Altri approcci: sono utili?

(1)

Rimini, 5-8 novembre 2015

Altri approcci: sono utili?

A. Paoletta

Endocrinologia Cittadella - (Padova)

Simposio con SIE

Cli materio e menopausa: ruolo dell’endocrinologo

Sabato 7 Novembre 2015

(2)

Ai sensi dell’art. 3.3 sul conﬂi>o di interessi, pag 17 del Regolamento ApplicaBvo Stato-Regioni del

5/11/2009, dichiaro che negli ulBmi 2 anni non ho avuto rapporB direG di ﬁnanziamento con soggeG portatori di interessi commerciali in campo sanitario.

Conflitti di interesse

(3)

Preferisco resistere!

Ho paura degli ormoni!

(4)

Controindicazioni alla TOS

Controindicazioni assolute

alla TOS in menopausa

!  Trombosi venosa in atto o recente

!  Storia di neoplasia mammaria o endometriale

!  Patologia epatica attiva o cronica

!  Cardiopatia coronarica

!  Ipertensione arteriosa non trattata

!  Porfiria cutanea tarda

Controindicazioni relative

alla TOS in menopausa

!  Storia familiare di malattie di tipo tromboembolico

!  Storia familiare di cancro mammario

!  Calcoli della colecisti

!  Leiomioma uterino

(5)

(6)

Posadzki P, Lee MS, Moon TW, Choi TY, Park TY, Ernst E. Prevalence of complementary and alternative

medicine (CAM) use by menopausal women: a systematic review of surveys. Maturitas. 2013 May;75(1):34-43

Una revisione di 26 studi epidemiologici sull’uso delle CAM in menopausa pubblicati dal 2000 al 2012, con dati riguardanti 32.465 donne di Australia, Canada, Danimarca,

Norvegia, Spagna Italia, Spagna, Corea del Sud e Stati Uniti ha mostrato che:

> 50% delle donne in menopausa

ha utilizzato specificamente CAM per i disturbi menopausali

La conclusione degli autori è che l’uso delle CAM in menopausa è elevato

Complementary and Alternative Medicine for Women in Menopause

Le ragioni che spingono le donne a rivolgersi alla CAM in menopausa sono varie

ma soprattutto il timore degli effetti collaterali della TOS

(7)

More women turning to CAM for menopause without medical guidance

The North American Menopause Society (NAMS) 10-jun-2015

•  It is estimated that 53% of menopausal women use at least one type of CAM for the management of such menopause-related symptoms

•  This raises major safety concerns, according to the authors, since much of the use of self-prescribed CAM products is done without a medical consultation.

Complementary and Alternative Medicine for

Women in Menopause

(8)

Drugs

•  Antidepressants

•  Antiepileptics

•  Alpha-adrenergic agonists

Others

•  Phytoestrogens

•  Herbals

•  Acupuncture

•  Hypnosis

•  Exercise

•  Cognitive Behavioral Modification

•  Omega-3,Vitamin E

•  Stellate ganglion block

Other approaches

(9)

Stuenkel et al Guideline on Menopause J Clin Endocrinol Metab 2015

Hot Flash frequencies

< 25-69%

Hot Flash score

< 27-61%

Antidepressant (SSRI and SNRI) and Antiepilectics drugs Hot flash frequency and composite score

for relief of VMS

(10)

Menopause. 2013 :1027-35.

Low-dose Paroxetine (SSRI) 7.5 mg for menopausal vasomotor symptoms:

two randomized controlled trials.

Simon JA, Portman DJ, Kaunitz AM, Mekonnen H, Kazempour K, Bhaskar S, Lippman J.

CONCLUSIONS: Paroxetine 7.5 mg is effective in reducing the frequency and severity of menopausal vasomotor symptoms, and demonstrates persistence of treatment benefit through 24 weeks of treatment

Nel 2013 la FDA ha approvato il primo trattamento non-ormonale ( Paroxetina ) per trattare i sintomi vasomotori in menopausa

591 participants were randomly assigned to treatment with paroxetine 7.5

mg, and 593 participants were randomly assigned to treatment with placebo

(11)

Paroxetine (10-20 mg/d) 33%–67% reduction in hot flash frequency compared to

13.7%–37.8% reductions with placebo in patients both with and without a history of

breast cancer.

(12)

Venlafaxine 75-150 mg/d reduced hot flashes

by 37% to 61%

Desvenlafaxine 100-150 mg/d reduced hot flashes

by 55% to 69%

Conclusion: Based on the evidence, venlafaxine and desvenlafaxine are both viable options for reducing the frequency and severity of hot flashes.

Pharmacy Practice 2011 Jul-Sep;9(3):117-121

(13)

Gabapentina

Guttuso T et al. Gabapentin’s effects on hot flashes in postmenopausal women: A randomized controlled trial. Obstet Gynecol 2003;101:337–345.

Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised doubleblind placebo-controlled trial. Lancet. 2005;366:818–824.

Reddy SY et al. Gabapentin, estrogen, and placebo for treating hot flushes: A randomized controlled trial. Obstet Gynecol 2006;108:41– 48.

Loprinzi CL et al. Newer antidepressants and gabapentin for hot flashes: An individual patient pooled analysis. J Clin Oncol 2009;27:2831–

2837.

300-1.200 mg al momento di coricarsi

< 35%-38% incidenza vampate di calore

Promettente ma efficacia solo a lungo termine e

sicurezza non confermata

(14)

ESCITALOPRAM

205 women (95 African American; 102 white; 8 other )

Escitalopram 10-20 mg/d

Hot flashes

< 50%

(15)

SSRI

Adverse Events Nausea

(RR 1.7; CI 0.81 to 3.59),

Fatigue/tiredness

(RR 1.07; CI 0.60 to 1.92),

Somnolence/drowsiness

(RR 1.50; CI 0.42 to 5.35),

Palpitation

(RR 1.04;CI 0.53 to 2.06),

Dry mouth

(RR 1.29; CI 0.69 to 2.40),

Sleep disturbance

(RR 1.32; CI 0.36 to 4.90),

Sweating

(RR 1.12; CI 0.25 to 5.03),

Dizziness/vertigo

(RR 1.5; CI 0.26 to 8.68),

Headache

(RR 0.85; CI 0.49 to 1.5),

Decreased libido

RR 1.81; CI 0.21 to 15.48)

Rash

(RR0.53; CI 0.15 to 1.87).

2.069 women follow-up 1–9 months

J Gen Intern Med 29(1):204–13

(16)

SSRI-SNRI mg/die

in menopausa Nome commerciale

Paroxe8na

An8depressivo SSRI 7.5-25 Sereupin, Seroxat, EuBmil,

Daparox Venlafaxina

An8depressivo SNRI 75-150 Efexor,Faxine,Venlafax

Citalopram

An8depressivo SSRI 10-20 Seropram, Elopram,

Escitalopram

An8depressivo SSRI 10-20 Entact, Cipralex

Gabapen8na

An8 epileHco 300-1200 NeuronBn

Pregabalina

An8 epileHco 150-300 Lyrica

(17)

Dosi orali (0.1 mg/die) o transdermiche (1 mg/settimana) riducono in modo significativo (< 30-50%) gli episodi vasomotori.

Gli effetti collaterali

(xerostomia, insonnia, depressione) ne limitano l'impiego

Consider as first line therapy

in women with co-existent hypertension

Pandya KJ et al. 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 2000,132:788-93.

Goldberg RM et al. Transdermal clonidine for ameliorating tamoxifen induced hot flashes. J Clin Oncol 1994;12:155– 158.

Nelson HD et al. Non hormonal 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;9:CD004923.

Clonidina

α-2 adrenergic-agonist

(18)

Terapie Alternative

Actaea

racemosa, Arnica montana ,

Glonoinum ,

Lachesis mutus , Sanguinaria

canadensis OMEGA 3

(19)

Agenti che producono

modesti benefici

Agenti che non producono benefici nella maggior parte dei casi

Agenti che

necessitano di

ulteriori studi

(20)

Fitoestrogeni

Isoflavoni

•   Genisteina

•   Daidzeina

•   Glycetina

•   Formomonetina

•   Biochanina A

Lignani

Cumestrani

•   Enterodiolo

•   Enterolactone

•   Secoisolariciresinol( ^SECO )

•   Matairesinolo ( MAT )

•   Coumestrolo

• Soia

• Trifoglio rosso (Red clover)

• Semi di lino

• Grani

• Bacche

• Germogli di soia

• Alfa-alfa

(21)

1.  Phytoestrogens demonstrate higher affinity for estrogen receptor-beta than receptor- alpha, and possess either estrogenic or antiestrogenic activity

2.  Phytoestrogens are absorbed

after being hydrolyzed by

bacteria in the intestine

(22)

Daidzein Metabolism to Equol

% of Intestinal flora to produce Equol

28.2% in Europe 27.6% in USA

31.3% in Australia

50% - 60% in Asia and Western adult vegetarians

(23)

Sono veramente efficaci ^?

(24)

Dosaggi di 50-60 mg/die

Riducono i sintomi

Nel 24%- 60% dei casi

(25)

Metanalysis of the ten studies that reported hot flush data indicated that

phytoestrogens result in a significantly greater reduction in hot flush frequency compared to placebo (pooled mean difference 0.89, p < 0.005).

Conclusion: Phytoestrogens appear to reduce the frequency of hot

flushes in menopausal women

(26)

In general, no conclusive evidence showed a benefit of phytoestrogen for menopausal vasomotor symptoms, with the exception of products containing a minimum of 30 mg per day of Genistein (< 30%-50% vs placebo), which have been evaluated for up to 2 years in four studies.

Further research is needed to confirm this efficacy!!!

43 randomised controlled trials (4.364 partecipants)

Studies were randomised controlled comparisons of high levels of phytoestrogens

(e.g. at least 30 mg/d of isoflavones) for more than 12 weeks versus placebo

(27)

Herbals

(28)

Black Cohosh (Actaea racemosa)

( ex Cimicifuga racemosa)

(29)

The action of black cohosh is known to be mediated by serotonin , opioid or dopamine receptors

Black Cohosh (Actaea racemosa)

( ex Cimicifuga racemosa)

(30)

16 randomised controlled trials, recruiting a total of 2027 perimenopausal or postmenopausal women

All studies used oral monopreparations of black cohosh at a median daily dose of 40 mg, for a mean duration of 24 weeks

Authors’ conclusions: There is currently insufficient evidence to support the use of black cohosh for menopausal symptoms. However, there is adequate justification for conducting further studies in this area

2012

(31)

Acupuncture for vasomotor menopausal symptoms: a systematic review

SH Cho and WW Whang. Review published: 2009.

A systematic review, including 11 randomised controlled trials with a total of 764 patients Authors' conclusions

None found a significant difference between groups.

There was no consistent evidence that acupuncture was effective for treating

menopausal vasomotor symptoms compared to sham acupuncture or hormone therapy; further research was required.

Acupuncture for menopausal hot flushes

Dodin S. et. al. Cochrane Database Syst Rev. 2013

Sixteen studies, with 1155 women, were eligible for inclusion.

Authors' conclusions

No significant difference was found between the groups for hot flush frequency but

flushes were significantly less severe in the acupuncture group.

(32)

clinical hypnosis was associated with a 74.2% reduction in hot flashes

compared with a

17.1% reduction in women randomized to structured attention control

(P .001)

clinical trial involving 187 postmenopausal women reporting a minimum of seven hot flashes per day

Texas

(33)

Cognitive Behavioral Modification

Alcuni trials clinici randomizzati e in doppio cieco hanno dimostrato che i trattamenti cognitivo-comportamentali, che associno tecniche di rilassamento, igiene del sonno e

l’imparare ad assumere un atteggiamento positivo e salutare nei confronti dei disturbi della menopausa, sono molto efficaci nel ridurre la percezione negativa delle donne nei confronti delle vampate, anche se non il loro numero.

Cognitive behavioral therapy (CBT) is an effective treatment for bothersome VMS for both breast cancer survivors and menopausal women.

POSITION STATEMENT

Non hormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society

Level I evidence

(34)

Stellate ganglion block

Emerging evidence suggests that stellate ganglion blockade (SGB), a widely used anesthesia treatment for pain management, is a promising treatment for VMS, but larger trials are needed.

Findings suggest that SGB might be an effective non hormonal treatment for moderate to very severe VMS, but larger studies are needed.

van Gastel P,Kallewaard JW, van der Zanden M, de Boer H. Stellateganglion block as a treatment for severe postmenopausal flushing.Climacteric 2013;16:41-47.

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

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 Oncol2012;23:1449-1454.

A stellate ganglion

block is an injection of

local anesthetic in the

sympathetic nerve

tissue of the neck.

(35)

Non hormonal treatment of

genitourinary syndrome of menopause

Vaginal moisturizers and lubricants for genitourinary menopause

A number of over-the-counter vaginal lubricants (water-, silicone-, or oil-based) and vaginal moisturizers (eg, polycarbophil-based, hyaluronic acid-based preparations, and a pectin based preparation), when used regularly (at least twice weekly), may provide an effective non hormonal approach to alleviating symptoms of vaginal atrophy.

Loprinzi CL, Abu-Ghazaleh S, Sloan JA, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophilbased vaginal moisturizer in women with breast cancer. J Clin Oncol. 1997;15:969–973.

Caswell M, Kane M. Comparison of the moisturization efficacy of two vaginal moisturizers: pectin versus polycarbophil technologies.

J Cosmet Sci. 2002;53:81–87.

The North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20: 888-902; quiz 3-4

.

(36)

•  Evitare il fumo e limitare gli alcolici

•  Fare almeno mezz’ora di movimento fisico al giorno

•  Dieta equilibrata: scegliere un’alimentazione povera

di grassi saturi e zuccheri semplici, preferendo frutta e

verdura, cereali e legumi, pesce, carne bianca, latte e

formaggi freschi; se esistono intolleranze ai latticini,

integrare la dieta con 1000-1500 mg di calcio al dì, più

vitamina D

(37)

Altri approcci: sono utili?