Laser therapy for genitourinary syndrome of menopause: systematic review and meta-analysis of randomized controlled trial

Associate Editor Lucia Helena Simões da Costa Paiva (https://orcid.org/0000-0003-4796-2429) Universidade Estadual de Campinas, Campinas, SP, Brazil

	Cochrane Library search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	pH
12	Dyspareunia
13	Itching
14	Burning
15	Dysuria
16	Urinary tract infections
17	Urinary frequency
18	Urinary incontinence
19	Vulvovaginal atrophy
20	6 AND 10 AND 20
	EMBASE search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	pH
12	Dyspareunia
13	Itching
14	Burning
15	Dysuria
16	Urinary tract infections
17	Urinary frequency
18	Urinary incontinence
19	Vulvovaginal atrophy
20	6 AND 10 AND 20
	MEDLINE search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	pH
12	Dyspareunia
13	Itching
14	Burning
15	Dysuria
16	Urinary tract infections
17	Urinary frequency
18	Urinary incontinence
	MEDLINE search strategy
Number	Search items
19	Vulvovaginal atrophy
20	6 AND 10 AND 20
	Scopus search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	pH
12	Dyspareunia
13	Itching
14	Burning
15	Dysuria
16	Urinary tract infections
17	Urinary frequency
18	Urinary incontinence
19	Vulvovaginal atrophy
20	6 AND 10 AND 20
	Web of Science search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	pH
12	Dyspareunia
13	Itching
14	Burning
15	Dysuria
16	Urinary tract infections
17	Urinary frequency
18	Urinary incontinence
19	Vulvovaginal atrophy
20	6 AND 10 AND 20
	Clinical trial databases search strategy
Number	Search items
1	Postmenopausal
2	Postmenopausal women
3	Menopausal genitourinary syndrome
4	Vaginal atrophy
5	Vulvovaginal atrophy
6	OR/1-6
7	Laser
8	Laser therapy
9	Vaginal laser therapy
10	OR/7-10
11	6 AND 10

Author, year	Country	Study design	Intervention	Control/comparator	Participants, No.				Mean age (years)		Inclusion criteria	Therapeutic protocol	Follow-up duration	Outcomes measured
					Enrollment		Lost to follow up		Intervention group	Control group
					Intervention	Control	Intervention	Control	Intervention group	Control group
Cruz et al. (2018)(³⁰30 Cruz VL, Steiner ML, Pompei LM, Strufaldi R, Fonseca FL, Santiago LH, et al. Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women. Menopause. 2018;25(1):21-8. doi: 10.1097/GME.0000000000000955 https://doi.org/10.1097/GME.000000000000... )	Brazil	RCT	CO2-laser	Vaginal estriol	Randomized 45 Allocated 15 Analyzed 13	Randomized 45 Allocated 15 Analyzed 14	2	1	55.9 ± 5.2^a a Mean ± Standard Deviation;	56.9 ± 6.0^a a Mean ± Standard Deviation;	Aged 45–70 years who presented with amenorrhea for 24 months or longer and at least one moderate symptom of VVA.	2 laser therapies every 4 weeks	20 weeks	Primary outcomes include improvement of VHI and VVA symptoms (VAS). Secondary outcomes include improvement of sexual function (FSFI).
Girardelli et al. (2017)(²⁸28 Girardelli S, Pitsouni E, Athanasiou S, Marotta E, Candiani M, Salvatore S. A double-blind randomised controlled trial of microablative fractional CO2 laser vs sham therapy on sexual function of women with vulvovagina atrophy (VVA): an interim analysis. Neurourol Urodyn. 2017;36 Suppl 2:S12-3. doi: 10.1002/nau.23302 https://doi.org/10.1002/nau.23302... )	Greece	RCT	CO2-laser	Sham-laser	Randomized 55 Allocated 27 Analyzed 27	Randomized 55 Allocated 28 Analyzed 28	0	0	-	-	Women with postmenopausal VVA.	3 laser therapy every 1 month	4 months	FSFI, UDI-6, VAS for various genital symptoms (more specifically dyspareunia, dysuria, vaginal dryness, vaginal itching and vaginal burning sensation).
Ruanphoo and Bunyavejchevin (2020)(²⁷27 Ruanphoo P, Bunyavejchevin S. Treatment for vaginal atrophy using microablative fractional CO2 laser: a randomized double-blinded sham-controlled trial. Menopause. 2020;27(8):858-63. doi: 10.1097/GME.0000000000001542 https://doi.org/10.1097/GME.000000000000... )	Thailand	RCT	CO2-laser	Sham-laser	Randomized 63 Allocated 31 Analyzed 29	Randomized 63 Allocated 32 Analyzed 30	2	2	-	-	Postmenopausal women at fifty years of age or more with moderate to severe intensity of any symptoms of vaginal atrophy.	3 laser therapies every 4 weeks	12 weeks	VHI, VAS, and scores of ICIQ-VS questionnaire in terms of vaginal dryness, vaginal symptom, sexual matter and quality of life.
Politano et al. (2019)(³¹31 Politano CA, Costa-Paiva L, Aguiar LB, Machado HC, Baccaro LF. Fractional CO2 laser versus promestriene and lubricant in genitourinary syndrome of menopause: a randomized clinical trial. Menopause. 2019;26(8):833-40. doi: 10.1097/GME.0000000000001333 https://doi.org/10.1097/GME.000000000000... )	Brazil	RCT	CO2-laser	Promestriene IV 10mg Vaginal gel lubrificant	Randomized 72 Allocated 24 Analyzed 24	Promestriene group Randomized 72 Allocated 24 Analyzed 24 Lubrificant group Randomized 72 Allocated 24 Analyzed 24	2	Promestriene group 5 Lubrificant group 9	57.8 ± 5.0^a a Mean ± Standard Deviation;	Promestriene group 57.2 ± 5.7^a a Mean ± Standard Deviation; Lubricant group 56.8 ± 5.3^a a Mean ± Standard Deviation;	Aged 50 to 70 years; physiological amenorrhea for at least 12 months; symptoms of vaginal dryness with or without dyspareunia, vaginal burning, or pruritus; and no use of hormonal medications to treat vaginal symptoms in the prior 6 months.	3 laser therapies every 30 days	14 weeks	Vaginal maturation, VHI score, and sexual function (FSFI)
Singwongsa and Vallibhakara (2019)(²⁵25 Singwongsa A, Vallibhakara O. The effect of vaginal Erbium-YAG laser treatment for the genitourinary syndrome of menopause: a randomized controlled study. Maturitas. 2019;124:153-4. doi: 10.1016/j.maturitas.2019.04.124 https://doi.org/10.1016/j.maturitas.2019... )	Thailand	RCT	Erbium: YAG laser	Sham-laser	Randomized 34 Allocated 17 Analyzed 17	Randomized 34 Allocated 17 Analyzed 17	-	-	-	-	-	3 laser therapies every 4 weeks	12 weeks	VAS, VHI, vaginal pH, VMI
Aguiar et al. (2020)(²⁹29 Aguiar LB, Politano CA, Costa-Paiva L, Juliato CR. Efficacy of fractional CO2 laser, promestriene, and vaginal lubricant in the treatment of urinary symptoms in postmenopausal women: a randomized clinical trial. Lasers Surg Med. 2020;52(8):713-20. doi: 10.1002/lsm.23220 https://doi.org/10.1002/lsm.23220... )	Brazil	RCT	CO2-laser	Promestriene IV 10mg Vaginal lubrificant	Randomized 72 Allocated 24 Analyzed 24	Promestriene group Randomized 72 Allocated 24 Analyzed 24 Lubrificant group Randomized 72 Allocated 24 Analyzed 24	2	Promestriene group 5 Lubrificant group 7	57.8 ± 5.0^a a Mean ± Standard Deviation;	Promestriene group 57.2 ± 5.3^a a Mean ± Standard Deviation; Lubrificant group 56.8 ± 5.3^a a Mean ± Standard Deviation;	Women aged ≥ 50 years, who were amenorrhoeic for at least 1 year, with symptoms related to GSM, and who did not use hormonal therapy for at least last 6 months previously and any kind of medication for OAB (oral anti-muscarinics or oral β3-adrenoceptor agonists).	3 laser therapies every 30 days	14 weeks	Urinary symptoms (ICIQ-UI SF, and the ICIQ-OAB).
Li et al. (2021)(²⁶26 Li FG, Maheux-Lacroix S, Deans R, Nesbitt-Hawes E, Budden A, Nguyen K, et al. Effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms: a randomized clinical trial. JAMA. 2021;326(14):1381-9. doi: 10.1001/jama.2021.14892 https://doi.org/10.1001/jama.2021.14892... )	Australia	RCT	CO2-laser	Sham-laser	Randomized 85 Allocated 43 Analyzed 38	Randomized 85 Allocated 42 Analyzed 40	5	2	55 ± 7^a a Mean ± Standard Deviation;	58 ± 8^a a Mean ± Standard Deviation;	Women aged 18 years and older who were fluent in English and had not previously received vaginal energy-based treatment for menopausal symptoms. Participants must have been amenorrheic for at least 12 months, either naturally or iatrogenically, and experiencing 1 or more of the following vaginal symptoms: dyspareunia, burning, itching, or dryness severe enough to prompt presentation to seek further treatment.	3 laser therapies every 1 month (minimum, 4 weeks; maximum, 8 weeks)	12 months	Severity of overall vaginal symptoms and individual symptoms of dyspareunia, dysuria, vaginal dryness, burning, and itching were assessed on a VAS; The VSQ is a 21-item validated instrument to measure vulvovaginal symptoms in postmenopausal women. This questionnaire assesses 4 domains (symptoms, emotions, life impact, and sexual-impact); Assessment of Quality of Life–6D scale13 and sexual satisfaction (Monash University Women's Health Program Female Sexuality Satisfaction Questionnaire; Vaginal Health Index Score (VHI- vaginal elasticity, vaginal fluid amount, pH, epithelial integrity, and hydration); vaginal skin biopsy (changes to collagen (reduced type I to type III fibril ratio, loss of trabecular disposition, absent fibrillogenesis), lamina propria (absence of activated fibroblasts, loss of mucopolysaccharides), epithelium (thinning of superficial layer; superficial keratinization; loss of rugae, elastic fibers, and subepithelial papillae; increase in subepithelial connective tissue), and decreased vascularization).
Paraiso et al. (2020)(⁸8 Paraiso MF, Ferrando CA, Sokol ER, Rardin CR, Matthews CA, Karram MM, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: the VeLVET trial. Menopause. 2020;27(1):50-6. doi: 10.1097/GME.0000000000001416 https://doi.org/10.1097/GME.000000000000... )	USA	RCT	CO2-laser	Vaginal estrogen cream	Randomized 69 Allocated 34 Analyzed 30	Randomized 69 Allocated 35 Analyzed 32	2	1	61 ± 8^a a Mean ± Standard Deviation;	60 ± 7^a a Mean ± Standard Deviation;	Menopausal women with absence of menstruation for at least 12 months and reported bothersome vaginal dryness of ≥7 cm on VAS.	3 laser therapies every 1 month	6 months	The primary outcome includes improvement of vaginal dryness (VAS). Secondary outcomes included VHI, VMI scores, quality of life (DIVA), sexual function (FSFI) and the urinary symptoms (UDI−6).
Salvatore et al. (2021)(²³23 Salvatore S, Pitsouni E, Grigoriadis T, Zacharakis D, Pantaleo G, Candiani M, et al. CO2 laser and the genitourinary syndrome of menopause: a randomized sham-controlled trial. Climacteric. 2021;24(2):187-93. doi: 10.1080/13697137.2020.1829584 https://doi.org/10.1080/13697137.2020.18... )	Greece and Italy	RCT	CO2-laser	Sham-laser	Randomized 60 Allocated 30 Analyzed 28	Randomized 60 Allocated 30 Analyzed 30	0	0	57.0 ± 6.9^a a Mean ± Standard Deviation;	58.4 ± 6.0^a a Mean ± Standard Deviation;	Postmenopausal women with GSM diagnosis according to the definition by the International Society for the Study of Women's Sexual Health and The North American Menopause Society, with no age limit. Dryness and dyspareunia related to GSM had to be the two most bothersome symptoms in all women.	3 laser therapies every 1 month	4 months	Changes in dryness and dyspareunia intensity; Changes in aspects of sexual functioning; Changes in itching; Burning, and dysuria intensity; Changes in UDI-6; Changes in dryness and dyspareunia incidence; Changes in sexual dysfunction incidence; Urinary incontinence; and Adverse Events.
Cruff and Khandwala (2021)(²⁴24 Cruff J, Khandwala S. A double-blind randomized sham-controlled trial to evaluate the efficacy of fractional carbon dioxide laser therapy on genitourinary syndrome of menopause. J Sex Med. 2021;18(4):761-9. doi: 10.1016/j.jsxm.2021.01.188 https://doi.org/10.1016/j.jsxm.2021.01.1... )	USA	RCT	CO2-laser	Sham-laser	Randomized 30 Allocated 14 Analyzed 11	Randomized 30 Allocated 16 Analyzed 12	2	0	61 (54−66)^b b Median (interquartile range). Randomized controlled trials (RCT), Vulvovaginal Atrophy (VVA), Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI), Intravaginal (IV), Genitourinary Syndrome of Menopause (GSM), Vaginal Health Index (VHI), Vaginal Maturation Index (VMI), International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ), Vulvovaginal Symptom Questionnaire (VSQ), Radiofrequency (RF), Urge urinary incontinence (UUI), Urinary Distress Inventory, Short Form (UDI-6)	59 (56−65)^b b Median (interquartile range). Randomized controlled trials (RCT), Vulvovaginal Atrophy (VVA), Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI), Intravaginal (IV), Genitourinary Syndrome of Menopause (GSM), Vaginal Health Index (VHI), Vaginal Maturation Index (VMI), International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ), Vulvovaginal Symptom Questionnaire (VSQ), Radiofrequency (RF), Urge urinary incontinence (UUI), Urinary Distress Inventory, Short Form (UDI-6)	Menopausal women (or status-post bilateral oophorectomy) with dyspareunia or vaginal dryness rated as moderate-severe and who were desirous of sexual function, had vaginal atrophy based on a Gloria Bachmann VHI 28 score <15 and a vaginal pH > 5, prolapse less than Pelvic Organ Prolapse Quantification System (POP-Q)29 stage III, no pelvic reconstructive surgery within 6 months of treatment, ability to provide consent, and willing and able to attend all treatments and follow-up.	3 laser therapies every 6 weeks	6 months	Primary endpoint was improvement in GSM-related dyspareunia. Secondary objectives were to determine the impact of treatment on vaginal health, GSM symptoms, bothersome LUTS, sexual function, safety, and impact on quality-of-life.
Eftekhar et al. (2020)(²⁰20 Eftekhar T, Forooghifar T, Khalili T, Shariat M, Haghollahi F. The effect of the CO2 fractional laser or premarin vaginal cream on improving sexual function in menopausal women: a randomized controlled trial. J Lasers Med Sci. 2020;11(3):292-8. doi: 10.34172/jlms.2020.49 https://doi.org/10.34172/jlms.2020.49... )	Iran	RCT	CO2-laser X RF	Sham-laser	CO2-laser group Randomized 246 Allocated 82 Analyzed 78 RF group Randomized 246 Allocated 82 Analyzed 80	Randomized 246 Allocated 82 Analyzed 79	CO2-laser 4 RF group 2	3	CO2-laser group 56.3 ± 7.2^a a Mean ± Standard Deviation; and RF group 57.7 ± 7.3^a a Mean ± Standard Deviation;	54.8 ± 11.5^a a Mean ± Standard Deviation;	Women with history of UI symptoms, sexual intercourse, sexual problems due to VVA, at least one year after the termination of menstruation, the presence of VVA symptoms, and sexual dysfunction.	CO2-laser group 3 laser therapies every 4 weeks RF group 3 RF sessions every 4 weeks	6 weeks	Urinary incontinence was evaluated using the ICIQ. In addition, pelvic organ prolapse/urinary incontinence sexual questionnaire (PISQ-12), VHI and VAS were used to determine sexual satisfaction.
Page et al. (2023)(³²32 Page AS, Verbakel JY, Verhaeghe J, Latul YP, Housmans S, Deprest J. Laser versus sham for genitourinary syndrome of menopause: a randomised controlled trial. BJOG. 2023;130(3):312-9. doi: 10.1111/1471-0528.17335 https://doi.org/10.1111/1471-0528.17335... )	Belgium	RCT	CO2-laser	Sham-laser	Randomized 60 Allocated 30 Analyzed 28	Randomized 60 Allocated 30 Analyzed 29	2	1	57.40 ± 7.07^a a Mean ± Standard Deviation;	56.20 ± 6.30^a a Mean ± Standard Deviation;	Women with moderate to severe symptoms of GSM (i.e. vaginal dryness, vaginal itching, vaginal burning, dyspareunia and dysuria) shown by an Most Bothersome Symptom score of 2 or more	3 laser therapies every 4 weeks	3 months	Dyspareunia; Vaginal dryness; Dysuria; Vaginal burning; VAS score; Vaginal burning; Vaginal itching; FSFI score; ICIQ-OAB score; VHI score; Vaginal pH

Outcomes	N° of participants (studies) Follow-up	Anticipated absolute effects	Certainty of the evidence (GRADE)
Outcomes	N° of participants (studies) Follow-up	Risk difference with [Laser therapy]	Certainty of the evidence (GRADE)
Vaginal Assessment Scale (VAS)	448 (6 RCTs) 3 weeks-12 months	MD 1.21 lower (2.35 lower to 0.07 higher)	⨁⚪⚪⚪ Very low^a,b
VHI	528 (8 RCTs) 4 weeks-12 months	SMD 0.4 SD higher (0.16 higher to 0.64 higher)	⨁⨁⚪⚪ Low
FSFI	308 (6 RCTs) 3 weeks-12 months	MD 2.46 higher (3.6 lower to 8.52 higher)	⨁⨁⚪⚪ Low^c
Vaginal pH	198 (3 RCTs) 3 weeks-12 months	SMD 1.14 SD lower (2.6 lower to 0.32 higher)	⨁⚪⚪⚪ Very low^d,e,f,g
Dyspareunia	249 (4 RCTs) 12 weeks-12 months	SMD 0.85 SD lower (1.59 lower to 0.1 lower)	⨁⨁⚪⚪ Low^h,i,j
Dysuria	256 (4 RCTs) 3 weeks-12 months	MD 1.12 lower (1.6 lower to 0.64 lower)	⨁⨁⚪⚪ Low
Dryness	194 (3 RCTs) 12 weeks-12 months	SMD 0.62 SD lower (1.12 lower to 0.12 lower)	⨁⨁⚪⚪ Low
Burning	194 (3 RCTs) 12 weeks-12 months	SMD 0.64 SD lower (1.28 lower to 0.01 lower)	⨁⨁⚪⚪ Low
Itching	257 (4 RCTs) 3 weeks-12 months	SMD 0.43 SD lower (1.04 lower to 0.17 higher)	⨁⨁⚪⚪ Low
Urinary frequency (ICIQ-UI)	106 (2 RCTs) 3 weeks-12 months	SMD 0.64 SD lower (1.13 lower to 0.14 lower)	⨁⨁⚪⚪ Low
Urinary incontinence	205 (2 RCTs) 3 weeks-12 months	MD 1.04 lower (1.55 lower to 0.54 lower)	⨁⨁⚪⚪ Low

[1] Corresponding author Ricardo Ney Cobucci E-mail: ricardo.cobucci.737@ufrn.edu.br

Brasil

Brasil

Laser therapy for genitourinary syndrome of menopause: systematic review and meta-analysis of randomized controlled trial

Abstract

Objective:

Data sources:

Studies selection:

Data collection:

Data synthesis:

Conclusion: