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therapy option because of the lack of evidence regarding the long-term safety issue
[51]. On the other hand, androgen receptors present throughout the urogenital tract.
After menopause not only a decrease in estradiol levels in the circulation is seen, but
also a decrease in circulating levels of testosterone is detected. In accordance with
this decrease in testosterone levels in the circulation, there is an extinction of andro-
gen receptors in the tissue of the urogenital tract likewise all other different types
of tissues expressing the androgen receptors. However, androgen supplementation
induces the replenishment of androgen receptors in the tissue of the urogenital tract
[52]. In addition, the vaginal epithelium expresses the aromatase activity which
converts the androgens to estrogens [53].
Recently, the use of intravaginal testosterone for treatment of vulvovaginal atro-
phy in women has been reviewed for efcacy and safety issues in six clinical tri-
als of which three included the women taking AIs [54]. The publication suggests
that intravaginal testosterone decreases vaginal pH, provides the vaginal dominance
of Lactobacilli, and improves the vaginal maturation index [53]. GSM, including
dryness and dyspareunia, is improved signicantly by the application of intravagi-
nal testosterone. However, there are some weak points of the studies such as the
duration of the use of intravaginal testosterone, the number of patients, the lack of
placebo group, and nally the uncertainty of the effect on sexual function. These
prevent us to reach a rm conclusion regarding the safety and efcacy of intravagi-
nal use of testosterone.
Another weak androgen is dehydroepiandrosterone (DHEA) which is mainly
produced in surrenal gland and has been recently used for the treatment of GSM
[55, 56]. DHEA starts to decrease at around the age of 30. For insufcient produc-
tion of estrogens and androgens after menopause, DHEA becomes the exclusive
source for these sex steroids in peripheral tissues. Indeed, each peripheral tissue
having the ability of expression of some specic steroid-forming enzymes trans-
forms DHEA into the appropriate small amounts of estrogens and androgens for the
absolutely intracellular and local action [57]. On the other hand, there are intracel-
lular steroid-inactivating enzymes in humans which inactivate the estrogens and
androgens at the site where they are synthesized inside the cell.
Local use of vaginal DHEA successfully treats women with GSM.The clini-
cal data regarding the small dose of intravaginal DHEA shows an improvement in
the vaginal maturation index and PH without signicant changes in serum estra-
diol and testosterone levels [
57]. Intravaginal DHEA provides improvement in
sexual desire/interest, arousal and orgasm and lessens pain during sexual activity. It
relieves dyspareunia, vaginal dryness, irritation, or itching without systemic effect.
It also ameliorates vaginal epithelial thickness, integrity, and color and increases
the vaginal secretion [55]. It can be concluded that the daily intravaginal admin-
istration of 0.50% (6.5mg) DHEA is effective in the treatment of GSM without
systemic effect. Moreover, daily use of 6.5mg (0.50%) DHEA has been found to be
comparable efcacious with 0.3mg CEE or 10μg E2in the treatment of GSM [56].
There is no clinical evidence regarding the intravaginal use of DHEA on specically
urological symptoms. Although there is not any evidence regarding the intravaginal
use of DHEA in breast cancer survivor, the recommendation has been thought to be
acceptable by some authors [10, 11].
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11.6.4 Laser Treatment
Light amplication by stimulated emission of radiation (LASER) is currently sug-
gested to be used for the treatment of GSM [2, 8, 58–62]. Before looking into the
available clinical evidence regarding the results of laser treatment in women with
GSM, it would be better to mention briey the laser basics and its tissue effects.
Three important characteristics of laser light are collimation, monochromy, and
coherence. Wavelength of laser light can be in the different electromagnetic spec-
trum ranging from the ultraviolet (157–400 nm), visible (400–800 nm), near-
infrared (800–3000nm), mid-infrared (3000–30,000nm) to far infrared (more than
30,000nm). Laser light may be absorbed, transmitted, reected, and scattered by
the tissue. Absorption of laser light by the target tissue which is the most important
effect may cause photothermal (most desirable effect), photochemical, and photo-
mechanical reactions. Besides the energy power applied, the different wavelength
and tissue chromophore (such as melanin and hemoglobin) and water content deter-
mine the photothermal effects of laser light in the tissue. Melanin and hemoglobin
absorb the light in the spectrum of visible and near-infrared, while the water in the
mid-infrared. On the other hand, the same applied energy may cause a different
effect in the tissue (such as supercial carbonization, coagulation, and cell activa-
tion due to thermal conduction) by changing the parameters of power and exposure
time of the laser light [58].
Nowadays, two forms of laser are mainly used for the treatment of GSM in the
market: carbon dioxide (CO
2
) and erbium:yttrium-aluminum-garnet (Erb:YAG).
Emitted wavelength of CO
2
laser light is 10,600nm, while it is 2940nm for Erb:YAG
laser. When compared to the Erb:YAG laser to CO
2
laser in terms of their techni-
cal features and tissue effects, Erb:YAG laser has nearly 16 times more absorption
rate in water, less penetration depth, and thermal diffusion without ablation. Hence,
Erb:YAG laser usually has less discomfort, erythema, edema, and faster recovery
rate [58, 60].
There are two types of laser beam delivery techniques: fractional ablative and
non-ablative techniques. Fractional laser beams create microscopic tissue injury
columns alongside the non-traumatized tissue columns which stimulate the recov-
ery. In the non-ablative technique, Erb:YAG laser is used in the smooth mode pulse
by altering the pulse duration without causing ablation in the tissue [58]. There are
two types of laser effects in the target tissue in terms of timing: early or immediate
effect and late effect [58, 59]. The rst and early effect is the thermomechanical
effect. Thermomechanical effect which usually occurs when the epithelial tissue
heats above the 60–65°C is the tissue ablation and then the tissue tightening by
the immediate shrinkage of the collagen. Moreover, the heat conduction is trans-
mitted to the deeper layer of the epithelium by decreasing temperature down to
40–45°C.This range of tissue temperature is ideal for the breakdown of the col-
lagen brils and also cell activation. This is the second or late effect of laser light
in the target tissue. This effect takes time. Because at this point, 40–45 °C tem-
perature increases the heat shock response (HSR); in turn heat shock protein pro-
duction by the tissue increases [58]. HSP70 especially plays an important role in
the expression of some growth factors (such as transforming growth factor-β, basic
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broblast growth factor, epidermal growth factor, vascular endothelial growth fac-
tor, platelet- derived growth factor), cytokines (such as tumor necrosis factor-α), and
interleukin-1β in the target tissue [58]. These local factors are responsible from the
inammatory response, brogenic process, and the new production of collagen and
extracellular matrix. In addition, these substances improve the microvascularization
and enhance the oxygenation of the tissue.
Indeed, histopathologic studies verify collagen remodeling, new collagen syn-
thesis (neocollagenogenesis), the increase in elastin content (elastogenesis), and
new formation of blood capillaries (neoangiogenesis) after an immediate tissue
shrinkage following laser treatment [58, 59, 63–65]. There is an increase in tissue
collagen and elastin content. The vaginal epithelium gets thicker. Rugae formation
reappears. The vagina becomes tight and elastic. Supercial epithelial cells of the
vagina contain glycogen; thus, vaginal microbiata changes to normal ora and the
vaginal PH decreases [58–62, 66, 67].
Laser treatment for GSM can be applied by a specically designed vaginal or
urethral cannula or external beam shot directed to the vulva. Although both laser
types (CO
2
and Erb:YAG) can be applied to vulvovaginal area, intraurethral can-
nula is recently present only for the application of the Erb:YAG laser [68]. Even
the intraurethral cannula can safely be inserted along the urethra under the ultraso-
nographic guidance [69]. Although most of the studies are lacking solid evidence,
they reach a consensus on that both types of laser treatments improve the atrophic
vaginal epithelium [58–67, 70–76]. The studies usually have the limited number of
patients, short duration of follow-up, no consistency regarding the evaluation and
treatment protocols, and nally lack of control groups and proper randomization.
However, available data has shown that the intravaginal laser application improved
the Vaginal Health Index Score (VHIS) which includes vaginal elasticity, pH, dis-
charge, mucosal integrity, and moisture [60–62, 70–76]. Another consisting result
is the fact that Visual Analog Scale (VAS) for the vaginal dryness, dyspareunia,
itching, burning, and dysuria has shown an improvement after the vaginal laser
treatment of GSM [60–62, 70–76]. Usually, three laser sessions have been recom-
mended for the treatment of symptoms due to the vaginal atrophy, but an extra
fourth or fth sessions might further increase the GSM symptom-free rate [60, 62,
70–72, 74]. Recently, it has reported that the improvement in the atrophic vaginal
epithelium provided by the laser treatment was found to be comparable with the
estrogen treatment [60, 70]. Even the laser treatment is better, since its mainte-
nance of vaginal health continues longer duration after the cessation of therapy
[60]. Its effect on the vaginal health can last ranging from 12 to 24months [71, 72,
76]. Intravaginal laser treatment also provides an increase in sexual gratication
[63, 73, 74, 76–78]. This improvement in sexual function is not only due to vagi-
nal health, but it also ameliorates the vaginal relaxation in some degree [60, 63].
Moreover, intravaginal laser application was dened as an acceptable procedure by
most of the patients [66]. Breast cancer survivors with vulvovaginal atrophy may be
treated safely and effectively by intravaginal laser application [71, 75]. In addition
to vaginal atrophy symptoms, other symptoms (such as pain, itching, burning) due
to lichen sclerosus et atrophicus, lichen planus, and other atrophic changes in the
vulva may be improved by the application of laser light [58].
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Intravaginal laser application may treat the urological components of the GSM
such as dysuria, frequency, urgency, and urinary incontinence [58–60, 74, 76–82].
After the laser application, most of the studies report an improvement in uro-
logical symptoms which are usually determined by the International Consultation
on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF).
Although there is not a randomized controlled trial, intravaginal laser treatment
may relieve the symptoms of stress urinary incontinence (SUI) [77–82]. Erb:YAG
laser has been used to treat the SUI in most of the studies. It has been suggested
that younger age and normal BMI women with moderate to severe SUI showed
better improvement [79]. The patients who had more severe UI had the greatest
benet from the laser therapy [78, 81]. On the other hand, patients with SUI had
a higher rate of improvement than those with mixed urinary incontinence [81].
In addition to the success of laser therapy for SUI, a study reported a decrease in
pad weights before and after the operation, while no differences were found in
urodynamic values [77]. Three years after the initial treatment, the laser therapy
might be repeated in some patients with mild incontinence [81]. Optimal results
can be achieved after three sessions with 3–4-week interval. Specic group of
patient having SUI with poor intrinsic sphincter function who is dened as intrin-
sic sphincter deciency (ISD) may be treated by the application of an intraurethral
cannula with non- ablative Erb:YAG laser tip [68]. During this treatment, ultra-
sound guidance of the intraurethral laser cannula allows us to treat the patients
with ISD, safely [69].
References
1. Portman DJ, Gass ML, Vulvovaginal Atrophy Terminology Consensus Conference Panel.
Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from
the International Society for the Study of Women’s Sexual Health and the North American
Menopause Society. Menopause. 2014;21:1063–8.
2. Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA.Genitourinary syndrome of
menopause: an overview of manifestations, pathophysiology, etiology, evaluation, and man-
agement. Am J Obstet Gynecol. 2016;215(6):704–11.
3. Faubion SS, Sood R, Kapoor E.Genitourinary syndrome of menopause: management strate-
gies for the clinician. Mayo Clin Proc. 2017;92(12):1842–9.
4. Palacios S, Mejia A, Neyro JL. Treatment of the genitourinary syndrome of menopause.
Climacteric. 2015;18(Suppl 1):23–9.
5. Palma F, Volpe A, Villa P, Cagnacci A, as the Writing Group of the AGATA Study. Vaginal atro-
phy of women in postmenopause. Results from a multicentric observational study: the AGATA
study. Maturitas. 2016;83:40–4.
6. Nappi RE, Kokot-Kierepa M.Vaginal health: insights, views & attitudes (VIVA)—results from
an international survey. Climacteric. 2012;15:36–44.
7. Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in post-
menopausal women: ndings from the REVIVE (Real Women’s VIews of treatment options
for menopausal vaginal ChangEs) survey. J Sex Med. 2013;10:1790–9.
8. Hutchinson-Colas J, Segal S.Genitourinary syndrome of menopause and the use of laser ther-
apy. Maturitas. 2015;82:342–5.
9. Sousa MS, Peate M, Jarvis S, Hickey M, Friedlander M.A clinical guide to the management of
genitourinary symptoms in breast cancer survivors on endocrine therapy. Ther Adv Med Oncol.
2017;9(4):269–85.
11 Current Treatment Modalities fortheGenitourinary Syndrome ofMenopause
https://t.me/med1917
200
10. Biglia N, Bounous VE, Sgro LG, D’Alonzo M, Pecchio S, Nappi RE.Genitourinary syn-
drome of menopause in breast cancer survivors: are we facing new and safe hopes? Clin Breast
Cancer. 2015;15(6):413–20.
11. Monteleone P, Mascagni G, Giannini A, Genazzani AR, Tommaso Simoncini T.Symptoms
of menopause—global prevalence, physiology and implications. Nat Rev Endocrinol.
2018;14:199–215.
12. Palacios S, Castelo-Branco C, Currie H, Mijatovic V, Nappie RE, Simon J, Rees M.Update
on management of genitourinary syndrome of menopause: a practical guide. Maturitas.
2015;82:307–12.
13. Brincat MP, Baron YM, Galea R.Estrogens and the skin. Climacteric. 2005;8:110–23.
14. Thornton MJ.Estrogens and aging skin. Dermatoendocrinology. 2013;5(2):264–70.
15. Iglesia CB. What’s new in the world of postmenopausal sex? Curr Opin Obstet Gynecol.
2016;28:449–54.
16. Nappia RE, Palacios S, Panay N, Particco M, Krychman ML.Vulvar and vaginal atrophy
in four European countries: evidence from the European REVIVE Survey. Climacteric.
2016;19(2):188–97.
17. Kingsberg SA, Krychman M, Graham S, Bernick B, Mirkin S. The Women’s EMPOWER
Survey: identifying women’s perceptions on vulvar and vaginal atrophy and its treatment. J
Sex Med. 2017;14(3):413–24.
18. Simon JA, Kokot-Kierepa M, Goldstein J, Nappi RE.Vaginal health in the United States: results
from the vaginal health: insights, views & attitudes survey. Menopause. 2013;20:1043–8.
19. Nappi RE, Mattsson LA, Lachowsky M, Maamari R, Giraldi A.The CLOSER survey: impact
of postmenopausal vaginal discomfort on relationships between women and their partners in
northern and southern Europe. Maturitas. 2013;75:373–9.
20. Simon JA, Nappi RE, Kingsberg SA, Maamari R, Brown V. Clarifying vaginal atrophy’s
impact on sex and relationships (CLOSER) survey: emotional and physical impact of vagi-
nal discomfort on North American postmenopausal women and their partners. Menopause.
2014;21(2):137–42.
21. Management of symptomatic vulvovaginal atrophy: 2013 position statement of the North
American Menopause Society. Menopause. 2013;20(9):888–904.
22. Armeni E, Lambrinoudaki I, Ceausu I, Depypered H, Muecke A, Pérez-López FR, van der
Schouw YT, Senturk LM, Simoncini T, Stevenson JC, Petra Stute P, Rees M. Maintaining
postreproductive health: a care pathway from the European Menopause and Andropause
Society (EMAS). Maturitas. 2016;89:63–72.
23. Karamanidis D1, Tamiolakis D, Koutsougeras G, Tripsanas CH, Retzos K, Karidis S, Liberis
B. Cigarette smoking and the degree of maturation of the vaginal squamous epithelium in
postmenopausal women. Clin Exp Obstet Gynecol. 2001;28(4):274–6.
24. Mercier J, Morin M, Lemieux MC, Reichetzer B, Khalifé S, Dumoulin C.Pelvic oor muscles
training to reduce symptoms and signs of vulvovaginal atrophy: a case study. Menopause.
2016;23(7):816–20.
25. Edwards D, Panay N. Treating vulvovaginal atrophy/genitourinary syndrome of meno-
pause: how important is vaginal lubricant and moisturizer composition? Climacteric.
2016;19(2):151–61.
26. Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JAV, Santen
RJ. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice
Guideline. J Clin Endocrinol Metab. 2015;100:3975–4011.
27. Caserta D, Maranghi L, Mantovani A, Marci R, Maranghi F, Moscarini M.Impact of endocrine
disruptor chemicals in gynaecology. Hum Reprod Update. 2008;14(1):59–72.
28. Edwards TM, Myers JP. Environmental exposures and gene regulation in disease etiology.
Environ Health Perspect. 2007;115:1264–70.
29. Brown JM, Hess KL, Brown S, Murphy C, Waldman AL, Hezareh M.Intravaginal practices
and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the
United States. Obstet Gynecol. 2013;121(4):773–80.
C. T. Erel
https://t.me/med1917
201
30. Juliato PT, Rodrigues AT, Stahlschmidt R, Juliato CRT, Mazzola PG.Can polyacrylic acid
treat sexual dysfunction in women with breast cancer receiving tamoxifen? Climacteric.
2017;20(1):62–6.
31. Rees M, Pérez-López FR, Ceasu I, Depypere H, Erel T, Lambrinoudaki I, Schenck-Gustafsson
K, Simoncini T, van der Schouw Y, Tremollieres F, EMAS.EMAS clinical guide: low-dose
vaginal estrogens for postmenopausal vaginal atrophy. Maturitas. 2012;73(2):171–4.
32. Baber RJ, Panay N, Fenton A, IMS Writing Group. 2016 IMS recommendations on women’s
midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109–50.
33. Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed
H, Balk EM, Murphy M, for the Society of Gynecologic Surgeons Systematic Review Group.
Vaginal Estrogen for genitourinary syndrome of menopause: a systematic review. Obstet
Gynecol. 2014;124(6):1147–56.
34. The 2017 hormone therapy position statement of the North American Menopause Society:
position statement. Menopause. 2017;24(7):728–53.
35. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal
women (review). Cochrane Database Syst Rev. 2016;(8):CD001500.
36. Archer DF, Kimble TD, Lin FDY, Battucci S, Sniukiene V, Liu JH.A randomized, multicenter,
double-blind, study to evaluate the safety and efcacy of Estradiol vaginal cream 0.003% in
postmenopausal women with vaginal dryness as the most bothersome symptom. J Womens
Health. 2018;27(3):231–7.
37. Constantine GD, Bouchard C, Pickar JH, Archer DF, Graham S, Bernick B, Mirkin
S.Consistency of effect with a low-dose, estradiol vaginal capsule (TX-004HR): evaluating
improvement in vaginal physiology and moderate-to-severe dyspareunia in subgroups of post-
menopausal women. J Womens Health. 2017;26(6):616–23.
38. Pickar JH, Amadio JM, Hill JM, Bernick BA, Mirkin S.A randomized, double-blind, placebo-
controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized
estradiol. Menopause. 2016;23(5):506–10.
39. Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Williams RS, McGovern PG, Young
RL, Wells EC, O’Sullivan MJ, Chen B, Schenken R, Johnson SR, Women’s Health Initiative
Investigators. Menopausal symptoms and treatment-related effects of estrogen and progestin
in the women’s health initiative. Obstet Gynecol. 2005;105:1063–73.
40. Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, Grob P, Ortmann
O, Buchholz S. Ultra-low-dose estriol and lactobacillus acidophilus vaginal tablets
(Gynoor®) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhib-
itors: pharmacokinetic, safety, and efcacy phase I clinical study. Breast Cancer Res Treat.
2014;145(2):371–9.
41. Erel CT, Senturk LM, Kaleli S. Tibolone and breast cancer. Postgrad Med J.
2006;82(972):658–62.
42. Sismondi P, Kimmig R, Kubista E, Biglia N, Egberts J, Mulder R, Planellas J, Moggio G, Mol-
Arts M, Kenemans P.Effects of tibolone on climacteric symptoms and quality of life in breast
cancer patients—data from LIBERATE trial. Maturitas. 2011;70(4):365–72.
43. Komm BS, Mirkin S.An overview of current and emerging SERMs. J Steroid Biochem Mol
Biol. 2014;143:207–22.
44. Mirkin S, Archer DF, Taylor HS, Pickar JH, Komm BS.Differential effects of menopausal
therapies on the endometrium. Menopause. 2014;21(8):899–908.
45. Simon JA, Lin VH, Radovich C, Bachmann GA, The Ospemifene Study Group. One year
long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy
in postmenopausal women with a uterus. Menopause. 2013;20:418–27.
46. Portman DJ, Bachmann GA, Simon JA, Ospemifene Study Group. Ospemifene, a novel selec-
tive estrogen receptor modulator for treating dyspareunia associated with postmenopausal vul-
var and vaginal atrophy. Menopause. 2013;20:623–30.
47. Portman D, Palacios S, Nappi RE, Mueck AO.Ospemifene, a non-oestrogen selective oestro-
gen receptor modulator for the treatment of vaginal dryness associated with postmenopausal
11 Current Treatment Modalities fortheGenitourinary Syndrome ofMenopause
https://t.me/med1917
202
vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial. Maturitas.
2014;78:91–8.
48. Simon JA, Altomare C, Cort S, Jiang W, Pinkerton JAV.Overall safety of ospemifene in
postmenopausal women from placebo-controlled phase 2 and 3 trials. J Womens Health.
2018;27(1):14–23.
49. Archer DF, Carr BR, Pinkerton JAV, Taylor HS, Constantine GD.Effects of ospemifene on
the female reproductive and urinary tracts: translation from preclinical models into clinical
evidence. Menopause. 2014;22(7):786–96.
50. Mirkin S, Komm BS. Tissue-selective estrogen complexes for postmenopausal women.
Maturitas. 2013;76:213–20.
51. Brotto LA.Evidence-based treatments for low sexual desire in women. Front Neuroendocrinol.
2017;45:11–7.
52. Traish AM, Vignozzi L, Simon JA, Goldstein I, Kim NN. Role of androgens in female
genitourinary tissue structure and function: implications in the genitourinary syndrome of
menopause. Sex Med Rev. 2018;6(4):558–71.
53. Bertin J, Ouellet J, Dury AY, Pelletier G, Labrie F.Expression of the estrogen receptors and
steroidogenic enzymes involved in estradiol formation in the monkey vagina. Am J Obstet
Gynecol. 2014;211(5):499.e1–9.
54. Bell RJ, Rizvi F, Islam RM, Davis SR. A systematic review of intravaginal testosterone for the
treatment of vulvovaginal atrophy. Menopause. 2018;25(6):704–9.
55. Labrie F, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M,
Côté I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur E,
and the members of the VVA Prasterone Research Group. Efcacy of intravaginal dehydro-
epiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms
of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause.
2016;23(3):243–56.
56. Archer DF, Labrie F, Montesino M, Martel C. Comparison of intravaginal 6.5 mg (0.50%)
prasterone, 0.3mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal
atrophy. J Steroid Biochem Mol Biol. 2017;174:1–8.
57. Labrie F, Bélanger A, Pelletier G, Martel C, Archer DF, Utian WH.Science of intracrinology
in postmenopausal women. Menopause. 2017;24(6):702–12.
58. Tadir Y, Gaspar A, Lev-Sagie A, Alexiades M, Alinsod R, Bader A, Calligaro A, Elias JA,
Gambaciani M, Gaviria JE, Iglesia CB, Martinec KS, Mwesigwa PL, Ogrinc UB, Salvatore
S, Scollo P, Zerbinati N, Nelson JS. Light and energy based therapeutics for genitourinary
syndrome of menopause: consensus and controversies. Lasers Surg Med. 2017;49(2):137–59.
59. Vizintin Z, Lukac M, Kazic M, Tettamanti M. Erbium laser in gynecology. Climacteric.
2015;18(Suppl 1):4–8.
60. Gambacciani M, Palacios S.Laser therapy for the restoration of vaginal function. Maturitas.
2017;99:10–5.
61. Arunkalaivanan A, Kaur H, Onuma O.Laser therapy as a treatment modality for geni-
tourinary syndrome of menopause: a critical appraisal of evidence. Int Urogynecol J.
2017;28:681–5.
62. Athanasiou S, Pitsouni E, Falagas ME, Salvatore S, Grigoriadis T.CO2-laser for the genitouri-
nary syndrome of menopause. How many laser sessions? Maturitas. 2017;104:24–8.
63. Lee MS.Treatment of vaginal relaxation syndrome with an erbium:YAG laser using 90° and
360° scanning scopes: a pilot study & short-term results. Laser Ther. 2014;23(2):129–38.
64. Lapii GA, Yakovleva AY, Neimark AI. Structural reorganization of the vaginal mucosa in
stress urinary incontinence under conditions of Er:YAG laser treatment. Bull Exp Biol Med.
2017;162(10):510–4.
65. Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligar
A.Microscopic and ultrastructural modications of postmenopausal atrophic vaginal mucosa
after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015;30:429–36.
66. Gambacciani M, Torelli MG, Martella L, Bracco GL, Casagrande AG, Albertin E, Tabanelli
S, Viglietta M, D’Ambrogio G, Garone G, Cervigni M.Rationale and design for the Vaginal
C. T. Erel
https://t.me/med1917
203
Erbium Laser Academy Study (VELAS): an international multicenter observational study
on genitourinary syndrome of menopause and stress urinary incontinence. Climacteric.
2015;18(Suppl 1):43–8.
67. Athanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME, Grigoriadis
T.The effect of microablative fractional CO2 laser on vaginal ora of postmenopausal women.
Climacteric. 2016;19(5):512–8.
68. Gaspar A, Brandi H.Non-ablative erbium YAG laser for the treatment of type III stress urinary
incontinence (intrinsic sphincter deciency). Lasers Med Sci. 2017;32:685–91.
69. Erel CT.Ultrasound guided intraurethral laser application: new and safe approach. Accepted
for poster presentation in IMS 16 World Congress on Menopause, Vancouver, 6–9 June 2018.
70. Gaspar A, Brandi H, Gomez V, Luque D.Efcacy of erbium:YAG laser treatment compared to
topical estriol treatment for symptoms of genitourinary syndrome of menopause. Laser Surg
Med. 2017;49:160–8.
71. Gambacciani M, Levancini M.Vaginal erbium laser as second-generation thermotherapy for
the genitourinary syndrome of menopause: a pilot study in breast cancer survivors. Menopause.
2016;248(3):316–9.
72. Gambacciani M, Levancini M, Russo E, Vacca L, Simoncini T, Cervigni M.Long-term effects
of vaginal erbium laser in the treatment of genitourinary syndrome of menopause. Climacteric.
2018;21(2):148–52.
73. Sokol ER, Karram MM.Use of a novel fractional CO2 laser for the treatment of genitourinary
syndrome of menopause: 1-year outcomes. Menopause. 2017;24(7):810–4.
74. Pitsouni E, Grigoriadis T, Falagas ME, Salvatore S, Athanasiou S. Laser therapy for the
genitourinary syndrome of menopause. A systematic review and meta-analysis. Maturitas.
2017;103:78–88.
75. Mothes AR, Runnebaum M, Runnebaum IB. Ablative dual-phase erbium:YAG laser treatment
of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hor-
monal treatment. J Cancer Res Clin Oncol. 2018;144:955–60.
76. Behnia-Willison F, Sarraf S, Millerc J, Mohamadid B, Care AS, Lam A, Willisonf N, Behnia
L, Salvatore S.Safety and long-term efcacy of fractional CO2 laser treatment in women
suffering from genitourinary syndrome of menopause. Eur J Obstet Gynecol Reprod Biol.
2017;213:39–44.
77. Tien YW, Hsiao SM, Lee CN, Lin HH. Effects of laser procedure for female urodynamic
stress incontinence on pad weight, urodynamics, and sexual function. Int Urogynecol J.
2017;28(3):469–76.
78. Pardo JI, Solà VR, Morales AA.Treatment of female stress urinary incontinence with erbium-
YAG laser in non-ablative mode. Eur J Obstet Gynecol Reprod Biol. 2016;204:1–4.
79. Fistonić N, Fistonić I, Lukanovič A, Guštek FS, Turina ISB, Franić D.First assessment of
short-term efcacy of Er:YAG laser treatment on stress urinary incontinence in women: pro-
spective cohort study. Climacteric. 2015;18(Suppl 1):37–42.
80. Fistonić N, Fistonic I, Guštek SF, Turina ISB, Marton I, Vižintin Z, Kažič M, Hreljac I,
Perhavec T, Lukač M.Minimally invasive, non-ablative Er:YAG laser treatment of stress uri-
nary incontinence in women—a pilot study. Lasers Med Sci. 2016;31:635–43.
81. Ogrinc UB, Sencar S, Lenasi H.Novel minimally invasive laser treatment of urinary inconti-
nence in women. Laser Surg Med. 2015;47:689–97.
82. Erel CT, Mut A, Cebi S, Senturk ML. A new approach in the treatment of stress urinary
incontinence: short-term results of a preliminary study. Poster presentation in IMS 16 world
congress on menopause, Vancouver, 6–9 June 2018.
11 Current Treatment Modalities fortheGenitourinary Syndrome ofMenopause
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© Springer Nature Switzerland AG 2019
F. R. Pérez-López (ed.), Postmenopausal Diseases and Disorders,
https://doi.org/10.1007/978-3-030-13936-0_12
M. Gambacciani (*)
Department of Obstetrics and Gynecology, Pisa University Hospital, Pisa, Italy
12
Laser Treatment forVulvovaginal
Atrophy
MarcoGambacciani
12.1 Introduction
The genitourinary syndrome of menopause (GSM) is a chronic and progressive con-
dition that includes a constellation of symptoms related to the decline of circulating
ovarian hormones, as vulvovaginal atrophy (VVA), vaginal dryness, dyspareunia,
recurrent urinary tract infections, and urinary incontinence [1–5]. GSM can affect
up to 70% of women [1–5]. GSM is dened as a collection of signs and symp-
toms involving changes to the vulva, vagina, urethra, and bladder, including, but
not limited to, dryness, burning and irritation, poor lubrication, discomfort or pain,
impaired sexual function, and urinary symptoms of urgency, dysuria, and recurrent
urinary tract infections [1–5].
The diagnosis of GSM is clinical, based upon characteristic symptoms, associ-
ated with typical signs on physical examination. Classic vaginal ndings include a
pale, dry vaginal epithelium that is smooth and shiny, with loss of most rugation.
Women may present with some or all of the signs and symptoms, which must be
bothersome jeopardizing sexual activity and the quality of life [1–5].
Several therapeutic options are available to alleviate GSM symptoms, including
hormonal and non-hormonal products. The non-hormonal moisturizers and lubri-
cants may provide only a temporary relief. Local vaginal estrogen administration
is nowadays considered the treatment of choice [1–5]. However, some women may
not wish to take hormone preparation for long term or have absolute contraindica-
tions to estrogen therapy [1–5]. In addition, different studies report that the compli-
ance to local therapies is very low, and the rate of discontinuation in the rst few
months is high.
Recently a selective estrogen receptor modulator (SERM), ospemifene, has been
introduced as oral agent for dyspareunia treatment. It provides an alternative to
oral and local estrogen therapies [6–8]. New management strategies for GSM can
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206
increase our armamentarium in order to offer a wide range of options to enable
women to choose, considering the benets and risks associated with each strategy.
Today the laser therapy may offer new options in order to stimulate tissue repair and
to restore normal vaginal functions.
12.2 Principles ofLaser
Current medical lasers emit wavelengths from the ultraviolet to the mid-infrared
portions of the spectrum [9]. Laser treatment has been safely and effectively used
in many areas including gynecology. The different wavelengths are specically
absorbed by a tissue component, a specic chromophore, including hemoglobin,
melanin, and water [9].
The concept behind laser procedures to treat vulvovaginal conditions is to use a
wavelength having high water absorption, such as the carbon dioxide (CO
2
) laser
and the Erbium (Er:YAG) [9, 10]. Laser treatment induces tissue remodeling, with
histological evidence of the restoration of vaginal mucosa, a thickening of the epi-
thelium, with the maturation of epithelial cells, a new formation of papillae indent-
ing the epithelium with newly formed and extended small vessels. In addition, in
the connective tissue underlying the epithelium, the formation of new thin brils
and morphological features of broblasts supporting a renewal of the extracellular
matrix with functional restoration [9, 10] are generated.
12.3 Types andMechanisms ofAction ofLaser Used
inVaginal Atrophy
Fractional CO
2
laser was the rst used to treat vaginal atrophy. According to the con-
cept of fractional photothermolysis, these lasers ablate a fraction of the vaginal mucosa
in the treatment area. An array of microscopic thermal wounds is created that ablates
the vagina within very tiny zones; adjacent to these areas, the mucosa is spared and
leads to natural healing process that builds new healthy tissue. In 2011, Gaspar etal.
[11] rst demonstrated that vaginal fractional CO
2
laser treatment induced a signi-
cant improvement of clinical and histological signs of vaginal atrophy. Successively,
Salvatore etal. [12] reported in a short-term study that after CO
2
laser treatment, vagi-
nal symptoms and dyspareunia improved in postmenopausal women.
The microablative fractional CO
2
laser effects on vaginal atrophy lead to an
improvement of both sexual function and quality of life [13]. These papers opened a
new era for non-hormonal treatment of GSM.All the above data were obtained with
the same microablative fractional CO
2
laser technology [11–13]. Other CO
2
laser
systems are marketed for the treatment of GSM, using different devices and differ-
ent technologies, claiming the effects obtained using the abovementioned apparatus
[11–13]. However, at the moment no solid efcacy gures and convincing safety
data are available for GSM treatment with different CO
2
lasers.
At variance of CO
2
laser, the second-generation vaginal erbium laser (VEL
®
)
stimulates photothermal effects by a non-ablative thermal diffusion to the vag-
inal walls [9, 14]. The studies of the thermal effects of a non-ablative 2940nm
M. Gambacciani
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