The document discusses the effects of phytoestrogens like isoflavones on vaginal health. It summarizes several clinical studies that have investigated the impact of isoflavone supplements on vaginal maturation index and symptoms. While some studies found improvements in vaginal symptoms, the evidence is still limited and topical estrogen remains the standard treatment for vaginal atrophy.

1. SALUD VAGINAL A.Cabero Barcelona, 2008

3. NA 139 49 2 Soy hot dog, tempeh burger NA 260 79 3 Miso paste (rice or barley) NA 376 266 2 Miso paste ND 171 159 6 Soybean paste NA 320 190 3 Tempeh NA 729 546 1 Soybean, green 7 230 138 3 Soybean sprouts ND ND ND 1 Mung bean sprouts 47 ND ND 1 Alfalfa sprouts ND 3 <1 3 Soy-based specialty formula ND 26 18 10 Soy Milk ND 5 8 3 Soy Sauce ND 166 76 15 Tofu Coumestrol, µg/g Wet Wt Genistein, µg/g Wet Wt Daidzein, µg/g Wet Wt No. of foods analyzed Food

4. Wood, 2006 Cynomolgus monkey

5. Indice de maduración vaginal Indice cariopicnótico Indice eosinofilia Indice plegamiento celular

6. Rimoldi,2007 E2 low: 0,17mg/kg E2 high: 0,7mg/kg Gen low: 5,4mg/kg Gen high: 54mg/kg ISOFLAVONAS EN LA RATA

8. Wood, 2006 IM INDICE MADURACION VAGINAL. CYNOMOLGUS MONKEY NS 509mg/isof 1020mg/ equol

9. EFECTOS DE 70mg/d DE FITOESTROGENOS Albertazzi,1998 % sof N=104 Disminución de –1,59 sof /d comparado con placebo Sin cambios en otras variables del Síndrome climatérico

10. FITOESTROGENOS Y S CLIMATERICO Indice vaginal 60 57 38 20 FSH mIU/ml (Scambia, 2000)

12. Fitoestrógenos y mucosa vaginal NS 64 pacientes, 3 m Isoflavonas, 114mg/d v plac Ensayo clínico Nikander,2005 P<0,05 IM, soja,linseed 25 pacientes 2 semanas Soja, trébol, linseed Cuadrado latino Wilcox,1990 P<0,05 IM 3 meses Cimicifuga racemosa, 60mg/ v lacebo Ensayo clínico abierto Warnecke,1985 P<0,05 IM 80 pacientes, 3 mess Cimicifuga racemosa, 80mg/d v placebo Ensayo clínico Stoll,1987 P<0,05 60 pacientes,3m Trébol rojo v placebo, 80mg/d Ensayo clínico Hidalgo L, 2005 P<0,05 para 75mg/d 60 pacientes,13 sem Isoflavonas oral y transdérmica Ensayo clínico simple Colacurci, 2004 P<0,05 IM 71 pacientes,24 sem Pueraria mirifica 3 dosis v placebo Ensayo clínico Manonai, 2007 NS 45 pacientes, 12 sem 80-138mg no extractados Ensayo clínico Murkies, 1995 P<0,05 sec vag 165 pacientes, 12 sem 50mg/d v placebo Ensayo clínico Brzezinsky,1996 NS 227 pacientes,12 m Genisteína, 54mg/d v placebo Ensayo clínico D’Anna, 2007 NS 20 pacientes, 6 sem 6 semanas 50mg/d v placebo Ensayo clínico Scambia, 2000 P<0,05 IM N ?12 semanas Soja v dieta pobre en soja Ensayo clínico cruzado Dalais FS, 1998 P<0,05 IP 187 pacientes, 6 meses Soja, THS v placebo Ensayo clínico cuzado Chiechi LM, 2003 NS 36 pacientes, 3 m Soja v placebo Ensayo clínico Manonai J,2006

13. Efecto de 80 mg de Isoflavonas, principalmente de GENISTÍNA, sobre la SINTOMATOLOGÍA MENOPÁUSICA de intensidad moderada-severa. (Albert A. Et al, Phytomedicine 2002; 9: 85-92) 2,9% 30,4% 41,2% Cefaleas Pérdida líbido Sequedad vaginal Palpitaciones Dolores óseos/articulares Fatiga - Debilidad Ánimo depresivo Irritabilidad - Nerviosismo Insomnio Sudoraciones Sofocaciones SÍNTOMAS (%) 4,9% 32,4% 78,4% 6,9% 42,1% 70,6% 2,9% 30,4% 46,1% 4,9% 32,4% 80,4% 8,8% 34,3% 63,72% 4,9% 32,4% 52,9% 8,8% 43,1% 74,5% 3,9% 62,8% 86,3% 4,9% 61,8% 96,1% 1,0% 81,4% 100% Empeoran Mejoran Intensidad inicial Leve a Severa

14. D’Anna, 2007

15. D’Anna, 2007 GENISTEINA Y TRACTO GENITAL 54 MG/D GENISTEÍNA PURA (98%)

16. Ensayo clínico controlado de la acción de las isoflavonas sobre vagina y endometrio 64 pacientes con cáncer de mama 114mg/d iso de soja versus placebo, cruzado 3 meses de tratamiento con 2 meses washout RESULTADOS: Sin efecto sobre endometrio Sin alteración del índice de maduración vaginal Nikander E y cols Fertil Steril, 2005

17. ISOFLAVONAS TRANSDERMICAS - Colacurci N, 2004 -Vanttinen, 2001 -Carranza-Lira, 2001

18. WHITE KWAO KRUA (Pueraria mirifica)

19. Manonai,2007 Pueraria mirifica 46:43:11 11:65:24 Puerarina Genisteína Daidzeína Genistina Daidzina Miroestrol Deoximiroestrol Espinasterol Placebo 48:42:10 44:45:12 Pueraria Basal 6meses

20. Cimicifuga racemosa A systematic review of its Clinical efficacy. Francesca Borrelli and Edzard Ernst J Clin Pharmacol, 2002 “… No se ha demostrado su eficacia clínica para el tratamiento de la sintomatología postmenopáusica.” Effects of black cohosh on menopausal complaints 62 pacientes, 12 semanas, contra placebo “ .. Acción estrogénica débil sobre el trofismo vaginal” Wuttke W, Menopause, 2006

21. 50mg + Upmalis, 2000 177 80mg - St Germain, 2001 24 55mg - Hodgson,1998 13 50mg - + Scambia 2000 50 38mg - Howes,2000 66 40mg - + Nachtigall, 1999 25 34mg + - Washburn,1999 51 40-80mg + Nestel, 1998 17 52-88mg + + Potter, 1998 66 76mg + Albertazzi,1998 104 40mg - Baber,1998 51 45mg - + Murkies,1995 58 Dosis DO RCV SC N

22. Williamson-Hughes, 2006 Genisteína versus isoflanonas totales

23. Meta-análisis Williamson-Hughes Gynecol Endocrinol, 2005

24. Figure 1 PD formation in 3 dimensional human reconstituted skin (EpiDermTM FT) Magnification (40 X). ( A ) Sham irradiation, ( B ) 20 mJ/cm2 of UVB plus vehicle (0.1% DMSO), ( C ) 60 mJ/cm2 of UVB plus vehicle (0.1% DMSO). Scale Bar = 50 microns. Moore, 2006 Carcinogenesis

25. Figure 2 Effects of Genistein on the immunolocalization of UV induced PD formation in human reconstituted skin (EpiDermTM FT) exposed to 20 mJ/cm2 of UVB. Magnification (40X). (Inset) represents sham control. ( A ) Vehicle (0.1% DMSO) + UVB at 20 mJ/cm2, ( B ) 10 µM Genistein + UVB. ( C ) 20 µM Genistein + UVB. ( D ) 50 µM Genistein + UVB. Scale Bar = 50 microns. Arrows demarcate areas of positively stained cells consistent with nuclear immunoreactivity Moore, 2006 Carcinogenesis

26. Figure 5 Effects of Genistein on PCNA expression in human reconstituted skin samples (EpiDermTM FT) exposed to 20 mJ/cm2 of UVB. Magnification (40X). (Inset) represents sham control ( A ) Vehicle (0.1% DMSO) + UVB at 20 mJ/cm2, ( B ) 10 µM Genistein + UVB, ( C ) 20 µM Genistein + UVB, ( D ) 50 µM Genistein + UVB. Scale Bar = 50 microns. Arrows demarcate areas of positively stained cells consistent with nuclear immunoreactivity. Moore, 2006 Carcinogenesis

27. Figure 7 Comparative graphical quantification of PD and PCNA immunoreactivity profiles relative to the pre-treatment genistein concentrations and UVB flucences of 20 and 60 mJ/cm2. * P -value < 0.05 compared to sham samples stained for PD. t represents P -value < 0.05 compared to sham samples stained for PCNA. Moore, 2006 Carcinogenesis PD:Dímeros pirimidina PCNA: Proliferating cell nuclear antigen

28. FIGURE 1 Representative photograph of a complete photocarcinogenesis in mice treated with genistein. ( A ) Hairless mice irradiated with 0.3 kJ/m2 thrice weekly for 25 wk; ( B ) mice treated with 1 µ mol genistein before UVB exposure; ( C ) mice treated with 5 µ mol genistein before UVB irradiation. Huachen Wei, 2003 J Nutritio

29. FIGURE 2 Effect of topical genistein on initiation and promotion and on complete photocarcinogenesis. Tumor multiplicity was measured in 20 hairless mice. Mice in each experiment were treated as described in the text and genistein doses used were 1 and 5 µ mol. ( A ) UVB initiation study: ( ) negative controls [sham irradiation plus 12- O -tetradecanoyl phorbol-13-acetate (TPA)]; (•) positive controls (UVB + TPA); ( ) 5 µ mol genistein + UVB + TPA; and ( ) UV irradiation only. ( B ) UVB promotion study: ( ) negative controls [7,12-dimethylbenz[a]anthracene (DMBA) alone plus sham irradiation]; (•) positive controls (DMBA + UVB); ( ) acetone/UVB irradiation only; and ( ) DMBA/ 5 µ mol genistein +UVB. ( C ) Complete photocarcinogenesis study: ( ) negative controls (sham irradiation); (•) positive controls (UVB of 0.3 kJ/m 2 thrice weekly); ( ) 1 µ mol genistein + UVB; and ( ) 5 µ mol genistein + UVB. Huachen Wei, 2003 J Nutritio

30. SHAM POSITIVE GENISTEIN Huachen Wei, 2003 J Nutrition Lesión cutánea por irradiación

31. FIGURE 7 Effect of genistein on UVB-induced erythema in human skin. The study was performed in the phototherapy unit in the Department of Dermatology, Mount Sinai Hospital. UVB fluences used a range from 0 to 100 mJ/cm2 as described in the text. Genistein was applied to dorsal skin either 60 min before or 5 min after UVB exposure. Photographs were taken 24 h after UVB irradiation. A minimal erythema dose (MED) for this individual was 40 mJ/cm2. Lane 1: Vehicle plus UVB; lane 2: blank plus UVB; lane 3: pre-UVB application, 1 µ mol genistein/cm2 of skin plus UVB; lane 4: post-UVB application, UVB plus 1 µ mol genistein/cm2 of skin; and lane 5: dose response of topical genistein at a dose ranging 0.05—5 µ mol. UVB dose was 1 MED (40 mJ/cm2 ). Huachen Wei, 2003 J Nutrition

33. CONCLUSIONES -Las evidencias actuales no son suficientes para apoyar un efecto clínico apreciable de los fitoestrógenos sobre el trofismo vaginal .La aplicación ntópica estrogénica es el referente actual de la atrofia vaginal