CARDIO 015 Hormone replacement therapy : actuelle ou obsolète?

Transcription

1 CARDIO 015 Hormone replacement therapy : actuelle ou obsolète? Serge Rozenberg CHU St Pierre VUB- ULB Belgium serge_rozenberg@stpierre- bru.be In the center of the city, in the center of life, with passion for care

2 Conflict of interest & Disclosure Conflicts of interest: None for this presentation Disclosures Research funding IRIS- King Baudouin Fondation, Vesale research Foundation, Amgen, MSD Speakers bureau &/or Advisory Boards Abbot, Pfizer, Will, Gedeon Richter, MSD, Amgen, Mithra

3 Overview Overview of risk- benefit Symptoms Osteoporosis CVD DVT- PE Breast cancer

4 Should Women use HRT? Pendulum Swing Yes HRT: Hormone Replacement Therapy WHI: Women s Health IniOaOve

5

6

7

8 Age at menopause as a risk factor for cardiovascular mortality Yvonne Van der Schouw et al 1996

9 Should Women use HRT? 1 Pendulum Swing HRT: Hormone Replacement Therapy NO

10 - 46 fractures WHI : E+P per woman years + 8 breast cancer + 9 stroke + 12 DVT, deep, + 9 pulmonary embolism Other events that increased with estrogen + progeson treatment included deaths from lung cancer, gallbladder disease, probable demenoa and urinary incononence H Nelson et al Ann Intern Med. 2012;157:

11 Antoine, Ameye, Paesmans Rozenberg Maturitas 2014

12 Should Women use HRT? New data WHI, DOPS, KEEPS, ELITE, E3N Pendulum Swing Yes? HRT: Hormone Replacement Therapy WHI: Women s Health IniOaOve DOPS: Danish PrevenOon Osteoporosis Study KEEPS : Kronos Early Estrogen Prevention Study ELITE: Early versus Late Intervention Trial with Estradiol

13 What are the indications for MHT?

14 Flushes Over half (50.3%) of postmenopausal women experienced either mild (24.6%), moderate (17.6%), or severe (8.1%) VMS. DiBonaventura et al Int J Womens Health May 24;5:261-9.

15 HRT reduces symptom frequencye and severity as compared with placebo OR= 0.13, 95% CI MacLennan et al Climacteric Mar;4(1):58-74./Cochrane review

16 Menopause and Urogenital Ageing National Geographic. Photo: Brendan McCarthy

17 Atrophic Vagini.s 1 Atrophic vaginios Recurrent urinary tract infecoon (UTI) Discharge and odour Pain Sexual dissatisfaction Decrease in blood flow Loss of elasocity Decrease in lubricaoon 1. Adapted from Castelo-Branco C, et al. Maturitas 2005; 52S: S46-52

18 Osteoporosis : Definition Consensus Development 1993 Normal trabecular bone Osteoporotic trabecular bone

19 SequenOal Treatment Risk of a Fragility Fracture Risk Strontium ranelate PTH New druggs Odanacatib? Bisphosphonates Denosumab HRT SERMs TSEC Age Palacios S. Drugs of Today 2011, 47(3):

20 Take Home message Use it if you need it!

21

22

23 Holy Smoke!

24

25

26 Cumula.ve Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen- Alone Trial According to 10- Year Age Groups at Enrolment 1 1. LaCroix, A. Z. et al. JAMA 2011;305:

27 Atherosclerosis 1 1. Ross. N Engl J Med 1999; 340:

28 DOPs (Danish Osteoporosis Prevention Study), 20 yr study, partly randomised, tests hypothesis that HRT inioated shortly ajer menopause reduces the risk of later osteoporooc fractures. Adapted from Schierbeck et al BMJ 2012

29 Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial Schierbeck et al BMJ 2012

30 Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial Young & early menopause Schierbeck et al BMJ 2012

31 Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial HRT users less at risk Schierbeck et al BMJ 2012

32 Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial Schierbeck et al BMJ 2012

33 ELITE: Early versus Late Intervention Trial ELITE: Early versus Late IntervenOon RCT to determine HT effects on subclinical atherosclerosis across menopause strata. Double blind, 2 2 factorial design (n=643 free of CVD) 1mg E2 (vaginal progesterone gel) or placebo for up to 6 to 7 years according to Ome since menopause (<6 or 10 y) measurements of the carood artery. CaroOd artery inoma- media thickness (CIMT) every six months. cardiac computed tomography Hodis HN et al Menopause Apr;22(4):

34 CIMT outcome Menopause stratum CIMT rate (95%CI) E2 (n=297) < 6 YRS ( ) > 10 YRS ( ) P VALUE P<0.001 CIMT rate (95%CI) Placebo (n=299) ( ) ( ) P value within stratum P value interac.on Not Significant Rate of change in common carotid artery intima- media thickness measured every 6 months Adapted from Hodis IMS Cancun 2014

35 KEEPS: RCT Kronos Early Estrogen PrevenOon Study. CEE or transdermal E2 on atherosclerosis. Healthy menopausal women aged years, between 6 and 36 months from last menses without prior CVD Coronary artery calcium (CAC) score less than 50 Agatston units and had not received estrogen or lipid- lowering therapy for at least 90 days. IntervenOon: Oral (o- CEE), 0.45 mg/d, or transdermal 17- estradiol (t- E2), 50 mcg/d, each with 200 mg of oral progesterone for 12 days per month, or placebo for 48 months.

36 Arterial Imaging Outcomes and Cardiovascular Risk Factors in Recently Menopausal Women (KEEPS) Not Significant Harman, et al Ann Intern Med. 8/ 2014

37 Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. 28 trials (3360 paoents). Low- dose HT vs placebo or convenoonal- dose HT did not effect weight, BMI, BP, CRP or HDL- C. Casanova G et al J Clin Endocrinol Metab Mar; 100(3): doi: /jc Epub 2014 Dec 16.

38 Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. low- dose HT was associated with bever lipid profile vs placebo, and induced higher total and LDL- C and lower triglycerides vs convenoonal- dose HT. Casanova G et al JCEM 2015 Mar;100(3):

39 COMMITTEE OPINION juin 2013 (Replaces No. 420, November 2008) Committee on Gynecologic Practice (ACOG)

40 VTE

41 Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism :Results From the E3N Cohort Study Canonico et al Arterioscler Thromb Vasc Biol. 2010;30:

42 Through the eyes of an amazone Marie Mandy

43 No increase increase

44 Anderson et al Lancet Oncology 2012 Decrease

45 Invasive Breast Cancer in WHI studies: Absolute risk events/10,000 women-years in the two WHI trials 1, E + P Placebo E only Placebo Women aged years WHI: Women s Health IniOaOve E +P: Estrogen plus ProgesOn 1. Adapted from Chlebowski RT, et al. JAMA 2010; 304: Adapted from Anderson GL, et al. Lancet Oncology 2012: 13:

46 From Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort Fournier A et al 2014

47 From Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort Fournier A et al 2014

48 From Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort Fournier A et al 2014

49 Take Home message Don t use it if you don t need it!

50 Take Home message Use the smallest needed dose and the safest regimens!

51 Key points Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in paoents aged <60 years with climacteric symptoms Low doses of PMHT should be used when possible PMHT can be prescribed for a short period of Ome to treat osteoporosis when non- oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis Postmenopausal hormone therapy: risks and benefits. Rozenberg S, Vandromme J, Antoine C. Nat Rev Endocrinol Feb 19.

52 Key points PMHT for PrevenOon of coronary heart disease? For young healthy women not an indicaoon but no certainly no contra- indicaoon Oestrogen therapy might reduce the risk of atherosclerosis in young women early ajer menopause, but risk of coronary heart disease might be worsened as a result of thrombosis in at- risk and elderly paoents PMHT may increase Breast cancer risk : Use of a estrogen only (hysterectomized women), sequenoal progeson and a non- androgenic progeson might be safer than use of cononuous androgenic progeson Short term (< 5 yrs entails less or no risk) long- term (>5 years) EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years ajer treatment cessaoon Postmenopausal hormone therapy: risks and benefits. Rozenberg S, Vandromme J, Antoine C. Nat Rev Endocrinol Feb 19.

53