Modalità d azione ed effetti del laser in donne con atrofia vaginale e/o incontinenza urinaria Stefano Salvatore

Transcription

1 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele Italy Modalità d azione ed effetti del laser in donne con atrofia vaginale e/o incontinenza urinaria Stefano Salvatore

2 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Background To The Health Issue During , the average life expectancy of a woman in Australia was 50.8 years, ie., The end of their childbearing years. Now life expectancy is 84.3 years. The average age for menopause is 51 years old. Women now have 30+ years to live after menopause. Data from: Australian Bureau of Statistics

3 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Definition Vulvar and vaginal atrophy (VVA) Is a condition that results from decreased estrogen in the vulvovaginal tissues 1 can be diagnosed based on patient-reported symptoms and a physical examinations 2,3 1. Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc 2010;85: Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician. 2000;61(10): Gass ML, Cochrane BB, Larson JC, et al. Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women s Health Initiative. Menopause. 2011;18(11):

4 VAGINAL ATROPHIC: CHANGES Senile changes in the vagina involve: The vaginal walls become thinner, less elastic, with loss of rugation The vaginal surface becomes friable with petechiae, ulcerations, and bleeding often occurring after minimal trauma. Shortening and narrowing of the vaginal canal Vaginal Hystology Posmenopausal changes: Ultrastructurally the vaginal epithelial surface is flattened There may be a superficial keratiniztion

5 VAGINAL ATROPHIC: CHANGES Senile changes in the vagina involve: Loss of glycogen content Loss of Lactobacilli easily replaced by pathogenic bacteria Increase of vaginal ph from to Changes in the quantity and quality of vaginal secretions

6 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Epidemiology 40% of postmenopausal women can complain of VA affecting their sexual function and QoL 25% of Gynecological consultation after menopause Bachman GA, et al. Am Fam Physician 2000;61: Cardozo L, et al. Obstet Gynecol 1998;92:722 7 Vaginal dryness is the cardinal symptom affecting up to 75% of symptomatic women D. W. Sturdee and N. Panay. Climateric 2010;

7 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy The VIVA (Vaginal Health: Insights, Views & Attitudes) - online survey 80% considered it to negatively affect their lives 75% reported negative consequences on sex life 68% reported that it makes them feel less sexual 36% reported that it makes them feel old 33% reported negative consequences on marriage/ relationship 26% reported a negative effect on self-esteem 25% reported that it lowers QOL 1. Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, Views & Attitudes (VIVA)Vresults from an international survey. Climacteric 2012; 15: Simon JA, Kokot-Kierepa M, Goldstein J, Nappi RE. Vaginal health in the United States: results from the Vaginal Health: Insights, Views & Attitudes survey [published online ahead of print April 15, 2013]. Menopause doi: /GME.0b013e d.

8 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy The REVIVE (Real Women sviews of Treatment Options for Menopausal Vaginal Changes) 85% of partnered women had some loss of intimacy 59% indicated VVA symptoms detracted from enjoyment of sex 47% of partnered women indicated VVA interfered with their relationship 29% reported VVA had a negative effect on sleep 27% reported VVA had a negative effect on their general enjoyment of life Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (Real Women_s Views of Treatment Options formenopausal Vaginal Changes) survey [published online ahead of print May 16, 2013]. J Sex Med doi: /jsm

9 Vaginal Atrophic Changes Symptoms Vaginal dryness Vaginal irritation or itching Vaginal discharge Dyspareunia Dysuria Urinary frequency Urinary incontinence

10 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Symptoms Kingsber SA et al J Sex Med 2013;10:

11 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Prevalence of Vaginal Dryness after Menopause 47% 32% 21% 25% 3% 4% Premenopause Early perimenopause Late Perimenopause 1 yr Post menopause 2 yrs Post menopause 3 yrs Post menopause Adapted from: Dennerstein L, et al. Obstet Gynecol 2000;96:351-8

12 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Epidemiology Parish SJ, Nappi RE et al International Journal of Women s Health 2013:

13 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Treatment Estrogen therapy effectively alleviates atrophic vaginal symptoms related to menopause. Local therapy is advised for the treatment of women with only vaginal symptoms. [Level A] The FDA approved ospemifene for treating moderate-to-severe dyspareunia in postmenopausal women. [Level A] Nonestrogen water-based or silicone-based vaginal lubricants and moisturizers may alleviate vaginal symptoms related to menopause. [Level B]

14 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy - Treatment Lubricants and moisturizers may alleviate vaginal symptoms - but they do not treat Local estrogen therapies are effective 1-3 but: the rate of medication adherence is quite variable (52-74%) 4, mainly due to safety concerns, inconvenience, and inadequate symptom relief 5,6 even though they do not seem to increase the risk of (VTE) 7, no data are available in high-risk patients 8-10 women with breast cancer and other estrogendependent malignancies require special consideration and an individualized counselling Castelo-Branco C et al Maturitas Archer DF Menopause Simon JA J Womens Health Shulman LP et al. J Womens Health Kingsberg SA et al J Sex Med 2013; 10: Kingsberg SA et al J Sex Med 2013; 10: Suckling J et al Cochrane Database Syst Rev Sturdee DW et al Climateric NAMS Menopause Pruthi S et al Breast J 2011

15 LIMIT OF ESTROGEN TREATMENT The use of exogenous estrogen delivered to the chronically estrogen-deprived vaginal cell may only partially effect change in these atrophic cells, which are already deplete of intracellular estrogen, and the full effect of the intervention may not be realized Patient preference and compliance Gorodeski GI. Menopause 2005;12:

16 Menopausal women suffering from vaginal atrophy Postmenopausal women with vaginal atrophy worldwide 1 Key trends 75% 25% 294 million women 294 million women worldwide with symptoms of VA 221 million women untreated worldwide Average duration of treatment: 43% > 1 year 2 Treated Untreated 1. The World Bank 2. Market Research: Market Landscape & Pricing; Hall & Partners Healthcare 2008

17 Laser

18 Lasers

19 Lasers

20 Lasers

21 Laser set-up

22 Laser set-up

23 Laser set-up

24 Laser set-up

25 Dot Laser emission Micro-areas of thermal damage Rapid tissue repair Reduction in Recovery Time Dot Therapy

26 Specifically developed for VVA treatment SmartXide 2 and Smartxide Touch V 2 LR systems deliver the energy through a special pulse designed for the peculiar features of the vaginal mucosa: the DEKA- Pulse or D-Pulse. DEKA-Pulse consists of: an initial part for rapid superficial ablation of the epithelial component of atrophic mucosa characterized by low water content; a second part that allows the laser energy heat to penetrate in depth, stimulating the synthesis of new collagen and of the components of the ground substance of the matrix.

27 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy

28 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Can thermal lasers promote skin wound healing? The generated supraphysiologic level of heat obtained with CO 2 laser is able to induce a heat shock response (HSR), which can be defined as the temporary changes in cellular metabolism. These changes are rapid and transient, and are characterized by the production of a small family of proteins termed the heat shock proteins (HSP). HSP 70, which is over-expressed following laser irradiation, could play a role transforming growth factor (TGF)-beta. TGF-beta is known to be a key element in the inflammatory response and the fibrogenic process. In this process, the fibroblasts are the key cells since they produce collagen and extracellular matrix. Capon A & Mordon S Am J Clin Dermatol. 2003;4(1):1-12.

29 MICROABLATIVE FRACTIONAL CO2 LASER Acute Thermal Damage Phase (48-72 hours) Edema Release of chemical mediators Collagen Shrinkage Proliferation Phase (30 days) Remodelling Phase Fibroblastic Recruiting New dermal matrix molecules New collagen fibers Extinction of Inflammatory Infiltration Matured Collagen fibers Increase of Collagen Fiber Strain New Elastic fibers CO2 laser induce a heat shock response Production of heat shock proteins (70, 47) Activation of growth factos Activation of fibroblasts cell Production of collagen and extracellular matrix Am J Clin Dermatol. 2003

30 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Vulvo-Vaginal Atrophy Histological Findings Clinical Efficacy Ongoing Studies

32 : The Technique Hi-Scan V 2 LR with 90 and 360 Vaginal Probe

34 EP 200 μm CT 200 μm CT Postmenopausal vaginal mucosa Same magnification for both Postmenopausal vaginal mucosa 1 month after fractional CO 2 laser treatment Remark in the right image the much more thick epitelium (EP) and the wide columns of large epithelial cells rich in glicogen (red). Compare the most superficial layers of the epithelium before and after tratment: small and closely compacted cells (left) and large detaching cells rich in glycogen (right). A much better organized connective tissue (CT) in the right image both in lamina propria and in the core of papille (right) is also visible. (Same magnification, "Periodic Acid - Schiff reagent" reaction)

35 MICROABLATIVE FRACTIONAL CO2 LASER

36 MICROABLATIVE FRACTIONAL CO2 LASER

38 The procedure

39 Materials and Methods Study protocol Fractional microablative CO 2 laser system (SmartXide 2 V 2 LR, Monalisa Touch, DEKA, Florence, Italy) A treatment cycle included 3 laser applications (every 4 weeks) Dot power 30 watt, dwell time 1000 μs, dot spacing 1000 μm and the smart stack parameter from 1 to 3 Time points of the study were: baseline (T 1 ), week 4 (T 2 ), week 8 (T 3 ) and week 12 (T 4 ) The procedure was performed in the outpatient clinic and did not require any specific preparation (e.g., analgesia/anaesthesia)

40 Materials and Methods Data collection Assessment of VVA symptoms Vaginal dryness, vaginal burning, vaginal itching, dyspareunia and dysuria Presence Intensity (10 cm-vas) Assessment at T 1, T 2, T 3 and T 4 Assessment of sexual function and overall satisfaction with sexual life Italian version of the female sexual function index (FSFI) at T 1 and T 4 10 cm-vas at T 1 and T 4 Assessment of quality of life Italian version of the Short Form 12 (SF-12) to assess physical (PCS12) and mental (MCS12) components at T 1 and T 4

42 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Efficay Evaluation using the VHI * * P < compared to baseline

43 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Efficay Evaluation using the 10-point VAS * * * * * P < compared to baseline

44 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Procedure Discomfort Evaluation using the 10-point VAS * * * P < compared to baseline

45 Results Sexual life Baseline (T 1 ) 12-week follow-up (T 4 ) p FSFI total score (mean ± SD) 14.8 ± ± 5.6 < Overall satisfaction with sexual life (mean ± SD) 4.3 ± ± 1.6 < Sexually active women (n, %) 57 (74.0%) 74 (96.1%) < Baseline (T1) 12-week follow-up (T4) Baseline (T1) 12-week follow-up (T4) FSFI total score Overall satisfaction with sexual life

46 Results FSFI Domains Desire Arousal Lubrication Orgasm Satisfaction Pain Baseline (T 1 ) 2.4 ± ± ± ± ± ± week follow-up (T 4 ) 3.6 ± ± ± ± ± ± 2.0 p < < < < < < Baseline (T1) 12-week follow-up (T4) 1 0 Desire Arousal Lubrication Orgasm Satisfaction Pain

47 Sexual Health According to the World Health Organization, a healthy sexuality cannot be merely defined as the absence of sexual dysfunction, but as a state of physical, emotional, mental, and social wellbeing related to sexuality.

48 Conclusions Fractional microablative CO 2 laser improves sexual function and Satisfaction with sexual life in postmenopausal women by treating VVA symptoms

49 VAGINAL ATROPHY AND BREAST CANCER Breast cancer is the most common female cancer worldwide Most women at diagnosis of breast cancer are in postmenopausal Menopause occurring in many premenopausal women as a result of breast cancer treatment Menopausal symptoms are well known treatments side-effects in women with breast cancer Vaginal atrophy-related symptoms are common in patients with a history of breast cancer American Cancer Society, 2014.

50 BREAST CANCER 50-70% of breast cancer survivors indicate in surveys that they experience one or more symptoms of urogenital atrophy. Compared to 2000 breast cancer increased by 27% in women < 50yrs Italian Institue of Helath 2015

51 METHODS Treatment cycle: 5 laser applications every 4 weeks Follow-up: 20 weeks from the base line The procedure was performed in the outpatient clinic and did not require any specific preparation

52 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Efficay Evaluation using the VHI * * P < compared to baseline

53 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Efficay Evaluation using the 10-point VAS * * * * * P < compared to baseline

54 RESULTS Changes in sexual function at baseline and at 20-weeks follow-up FSFI A significant improvement of FSFI total score was ob served at the 20- weeks follow-up (26,8 ±6,7; p<0,001) in respect to baseline (18,8 ± 8,4) No difference between group 1 and group 2

55 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy Best Abstract Nicola Zerbinati Alberto Calligaro

56

57 Ongoing Studies Long term results (Italy Milan) Vaginal Microbiota (Italy Milan) RCT tx vs sham (Italy Milan) Women with history of breast cancer and VVA (Italy Milan) Prospective longitudinal cohort study (US) RCT Tx vs local oestrogens (US) Vaginal cytology and vaginal flora (Greece Athens) Long term histology (Greece Athens)

58 In God we trust All others must bring data!! WE Deming

59 IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele - Italy THANK YOU!