Transcript Menopausa e terapie alternative
LE TERAPIE ALTERNATIVE
A.Becorpi Z.Tredici
Servizio Fisiopatologia della Menopausa e Menopausa Oncologica Dipartimento di Ginecologia, Perinatologia e Fisiopatologia della Riproduzione Umana Azienda Ospedaliero-Universitaria Careggi Firenze
… l
’
essenza della vita è il cambiamento … ... la menopausa è una transizione naturale ...
SALUTE DELLA DONNA IN MENOPAUSA Approccio medico attuale
Attenzione alle problematiche della donna Prevenzione di patologie e disabilità Promozione di uno stile di vita sano Trattamento dei sintomi climaterici : corretta valutazione rischi/benefici
MIGLIORE QUALITÀ DI VITA
Prevalenza sintomi climaterici Progetto Menopausa Italia
sintomo intensità %
Vampate/sudorazione
Moderata Severa 30.9 22.9
sintomo intensità %
Deficit memoria
Moderata / severa 45.2
Umore depresso
Moderata / severa 44.9
Difficoltà nell
’
addormentarsi
Moderata / severa 47.0
Irritabilità
Moderata / severa 50.6
Cefalea Problemi urinari
Moderata / severa Moderata / severa 35.5
27.4
Becorpi 2006
Menopausal Complaints Are Associated With Cardiovascular Risk Factors
Flushing was associated with hypercholesterolemia (odds ratio: 1.52; 95% CI: 1.25 to 1.84) and hypertension (OR: 1.20; 95% CI: 1.07 to 1.34).
Gerrie-Cor M. Gast et al, Hypertension 2008
Menopause after oncological diseases
Owing to the protocols for have seen an menopause secondary to integrated oncological treatments or surgical, pharmacological or radiological therapies.
Particularly if it is oncological diseases increase in the , in the number last few years of women in we iatrogenic premature , menopause in these subjects, who are already strongly debilitated by the primary pathology, have improved effectiveness heavy psychic and physical effects significant repercussions on the as of the treatment osteoporosis quality of life .
may and Baldi and Becorpi Clin Cases Miner Bone Metab, 2009
Menopause in Breast Cancer Survivors
Changes in
body image
associated the
loss
of a
breast
or weight gain, vasomotor symptoms,
depressive mood, decreased libido, dryness , dyspareunia, difficulty
with
arousal
and
orgasm
and
concern
over
fertility
and
health
Melisko et al 2010, J.Cancer Survivor
Aromatase Inhibitors : induce more menopausal symptoms and worse sexual function compared with other drugs as tamoxifen
Van Calster et al 2011
Servizio Menopausa Oncologica
SOD Ginecologia e Ostetricia I e II Dipartimento Materno-Infantile SOD Ginecologia Onologica Medica DAI Oncologia Azienda Ospedaliero-Universitaria Careggi
Giugno 2001-Dicembre 2009
1272 Accessi
(prime visite/controlli)
Ambulatorio Menopausa Oncologica
SOD Ginecologia e Ostetricia – Dipartimento ad Attività Integrate Materno Infantile SOD Ginecologia Oncologica Medica - Dipartimento ad Attività Integrate di Oncologia Azienda Ospedaliero-Universitaria Careggi
Menopausa Indotta Radiologica Farmacologica (MIRF)
Becorpi et al., Toscana Medica 2010
Ambulatorio Menopausa Oncologica
Becorpi et al., Toscana Medica 2010
Non-hormonal therapies for menopausal hot flashes : Systematic review and meta-analysis.
Nelson HD, Vesco KK, Haney et al JAMA 295: 2057-2071, 2006
Trattamenti alternativi alla Terapia Ormonale Sostitutiva per il trattamento dei disturbi vasomotori
Nonhormonal Therapies for Menopausal Hot Flashes: Systematic review and meta-analysis
From 4249 abstracts,43 trials met inclusion criteria, including 10 trials of antidepressants,10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily
hot flashes decreased compared with placebo
in meta-analyses of 7 comparisons of
selective serotonin reuptake inhibitors (SSRIs)
or
serotonin norepinephrine reuptake inhibitors (SNRIs)
(mean difference, –1.13; 95% confidence interval [CI], –1.70 to – 0.57), 4 trials of
clonidine
( –0.95; 95% CI, –1.44 to –0.47), and 2 trials of
gabapentin
( –2.05; 95% CI, –2.80 to –1.30). Frequency was
not reduced
in meta-analysis of trials of
red clover isoflavone extracts
and results were
mixed for soy isoflavone extracts
. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined.
Summary of Trials
Nelson HD, 2006
Nonhormonal Therapies for Menopausal Hot Flashes: Systematic review and meta-analysis
To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials.
Trials of Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Nelson HD, 2006
SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND BREAST CANCER MORTALITY IN WOMEN RECEIVING TAMOXIFEN: A POPULATION BASED COHORT STUDY Objective
To characterise whether some selective serotonin reuptake inhibitor
(SSRI) antidepressants reduce tamoxifen ’s effectiveness
by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6).
Participants
Women living in Ontario aged 66 years or older treated with tamoxifen for breast cancer between
1993 and 2005
who had overlapping treatment with a single SSRI.
Main outcome
measures
Risk of death from breast cancer
after completion of tamoxifen treatment,
as a function of the proportion of time on tamoxifen during which each SSRI had been co-prescribed .
Results
Of
2430
women treated with tamoxifen and a single SSRI, 374 (15.4%) died of breast cancer during follow-up (mean follow-up 2.38 years, SD 2.59). After adjustment for age, duration of tamoxifen treatment, and other potential confounders, absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were associated with 24%, 54%, and 91% increases in the risk of death from breast cancer, respectively (P<0.05 for each comparison). By contrast, no such risk was seen with other antidepressants. We estimate that use of
paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 (95% confidence interval 12.5 to 46.3)
patients so treated; the risk with more extensive overlap would be greater.
Conclusion : Paroxetine use during tamoxifen treatment is associated with an increased risk of death from breast cancer, supporting the hypothesis that paroxetine can reduce or abolish the benefit of tamoxifen in women with breast cancer
Kelly, C. M et al. BMJ 2010;340:c693
Risk of breast cancer mortality associated with increasing proportions of antidepressant use during tamoxifen treatment
Kelly, C. M et al. BMJ 2010
SSRI E TAMOXIFENE NEL PREGRESSO Ca MAMMARIO
Il Tamoxifene è un SERM (Selective estrogen receptor modulator) che viene convertito dall ’ isoenzima 2D6 del citocromo P450 (CYP2D6) nei suoi metaboliti endoxifene e 4OH Tamoxifene.
La paroxetina inibiscono e, in misura molto minore la fluoxetina e la sertralina , l ’ attività dell ’ isoenzima CYP2D6 a differenza degli SNaRIs (venlafaxina) e degli NaSSA (Mirtazapina) Brauch et al., 2009
1 ° gennaio 2000 al 27 ottobre 2012 32.465 donne di Australia, Canada, Danimarca, Norvegia, Spagna Italia, Spagna, Corea del Sud e Stati Uniti - 6 studi 32,9%di donne ha utilizzato CAM in modo regolare - 9 studi 50,5%di donne ha utilizzato CAM per i disturbi della menopausa La prevalenza media di uso in 12 mesi è stata del 47,7% (range: 33.1–56.2)
Le terapie non convenzionali in Italia Persone che nei 3 anni precedenti l
’
intervista hanno fatto uso di terapie non convenzionali, per tipo di terapia e sesso – Anno 2005 (per 100 persone dello stesso sesso)
2007
FITOESTROGENI:
Evidenze
sintomi menopausali end point intermedi del rischio cardio-vascolare end point intermedi del metabolismo osseo azione antiradicali liberi
Aspettative
eventi cardio e cerebrovascolari fratture rischio di cancro mammario, endometriale ed ovarico deterioramento cognitivo senile presidio antinvecchiamento per cute e mucose Del Pup, SIGITE 2006
FITOESTROGENI
G ENCEL VB ET AL , 2012
P RINCIPALI FONTI DI DAIDZEINA E GENISTEINA Alimenti derivati dalla soia Fagioli di soia Latte di soia Yogurt alla soia Tempeh Tofu Vegetali Alfalfa germogli Trifoglio germogli Frutta a guscio Semi di lino Pistacchi Noci Daidzeina μg/100 g
56621.4
921.3
3364.4
6974.8
9337.5
151.7
71.3
58.2
73.1
35.2
Genisteina μg/100 g
44213.4
1852.2
6565.1
10729.6
17050.2
117.6
70.9
173.2
103.3
tracce
GENCEL VB et al, 2012
GENCEL VB et al, 2012
ATTIVITÀ DI GENISTEINA E DAIDZEINA SUI RECETTORI DEGLI ESTROGENI
ISOFLAVONE ATTIVITA
’ ’
Genisteina
ha un ’ alta affinità per ERβ, ed è simile a quella del 17 (E2), mentre la sua affinità per ERα è solo il 6% di E2 estradiolo
Daidzeina
Ha una debole affinità di legame sia per ER affinità relativa per ER che per ER , ma la sua è superiore a quello per ER
Gencel VB, 2012; Barnes S, 2004
… Phytoestrogens-induced NO release from endothelial cells.
G ENCEL VB ET AL , 2012
….Effects of phytoestrogens on ECs and VSMCs
G ENCEL VB ET AL , 2012
….FITOESTROGENI e MALATTIE CARDIOVASCOLARI G ENCEL VB ET AL , 2012
Menopause 2002
State of Science Conference the management of menopause-related symptoms of National Institute of Health “… Trials of dietary soy are mixed; the majority of studies did not show any benefit ….Because most of these products are not manufactured in a standardized way , they may differ in composition from trial to trial …”
NIH 2005
Critical review of health effects of soybean phyto-oestrogens - RCT (randomized controlled trials), placebo-controllo, doppio cieco Inclusi solo studi con più alto grading in base ai Criteri di Harbour e Miller (≥1+) A. Cassidy et al.2006
BONE HEALTH
- 31 Studi hanno esaminato gli effetti dei fitoestrogeni sulla massa ossea ed il turnover osseo 6 Studi A. Cassidy et al.2006
SINTOMI CLIMATERICI
16 STUDI A. Cassidy et al.2006
EFFETTI CARDIOVASCOLARI
Il consumo di
cibi contenenti soia o di proteine isolate di soia (SPI)
positivi sui marcatori lipidici di rischio cardiovascolare ha effetti Il consumo di
isoflavoni isolati
non influenza i livelli dei lipidi o la pressione sanguigna ma migliora la funzione endoteliale A. Cassidy et al.2006
In conclusion, the use of soyabean products and soyabean isoflavones may be beneficial in post menopausal women for bone, cardiovascular risk and hot flushes. However, the benefits are subtle and do not appear in all individuals .
There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function.
A. Cassidy et al.2006
Isoflavoni ed influenze su endometrio e ghiandola mammaria
Isoflavone treatment for acute menopausal symptoms
The treatment did not change the levels of circulating estradiol or follicle-stimulating hormone. Immunohistochemical staining of endometrial and breast biopsy specimens revealed that isoflavones did not affect expression levels of steroid receptors ; estrogen receptors alpha, beta, and betacx; progesterone receptors A and B; or the proliferation marker Ki67.
Cheng G et al; Menopause, 2007
Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis.
Impiego della soia (dieta , estratto o concentrato)versus placebo, nella riduzione della sintomatologia vasomotoria in menopausa
19 STUDI
Although the overall combined results and the results by subgroups (according to the type of supplement used) showed a significant tendency in favour of soy, it is still difficult to establish conclusive results given the high heterogeneity found in the studies.
Bolaños R et al Menopause 2010 May .
In general , no conclusive evidence showed a benefit of phytoestrogen-enriched or -derived products for menopausal vasomotor symptoms , with the exception of products containing a minimum of 30 mg per day of genistein , which have been evaluated for up to two years in four studies. Further research is needed to confirm this efficacy. No evidence of safety concerns in the short term was found. Limited data suggest that phytoestrogen supplements were well tolerated.
It has been claimed that only 20 –30% of the general population in the United States possess gut microflorae that convert more oestrogenic dihydroxy isoflavan equol the isoflavone, daidzein , to the in comparison with 50 –60% of Asians.
Investigators in one trial stated that isoflavone supplementation improved symptoms only in women with the ability to produce equol and the Aso study found benefit from S-Equol in equol-non producing post-menopausal Japanese women.
Further research should consider the role of equol production and also whether phytoestrogens are more effective in women with more severe symptoms. Maturitas, Article in PRESS
EQUOLO
• L ’
Equolo
è il metabolita della daidzeina, e risulta formarsi dopo idrolisi a livello intestinale • Nella popolazione umana soltanto il 20 –50% degli adulti riesce a produrre
Equolo
dopo ingestione di prodotti a base di soia o isoflavoni • La percentuale è più elevata nei vegetariani e negli individui asiatici
Setchell KD, 2002, 2006; Song KB, 2006
Formula di struttura
EQUOLO
- Composto diidrossifenolico, identificato per la prima volta nel 1932 nell ’ urina di cavalle gravide.
- 2 enantiomeri R(+) Equolo e S (-) Equolo
Equolo Principali azioni in perimenopausa
• • •
Azione estrogenica: riduzione sintomi vasomotori Azione positiva sul metabolismo osseo Azione cardioprotettiva
Equol Improves Menopausal Symptoms in Japanese Women Effects of natural S-equol on the menopausal symptom total score (A) and somatic score (Greene climacteric scale) (B) in Japanese women. Studio randomizzato, doppio cieco, placebo controllo; 127 pazienti EQ-1: 10 mg Equolo/die per 12 settimane EQ-3: 30 mg Equolo/die per 12 settimane Riduzione intensità e frequenza di vampate, rigidità del collo e delle spalle, irritabilità e sintomi somatici.
Takeshi Aso,2010
A Pilot Study on the Effects of S-Equol Compared to Soy Isoflavones on Hot Flash Frequency Belinda H. Jenks et al;Journal of women ’ s health ,2012
Cardiovascular Risks in Relation to Daidzein Metabolizing Phenotypes • • •
Studio trasversale o cross-sectional Aprile-Dicembre 2011 726 donne (Hong Kong) con precedente diagnosi di ipertensione o con
•
ipertensione diagnosticata in perimenopausa Produzione di Equolo e O-DMA (O-desmetilangolensina) sulle urine delle 24 ore dopo 7 giorni di assunzione consecutiva di 60 mg di Daidzeina /die
Scopo: valutare la relazione fra fenotipi produttori e Non Equol Producers e O DMA (O-desmetilangolensina) ed i rischi cardiovascolari.
La prevalenza di Equol e O-DMA producers era del 53,2% e 60,9% rispettivamente.
Zhao-min Liu 2014
Equol producers
: maggiore massa magra , più bassa pressione sistolica e diastolica , più bassi valori di triglicedridi ed acidi grassi liberi rispetto ai non produttori.
O-DMA producers
: più bassa % di massa grassa, pressione sistolica e colesterolo totale rispetto ai non prduttori.
Zhao-min Liu 2014
Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated women with type 2 diabetes:a double-blind randomized controlled trial -Studio randomizzato, doppio cieco, placebo-controllo (University of East Anglia,United Kingdom) - 118 pazienti in menopausa con Diabete Mellito Tipo 2 ed in tp con statine Placebo 100 mg isoflavoni+ 90 mg epicatechina /die per 1 anno 93 pazienti Peter J Curtis et al, Am J Clin Nutr 2013
Assenza di differenze statisticamente significative fra il gruppo placebo e controllo in relazione a: CCA-IMT (Intima media thickness of the common carotid artery) e Pressione arteriosa .
Le pazienti Equol Producers presentavano una riduzione statisticamente significativa della Pressione Diastolica e della Pressione Arteriosa Media .
Equol Producers : più elevata concentrazione plasmatica di NO rispetto ai non produttori (equol producers: 61.1 6 6.5 mmol/L; non –equol producers: 40.3 6 3.4 mmol/L; P , 0.01).
Peter J Curtis et al, Am J Clin Nutr 2013
Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods 85 pazienti ipercolesterolemiche (Canadian University Hospital Research Center) Dieta con isoflavoni di soia per 1 mese Julia MW Wong et al, Am J Clin Nutr 2012
Julia MW Wong et al, Am J Clin Nutr 2012
Riduzione significativa di colesterolo LDL Producers (-0.43 ± in Equol Producers e in Non 0.11 compared with -0.54 ± 0.08 mmol/L, respectively).
Riduzione significativa di APO B in Equol Producers e Non Producers Significativa riduzione della Pressione Arteriosa in Equol Producers e Non Producers, ma non differenze significative fra i 2 gruppi Significativa riduzione in colesterolo HDL era osservata in pz Non Equol Producers mentre non era presente fra le Equol Producers (-0.07 ± 0.02
compared with 0.0 ± 0.03 mmol/L, respectively; P = 0.036).
Un simile risultato era osservato anche per APO A-I (-0.08 ± compared with -0.02 ± 0.02 g/L, respectively; P = 0.010).
0.02 Gli effetti sul colesterolo HDL da parte dell ’ Equolo possono essere dovuti alla sua maggior azione sui recettori estrogenici rispetto al suo precursore Daidzeina Julia MW Wong et al, Am J Clin Nutr 2012
Pasta Naturally Enriched with Isoflavone Aglycons from Soy Germ Reduces Serum Lipids and Improves Markers of Cardiovascular Risk - 62 pz con ipercolesterolemia Studio a gruppi paralleli, randomizzato, in cieco - University of Perugia Hospital - 80 g di pasta al giorno arricchita con 33 mg di isoflavone aglicone per 4 settimane Nelle pz che assumevano pasta arricchita con isoflavoni era osservata una riduzione statisticamente significativa di Colesterolo Totale e LDL rispetto al gruppo controllo mentre non vi erano differenze statisticamente significative in relazione ad HDL e Triglicedridi.
Clerici C et al 2007
Fra gli Equol producers si osservava una significativa riduzione di Colesterolo Totale,LDL e Protein C Reattiva ed una significativa maggiore vasodilatazione rispetto agli Non Equol producers.
Clerici C et al 2007
Emerging evidence of the health benefits of S-equol, an estrogen receptor b agonist Plasma S-equol concentrations in intervention studies that showed a clinically beneficial effect on vasomotor symptoms (VMS), osteoporosis, and cardiovascular diseases (CVD)
Richard L Jackson et al 2011
Efficacy of black cohosh (
Cimicifuga racemosa L.
) in treating early symptoms of menopause: a randomized clinical trial Studio randomizzato, doppio cieco, placebo-controllo Placebo 6,5 mg di estratto secco di Cimicifuga Racemosa Greene climacteric scale (GCS) scores fra 15 e 42 Mohammad-Alizadeh-Charandabi et al. Chinese Medicine 2013
Black cohosh reduced the GCS total score and all GCS subscale scores (vasomotor, psychiatric, physical, and sexual symptoms) during 4 and 8 weeks of treatment.
Mohammad-Alizadeh-Charandabi et al. Chinese Medicine 2013
Black Cohosh Hepatic Safety: Follow-up of 107 Patients Consuming a Special Cimicifuga racemosa rhizome Herbal Extract and Review of Literature
European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) on July 2006 have released an alert to get European sanitary authorities consuming aware of 42 cases of suspected hepatotoxic reactions
Cimicifuga racemosa rhizome.
in patients We followed-up 107 women , and asked them by telephone (33/107) and/or after anamnesis and clinical examination (74/107) to undergo a blood sample examination.
In all the patients there was no sign of hepatic disease, or worsening of already altered but stable parameters.
these data and current literature We think on the base of
C. racemosa rhizome extract should not be considered a potential hepatotoxic substance.
F. Firenzuoli et al;Evidence-Based Complementary and Alternative Medicine; 2007
Menopausal Transition and related
Lipid Profile Variation
CARDIOVASCULAR RISK Factors associated with total cholesterol levels in women around menopause attending menopause clinics in Italy
Progetto Menopausa Italia Study Group
BECORPI Berlin 2003
Italian Menopause Project
Age (years) <50 50-52 53-56 >57 No. of women Mean (mg/dl) 4.240
4.566
5.461
5.671
215 222 226 234 Total cholesterol level (mg/dl) <210 % 210-250 % 251-290 % >290 % 50,3+ 42,6 38,9 32,9 34,7 38,9 38,4 40,3 11,9 14,3 17,6 20,2 3,2 4,1 5,1 6,6
BECORPI Berlin 2003
Dyslipidemia in Menopause
Lifestyle modification
Lipid-lowering agents
Compliance Side effects
Alternative and complementary therapies
Alternative and complementary therapies for Dyslipidemia
RED YEAST RICE BERBERINE GARLIC BERGAMOT ARTICHOKE STEROLS and STANOLS
RED YEAST RICE
Monascus Purpureus
= =
A S T A T L O V I N MONACOLI K
Inhibitors of hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase
Red yeast rice lowers cholesterol in physicians a double blind, placebo controlled randomized trial • Double blind placebo controlled randomized trial • March to June 2012 • Men and women over age 18 with a total fasting cholesterol level above 200 mg/dL • Exclusion criteria were present treatment with statins, triglyceride values >400 mg/dL
Verhoeven et al. BMC Complementary and Alternative Medicine 2013
Monakolin K 5,025 mg Co-enzime Q-10 30 mg Procyanidins (Vitis Vinifera) 20 mg Lecithin 100 mg PLACEBO
2 capsules every evening for 8 weeks
Verhoeven et al. BMC Complementary and Alternative Medicine 2013
Verhoeven et al. BMC Complementary and Alternative Medicine 2013
Verhoeven et al. BMC Complementary and Alternative Medicine 2013
Tolerability of Red Yeast Rice (2,400 mg Twice Daily) Versus Pravastatin (20 mg Twice Daily) in Patients With Previous Statin Intolerance
The primary goal of the study was to compare the effect of red yeast rice versus pravastatin on the rate of myalgia recurrence in subjects with a history of SAM (
statin-associated myalgia ).
Steven C Halbert et al Am J Cardiol 2010
Steven C Halbert et al Am J Cardiol 2010
No significant difference was found between the 2 treatment groups in the mean pain severity score
5% RYR Treatment discontinuation for myalgia 9% Pravastatin
No difference was found in muscle strength between the 2 groups at week 4 (p 0.61), week 8 (p 0.81), or week 12 (p 0.82).
Steven C Halbert et al Am J Cardiol 2010
The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group.
Steven C Halbert et al Am J Cardiol 2010
Red Yeast Rice for Dyslipidemia in
Statin-Intolerant Patients
A Randomized Trial
Inclusion criteria:
-21 to 80 years of age
-
hypercholesterolemia discontinuance at least 1 statin because of myalgias , with resolution of muscle pain when the medication was discontinued David J. Becker et al. 2009 American College of Physicians
Red yeast rice group: three 600-mg red yeast rice capsules twice daily Placebo group: three placebo capsules twice daily Week-12 laboratory tests and measurements Week-24 laboratory tests and measurements
David J. Becker et al. 2009 American College of Physicians
David J. Becker et al. 2009 American College of Physicians
Plasma Lipid Measures
David J. Becker et al. 2009 American College of Physicians
Secondary Outcome Measures
David J. Becker et al. 2009 American College of Physicians
•
the aim of evaluating the possible ‘ signal alarms ’ due to herbal medicines and muscle injuries
•
a panel of: medical toxicologist, pharmacist and physician expert in herbal medicine
•
from April 2002 to December 2007, nine reports of muscle disorders were identified
Tuscan Regional Centre of Pharmacovigilance, Department of Preclinical and Clinical Pharmacology, University of Florence,Regional Agency for Healthcare Services of Tuscany, Epidemiology Unit, Florence, National Centre of Epidemiology, Surveillance and Health Promotion, National Institute of Health, Rome and Centre of Natural Medicine, S. Giuseppe Hospital, Empoli, Italy
F.Lapi et al. British Journal of Clinical Pharmacology 2008
F.Lapi et al. British Journal of Clinical Pharmacology 2008
Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient.
Cyclosporine
X
cytochrome P450 system
Rhabdomyolisis
Monakolin K
hydroxymethylglutaryl reductase
X
CK 2600 IU/L
Transplantation 2002
Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products
12 commercial red yeast rice products
David J.Becker et al. Arch Intern Med. 2010
Citrinin: a nephrotoxic mycotoxin
..need for improved standardization of RYR products and product labeling.
David J.Becker et al. Arch Intern Med. 2010
Monakolin K: 3 or 10 mg?
Italian Ministry of Health (2003) 3 mg/day
Official Journal of the European Union
(25/05/2012)
10 mg/day
Which are possible indications for RYR therapy in clinical practice?
alternative for patients with a history of statin-related adverse effects refuse to take statins, synthetic drugs Patients with elevated cholesterol-LDL levels but who still have a low cardiovascular risk Verhoeven et al. BMC Complementary and Alternative Medicine 2013
BERBERINE
The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials.
eleven randomized controlled trials (including a total of 874 participants)
BERBERINE:
total cholesterol
(mean difference - 0.61 mmol/L; 95 % confidence interval - 0.83 to - 0.39)
triglycerides
(mean difference - 0.50 mmol/L; 95 % confidence interval - 0.69 to - 0.31)
low-density lipoprotein cholesterol
(mean difference - 0.65 mmol/L; 95 % confidence interval - 0.76 to - 0.54)
high-density lipoprotein
(mean difference 0.05 mmol/L; 95 % confidence interval 0.02 to 0.09)
No serious adverse effects of berberine have been reported.
Planta Med 2013
AGOPUNTURA
EFFETTI:
Antalgico/ analgesico Immunomodulatore Neuroendocrino Trofico Vasomodulatore
A review of acupuncture for menopausal problems.
Acupuncture is one of the complementary therapies that are increasingly used by women with menopausal hot flushes
. Acupuncture can be understood as a form of neurological stimulation. Clinical trials of acupuncture use different control groups according to whether they wish to provide practical information on the role of acupuncture in health care, or theoretical information on the specific needle effect. Controls for the latter research question are highly problematic, and no convincingly inert 'placebo' needle has yet been designed.
For
natural menopause
, one large study has shown acupuncture to
be superior to self-care alone in reducing the number of hot flushes and improving the quality of life;
five small studies have been unable to demonstrate that the effect of acupuncture is limited to any particular points, as traditional theory would suggest; and one study showed acupuncture was superior to blunt needle for flash frequency but not intensity.
acupuncture For flushes associated with induced menopause, clearly is useful for reducing flushes in clinical practice, but there is mixed evidence on the nature of the effect:
one trial found genuine acupuncture superior to control needling, but another showed no significant difference between acupuncture and blunt needle. The possible mechanisms of acupuncture for hot flushes are discussed. Current evidence clearly justifies further research into the most cost effective form of acupuncture for treating hot flushes. Borud B et al., Mauritas, 2010
Acupuncture and TCM in the treatment of climacteric syndrome: a randomized controlled trial
Sonia Baccetti, Marina Faedda, Antonella Guerrera, M.Valeria Monechi, Rosa Maria Munizzi, Fior di Prugna, referring Center for complementary medicine, Tuscany Region, Italy Monica Da Frè, Epidemiology Unit, Regional Health Agency of Tuscany, Italy Angelamaria Becorpi, It. Soc. Gynaec. the Elderly Age, Dep.Obstetrics and Gynaecology AOU Careggi, Florence, Italy Fabio Parazzini, Obst. and Gynec. Department, IRCCS Foundation, Milan University, Milan, Italy
T
he Journal of Alternative and Complementary Medicine In Press 100 women were recruited and randomized in two Groups Group A:
diet, self-massage training and treatment (electroacupuncture, seven-star needle stimulation, twice a week for 6 consecutive weeks)
Group B :
the same diet and self-massage training, but the treatment with acupuncture started 6 weeks after their enrolment in the study Treatment: 3 Medical doctors specialised in acupuncture with specific training (8 hours)
Therapeutic Protocol
•
12 sessions (35 ’) twice weekly for 6 consecutive weeks :
-
stimulation (C7-D5, 5
’
) with seven star needle in the paravertebral lines
-
electroacupuncture (30 ’)
-dispersion
(100 cycles/sec) on GV 23 (shangxing) ; CV 22 (tiantu); BL 2 (zanzhu); LI 11 (quchi); LI 4 ( hegu)
-tonification
(40 cycles/sec) on SP 10 (Xuehai); SP6 (sayinjiao) GV 20 (Baihui); CV 4 (guanyuan); CV 6 (qihai); ST 37 (shangjuxu); LR 3 (taichong)
% reduction in the frequency of symptoms: group A at the end of treatment vs group B before treatment
82 20 Hot flushes Group A 81 27 Sudden sweating Group B At the end of treatment
the women in group A reported a reduction in the frequency of
hot flushes
by 82%, a significantly higher proportion compared to the women in group B (20%).
The difference was also significant for
sudden sweating
(81% vs 27%).
No relevant adverse events
General health conditions: group A at the end of treatment vs group B before treatment
40 42 86
Health conditions
of patients in
group A
at the end of treatment were definitely better (40%) and slightly better (42%), while 86% of women in
group B
, declared after 6 weeks that their health conditions were
more or less the same
study as when they started the 4 Better 12 2 0 4 0 2 Slightly better More or less the same A little worse Significantly worse Group A Group B
OMEOPATIA
Sistema medico che si basa sulla somministrazione di piccole quantità di medicamenti selezionati in base alla legge dei simili ovvero
‘
Similia similibus curentur
’
.
Pur essendo ancora lontani da una soddisfacente spiegazione sulla natura fisicochimica delle alte diluizioni omeopatiche (ultramolecolari), esiste una solida base sperimentale per affermare che la modalità di conformazione dell
’
acqua e dei suoi soluti a livello di nanostrutture giochi un ruolo decisivo.
La farmacologia delle alte diluizioni/dinamizzazioni sta quindi emergendo come la nuova frontiera della nanomedicina che potrà fornire spiegazioni plausibili al meccanismo d
’
azione del farmaco omeopatico in un futuro non molto lontano.
Treating hot flushes in menopausal women with homeopathic treatment
RESULTS: Ninety-nine physicians in 8 countries took part in this study and included 438 patients with an average age of 55. Homeopathic medicines were prescribed to all patients; 98% of the prescription lines were for homeopathic medicines. Lachesis mutus, Belladonna, Sepia officinalis, Sulphur and Sanguinaria canadensis were the most prescribed. This observational study
revealed a significant reduction (p<0.001)
in the
frequency of hot flushes
by day and night and a
significant reduction in the daily discomfort they caused
(mean fall of 3.6 and 3.8 points respectively, on a 10cm visual analogue scale;
p<0.001
).
90%
of the women reported
disappearance or lessening of their symptoms
, these changes mostly taking place within 15 days of starting homeopathic treatment.
CONCLUSIONS: The results of this observational study suggest that homeopathic treatment for hot flushes in menopausal women is effective.
Further studies including randomized controlled trials should be conducted .
Bordet MF, et al,2008
YOGA E MENOPAUSA
Riduzione significativa dei sintomi vasomotori e dei disturbi del sonno
C.Booth-La Force et al. 2007 , S.Berardino et al. 2008
YOGA E MENOPAUSA
Studio Swami Vivekananda Yoga Anusandhana Samsthana: condotto su 120 donne in menopausa , età 40 -55 anni (età media 47, 5 aa) suddivise in due gruppi: 1.Il primo ha svolto regolarmente esercizi di yoga accompagnati da letture su come utilizzare le tecniche di rilassamento orientale per gestire lo stress. 2.Il secondo gruppo ha svolto per lo stesso tempo esercizi di stretching e ginnastica, abbinati a letture su come ridurre il peso corporeo. Dopo otto settimane le appartenenti al primo gruppo hanno mostrato una significativa riduzione di vampate di calore, sudorazione notturna e disturbi del sonno rispetto alle altre. Berardino S et al,2008
YOGA E MENOPAUSA
“
lo stress emotivo è un comune elemento scatenante le vampate.
Tecniche che promuovono il rilassamento ed una migliore gestione dello stress possono essere particolarmente utili; tra queste lo Yoga è appunto una tecnica utile al miglioramento della sintomatologia climaterica o dell
’
adattamento alla presenza di questa
”
Booth C-La Force et al, 2008
A Randomized Controlled Trial of Relaxation Training to Reduce Hot Flashes in Women with Primary Breast Cancer
Relaxation may be a useful component of a program of measures to relieve hot flashes in women with primary breast cancer Fenion DR, 2008
Psychoeducational interventions to alleviate hot flashes: a systematic review
Psychoeducational interventions , including
relaxation
, seem to alleviate hot flashes in menopausal women and breast cancer survivors; however, the methodological quality of published research is either fair or poor. More studies are required , especially in the breast cancer population where only a few studies are available, before psychoeducational interventions are offered as a treatment option.
Tremblay A, 2008
Applied relaxation and oral estradiol treatment of vasomotor symptoms in postmenopausal women
In
a prospective study
, postmenopausal women with vasomotor symptoms were
randomized to applied relaxation
or
oral estradiol
treatment during
12 weeks
with
6 months follow-up
. Number and severity of flushes were registered daily and Kupperman ’s Index and a general estimate of climacteric symptoms, Mood Scale and Symptom Check List were completed at baseline, 4, 8 and 12 weeks of treatment, and 3 and 6 months after therapy.
Results
: After 12 weeks of treatment, the
number of flushes/24h decreased significantly over time in both treatment groups.
In the group receiving
applied relaxation
, the mean number of flushes/24h decreased
from 6.0 (95% CI 4.5
–7.6
) to 3.0 (95% CI 2.1
–3.9) after 12 weeks
of treatment. The mean number of flushes/24h was 1.7 (95% CI 0.7
–2.5) at 6 months follow-up; i.e. a
72% decrease.
In the
estrogen group
, the mean number of flushes/24h decreased from
8.4 to 0.8
; i.e
90% decrease in the number of flushes after 12 weeks
of treatment. […]Estrogen therapy reduced flushes significantly faster than applied relaxation. General climacteric symptoms according to the Visual Analogue Scale and the Kupperman ’s Index decreased significantly over time in both groups. General mood (Mood Scale) increased significantly in the estrogen group, but not in the group receiving applied relaxation. Psychological wellbeing according to Symptom Checklist, increased significantly from baseline to 12 weeks in both groups.
Conclusions:
We suggest that
applied relaxation may be used as an alternative treatment of vasomotor symptoms for postmenopausal women but should be further evaluated.
Nedstrand et al. 2005
Servizio Menopausa Oncologica SOD Ginecologia Oncologica Medica – DAI Oncologia DAI Dipartimento Materno-Infantile Azienda Ospedaliero-Universitaria Careggi, Firenze
Svolgimento di un corso di Hatha Yoga della durata di 6 mesi, proposto alle pazienti oncologiche Gruppo oncoematologia Dall ’ analisi del confronto dei punteggi della Scala di Greene somministrata prima e dopo lo svolgimento del corso Hatha Yoga è emerso:
Riduzione dei disturbi dell
’
area psicologica nel 100% dei casi; Riduzione della sintomatologia algica osteo-articolare nel 66% dei casi; Riduzione della sintomatologia vasomotoria nel 53% dei casi
.
2008
ESOPO
Epidemiological Study On the Prevalence of
Osteoporosis Popolazione femminile tra 40 e 79 anni
prevalenza osteopenia: 42.3% prevalenza osteoporosi: 22.8%
Adami et al., 2004
Objective
To study the epidemiological profile of women with Low Bone Density (LBD) and Osteoarthritis around menopause attending a network of first level outpatients menopause clinics in Italy
PROGETTO MENOPAUSA ITALIA STUDY GROUP ( 1997 )
Berlin 2008
Methods
1997 – 2006 Large cross-sectional study was conduced for a total of 49.122 women (mean age 54 years)
Out of the
25.133 cases considered, LBD was diagnosed in 3349
Berlin 2008
Incidence of Low Bone Density (LBD)
14%
Normal Bone Density (n=21784) LBD (n=3349)
86% Low Bone Density 3349 cases out 25133 : -
Osteopenia 51,4%
- Osteoporosis 48,6% Berlin 2008
MENOPAUSA: OSTEOPOROSI RISCHIO DI FRATTURA
AUMENTO INCIDENZA DI RISCHIO DI FRATTURA:
OSTEOPENIA: 1.8 VOLTE OSTEOPOROSI: 4 VOLTE -1 DS = -10% BMD = 2 VOLTE RISCHIO DI FRATTURA
E.S. Siris, et al. (NORA), Jama 2001
Prevalenza Osteoporosi in pazienti con
Osteoporosis and Rate of Bone Loss among Postmenopausal Survivors of Breast Cancer
Chen et al. 2005
Terapia oncologica integrata e densità ossea
Shapiro et al. 2001
Incidenza di fratture vertebrali in pazienti con carcinoma mammario
Kanis et al. 1999
CHEMIOTERAPIA E OSTEOPOROSI
STUDIO CONDOTTO SU DONNE IN TERAPIA CON CMF ( ciclofosfamide, metotrexate, fluorouracile ) 6 cicli di chemioterapia Misurazione del BMD con la metodica DXA •
dopo un anno di terapia riduzione del BMD – 4,5% alla colonna lombare e –4,4%
•
al collo del femore dopo due anni riduzione del BMD –6,5% alla colonna lombare e –4,5% al collo del femore Persistenza della riduzione del BMD alla sospensione della terapia
Fogelman I. et al, 2003
Inibitori Aromatasi - Tamoxifene
Perez et al. 2006
Side effects of aromatase inhibitors versus tamoxifen: the patients
’
perspective
We surveyed patients with ER+ breast cancers who received adjuvant hormonal therapy to determine how these medications impacted their quality of life and whether side effects or cost influenced decisions to continue therapy.
Results
Four hundred fifty-two of 902 surveys were returned for a 50% response rate. Eighty-two percent of respondents were placed on (adjuvant hormonal therapy) some form of estrogen-blocking therapy. Fifty-four percent of these were placed on tamoxifen and 46% on an AI. The most trouble some symptoms for
tamoxifen
and
AI users
, respectively, included
hot flashes (35%/30%), weight gain (14%/15%), insomnia (17%/17%),
and
joint aches (12%/ 23% ,
P
= .002). Thirty-nine percent of TAM users and 46% of AI users were taking medications to control their symptoms. Fifty percent of TAM users and 39% of AI users took vitamin E to help control hot flashes. Forty-two percent of TAM users versus 32% of AI users took Advil (Wyeth, Richmond, VA) for muscle/joint aches; 47.5% of AI users switched medication to improve symptoms as compared with only 37% of tamoxifen users (
P
= .015).
Conclusions
In our survey, both
tamoxifen
and
AI users reported significant
and
different side effects
.
AI users
suffered more frequently from
musculoskeletal complaints ,
and more
AI users switched therapy
. Both AI and tamoxifen users used adjunctive medications for symptom control. In both groups, a large number used vitamin E to help hot flashes despite weak evidence to support its effectiveness in this setting. Cost of therapy and symptom control was not a major barrier to care.
Garreau AJS 2006
ESCEO: Position Paper
BMD assessment by DXA and FRAX algorithm for the evaluation of clinical risk factors* Calcium, PTH and 25-OH Vitamin D levels (Markers of bone turnover ) Post-menopausal women with T-score < -2.5 or <-1.5 + = 1 clinical risk factor or T-score < -1.0
+ = 2 clinical risk factors or FRAX 10-year risk of hip fracture =3% Post-menopausal women with history of personal fragility fracture (any site) or Age = 75 years old (irrespective to BMD) Pre-menopausal women with ovarian suppression undergoing tamoxifen or therapy with T-score < -1.0 or presence of = 1 verteb fracture or history of fragility fracture (any site, Irrespective to BMD) Antiresorptive treatment with zoledronic acid 4mg i.v. every 6 months denosumab s.c., or possibly oral bisphosphonates (with caution to patients compliance to therapy) for the entire period of AI treatment
General Measures
suggest physical exercise and consider administration of vitamin D supplementation (> 800 IU/per day or 10.000 IU per week) plus calcium (intake of at least 1000 mg/day)
Ambulatorio Menopausa Oncologica
Becorpi et al., Toscana Medica 2010
Materiali e Metodi
Dipartimento ad Attività Integrate Materno – Infantile SOD di Ginecologia e Ostetricia + Dipartimento ad Attività Integrate di Oncologia SOD di Oncologia Medica Ginecologica Azienda Ospedaliero-Universitaria Careggi Firenze 54 pazienti
Ambulatorio Menopausa Oncologica • Pregresso carcinoma mammario • Terapia oncologica integrata • Stato menopausale iatrogeno o naturale • Dato densitometrico DXA lombare e femorale disponibile
Risultati:
VARIABILE
Età media (aa) BMI medio (kg/m 2 ) Stato menopausale (aa) T-score lombare T-score femorale Fratture maggiori Fratture minori Indice FRAX ( major osteoporotic ) Indice FRAX ( hip fracture )
RISULTATO
57,6 ± 8,9 24,5 ± 2,9 9,4 ± 6,9 -1,3+-1,0 -1,4+-1,0 3,7 % 11,1 % 5,05 % 1,9 %
… raccomandazioni di prevenzione primaria
Favorire un adeguato introito alimentare di calcio e vitamina D Intervenire sui disturbi del comportamento alimentare Mantenere un BMI non inferiore a 19 Kg/m2 Seguire stili di vita sani Documenti: NOF, IOF,NAMS,ASSR, SIOMMMS 2004 come l …interventi sullo stile di vita,
’
abolizione del fumo, il controllo del peso e la regolare attività fisica dovrebbero sempre essere presenti nella gestione della paziente in menopausa, trattata o meno con TOS, allo scopo di prevenire malattie degenerative Documento congiunto SIGiTE/SIM 2004
Fracture prevention with vitamin D supplementation
A meta-analysis of randomized controlled trials
Oral vitamin D
supplementation 700 - 800 IU/d
appears to
reduce the risk of hip and any nonvertebral fractures
in ambulatory or institutionalized elderly person
JAMA, May 11, 2005-vol 293, 18
VITAMINA D: PREVENZIONE DELLE FRATTURE
Bischoff-Ferrari et al, JAMA, 2005
The role of calcium in peri- and postmenopausal women: 2006 position statement of NAMS
The target
calcium intake
for most menopausal women is
1.200 mg/day
. Adeguate vitamin D status, defined as
30 mg/ml or more of serum 25OH vitamine D
(usually achieved with a daily oral
intake of at least 400 to 600 IU
) is required to achieve the nutritional benefit calcium
Menopause, 2006
Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1alfaOH vit D for treatment of postmenopausal bone loss Prospective randomized multicenter open-label 2 year trial The HRT group received a low dose of CEE at a dose of 0.31 mg/day +/- MPA 2.5 mg/day.
Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 microg/day.
This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause. Mizunuma et al.,J Bone Miner Metab. 2006;24(1):11-5
Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study.
METHODS: 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years
73% and 35% of women had serum 25-OH D
levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention.
11% of women had levels below 30 nmol/l.
Garnero et al.mBone. 2006 Nov 15
Vitamin D and prevention of breast cancer: pooled analysis BACKGROUND: Garland CF et al.
Inadequate photosynthesis or oral intake of Vitamin D
are associated with
high incidence and mortality rates of breast cancer
in ecological and observational studies, but the dose-response relationship in individuals has not been adequately studied. METHODS: A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with
1760 individuals
. Data were pooled to assess the dose-response association between serum 25(OH)D and risk of breast cancer. [...] CONCLUSIONS:
Intake of 2000 IU/day of Vitamin D(3),
and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated
with reduction by 50% in incidence of breast cancer
, according to observational studies.
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11
Vitamin D and prevention of colorectal adenoma: a meta-analysis
BACKGROUND:
Vitamin D status
is associated inversely with
risk of colorectal cancer
, but the association with adenoma risk is
less clear
.[...] METHODS: A meta-analysis composed of CONCLUSIONS: Both circulating
17 epidemiologic studies
25(OH)D, vitamin D intake, and colorectal adenomas. [...]
25(OH)D and vitamin D intake
[...] published before December 2007 was done to examine the association between circulating were
inversely associated
with
colorectal adenoma incidence
incidence and recurrence.
and
recurrent adenomas
. These results further support a role of vitamin D in prevention of colorectal adenoma Cancer Epidemiol Biomarkers Prev. 2008 Nov
Calcium plus vitamin D supplementation and the risk of colorectal cancer
[...]METHODS: We conducted a
randomized, double-blind
, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers [...]for an average of 7.0 years. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years
had no effect on the incidence of colorectal cancer
among postmenopausal women. [...] N Engl J Med. 2006 Feb
Effect of low dose vitamin K2 (MK-4) supplementation on bio indices in postmenopausal Japanese women Koitaya N et al [...] The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations.
Serum undercarboxylated OC (ucOC) concentration decreased,
and
the gamma-carboxylated OC (GlaOC)
and
GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation
. [...] J Nutr Sci Vitaminol (Tokyo). 2009 Feb
Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial.
Cheung AM et al.
Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia.
More studies are needed to further examine the effect of vitamin K on fractures and cancers.
PLoS Med. 2008 Dec
A recent meta-analysis of randomized controlled trials also showed that daily supplementation with
vitamin k2
reduces hip vertebral and all non vertebral
fractures
Arch Intern Med, 2006 In a recent study Knapen and colleagues suggest that vitamin K2 supplementation improves
bone strength
via bone geometry rather than BMD Osteoporosis Int, 2007
OSTEOPOROSI e Terapie
•sono disponibili numerosi trattamenti • tutti, tranne il teriparatide e il ranelato di stronzio, agiscono tramite l ’ inibizione del riassorbimento osseo • la maggior parte dei dati sull ’ efficacia nella riduzione delle fratture e sulla sicurezza dei trattamenti sono relativi a pazienti in menopausa naturale • poche informazioni sono disponibili circa l ’ efficacia di tali trattamenti nella prevenzione delle fratture osteoporotiche, nelle giovani donne,in particolare in quelle con menopausa precoce, specialmente nel lungo termine
Rees M., 2006
Intervento farmacologico: Tabelle Sinottiche (livelli di evidenza)
* = Evidenza derivata da studi post hoc o da meta-analisi (vedi testo) § = influenzata dal maggior peso molecolare dello stronzio •= Evidenza derivata da studi post hoc (vedi testo) Linee Guida S.I.O.M.M.M.S.2012
RACCOMANDAZIONI RELATIVE ALL
’
OSTEONECROSI DELLA MASCELLA/MANDIBOLA ASSOCIATA A TERAPIA CON BISFOSFONATI IN PAZIENTI CON OSTEOPOROSI: DOCUMENTO DI CONSENSO Maggior rischio di ONJ:
diabete mellito non controllato - terapia corticosteroidea cronica - abuso cronico di alcool /fumo - malattie ematologiche - trattamento immuno-soppressivo - sindrome da immunodeficienza acquisita Se è necessario un intervento chirurgico nel cavo orale anche di minima entità è consigliata una adeguata preparazione iniziale (igiene professionale,istruzione di igiene, ultrasuoni ect.) ed un ’ adeguata profilassi antibiotica (es.: amoxicillina/ac. clavulanico, eventualmente combinata a metronidazolo, per almeno 2 giorni prima e 7- 10 giorni dopo l ’ intervento), e, anche nel caso di estrazione, sutura ed eventuale chiusura con lembo e monitoraggio della ferita fino alla guarigione. Una sospensione del bisfosfonato per un periodo di alcune settimane prima e dopo l ’ intervento odontoiatrico invasivo può essere raccomandato in via cautelativa , anche se non esistono evidenze che ciò riduca il rischio di ONJ .
Linee Guida S.I.O.M.M.M.S.2012; Associazione Nazionale Dentisti Italiani (ANDI)
Terapie locali vulvo-vaginali
- Gel o capsule vaginali contenenti Vitamina A, Vitamina E con l
’
aggiunta di Colostro Bovino ed Acido Ialuronico o entrambi
Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical
trial. Eur Rev Med Pharmacol Sci 2008 - Gel contenente
Acido Ialuronico
Role of high molecular weight hyaluronic acid in postmenopausal vaginal discomfort.
Grimaldi EF, Restaino S, Inglese S, Foltran L, Sorz A, Di Lorenzo G, Guaschino S. Minerva Ginecol.2012
-
Ovuli contenenti centella asiatica; malva sylvestris; chamomilla recutita;silice colloidale; vitamina E; acetato; acido ialuronico; melaleuca;alternifolia
Conclusioni
MENOPAUSA
Medicina integrativa Variabilità interindividuale Approccio: • Farmacologico • Nutrizionale • Counseling sullo stile di vita
Personalizzazione dell
’
intervento preventivo e/o terapeutico
Salute & qualità di vita
Grazie per l
’
attenzione
Caso clinico
Storia clinica della Paziente GB
Anno di nascita: 1967 Impiegata 1 figlio di 10 aa Anamnesi fisiologica : ndp Anamnesi patologica remota : nel 2010 (43 anni) diagnosi di Carcinoma duttale QSE dx G1, ER 80%, PgR 60%, Ki 67 negativo, c-ErB-b2 negativo. Quadrantectomia dx seguita da Radioterapia e Analogo Gn RH
Anamnesi patologica prossima:
La paziente riferisce comparsa della sintomatologia climaterica.
In particolar modo: • Sintomi vasomotori (vampate di calore sia di giorno che di notte) •Disturbi del sonno •Riduzione della libido •Secchezza vaginale ha effettuato: • MOC lombare e femorale • Es. metabolismo fosfo-calcico •Es. metabolismo lipidico
25 OH Vitamina D: 18,6 ng/mL Colesterolo totale: 239 mg/dL HDL: 29 mg/dL
Terapia proposta:
Osteoporosi
- Risedronato sodico 35mg 1 cp alla settimana a digiuno - Vit. D 25.000 UI flaconi 1 fl ogni 2 settimane a stomaco pieno - Apporto giornaliero di calcio adeguato
Ipercolesterolemia
-Riso rosso fermentato ( Monascus P. titol. in Monakolina K 10 mg ) 1 busta al giorno al giorno
Secchezza vaginale
Gel contenente colostro, vitamina A, vitamina E, acido ialuronico (1 applicazione sull ’ esterno tutte le sere); 1 cpr vaginale 2 volte a settimana.
Sintomi vasomotori
Miscela di estratti vegetali Galenici (per compressa): 1 cp metà mattina e pomeriggio - Cimicifuga racemosa e.s. (estratto secco) 75 mg - Crataegus Oxyacantha e.s. 75 mg - Salvia Officinalis e.s. 250 mg - Equisetum e.s. 100 mg
Disturbi del sonno
Miscela di estratti vegetali Galenici (per compressa): 1 cp prima di coricarsi -Escholtzia Californica e.s. 200 mg - Valeriana Officinalis e.s. 250 mg - Melatonina 5 mg
Riduzione libido
Miscela di estratti vegetali Galenici: 1 cp al giorno -Panax Ginseng e.s. 15% 100 mg - Maca Lepidium Meyenii e.s. 300 mg