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2014 :Updated information on Hormone Replacement Therapy

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New information have been raised on HRT. It seems that with selecting the right regimn and right candidate, HRT could be back again

Text of 2014 :Updated information on Hormone Replacement Therapy

  • GDS_70000_Title_v1 1 HRT : An Update of Evidence Hesham Al-Inany, M.D, PhD
  • Outline Menopausal transition HRT modalities Risks & Benefits Emerging concept
  • What is Menopausal transition? Menopause : permanent cessation of menstruation resulting from loss of ovarian follicular activity (WHO, 2002) Menopausal transition: from the first features of approaching menopause until up to 1 year after final menstrual period Associated with significant hormonal variability over time Overall, decline in estrogen levels over the menopausal transition Burger HG et al. Hormonal changes in the menopause transition. J Clin Endocrinol Metab 2002;84:402530. Copyright 2002, The Endocrine Society. Years around menopause Estradiol(pmol/L) FSH(iu/L) 0 1 2 3 4 5-1-2-3-4 0 20 40 60 80 100 120 0 50 100 150 200 250 300
  • AMH & Menopausal transition (2014) prediction of age of menopause using AntiMullerian Hormone Both AMH and mother's ANM have added value in forecasting TTM for the daughter based on her age (Dlleman M et al, 2014)
  • Signs and Symptoms During the Menopausal Transition Adapted from Bungay G et al. Br Med J 1980;281:1813; Van Keep PA et al. Maturitas 1990;12:16370. Vasomotor Symptoms Sleep Disorders Mood Changes Urogenital Atrophy Dyspareunia Osteoporosis Atherosclerosis Coronary Heart Disease Cerebrovascular Disease 40 yrs 50 yrs Menopause 60 yrs Menstrual Disorders
  • Prevalence of Vasomotor Symptoms by Years to/from the Final Menstrual Period (2008) Meta-analysis of six studies to estimate the natural progression of vasomotor symptoms during the menopause transition : 4- 8 yrs Figure reproduced with kind permission from Springer Science+Business Media: J Gen Intern Med, Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. 23, 2008, 150713, Politi MC, Schleinitz MD, Col NF, Figure 2. Menopause 0 10 20 30 40 50 60 70 80 90 100 Percentagewithvasomotor symptomsvv Years to/from final menstrual period Y-8 Y-7 Y-6 Y-5 Y-4 Y-3 Y-2 Y-1 Y0 Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Y11 Y12 Y13 Y14 Y15 Y16 McKinlay (1974) Gutherie (2003) Thompson (1973) Oldenhave (1993) Berg (1988) Nedstrand (1996)
  • Penn Ovarian Aging Study 2007 Data on 404 women who were followed for a span of 9 years 50% White 50% African American Prevalence and Severity of Symptoms by Menopausal Stage Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, Sheng L. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol 2007;110:23040. 73% Subjects(%) Aches Subjects(%) Decreased libido Subjects(%) Depression 80 60 40 20 0 Subjects(%) Vaginal dryness Subjects(%) Hot flushes Subjects(%) Poor sleep Menopausal stage Menopausal stage Mild Moderate or severe 80 60 40 20 0 80 60 40 20 0 80 60 40 20 0 80 60 40 20 0 80 60 40 20 0
  • Figure modified with permission from Obermeyer CM, Menopause Across Cultures: A Review of the Evidence, Menopause, 7, 3:184-92. Comparative Frequencies of Hot Flushes in Different Parts of the World A review of cross-cultural evidence on vasomotor symptoms from available studies
  • HRT Remains the Most Effective Therapy for Vasomotor Symptoms 2006 No significant efficacy of botanicals in reducing vasomotor symptoms Newton KM et al. Ann Intern Med 2006;145:86979. Reprinted from Annals of Internal Medicine, 145, Newton et al, Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo, 869-879, Copyright (2006), with permission from American College of Physicians. Baseline 3 months 6 months 12 months 0 1 2 3 4 5 6 7 8 Vasomotorsymptomsperday Black Cohosh Multibotanical Multibotanical + soy HRT: CEE +/- MPA Placebo
  • Outline Menopausal transition HRT modalities Risks & Benefits Emerging concept
  • Uterus Sequential therapy without tablet break Regular bleeding at end of cycle How is HRT Given? Continuous Sequential HRT Estrogen Progestogen Day 14 De Villiers TJ et al. Climacteric 2013;16:316337. . Continuous Estrogen Estrogen No tablet break No bleeding as no uterus Uterus Continuous Combined HRT Estrogen Progestogen Day 14 Combined therapy without tablet break No bleeding at end of cycle
  • Estrogens Used in HRT 2007 Equivalent dose for bone endpoints* Estrogen Ultra Low Low Standard High Conjugated equine estrogens (mg) 0.151 0.3 0.625 1.25 Micronized 17-estradiol (mg) 0.52 1 2 4 Estradiol valerate (mg) 1 2 Transdermal 17-estradiol (g) 143 25 50 100 *Estrogenic effects may vary for other endpoints Table reproduced from Maturitas, 40, Gambacciani M, Genazzani AR. Hormone replacement therapy: the benefits in tailoring the regimen and dose. 195201, Copyright (2001), with permission from Elsevier. 1. Lindsay R et al. Obstet Gynecol 1984;63:75963; 2. Panay N et al. Climacteric 2007;10:12031; The Estrogen Dose Counts
  • Estradiol: Benefits on Vasomotor Symptoms Doseresponse effect for reducing moderate-to-severe hot flushes (n=333) Figure reproduced with permission from Notelovitz M, Lenihan JP, Mcdermott M, Kerber IJ, Nanavati N, Arce JC. Initial 17-Estradiol Dose for Treating Vasomotor Symptoms. Obstet Gynecol 2000;95:72631. *p