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Laura Baquedano Mainar
Hospital Universitario Miguel Servet. Zaragoza
Terapias no hormonales, no fitoterápicas para la
menopausia
¿Qué evidencia tenemos de su eficacia y seguridad?
¿ Qué más hay?
¿ A quién ?
No puedo, no quieroTH
Lo que he probado no me va bien
¿A TODAS?
Indice
• 1. Fármacos no hormonales
• 2. Modificaciones estilo de vida y dieta
• 3. Terapias conductuales
• 4. Medicina alternativa
EVIDENCIA
Fármacos no hormonales
ISRS
Fluoxetina (adofen,prozac)
Paroxetina (seroxat, motivan) 7.5mg—>20mg /día
Sertralina (besitran,aremis)
Citalopram (prisdal) 10—>20 mg /día
Escitalopram (cipralex, esertia) 10—>20 mg /día
Orleans RJ, Li L, Kim MJ, et al. FDA approval of paroxetine for menopausal hotflushes. N Engl J Med 2014;370:1777–9.
Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, Ullmer L,Gallagher A, Cullen J, Gehan E, Hayes DF, Isaacs C (2005) Paroxetine is an effective treatment for hot
flashes: results from a prospective randomized clinical trial. J Clin Oncol 23(28):6919–6930, doi:10.1200/ JCO.2005.10.08.
Barton DL, LaVasseur BI, Sloan JA, Stawis AN, Flynn KA, Dyar M, Johnson DB,Atherton PJ, Diekmann B, Loprinzi CL (2010) Phase III, placebo-controlled trial of three doses of
citalopram for the treatment of hot flashes: NCCTG trial N05C9. J Clin Oncol 28(20):3278–3283
Fármacos no hormonales
ISRSN
Venlafaxina (vandral,dobupal) 37.5—>150 mg /día
Desvenlafaxina (pristiq) 100—>150 mg/día
CS, Shelton RC (2007) Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist 12(1):124–135,
doi:10.1634/theoncologist.12-1-124
Joffe H, Guthrie KA, LaCroix AZ, et al. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for VMS: a randomized clinical trial. JAMA Intern Med
2014;174:1058-1066.
Caan B, LaCroix AZ, Joffe H, Guthrie KA, Larson JC, Carpenter JS et al. Effects of estrogen and venlafaxine on menopause-related quality of life in healthy postmenopausal
women with hot flashes: a placebo-controlled randomized trial. Menopause. 2015 Jun;22(6):607-15
Fármacos no hormonales
Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071
Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev 2010;CD004923
Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J Gen Intern Med 2014;29:204-213.
Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet
Invest 2013;75:255-262
Loprinzi CL, Sloan J, Stearns V, et al. Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis. J Clin Oncol 2009;27:2831-2837
Análisis combinados, metaanálisis y revisión Cochrane.
ISRS, ISRSN muestran mejoría leve-moderada de SVM
Independientemente de menop natural /quirúrgica
Mayor evidencia: paroxetina, citalopram, escitalopram,
(ECA d.ciego, placebo) venlafaxina, desvenlafaxina
Mejoría intensidad, frecuencia: 25-69%
Menor evidencia: sertralina, fluoxetina
Fármacos no hormonales
Ampliamente estudiados. Evidencia
eficacia
Mejoría rápida: 1-2 sem
Otros efectos beneficiosos
Receta médica
Supervivientes ca mama
RAM: nauseas, mareos.. disfunción sexual
(deseo, orgasmos) paroxetina, citalopram ++
ISRSN peor tolerancia. Ojo HTA
Retirada mejor gradual
Posible riesgo pérdida DMO
HiperPRL—> Ca mama? no evidencia
Interacción TAM (fluox, parox) Mejor ISRSN
Fármacos no hormonales
1º
2º/TAM
Fármacos no hormonales
ANALOGOS GABA
Gabapentina (neurontin ) 900—>2400 mg /día
Pregabalina (lyrica) 150—>300 mg/día
Reddy SY, Warner H, Guttuso T Jr, et al. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol 2006;108:41-48
Hayes LP, Carroll DG, Kelley KW. Use of gabapentin for the management of natural or surgical menopausal hot flashes. Ann Pharmacother 2011;45:388-394
Fármacos no hormonales
CLONIDINA
Catapresan 0,15 mg —>0,4 mg/día
Pandya KJ, Raubertas RF, Flynn PJ, Hynes HE, Rosenbluth RJ, Kirshner JJ, Pierce HI, Dragalin V, Morrow GR (2000) Oral clonidine in postmenopausal patients with breast
cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med 132(10):788–793,
Boekhout AH, Vincent AD, Dalesio OB, van den Bosch J, Foekema-Tons JH, Adriaansz S, Sprangers S, Nuijen B, Beijnen JH, Schellens JH (2011) Management of hot flashes
in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 29(29):3862–3868
Indice
• 1. Fármacos no hormonales
• 2. Modificaciones estilo de vida y dieta
• 3. Terapias conductuales
• 4.Medicina alternativa
Modificaciones del estilo de vida y
dieta
tª
Evidencia?
Smith RL, Gallicchio L, Miller SR, Zacur HA, Flaws JA. Risk Factors for Extended Duration and Timing of Peak Severity of Hot Flashes. PLoS One. 2016 May 5;11(5):e0155079
Hyde Riley E, Inui TS, Kleinman K, Connelly MT. Differential association of modifiable health behaviors with hot flashes in perimenopausal and post menopausal women. J Gen Intern
Med. 2004; 19: 740–746
Modificaciones del estilo de vida y
dieta
Caan BJ, Emond JA, Su HI, et al. Effect of postdiagnosis weight change on hot flash status among early-stage breast cancer survivors. J Clin Oncol 2012;30:1492-1497
Kroenke CH, Caan BJ, Stefanick ML, et al. Effects of a dietary intervention and weight change on VMS in the Women’s Health Initiative. Menopause 2012;19:980-988.
Thurston RC, Ewing LJ, Low CA, Christie AJ, Levine MD. Behavioral weight loss for the management of menopausal hot flashes: a pilot study. Menopause 2015;22:59-65
Obesidad: SVM, tr. sueño, ánimo. Objetivo IMC <25
Sobrepeso, obesidad: correlación pérdida de peso SVM
WHI. n= 17.500 (no TH). Dieta baja en grasas
Perder >/= 5Kg ó >/= 10% peso en 1 año —> < SVM
Tras Ca mama: en 2 años >/= 10% peso >SVM
Jenabi E, Poorolajal J. The association between hot flushes and smoking in midlife women: a meta-analysis. Climacteric. 2015;18(6):797-801
Tabaco antiestróg. Metaanálisis. n>27.000 > riesgo SVM:
Exfumadoras 1.31 (95% CI 1.22–1.41)
Fuma actual 1.97 (95% CI 1.81–2.14) dosis-respuesta
Modificaciones del estilo de vida y
dieta
Daley A, Stokes-Lampard H, Thomas A, MacArthur C. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2014;11:CD006108.
Daley A, Stokes-Lampard H, Macarthur C. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2011;CD006108
Daley A, MacArthur C, Mutrie N, Stokes-Lampard H. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007;CD006108
Bailey TG, Cable NT, Aziz N, et al. Exercise training reduces the frequency of menopausal hot flushes by improving thermoregulatory control. Menopause 2016;23:708-718.
Beneficios incuestionables para la salud en general
Menop: sueño, memoria, animo, función cognitiva, CV, hueso..
30´ej moderado 5/sem; 20´ej intenso 3/sem
Ej. fco aeróbico
Depende de la intensidad??
Modificaciones del estilo de vida y
dieta
Beneficios incuestionables para la salud en general
Menop: CV, flexibilidad, equilibrio, pfx caídas, estado ánimo. No SVM
2 días / sem no consecutivos. 8 grupos musculares
15´/día stretching: regulación SNA—> beneficios síntomas depresivos,
sueño
disminuye actividad simpática, aumenta parasimpática. Escala menop
++ n=40
Pilates
Bullo V, Bergamin M, Gobbo S, Sieverdes JC, Zaccaria M, Neunhaeuserer D, Ermolao A. The effects of Pilates exercise training on physical fitness and wellbeing in the elderly: A
systematic review for future exercise prescription. Prev Med 2015;75:1-11.
Barker AL, Bird ML, Talevski J. Effect of pilates exercise for improving balance in older adults: a systematic review with meta-analysis. Arch Phys Med Rehabil 2015;96(4):715-23
M. Bergamin S. Gobbo V. Bullo T. Zanotto B. Vendramin F. Duregon . Effects of a Pilates exercise program on muscle strength, postural control and body composition: results
from a pilot study in a group of post-menopausal women. AGE (2015) 37: 118
Yuko Kai, Toshiya Nagamatsu, Yoshinori Kitabatake, MS, Hiroomi Sensui. Effects of stretching on menopausal and depressive symptoms in middle-aged women: a randomized
controlled trial. Menopause, Vol. 23, No. 8, 2016
Indice
• 1. Fármacos no hormonales
• 2. Modificaciones estilo de vida y dieta
• 3. Terapias conductuales
• 4.Medicina alternativa
Terapias conductuales
Yoga
Márcia P. J, Danilo F. S, Isabella M.O. Pontes, Victor K.M. Shiramizu,Ezequiel B. Nascimento, Alícia Cabral. Hatha Yoga practice decreases menopause symptoms and improves quality of life:
A randomized controlled trial. Complementary Therapies in Medicine 26 (2016) 128–135
Daley A, Stokes-Lampard H, Thomas A, MacArthur C. Exercise for vasomotormenopausal symptoms. Cochrane Database Syst Rev 2014;11:CD006108.
Avis NE, Legault C, Russell G, Weaver K, Danhauer SC. Pilot study of integral yoga for menopausal hot flashes. Menopause 2014;21:846- 854.
Múltiples estudios en menopausia. Meditación, relajación
Beneficio en CV, estado ánimo,sueño
No evidencia clara en reducción de SVM
Avis et al: 90´/sem x 10 sem + práctica casa: reducción 66% SVM vs
63% (educación bienestar) vs 36% (placebo)
Cochrane (7 ECA): no diferencias yoga vs ej fco en SVM. Inf a TH
Terapias conductuales
Saensak S, Vutyavanich T, Somboonporn W, Srisurapanont M. Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst
Rev2014;7:CD008582
Mann E, Smith M, Hellier J, Hunter MS. A randomised controlled trial of a cognitive behavioural intervention for women who have menopausal symptoms following
breast cancer treatment (MENOS 1): trial protocol. BMC Cancer 2011;11:44.
Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and
night sweats (MENOS 2): a randomized controlled trial. Menopause 2012;19:749-759
Carmody JF, Crawford S, Salmoirago-Blotcher E, Leung K, Churchill L, Olendzki N. Mindfulness training for coping with hot flashes: results of a randomized trial.
Menopause 2011;18:611-620
Coronado PJ, Oliva A, Fasero M, Piñel C1, Herraiz MA, Pérez-López FR. Resilience and related factors in urban, mid-aged Spanish women. Climacteric.
2015;18(6):867-72
Pueden ser útiles en SVM. Evidencia escasa. Calidad pobre
Objetivo: relajación,reducción estrés. Resiliencia, información
Mejora calidad sueño, tr ánimo.. Xs estudios ca mama
Relajación
Terapia cognitivo conductual
Respiración controlada
Mindfulness (atención plena presente)
Indice
• 1. Fármacos no hormonales
• 2. Modificaciones estilo de vida y dieta
• 3. Terapias conductuales
• 4.Medicina alternativa
Medicina alternativa
Hipnosis
Elkins G, Marcus J, Stearns V, et al. Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J Clin Oncol 2008;26:5022-5026
Elkins GR, Fisher WI, Johnson AK, Carpenter JS, Keith TZ. Clinical hypnosis in the treatment of postmenopausal hot flashes: a randomized controlled trial. Menopause 2013;20:291-
298
Mejora calidad sueño, tr ánimo..
ECA : n=187 mujeres SVM severos. Tras 12s(5s/sem), diminuyó frecuencia,
intensidad y mejoró sig capacidad de control (55-75%)
Evidencia en Ca mama
Medicina alternativa
Chiu HY, Pan CH, Shyu YK, Han BC, Tsai PS. Effects of acupuncture onmenopause-related symptoms and quality of life in women in naturalmenopause: a meta-analysis of
randomized controlled trials. Menopause2015;22:234–44.
Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flushes.Cochrane Database Syst Rev 2013;7:CD007410
Garland SN, Xie SX, Li Q, Seluzicki C, Basal C, Mao JJ. Comparative effectiveness of electro-acupuncture versus gabapentin for sleep disturbances in breast cancer survivors with hot
flashes: a randomized trial.Menopause. 2016 Nov 21
Acupuntura
Mejora calidad sueño (= 900mg gabapentina), calidad de vida..
Grupo control-placebo ideal ?: nada / acup simulada (+ sist límbico?)
Rev Cochrane ´13: sup a no tto, = acupuntura simulada
Metaanálisis ´15: eficaz SVM, no siempre comparado con simulada
Evidencia en Ca mama
Medicina alternativa
Bloqueo del ganglio estrellado
Mejora calidad sueño
Mec acción desconocido. Utizado con fines analgésicos
C6-T2. Bilat. Iny anest local. Radioguiado. Invasivo
Efecto tardío: 2-4 meses. Pocos estudios
Grupo control-placebo ideal ?: nada / punción suero ?
SVM: 45-90% vs no tto. 20% vs punción simulada
Lipov EG, Joshi JR, Xie H, Slavin KV. Updated findings on the effects of stellate-ganglion block on hot flushes and night awakenings. Lancet Oncol 2008;9:819-820
Haest K, Kumar A, Van Calster B, et al. Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of
follow- up. Ann Oncol 2012;23:1449-1454.
Walega DR, Rubin LH, Banuvar S, Shulman LP, Maki PM. Effects of stellate ganglion block on VMS: findings from a randomized controlled clinical trial in postmenopausal women. Menopause 2014;21: 807-814.
CONCLUSIONES