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1. 2013 IMSrecommendations on menopausal hormone therapy and preventive strategies for midlife health – what’s new?Dobar Dan, Kako Ste?Nick PanayImmediate Past Chairman, British Menopause SocietyCo-Editor in Chief, Climacteric www.imsociety.org

2. Brijuni 2013 Memories!

3. Introduction – “the new consensus” The International Menopause Society took the initiative to arrange a round table discussion between representatives of the major regional menopause societies to agree on core recommendations regarding MHT It is acknowledged that in view of the global variance of disease and regulatory restrictions, these core recommendations should be read in the context of the more detailed recommendations prepared by the national and regional societies

4. Key aims of the workshop were, using new data, to reach a consensus on… • Global variations in presentation of menopause and usage of HRT and alternatives • The influence of age and time since menopause regarding HRT outcomes • The importance of dosage and type of estrogen and progestogen on safety and efficacy outcomes • Differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT)

5. IMS Consensus Workshop: 9th November 2012 Parishosted by Prof Anne Gompel • Introductory lectures, followed by updates from International experts and focused discussion on text of the new IMS recommendations to produce • A Global Consensus Document for simultaneous publication in Climacteric & Maturitas: April 2013 • Full evidence based updated recommendations : June 2013

6. Introduction 1 – Robert Langer: “Review of HT studies” Future data may come from patient registries and prospective observation of practice rather than RCTs Regimens with transdermal estradiol and natural progesterone should be studied in younger cohorts to confirm efficacy and safety outcomes such as breast cancer Journals should standardise they way in which data on HRT are presented to facilitate uniform reporting and interpretation of data by the media and public.

7. Introduction 2 – Rod Baber: “When East meets West” • Racial / ethnic differences evident in symptomatic responses to • menopause, • hormone levels, • burden of diseases • Results of Caucasian-based studies cannot be systematically extrapolated to Asian women • Any global consensus on the use of HRT should take into account global variations in menopausal symptoms and menopause related disorders

8. Introduction 3 – David Archer: “A world without HT” The WHI resulted in a significant decline in prescribing of Hormone Therapy Cardiovascular outcomes have not changed based on limited data – however, changes may be seen in the next 5-10 years Breast Cancer Incidence in the United States fell post WHI but had started to fall prior to initial reporting Hip Fracture Risk increased after Hormone Therapy was stopped Other outcomes e.g. mortality rates may become evident as time goes by……

9. Estrogen-only therapy in women aged 50 to 59 declined nearly 79 percent between 2001 and 2011 Minimum 18,601 – maximum 91,610 (probably around 50,000) excess deaths can be attributed to estrogen avoidance! Sarrel PM, Njike VY, Vinante V, Katz DL. The Mortality Toll of Estrogen Avoidance: An Analysis of Excess Deaths Among Hysterectomized Women Aged 50 to 59 Years. Am J Public Health. 2013; 103(9): 1583-1588.

10. Introduction 4 : Tom Parkhill: HT and the Media Any criticism of the media should be positive; the message is often complex – tell them what is important! There is a “media culture”. Bad news make headlines, but they have a responsibility to keep things in context Breast Cancer is the main issue because women fear this the most. Need to make journalists and public realise that WHI opinion has moved on Put benefits and risks into context – absolute rather than relative risk

11. Published in Climacteric and Maturitas April 2013

12. Published in Climacteric June 2013

13. Consensus 2013: MHT The option of MHT is an individual decision in terms of quality of life and health priorities as well as personal risk factors such as age, time since menopause and the risk of thrombo-embolism, stroke, ischemic heart disease and breast cancer The dose and duration of MHT should be consistent with treatment goals and should be individualized MHT is the most effective treatment for moderate to severe menopausal symptoms before the age of 60 years or within 10 years after menopause

14. Consensus 2013: MHT Local low dose estrogen therapy is preferred for women whose symptoms are limited to vaginal dryness or associated discomfort with intercourse. Estrogen as a single systemic agent is appropriate in women after hysterectomy but additional progestogen is required in the presence of a uterus The use of custom compounded bio-identical hormone therapy is not recommended

15. Consensus 2013: Osteoporosis MHT is an effective treatment for the prevention of fracture in at risk women before age 60 years or within 10 years after menopause Tobie De Villiers

16. Consensus 2013: Cardiovascular Disease Randomised clinical trials (RCT) and observational data as well as meta-analyses have provided strong evidence that standard dose estrogen alone MHT decreases coronary disease and all cause mortality in women younger than 60 years of age and within 10 years of menopause. Data on estrogen plus progestogen in this population show a similar trend but with less precision. Roger Lobo

17. Consensus 2013: Cardiovascular disease MHT does not cause an increase in coronary events in healthy women less than 60 years of age or within 10 years of menopause. Roger Lobo Key Data: KEEPS 2012 NAMS & DOPS 2012 BMJ

18. Consensus 2013: Venous thromboembolism The risk of venous thromboembolism (VTE) and ischemic stroke increases with oral MHT but the absolute risk is rare below age 60 years. Observational studies point to a lower risk with transdermal therapy. Genevieve Plu Bureau

19. Consensus 2013: Breast Cancer The risk of breast cancer in women over 50 years associated with MHT is a complex issue The increased risk of breast cancer is primarily associated with the addition of a progestogen to estrogen therapy and related to the duration of use Anne Gompel

20. Consensus 2013:Breast Cancer The risk of breast cancer attributable to MHT is small and the risk decreases after treatment is stopped. There is a lack of safety data supporting the use of MHT (estrogen therapy(ET) or estrogen progestogen therapy (EPT)) in breast cancer survivors. Anne Gompel

21. Consensus 2013: Early Menopause In women with premature ovarian insufficiency, systemic MHT is recommended until the average age of the natural menopause.

22. Recommendations 2013: Testosterone The primary indication for testosterone is for the treatment of desire/arousal disorder Several large placebo-controlled RCTs have consistently show benefits of testosterone for for sexual satisfaction, desire, arousal, pleasure and orgasm in.. …surgical, natural menopause, no HT and in pre menopause Susan Davis

23. Recommendations 2013: Testosterone Other potential benefits of testosterone therapy which require confirmation in large RCTs, include prevention of bone loss, maintenance of muscle mass and strength, maintenance of cognitive performance and favourable cardiovascular effects. Androgenic side effects with testosterone therapy are dose related and avoidable. There is no evidence from large placebo controlled RCTs that transdermal testosterone in appropriate doses for women results in adverse metabolic or endometrial effects Susan Davis

24. Recommendations 2013: Vaginal Atrophy • Postmenopausal women have a poor understanding of vaginal atrophy. Vaginal atrophy is still a taboo subject, even among mothers and their daughters • While most women say they would talk to their doctors about the symptoms of vaginal atrophy, in reality, many wait too long to discuss their symptoms with their doctors • It is essential that health-care attendants routinely engage in open and sensitive discussion with postmenopausal women about their urogenital health to ensure that symptomatic atrophy is detected early and managed appropriately. David Sturdee

25. Recommendations 2013: Vaginal Atrophy • All local estrogen preparations are effective and patient preference will usually determine the treatment used. • Use of local estrogen in women on tamoxifen or aromatase inhibitors needs careful counselling and discussion with the patient and the oncology team • Estriol and testosterone preparations may be more appropriate for such patients but studies are needed David Sturdee

26. Recommendations 2013: Cognitive Aging & Alzheimer’s For midlife women, observational evidence indicates no persisting effects of the natural menopause on memory or other cognitive functions. During the menopausal transition, some women experience transient problems. The long-term cognitive consequences of HRT initiated during the menopausal transition or early postmenopause are unknown. There remains an urgent need for further research in this area. For healthy postmenopausal women, there is clinical trial evidence that isoflavone supplements in a daily dose comparable to that consumed in traditional Asian diets has no overall effect on cognition. Victor Henderson

27. Updated IMS Recommendations 2013: What’s Next?

28. Updated IMS Recommendations 2013: What’s Next? 1)Health Departments & Regulators – Encourage change of policy 2)The Prescribers – Expand education and training in menopause 3)Media – Engage positively highlighting favourable data 4)Pharma Industry – Reverse negative commercial/R&D decisions 5)The Menopausal Woman – Improve her access to information 6) HRT – Clarification of differences in action/risk profile Six Action Points to Maximise Impact of Recommendations

29. Updated IMS Recommendations 2013 HVALA!