2. Genitourinary syndrom of menopause Current and emerging therapies

3. Genitourinary syndrome of menopause (GSM)
The terminology to describe
symptoms occurring secondary
to vulvovaginal atrophy.

4. How prevalent is GSM?
Approximately half of all postmenopausal women in the United States.

5. Menopause Hot flashes Weight gain Night sweets sex dysunction ual
Sexual 
Urogenital
syndrome
dysfunction
Fatigue
Fatigue
Skin
changes
Metabolic syndrome
Depressed mood

6. GSM Vaginal symptoms Vaginal dryness, Decreased lubrication
, Dysparonia,Post cuital bleeding
Urinary symptoms
Nocturia ,Dysuria,Urgency,Rec urinary infections
SEXUAL DYSFUNCTION
Low sexual desire,Decreased arousal ,orgasm

7. Shortening
vagina
loss of sup epithelial
cells
Narrowing
vagina
thinning of the tissue
Thinning of the
tissue
Loss of
elasticity
Loss of vaginal rugae
Loss of vaginal rugae

8. Treatment
Local Estrogen Ospemifene (Osphena) Fractional CO2 laser

10. To date, estrogen therapy is the most
effective treatment for moderate to severe GSM
although a direct comparison of estrogen and
ospemifene is lacking.
Endometrial safety has not been studied in clinical trials
beyond 1 year.
Data are insufficient to confirm the safety of
local estrogen in women with breast cancer. 

11. Fractional CO2 laser In September 2014, the FDA cleared for use
the SmartXide2CO2 laser system
(DEKA Medical) for“incision,excision,
vaporization and coagulation of body soft
tissues”in medical specialties that include
gynecology and genitourinary surgery.

12. Preliminary data on the use of a
fractionated CO2 microablative
laser to treat GSM suggest
therapy is feasible, effective, and
safe in the short term.

13. If these findings are confirmed by
larger, longer-term,
well-controlled studies, this laser will be an additional safe and effective treatment for this very common and distressing disorder.

14. Light amplification
Light amplification is achieved by placing the laser substances between two reflecting mirrors.
Mirror, 100% reflective
Mirror, partly reflective
Laser media
Parallel photons
The desired parallel direction of the emission is achieved by the mirrors, one being partly reflective.

15. Stimulated emission
When external energy is applied, the release of photons is stimulated.
Electron
High
Energy level
Photon
Photons
Low
When this stimulated emission takes place in a specific medium, e.g. CO2, all photons will be of the same wavelength, i.e. monochromatic.

16. monochrome
coherent
intensity
Low divergenc

17. Interaction of laser on tissue

18. The generated supraphysiologic
level of heat obtained with CO2
laser is able to induce a heat
shock response (HSR), which can
be defined as the temporary
changes in cellular metabolism.

19. HSP 70
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.
Fibroblasts are the key cells since they produce
collagen and extracellular matrix.

20. Collagen Remodelling and Stimulation-
Mechanism of Action   
Acute Thermal Damage Phase (48-72 hours)
Edema
Release of chemical mediators
Collagen Shrinkage
Proliferation Phase (30 days)
Fibroblastic Recruiting
New dermal matrix molecules
New collagen fibers
Remodelling Phase
Extinction of Inflammatory Infiltration
Matured Collagen fibers
Increase of Collagen Fiber Strain
New Elastic fibers

22. شکل دهی به پالس

23. Dot Therapy

25. A study in progress
With more than 1 billion menopausal women likely to be affected by vulvovaginal atrophy worldwide by 2025, the need for effective remedies is acute.

26. A look at the data To date, more than 2,000 women in Italy and more than 10,000 women worldwide with GSM have been treated with fractional CO2 laser therapy, and several peer-reviewed publications have documented its efficacy and safety.

27. In published studies, however, the populations have been small and the investigations have been mostly short term (12 weeks).

28. Refrences
Salvatore S, Nappi RE, Zerbinati N, et al. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014;17(4):363–369.
Salvatore S, Maggiore ULR, Origoni M, et al. Microablative fractional CO2 laser improves dyspareunia related to vulvovaginal atrophy: a pilot study. J Endometriosis Pelvic Pain Disorders. 2014;6(3):121–162.
Salvatore S, Nappi RE, Parma M, et al. Sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy. Climacteric. 2015;18(2):219–225.
Salvatore S, Maggiore LR, Athanasiou S, et al. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue; an ex vivo study. Menopause. 2015;22(8):845–849.
Zerbinati N, Serati M, Origoni M, et al. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015;30(1):429–436

29. Pilot study
Treatment cycle of 3 laser applications improved the most symptoms of vulvovaginal atrophy and improved scores of vaginal health at 12 weeks’ follow-up in 50 women
Salvatore S, Nappi RE, Zerbinati N, et al. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014;17(4):363–369

30. Two additional studies involving another 92 women that specifically addressed the impact of fractional CO2 laser therapy on dyspareunia and sexual function.

31. Salvatore S, Nappi RE, Parma M, et al
Salvatore S, Nappi RE, Parma M, et al. Sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy. Climacteric. 2015
Salvatore S, Maggiore LR, Athanasiou S, et al. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal

32. Studies showed statistically significant improvement in dyspareunia as well as Female Sexual Function Index (FSFI)
All women in these studies were treated in an office setting with no pretreatment anesthesia.
No adverse events were reported.

33. A study in progress
(Mickey Karram, MD, and Eric Sokol, MD) are performing a study of the fractional CO2 laser for treatment of (GSM) in the United States.
To date, 30 women with GSM have been treated with 3 cycles and followed for 3 months. Preliminary data show significant improvement in all symptoms, office setting ,no pretreatment or posttreatment analgesia
The laser settings for treatment included a power of 30 W, a dwell time of 1,000 µs, spacing between 2 adjacent treated spots of 1,000 µs, and a stack parameter for pulses from
1 to 3.
A treatment cycle included 3 laser treatments at 6-week
intervals. Each treatment lasted 3 to 5 minutes.

34. Initial improvement was noted in most patients, including increased lubrication within 1 week after the first treatment, with further improvement after each session.
To date, the positive results have persisted, and all women in the trial now have been followed for 3 months—all have noted improvement in symptoms.
They will continue periodic assessment, with a final subjective and objective evaluation 1 year after their first treatment.

35. Recently published histology data highlight significant changes 1 month after fractional CO2 laser treatment that included a much thicker epithelium with wide columns of large epithelial cells rich in glycogen.
Also noted was a significant reorganization of connective tissue, both in the lamina propria and the core of the papillae.

36. Zerbinati N, Serati M, Origoni M,
et al.
Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015;30(1):429–436.

37. Early-stage vaginal atrophy
This histologic preparation of vaginal mucosa sections reveals untreated early-stage vaginal atrophy (A), with thinning epithelium and the presence of papillae

38. same mucosa 1 month after treatment with fractional CO2laser therapy (B)

39. Atrophic vaginitis 
This histologic preparation of vaginal mucosa sections shows untreated atrophic vaginitis

40. the same mucosa 1 month after treatment with fractional CO2 laser therapy

41. Lasers have become a very costly option for the treatment of symptomatic VVA.
In all published trials to date, most studies are only 12 weeks in duration

47. بیمارستان امام خمینی دانشگاه علوم پزشکی تهران
60 خانم منوپوز
معیارهای ورود به مطالعه شامل:
رضایت جهت شرکت در مطالعه، محدوده سنی سال، گذشت حداقل یکسال از آخرین قاعدگی، داشتن آزمایش هورمونی با میزان FSH بیشتر از 40 واحد بین المللی، وجود علائم آزاردهنده آتروفی واژن (شامل خشکی با یا بدون دیسپارونی در محدوده متوسط و شدید)، داشتن رابطه جنسی و تک همسری.
ملاک های حذف شامل:
ابتلا به عفونت واژینال یا ادرای، داشتن هر گونه سابقه جراحی در ناحیه لگن و واژن، هر گونه بیماری مهم دستگاه ژنیتال، دریافت HRT و مصرف هورمونهاي جنسی طی 8 هفته قبل از مطالعه، داشتن خونریزی های رحمی یا لکه بینی، مصرف هر گونه لوبریکانت واژینال یا هرگونه داروی سنتی یا غیر سنتی در داخل واژن 30 روز قبل از شروع درمان با لیزر، داشتن بیماریهای روانی و مصرف سیگار

48. ابزار جمع آوری اطلاعات شامل چهار بخش بود.
بخش اول
اطلاعات دموگرافیک (سن، جنس، قد و وزن بیمار، مدت یائسگی، وضعیت اقتصادی، دفعات زایمان و داشتن ارتباط جنسی و سابقه ابتلا به بیماریهای دستگاه تناسلی)
بخش دوم
Vaginal Health Score Index شامل:
(خاصیت ارتجاعی یا الاستیسیتی، حجم مایع، PH،
Epithelial integrity و میزان رطوبت واژن)
هر پارامتر از کمترین نمره(1) تا بیشترین نمره(5)
نمره کل کمتر از 15 واژن آتروفیک

49. بخش سوم
علائم آزار دهنده آتروفی
شامل(خشکی، دیسپارونی، خارش، دفع هوا یا مایع از واژن و دفع بی اختیار ادرار) بود و به شکل معیار دیداری سنجش بصری علائم
(visual analog scale) نمره دهی میگردید.
پاسخ ها بر اساس مقیاس دیداری یک لیکرت 10 سانتی متری بود. به نحوی که عدد صفر
نشانه عدم وجود علامت و عدد 10 نشانه بالاترین شدت.
به این ترتیب عدد 1تا4 نشانه شدت کم علائم، عدد 4 تا 7 نشانه شدت متوسط علائم و
عدد 7 تا 10 نشانه شدت بالای علائم
بخش چهارم
ابزار مقیاس دیداری 10 سانتی متری درد بود.
از بیماران خواسته میشد با یک مقیاس لیکرت 5 قسمتی میزان درد در هنگام ورود پروپ لیزر
به داخل واژن را بر اساس (خیلی راحت، راحت، طبیعی، دردناک و بسیار دردناک) ارزیابی نمایند.

52. Although initial observational data
indicate potential utility, additional
data from randomized trials are
needed to further assess the
efficacy and safety of this
procedure in treating vulvovaginal
atrophy, particularly for long-term
benefit