Jueves 13.15 Dra. Baquedano

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


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


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


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


1º

2º/TAM


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


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




• 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


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


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??


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





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





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


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


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

Health & Medicine

Jueves 13.15 Dra. Baquedano