sayegh R, Awwad JT. Five decades of hormone therapy research: the long, the short, and the inconclusive. In: Essentials of menopause management. Springer; 2017.

    Google Scholar 

  6. Bush TL, et al. Estrogen use and all cause mortality: preliminary results from the lipid research clinics program follow-up study. JAMA. 1983;249:903–6.

    Article  CAS  PubMed  Google Scholar 

  7. Ross RK, et al. Menopausal oestrogen therapy and protection from death from ischemic heart disease. Lancet. 1981;1:858–60.

    Article  CAS  PubMed  Google Scholar 

  8. Pfeffer RI, et al. Coronary risk and estrogen use in postmenopausal women. Am. J Epidemiol. 1978;107:479–87.

    Article  CAS  Google Scholar 

  9. Bain C, et al. Use of postmenopausal hormones and risk of myocardial infarction. Circulation. 1981;64:42–6.

    Article  CAS  PubMed  Google Scholar 

  10. Lobo RA, Pickar JH, Stevenson JC, Mack WJ, Hodis HN. Back to the future: hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis. 2016;254:296–304.

    Article  CAS  Google Scholar 

  11. Stampfer MJ, et al. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63.

    Article  CAS  PubMed  Google Scholar 

  12. Grodstein F, et al. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997;336:1769–75.

    Article  CAS  PubMed  Google Scholar 

  13. Yaffe K, et al. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA. 1998;279:688–95.

    Article  CAS  PubMed  Google Scholar 

  14. Henderson BE, et al. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med. 1991;151:75–8.

    Article  CAS  PubMed  Google Scholar 

  15. Grady D, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016–37.

    Article  CAS  PubMed  Google Scholar 

  16. Stampfer MJ, et al. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med. 1985;313:1044–9.

    Article  CAS  PubMed  Google Scholar 

  17. Bush TL, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the lipid research clinics follow-up study. Circulation. 1987;75:1102–9.

    Article  CAS  PubMed  Google Scholar 

  18. Henderson BE, Paganini-Hill A, Ross RK. Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynecol. 1988;159:312–7.

    Article  CAS  PubMed  Google Scholar 

  19. American College of Physicians. Guidelines for counselling postmenopausal women about preventive hormone therapy. Ann Intern Med. 1992;117:1038–41.

    Article  Google Scholar 

  20. Greendale GA. Symptom relief and side effects of postmenopausal hormones: results from the PEPI trial Obstet. Gynecologie. 1998;92:982–8.

    CAS  Google Scholar 

  21. Writing Group for the PEPI trial. Effects of hormone therapy on bone mineral density: results from the PEPI tria. JAMA. 1996;276:1389–96.

    Article  Google Scholar 

  22. Hully S. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998;280:605.

    Article  Google Scholar 

  23. Miller V, Clarkson T. Women, hormones and clinical trials: a beginning, not an end. J Appl Physiol. 2005;99:381.

    Article  PubMed  Google Scholar 

  24. Langer RD. The evidence base for HRT: what can we believe. Climacteric. 2017;20:91–6.

    Article  CAS  PubMed  Google Scholar 

  25. Lobo R. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol. 2017;13:220.

    Google Scholar 

  26. Sprague BL, et al. Sustained decline in postmenopausal use: results from the National Health and Nutrition Examination Survey. Obstet Gynecol. 2012;120:595–603.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Karim R, et al. Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study from a large HMO. Menopause. 2011;18:1172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Islam S, et al. Trend in incidence of osteoporosis-related fractures among 40-69 year-old women: analysis of claims database, 2000-2005. Menopause. 2009;16:77–83.

    Article  PubMed  Google Scholar 

  29. Mikkola TS, Tuomikowski P, Lyytinen H, et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab. 2015;100(12):4588–94.

    Article  CAS  PubMed  Google Scholar 

  30. Sarrel P, et al. The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50-59 years. Am J Public Health. 2013;103:1583–8.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lacroix AZ, Chlebowski RT, Manson JE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305:1305–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Burger HG, et al. Evidence-based assessment of the impact of the WHI on women’s health. Climacteric. 2012;15:281–7.

    Article  CAS  PubMed  Google Scholar 

  33. Marko K, Simon JA. Clinical trials in menopause. Menopause. 2018;25:217.

    Article  PubMed  Google Scholar 

  34. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465–77.

    Article  CAS  PubMed  Google Scholar 

  35. Salpeter SR, Walsh JM, Grayber E, Salpeter EE. Brief report: coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med. 2006;21:363–6.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Clarkson TB, Mehaffey M. Coronary heart disease of females: lessons learned from nonhuman primates. Am J Primatol. 2009;71:785–93.

    Article  PubMed  Google Scholar 

  37. Clarkson TB, Melendez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause. 2013;20(3):342–53.

    Article  PubMed  Google Scholar 

  38. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308:1583–7.

    Article  CAS  PubMed  Google Scholar 

  39. Harman SM, Black DM, Naftolin F, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014;161:249–60.

    Article  PubMed  Google Scholar 

  40. Miller VM, Naftolin F, Asthana S, et al. The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned? Menopause. 2019;26(9):1–14.

    Google Scholar 

  41. Taylor HS, Tal A, Pal L, et al. Effects of oral versus transdermal estrogen therapy on sexual function in early post-menopause: ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. 2017;177:1471–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hodis HN, Mack WJ, Shoupe D, et al. Methods and baseline cardiovascular data from the early versus late intervention trial with estradiol testing the menopausal hormone timing hypothesis. Menopause. 2014;22(4):391–401.

    Article  Google Scholar 

  43. Sriprasert I, Hodis HN, Karim R, Stancyk FZ, Shoupe D, Henderson VW, Mack W. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early vs late postmenopause. J Clin Endocrinol Metab. 2019;104(2):2930300.

    Article  Google Scholar 

  44. Sturdee DW, Hunter MS, Maki PM, et al. The menopausal hot flush: a review. Climacteric. 2017;20(4):296–305.

    Article  CAS  PubMed  Google Scholar 

  45. Thurston RC. Vasomotor symptoms: natural history, physiology, and links with cardiovascular health. Climacteric. 2018;21(2):96–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Smith RL, Gallicchio LM, Flaws JA. Understanding the complex relationships underlying hot flashes: a Bayesian network approach. Menopause. 2018;25(2):182–90.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Carson MY, Thurston RC. Childhood abuse and vasomotor symptoms among midlife women. Menopause. 2019;26(10):1–7.

    Article  Google Scholar 

  48. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol. 2014;142:115–20.

    Article  CAS  PubMed  Google Scholar 

  49. Rance NE, Dacks PA, Mittleman-Smith M, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B, and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013;34:211–27.

    Google Scholar 

  50. Casper RF, Yen SSC. Menopausal flushes: effect of pituitary gonadotropin desensitization by a potent luteinizing hormone-releasing factor agonist. J Clin Endocrinol Metab. 1981;53:1056–8.

    Article  CAS  PubMed  Google Scholar 

  51. Gambone J, Meldrum DR, Laufer L, et al. Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes. J Clin Endocrinol Metab. 1984;59:1097–102.

    Article  CAS  PubMed  Google Scholar 

  52. Szeliga A, Czyzk A, Podfigurna A, Genazzani AD, Meczelalski B. The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications. Gynecol Endocrinol. 2018;34(11):913–9.

    Article  CAS  PubMed  Google Scholar 

  53. Skorupskaite K, George J, Anderson R. The Kisspeptin-GNRH pathway in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Padilla S, Johnson C, Barker F, Patterson M, Palmiter R. A neural circuit underlying the generation of hot flushes. Cell Rep. 2018;24:271–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Prague J, Roberts R, Dhillo W. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018;25(8):862–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Crandall CJ, Manson J, Hohensee C, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s Health Initiative study. Menopause. 2017;24:252–61.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Prague JK, Roberts RE, Comninos AN, et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389(10081):1809–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database System Rev. 2004;4:CD002978.

    Google Scholar 

  59. Ockene JK, Barad DH, Cochrane BB, et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005;294:183–93.

    Article  CAS  PubMed  Google Scholar 

  60. Brunner RL, Aragaki A, Barnabei V, et al. Menopausal symptom experience before and after stopping estrogen therapy in the Women’s Health Initiative randomized, placebo-controlled trial. Menopause. 2010;17:946–54.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Carpenter J, Gass M, Maki PM. Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of the North American Menopause Society. Menopause. 2015;22(11):1155–74.

    Article  Google Scholar 

  62. Simon JA, Portman DJ, Kaunitz AM, et al. Low-dose paroxetine 7.5 mg for menopausal VMS: two randomized controlled trials. Menopause. 2013;20:1027–35.

    Article  PubMed  Google Scholar 

  63. Reddy SY, Warner H, Guttoso T Jr, et al. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol. 2006;108:41–8.

    Article  CAS  PubMed  Google Scholar 

  64. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057–71.

    Article  CAS  PubMed  Google Scholar 

  65. Nappi RE, Palacios S, Particco M, Panay N. The REVIVE (real Women’s views of treatment options for menopausal vaginal changes) survey in Europe: country-specific comparisons of postmenopausal women’s perceptions, experiences, and needs. Maturitas. 2016;91:81–90.

    Article  PubMed  Google Scholar 

  66. Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, Views, and Attitudes (VIVA)—results from an international survey. Climacteric. 2012;15:36–44.

    Article  CAS  PubMed  Google Scholar 

  67. Nappi RE, Palacios S, Bruyniks N, et al. The burden of vulvovaginal atrophy on women’s daily living: implications on quality of life from a face-to-face real-life survey. Menopause. 2019;26(5):485–91.

    Article  PubMed  Google Scholar 

  68. Cook E, Iglehart E, Baum G, et al. Missing documentation in breast cancer survivors: genitourinary syndrome of menopause. Menopause. 2017;24(12):1360–4.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013;20(9):888–902.

    Google Scholar 

  70. Santen RJ. Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels. Climacteric. 2015;18:121–34.

    Article  CAS  PubMed  Google Scholar 

  71. Rahn DD, Carberry C, Sanses TV, et al. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2015;124:1147–56.

    Article  CAS  Google Scholar 

  72. Soe LH, Wurz GT, Koa CJ, et al. Ospemiphene for the treatment of dyspareunia associated with vulvar and vaginal atrophy: potential benefits in bone and breast Int. J Women's Health. 2013;5:605–11.

    Google Scholar 

  73. Labrie F, Archer D, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and the genitourinary syndrome of menopause. Menopause. 2016;25(11):1339–53.

    Article  Google Scholar 

  74. Labrie F, Belanger A, Pellitier G, Martel C, Archer D, Utian W. Science of intracrinology in postmenopausal women. Menopause. 2017;24(6):702–12.

    Article  PubMed  Google Scholar 

  75. Faubion S, Stuenkel C, Chism L, Kaunitz AM, Parish SJ, Pinkerton JV, Shapiro M, Simon JA, Kingsberg SA. Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: consensus recommendations from the North American Menopause Society and the International Society for the Study of Women’s Sexual Health. Menopause. 2018;25(6):596–608.

    Article  PubMed  Google Scholar 

  76. Martel C, Labrie F, Archer DF, et al. Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5 mg intravaginal prasterone for 12 weeks. J Steroid Biochem Mol Biol. 2016;159:142–53.

    Article  CAS  PubMed  Google Scholar 

  77. Hodgins M, Spike R, Mackie R, MacLean A. An immunohistochemical study of androgen, oestrogen, and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol. 1998;105:216–22.

    Article  CAS  PubMed  Google Scholar 

  78. Melisko M, Goldman M, Hwang J, et al. Vaginal testosterone cream vs estradiol vaginal ring for vaginal dryness or decreased libido in women receiving aromatase inhibitors for early-stage breast cancer: a randomized clinical trial. JAMA Oncol. 2017l;3:313–9.

    Article  PubMed  Google Scholar 

  79. Salvatore S, Maggiore ULR, Athanasiou S, et al. Histological study on the effects of micro-ablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015;22(8):845–9.

    Article  PubMed  Google Scholar 

  80. Pagano T, De Rosa P, Vallone R, et al. Fractional micro-ablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of non-estrogenic treatments: a retrospective study. Menopause. 2018;25:657–62.

    Article  PubMed  Google Scholar 

  81. Ogawa H, Nakayama M, Morimoto T. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134–41.

    Article  CAS  PubMed  Google Scholar 

  82. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375:725–42.

    Google Scholar 

  83. Mikkola TS, Tuomikoski P, Lyytinen H, et al. Estradiol-based post-menopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause. 2015;22:976–83.

    Article  PubMed  Google Scholar 

  84. Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab. 2012;23(11):576–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Savolainen-Peltonen H, Tuomikoski P, Korhonen P, et al. Cardiac death risk in relation to the age at initiation or the progestin component of hormone therapies. J Clin Endocrin Metab. 2016;101:2794–801.

    Article  CAS  Google Scholar 

  86. Nelson LM. Primary ovarian insufficiency. NEJM. 2009;360(6):606–14.

    Article  CAS  PubMed  Google Scholar 

  87. Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril. 2016;106(7):1588–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Scarabin PY, Oger E, Plu-Bureau G. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003;362:428–32.

    Article  CAS  PubMed  Google Scholar 

  89. Popat VB, Calis KA, Kalantaridou SN, et al. Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement. J Clin Endocrinol Metab. 2014;99:3148–26.

    Article  CAS  Google Scholar 

  90. Stanczyk FZ, Hapgood JP, Winer D, Mishell D Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34(2):171–208.

    Article  CAS  PubMed  Google Scholar 

  91. Gompel A. Micronized progesterone and its impact on the endometrium and breast vs. progestogens. Climacteric. 2012;15(1):18–25.

    Article  CAS  PubMed  Google Scholar 

  92. Mann E, Singer D, Pitkin J, Panay N, Hunter MS. Psychosocial adjustment in women with premature menopause: a cross-sectional survey. Climacteric. 2012;15:481–9.

    Article  CAS  PubMed  Google Scholar 

  93. Thurston RC, El Khoudary SR, Tepper PG, et al. Trajectories of vasomotor symptoms and carotid intima media thickness in the study of Women’s health across the nation. Stroke. 2016;47:12–7.

    Article  PubMed  Google Scholar 

  94. L’Hermite M. HRT optimization using transdermal estradiol plus micronized progesterone, a safer HRT. Climacteric. 2013;6(1):44–53.

    Article  CAS  Google Scholar 

  95. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107:103–11.

    Article  CAS  PubMed  Google Scholar 

  96. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol-progestogen therapy. Obstet Gynecol. 2009;113:65–73.

    Article  PubMed  Google Scholar 

  97. Schnatz P, Pinkerton J, Utian W, Appt S, de Villiers T, Henderson V, Hodis H, Kaunitz A, Maki P, Manson J, Richard-Davis G, Santoro N, Sarrel P, Shifren J, Simon J, Stuenkel C. NAMS translational science symposium report a conversation about hormone therapy: is there an appropriate dose, route, and duration of use. Menopause. 2017;24(11):1221–35.

    Article  Google Scholar 

  98. Kaunitz A, Manson J. Management of Menopausal Symptoms. Obstet Gynecol. 2015;126(4):859–76.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Chen W, Rosner B, Hankinson SE, Colditz GA, Willett WC. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA. 2011;306:1184–890.

    Google Scholar 

  100. US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: USPSTF Recommendation Statement. JAMA. 2017;318:2224–33.

    Article  Google Scholar 

  101. Langer R, Simon J, Pines A, Lobo R, Hodis H, Pickar J, Archer D, Sarrel P, Utian W. Menopausal hormone therapy for primary prevention: why the USPSTF is wrong. Menopause. 2017;24(10):1101–12.

    Article  PubMed  Google Scholar 

  102. Lobo R, Davis S, De Villiers T, et al. Prevention of diseases after menopause. Climacteric. 2014;17:540–56.

    Article  CAS  PubMed  Google Scholar 

  103. Walsh JM, Pignone M. Drug treatment of hyperlipidemia in women. JAMA. 2004;291:2243–52.

    Article  CAS  PubMed  Google Scholar 

  104. Petretta M, Costanzo P, Perrone-Filardi P. Impact of gender in primary prevention of coronary heart disease with statin therapy: a meta-analysis. Int J Cardiol. 2010;138:25–31.

    Article  PubMed  Google Scholar 

  105. Brughts JJ, Yetkin T, Hoeks SE. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trials. BMJ. 2009;338:b2376.

    Article  Google Scholar 

  106. Berger JS, Roncaglioni C, Avanzini F. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006;295:306–13.

    Article  CAS  PubMed  Google Scholar 

  107. Ridker PM, Cook NR, Lee IM. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM. 2005;352:1293–304.

    Article  CAS  PubMed  Google Scholar 

  108. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3(47):1–10.

    Google Scholar 

  109. Miller VM, Mitchell Harman S. An update on hormone therapy in postmenopausal women: mini-review for the basic scientist. Am J Physiol Heart Circ Physiol. 2017;313(5):H1013–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Hodis HN, Mack WJ. Cardiovascular risk after withdrawal of hormone therapy. Menopause. 2018;25(4):365–7.

    Article  PubMed  Google Scholar 

  111. Tepper P, Randolph J, Jones B, et al. Trajectory patterns of vasomotor symptoms over the menopausal transition in the study of women’s health across the nation. Menopause. 2013;20:1356.

    Google Scholar 

  112. Labrie F. Intracrinology and menopause: the science describing the cell-specific intracellular formation of estrogens and androgens from DHEA and their strictly local action and inactivation in peripheral tissues. Menopause. 2018;26(2):220–4.

    Article  Google Scholar 

  113. Modi M, Dhillo W. Neurokinin 3 receptor antagonism: a novel treatment for menopausal hot flushes. Neuroendocrinology. 2018;109(3):242–8. https://doi.org/10.1159/000495889.

    Article  CAS  PubMed  Google Scholar 

  114. Thurston RC, Johnson BD, Shufelt CL, Braunstein GD, Berga SL, Stanczyk FZ, Pepine CJ, Bittner V, Reis SE, Thompson DV, Kelsey SF, Sopko G, Merz CN. Menopausal symptoms and cardiovascular disease mortality in the Women’s Ischemia Syndrome Evaluation (WISE). Menopause. 2017;24(2):126–32.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Thurston RC, Chang Y, Barinas-Mitchell E, et al. Menopausal hot flashes and carotid intima media thickness among midlife women. Stroke. 2016;47:2910–5.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. NEJM. 1999;340(23):1801–11.

    Article  CAS  PubMed  Google Scholar 

  117. Hodis HN, Mack WJ, Henderson VW, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. NEJM. 2016;374(13):1221–31.

    Article  CAS  PubMed  Google Scholar 

  118. Baber RJ, Panay N, Fenton A, the IMS Writing Group. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lenox Hill Hospital, Mount Sinai Hospital, New York, NY, USA

    John Paciuc

Authors
  1. John Paciuc
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Professor Emeritus, Department of Pathology, Department of Obstetrics-Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Liane Deligdisch-Schor

  2. New York Medical College, Westchester Medical Center, Valhalla, NY, USA

    Angelica Mareş Miceli

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Paciuc, J. (2020). Hormone Therapy in Menopause. In: Deligdisch-Schor, L., Mareş Miceli, A. (eds) Hormonal Pathology of the Uterus . Advances in Experimental Medicine and Biology, vol 1242. Springer, Cham. https://doi.org/10.1007/978-3-030-38474-6_6

Download citation

Publish with us

Policies and ethics

Search

Navigation