. 2024 May 27;46:e-rbgo38. doi: 10.61622/rbgo/2024rbgo38

Chart 2. Characteristics of the studies included in the systematic review and meta-analysis.

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)⁽³⁰⁾	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	56.9 ± 6.0^a	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)⁽²⁸⁾	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)⁽²⁷⁾	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)⁽³¹⁾	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	Promestriene group 57.2 ± 5.7^a Lubricant group 56.8 ± 5.3^a	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)⁽²⁵⁾	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)⁽²⁹⁾	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	Promestriene group 57.2 ± 5.3^a Lubrificant group 56.8 ± 5.3^a	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)⁽²⁶⁾	Australia	RCT	CO2-laser	Sham-laser	Randomized 85 Allocated 43 Analyzed 38	Randomized 85 Allocated 42 Analyzed 40	5	2	55 ± 7^a	58 ± 8^a	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)⁽⁸⁾	USA	RCT	CO2-laser	Vaginal estrogen cream	Randomized 69 Allocated 34 Analyzed 30	Randomized 69 Allocated 35 Analyzed 32	2	1	61 ± 8^a	60 ± 7^a	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)⁽²³⁾	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	58.4 ± 6.0^a	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)⁽²⁴⁾	USA	RCT	CO2-laser	Sham-laser	Randomized 30 Allocated 14 Analyzed 11	Randomized 30 Allocated 16 Analyzed 12	2	0	61 (54−66)^b	59 (56−65)^b	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)⁽²⁰⁾	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 and RF group 57.7 ± 7.3^a	54.8 ± 11.5^a	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)⁽³²⁾	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	56.20 ± 6.30^a	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

Mean ± Standard Deviation;

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)