Emerging Facade of Menopausal Hormone Therapy

ABSTRACT

Menopausal hormone therapy (HT) has been around for 70 years, and in the 1980s and 1990s was considered a universal panacea for women's problems from midlife onward. However, this concept was challenged by the results of the Women's Health Initiative (WHI) and the Million Women Study (MWS) that were first published in 2002 and 2003. Since the publication of these studies, prescriptions of HT have markedly declined and there have been many media scares. An unfortunate sequel was an extrapolation of the observations from women in their 50s and older to those with early ovarian failure. This article discusses the WHI and the MWS with a focus on differences between HT regimens including doses, formulations, and routes, timing, and duration of HT. It addresses practical issues such as strategies for stopping HT, and discusses bioidentical hormones. The specialist knowledge now required to deliver post-reproductive health service has led to considerations that menopause management should be now the responsibility of a specialist and not a general gynecologist.

KEYWORDS

Menopause - hormone therapy - estrogen - progestogen - aging

REFERENCES

• 1 Wilson R A. Feminine Forever. New York, NY; Pocket Books 1968
• 2 Wittes J, Barrett-Connor E, Braunwald E et al. Monitoring the randomized trials of the Women's Health Initiative: the experience of the Data and Safety Monitoring Board.  Clin Trials. 2007;  4(3) 218-234
• 3 Rossouw J E, Anderson G L, Prentice R L Writing Group for the Women's Health Initiative Investigators et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA. 2002;  288(3) 321-333
• 4 Anderson G L, Limacher M, Assaf A R Women's Health Initiative Steering Committee et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.  JAMA. 2004;  291(14) 1701-1712
• 5 Beral V. Million Women Study Collaborators . Breast cancer and hormone-replacement therapy in the Million Women Study.  Lancet. 2003;  362(9382) 419-427
• 6 Shapiro S. Recent epidemiological evidence relevant to the clinical management of the menopause.  Climacteric. 2007;  10(Suppl 2) 2-15
• 7 Shapiro S. Explaining risk. A guide for health professionals.  Maturitas. 2009;  64(3) 143-144
• 8 Rochon P A, Gurwitz J H, Sykora K et al. Reader's guide to critical appraisal of cohort studies: 1. Role and design.  BMJ. 2005;  330(7496) 895-897
• 9 Jadad A R. Randomised Controlled Trials: A User's Guide. London, United Kingdom; BMJ Books 1998
• 10 American Cancer Society .Breast Cancer Facts & Figures 2007–2008. Available at: http://www.cancer.org/downloads/STT/BCFF-Final.pdf Accessed October 8, 2009
• 11 Chlebowski R T, Hendrix S L, Langer R D WHI Investigators et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.  JAMA. 2003;  289(24) 3243-3253
• 12 Manson J E, Hsia J, Johnson K C Women's Health Initiative Investigators et al. Estrogen plus progestin and the risk of coronary heart disease.  N Engl J Med. 2003;  349(6) 523-534
• 13 Hellgren M, Conard J, Norris L, Kluft C. Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone.  Maturitas. 2009;  62(3) 287-293
• 14 Hsia J, Langer R D, Manson J E Women's Health Initiative Investigators et al. Conjugated equine estrogens and coronary heart disease: the Women's Health Initiative.  Arch Intern Med. 2006;  166(3) 357-365
• 15 Weiderpass E, Adami H O, Baron J A et al. Risk of endometrial cancer following estrogen replacement with and without progestins.  J Natl Cancer Inst. 1999;  91(13) 1131-1137
• 16 Lacey Jr J V, Leitzmann M F, Chang S C et al. Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort.  Cancer. 2007;  109(7) 1303-1311
• 17 Pukkala E, Tulenheimo-Silfvast A, Leminen A. Incidence of cancer among women using long versus monthly cycle hormonal replacement therapy, Finland 1994–1997.  Cancer Causes Control. 2001;  12(2) 111-115
• 18 Anderson G L, Judd H L, Kaunitz A M Women's Health Initiative Investigators et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial.  JAMA. 2003;  290(13) 1739-1748
• 19 Weiderpass E, Baron J A, Adami H O et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study.  Lancet. 1999;  353(9167) 1824-1828
• 20 Canonico M, Plu-Bureau G, Lowe G D, Scarabin P Y. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.  BMJ. 2008;  336(7655) 1227-1231
• 21 Rossouw J E, Prentice R L, Manson J E et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause.  JAMA. 2007;  297(13) 1465-1477
• 22 Grodstein F, Manson J E, Stampfer M J. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation.  J Womens Health (Larchmt). 2006;  15(1) 35-44
• 23 Prentice R L, Manson J E, Langer R D et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause.  Am J Epidemiol. 2009;  170(1) 12-23
• 24 Miller V M, Black D M, Brinton E A et al. 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. 2009;  2(3) 228-239
• 25 Zandi P P, Carlson M C, Plassman B L Cache County Memory Study Investigators et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study.  JAMA. 2002;  288(17) 2123-2129
• 26 Shumaker S A, Legault C, Rapp S R WHIMS Investigators 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. 2003;  289(20) 2651-2662
• 27 Shumaker S A, Legault C, Kuller L Women's Health Initiative Memory Study 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) 2947-2958
• 28 Shuster L T, Rhodes D J, Gostout B S, Grossardt B R, Rocca W A. Premature menopause or early menopause: long-term health consequences.  Maturitas. 2010;  65(2) 161-166
• 29 Ewertz M, Mellemkjaer L, Poulsen A H et al. Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study.  Br J Cancer. 2005;  92(7) 1293-1297
• 30 Rivera C M, Grossardt B R, Rhodes D J et al. Increased cardiovascular mortality after early bilateral oophorectomy.  Menopause. 2009;  16(1) 15-23
• 31 Politi M C, Schleinitz M D, Col N F. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis.  J Gen Intern Med. 2008;  23(9) 1507-1513
• 32 Col N F, Guthrie J R, Politi M, Dennerstein L. Duration of vasomotor symptoms in middle-aged women: a longitudinal study.  Menopause. 2009;  16(3) 453-457
• 33 Al-Azzawi F, Barlow D, Hillard T, Studd J, Williamson J, Rees M. Writing Group on Osteoporosis for the British Menopause Society Council . Prevention and treatment of osteoporosis in women.  Menopause Int. 2007;  13(4) 178-181
• 34 Bagger Y Z, Tankó L B, Alexandersen P et al. Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study.  Bone. 2004;  34(4) 728-735
• 35 Gallagher J C, Sai A J. Molecular biology of bone remodeling: implications for new therapeutic targets for osteoporosis.  Maturitas. 2010;  65(4) 301-307
• 36 Kanis J A, McCloskey E V, Johansson H, Strom O, Borgstrom F, Oden A. National Osteoporosis Guideline Group . Case finding for the management of osteoporosis with FRAX—assessment and intervention thresholds for the UK.  Osteoporos Int. 2008;  19(10) 1395-1408
• 37 Compston J, Cooper A, Cooper C National Osteoporosis Guideline Group (NOGG) et al. Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK.  Maturitas. 2009;  62(2) 105-108
• 38 Ockene J K, Barad D H, Cochrane B B et al. Symptom experience after discontinuing use of estrogen plus progestin.  JAMA. 2005;  294(2) 183-193
• 39 Lindh-Astrand L, Brynhildsen J, Hoffman M, Hammar M. Vasomotor symptoms usually reappear after cessation of postmenopausal hormone therapy: a Swedish population-based study.  Menopause. 2009;  16(6) 1213-1217
• 40 Haskell S G, Bean-Mayberry B, Gordon K. Discontinuing postmenopausal hormone therapy: an observational study of tapering versus quitting cold turkey: is there a difference in recurrence of menopausal symptoms?.  Menopause. 2009;  16(3) 494-499
• 41 Beatty M N, Blumenthal P D. The levonorgestrel-releasing intrauterine system: safety, efficacy, and patient acceptability.  Ther Clin Risk Manag. 2009;  5(3) 561-574
• 42 Raudaskoski T, Tapanainen J, Tomás E et al. Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response.  BJOG. 2002;  109(2) 136-144
• 43 Backman T, Rauramo I, Jaakkola K et al. Use of the levonorgestrel-releasing intrauterine system and breast cancer.  Obstet Gynecol. 2005;  106(4) 813-817
• 44 Lyytinen H K, Dyba T, Ylikorkala O, Pukkala E I. A case-control study on hormone therapy as a risk factor for breast cancer in Finland: intrauterine system carries a risk as well.  Int J Cancer. 2010;  126(2) 483-489
• 45 Oskay U Y, Beji N K, Yalcin O. A study on urogenital complaints of postmenopausal women aged 50 and over.  Acta Obstet Gynecol Scand. 2005;  84(1) 72-78
• 46 Rees M, Stevenson J, Hope S. Management of the Menopause. 5th ed. Leeds, United Kingdom; Royal Society of Medicine Press 2009
• 47 Notelovitz M, Funk S, Nanavati N, Mazzeo M. Estradiol absorption from vaginal tablets in postmenopausal women.  Obstet Gynecol. 2002;  99(4) 556-562
• 48 Palacios S. Managing urogenital atrophy.  Maturitas. 2009;  63(4) 315-318
• 49 Chervenak J. Bioidentical hormones for maturing women.  Maturitas. 2009;  64(2) 86-89
• 50 Gebbie A, Rees M. Post-reproductive gynaecology.  In: Models of Care in Women's Health. London, United Kingdom; RCOG Press 2009: 81-88