Management of Perimenopausal symptoms
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1 Management of Perimenopausal symptoms Serge Rozenberg CHU St Pierre Université libre de Bruxelles Belgium
2 Conflict of interest & Disclosure Conflicts of interest: nil Disclosure Research funding IRIS- King Baudouin Fondation, Vesale research Foundation, Amgen, MSD Speakers bureau &/or Advisory Boards Abbot, Pfizer, Will
3 From Sherman Am J Med 2005 Climacteric
4 Bastian et al JAMA 2003
5 6% 37% Woods et al Am J Med 2005
6 Politi et al J Gen Intern Med 23(9):
7 Bastian et al JAMA 2003
8 From Santoro Am J Med 2005
9
10 Vasomotor symptoms How would you treat this patient?
11 HRT? Vasomotor symptoms
12 RCT (open) perimenopausal women irregular menstrual cycles and hot flushes randomized to micronized 17beta-E2 1 mg + dydrogesterone 10 mg sequential added n=60 subjects) or dydrogesterone 10 mg from day 15 to 28 (n=60 subjects) De Franciscis et al International Journal of Gynecology and Obstetrics (2007) 98,
13 Figure 5. Cumulative Annualized Incidence Rates for Clinical Outcomes in the Women's Health Initiative Estrogen-Alone Trial According to 10-Year Age Groups at Enrollment LaCroix, A. Z. et al. JAMA 2011;305:
14 Mean changes in symptom severity scores ( 95% CI): premenopausal and early peri-menopausal scores compared with late peri- and post-menopausal scores. Dennerstein et al Obstet Gyn 2000
15 BC Risk may be in relation to the Interval Between Menopause and Starting HT MWS WHI E3N Beral et al 2011
16 MWS Beral et al 2011
17 Prentice et al 2009 WHI
18 Prentice et al 2009 WHI
19 E3N Fournier JCO 2009
20 1.25 ( ) 4.55 ( ) Crandall et al Breast Cancer Res Treat 2011
21 Breast tenderness after initiation of CEE / CEE + MPA (WHI) and mammographic density change Crandall et al Breast Cancer Res Treat DOI /s
22 HRT & Breast cancer risk Use absolute risk and attribuable risk. Many risk factors play a major role. Dose and regiment influence breast cancer risk. For most symptomatic women, risks are moderate. Regimens having the lowest risks should be used. Low dose E alone in hysterectomised women Non-androgenic progestins or tibolone
23 Vasomotor symptoms Hormonal Contraceptives?
24 Unpredictable endocrinology of the menopause transition: clinical, diagnostic and management implications. Symptoms during the transitions may result from high or low E2 and can often be satisfactorily managed with low-dose oral contraceptives, which suppress pituitaryovarian function Burger HG. Menopause Int Dec;17(4): doi: /mi Epub 2011 Nov 25.
25 Oral contraceptive use in perimenopause Kaunitz Am J Obstet Gynecol 2001;185:S32-7 There is also good evidence that oral contraceptives relieve vasomotor symptoms in perimenopausal women.
26 Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three-year prospective study. Int J Fertil 1985;30: year, prospective cohort study N=100 perimenopausal women treated with a triphasic OC (EE 30/40/30 µg/lngl 0.05/0.075/0.125 mg) age-matched untreated women 90% of the OC users: complete relief vasomotor symptoms after 2 months use, and the remaining 10% responded after 3 months. By contrast, 60% of untreated women had no improvement in vasomotor symptoms during these 3- month observations. The failure to use blinding or a placebo group, however, limits the credibility of this study s findings.
27 Casper RF, Dodin S, Reid RL, and Study Investigators. The effect of 20 µg ethinyl estradiol/1 mg norethindrone acetate (Minestrin), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997;4: RCT 132 perimenopausal women low-dose, monophasic OC (20 µg EE/NETA 1 mg) decreased hot flashes. Among the 65% of subjects who experienced at least one hot flash daily (38 OC, 36 placebo), OC users experienced approximately 50% fewer hot flashes over the 6-month study period than placebo users. Similarly, the mean severity of hot flashes among OC users was half that of placebo users (mean severity scores were 66.9 and 131.2) respectively. However, these differences were not statistically significant in this small clinical trial
28 Others Vasomotor symptoms
29 Selected systematic reviews of strategies reducing vasomotor symptoms Black cohosh no proof of efficacy Leach MJ et al 2012 Phytoestrogens no proof of efficacy Eden 2012 Exercise no proof of efficacy Daley A Clonidine Mild effect Rada G, et al 2010 Nelson et al 2006 SSRIs and SNRIs Mild Moderate effect Rada G, et al 2010 Nelson et al Loprinsi et al 2009 Gabapentin Moderate Rada G, Loprinzi et al 2009 Toulis et al 2009 Nelson et al Relaxation Mild effect Rada G, et al 2010 Adapted from Rozenberg 2012 (submitted)
30 Metaanalysis of Clonidine 4 weeks 8 weeks Nelson, H. D. et al. JAMA 2006;295: Copyright restrictions may apply.
31 New antidepressants affecting serotonin and/or norepinephrine concentrations Venlafaxine Desvenlafaxine Fluoxetine Citalopram Sertraline and paroxetine.
32 Forest plots of hot flash reduction in newer antidepressant studies. Loprinzi C L et al. JCO 2009;27: by American Society of Clinical Oncology
33 Gabapentin GABA analogue used in the treatment of epilepsy, neurogenic pain, restless-leg syndrome,
34 Metaanalysis of gabapentin Loprinzi, 2009
35 Conclusion Lack of good data in peri-menopausal women HRT is probably efficient, but may be less well tolerated May be associated with increased breast cancer risk Favor low dose (Grade 2b) Contraception may be efficient Gabapentin, SSRI, Clonidine may be alternatives till early menopause
36 Conclusions MWS: BC incidence rates MWS/W HI MWS MWS WHI Non users E-P HT for 5 yr & started after 5yr of menopause E-P HT for 5 yr & started within 5yr of menopause E-P HT for 5 yr 0.30%/yr 0.46%/yr 0.61%/yr 0.43%/yr 15/1000/ 5 yr 23/1000/ 5 yr 30.5/1000/5 yr 21.5/1000/5yr Attrib 8/1000/5yr 15/1000/5yr 6/1000/5yr
37 HRT and/or vaginal Estrogen Systemic therapy (+ local )Vaginal tablets or creams Estradiol, Estriol, CEE Moisters Lubrifiants Sexual therapy
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