Efficacy and safety of visnadine in the treatment of symptoms of sexual dysfunction in heterosexual women: a systematic review of randomized clinical trials

Figures & data

Figure 1. Flow diagram for study selection.

Table 1. Studies excluded after full-text evaluation.

Author [reference]	Title	Exclusion reasons
Aquino et al. [27]	PNM-12 Double-blind randomized study on the effect of non-hormonal gel application to the genital area of women in the Menacme with Sexual Dysfunction Trial (NCT04015037).	Wrong publication type: conference abstract.
Lagana et al. [21]	Effects of a new vaginal cream containing visnadine, prenylflavonoids and bovine colostrum on Vaginal Health Index Score and Female Sexual Function Index in post-menopausal sexually active women affected by vaginal dryness: A pilot study.	Uncontrolled study. Wrong publication type: conference abstract and no further information could be obtained from the authors.
Caputo et al. [18]	Efficacy of an intimate oil solution containing visnadine in women self-reporting sexual symptoms.	Uncontrolled study.
Laganà et al. [22]	Preliminary results of a single-arm pilot study to assess the safety and efficacy of visnadine, prenylflavonoids and bovine colostrum in postmenopausal sexually active women affected by vulvovaginal atrophy (NCT03281655).	Uncontrolled study.
Sparavigna et al. [20]	A randomized single-blind placebo-controlled study of a visnadine emulgel formulation on healthy postmenopausal women.	Wrong outcome.
Caputo et al. [31]	An open trial of a visnadine emulgel topical application in postmenopausal superficial dyspareunia: daily vs. on-demand use.	Uncontrolled study.
Chaikittisilpa et al. [30]	Effects of visnadine, ethyl ximeninate, Coleus Barbatus and Millet in Emulgel on Sexual Function in Postmenopausal Women (NCT04579991).	Clinical trial not concluded.

Table 2. General characteristics of the clinical studies included in the systematic review.

Author (year)	Country	Study Design	Population	Age (years) Mean ± SD	Total FSFI score at baseline	Follow-up period	Groups	Intervention details	Outcomes	Funding
Bernorio et al. (2018) [17]	Italy	Randomized, double-blind placebo controlled-pilot study	Women with female sexual dysfunction (self-reported sexual symptoms)	38.3 ± 7.9 (intervention) 39.6 ± 6.8 (control)	25.0 ± 3.8 (intervention)	T1: 30 days	Intervention Two puffs of visnadine spray for a minimum of six times per month		FSFI scores, visnadine questionnaire	Not Reported
					25.4 ± 5.0 (control)		Control Two puffs of placebo spray for a minimum of six times per month
Caruso et al. (2018) [19]	Italy	Randomized, crossover study	Women with female sexual dysfunction (as defined by DSM-IV criteria)	32.5 ± 4.2	21.0 ± 3.0 (sequence A)	T1: 30 days T2: 60 days	Sequence A (on demand → washout → daily). Each woman had to apply two sprays on her clitoral area 15 min before starting sexual activity following her sexual desire on-demand phases, or every night during the daily phases.		FSFI, FSDS	Not reported
					21.2 ± 2.9 (sequence B)		Sequence B (daily → washout → on demand). Each woman had to apply two sprays on her clitoral area 15 min before starting sexual activity following her sexual desire on-demand phases, or every night during the daily phases.

SD: Standard deviation.

FSFI: Female Sexual Function Index.

FSDS: Female Sexual Distress Scale.

Figure 2. Risk of bias assessment for the included studies.

Table 3. Effects of visnadine on FSFI global and domain scores.

Author (year)	Comparisons	n	FSFI Global score		Desire (FSFI)		Arousal (FSFI)		Lubrication (FSFI)		Orgasm (FSFI)		Satisfaction (FSFI)		Dyspareunia (FSFI)
			Mean ± SD	p-value	Mean ± SD	p-value	Mean ± SD	p-value	Mean ± SD	p-value	Mean ± SD	p-value	Mean ± SD	p-value	Mean ± SD	p-value
Bernorio et al. (2018) [17]	Intervention vs. placebo (T0)	IG: 30 CG: 28	25.0 ± 3.8 vs. 25.4 ± 5.0	NS	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	Placebo (T1 vs. T0)	CG: 28	25.6 ± 4.7 vs. 25.4 ± 5.0	NS	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	Intervention (T1 vs. T0)	IG: 30	27.9 ± 2.4 vs. 25.0 ± 3.8	<0.001	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	Intervention vs. placebo (T1)	IG: 30 CG: 28	27.9 ± 2.4 vs. 25.6 ± 4.7	<0.001	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Caruso et al. (2018) [19]	Sequence A (T1 vs. T0)	T0: 19 T1: 15 T2: 15	21.4 ± 2.8 vs. 21.0 ± 3.0	NS	5.3 ± 0.9 vs. 5.4 ± 0.2	NS	2.9 ± 0.6 vs. 2.7 ± 0.4	NS	3.1 ± 0.5 vs. 2.9 ± 0.3	NS	3.6 ± 0.4 vs. 3.5 ± 0.2	NS	3.8 ± 0.8 vs. 3.4 ± 0.6	NS	4.0 ± 0.9 vs. 3.1 ± 0.9	0.007
	Sequence A (T2 vs. T0)		32.4 ± 4 vs. 21.0 ± 3.0	0.001	5.6 ± 0.8 vs. 5.4 ± 0.2	NS	5.3 ± 0.7 vs. 2.7 ± 0.4	0.001	5.8 ± 0.4 vs. 2.9 ± 0.3	0.001	5.1 ± 0.6 vs. 3.5 ± 0.2	0.001	5.4 ± 0.7 vs. 3.4 ± 0.6	0.001	5.1 ± 0.5 vs. 3.1 ± 0.9	0.001
	Sequence A (T2 vs. T1)		32.4 ± 4.0 vs. 21.4 ± 2.8	0.001	5.6 ± 0.8 vs. 5.3 ± 0.9	NS	5.3 ± 0.7 vs. 2.9 ± 0.6	0.001	5.8 ± 0.4 vs. 3.1 ± 0.5	0.001	5.1 ± 0.6 vs. 3.6 ± 0.4	0.001	5.4 ± 0.7 vs. 3.8 ± 0.8	0.001	5.1 ± 0.5 vs. 4.0 ± 0.9	0.001
	Sequence B (T1 vs. T0)	T0: 19 T1: 18 T2: 16	32.5 ± 3.5 vs. 21.2 ± 2.9	0.001	5.6 ± 0.9 vs. 5.3 ± 0.3	NS	5.5 ± 0.8 vs. 2.7 ± 0.4	0.001	5.8 ± 0.4 vs. 2.9 ± 0.4	0.001	5.1 ± 0.6 vs. 3.0 ± 0.4	0.001	5.4 ± 0.5 vs. 3.4 ± 0.6	0.001	5.1 ± 0.4 vs. 3.1 ± 0.4	0.001
	Sequence B (T2 vs. T0)		24.0 ± 2.5 vs. 21.2 ± 2.9	0.005	5.3 ± 0.9 vs. 5.3 ± 0.3	NS	3.3 ± 0.9 vs. 2.7 ± 0.4	0.010	3.5 ± 0.4 vs. 2.9 ± 0.4	0.010	3.7 ± 0.8 vs. 3.0 ± 0.4	0.002	4.0 ± 0.7 vs. 3.4 ± 0.6	0.010	3.6 ± 0.9 vs. 3.1 ± 0.4	0.030
	Sequence B (T2 vs. T1)		24.0 ± 2.5 vs. 32.5 ± 3.5	0.001	5.3 ± 0.9 vs. 5.6 ± 0.9	NS	3.3 ± 0.9 vs. 5.5 ± 0.8	0.001	3.5 ± 0.4 vs. 5.8 ± 0.4	0.001	3.7 ± 0.8 vs. 5.1 ± 0.6	0.001	4.0 ± 0.7 vs. 5.4 ± 0.5	0.001	3.6 ± 0.9 vs. 5.1 ± 0.4	0.001

SD: Standard deviation; FSFI: Female Sexual Function Index; NS: Non-significant; NA: Not applicable.

In the study of Bernorio et al. [17] used: IG: Intervention group; CG: Control group;.

In the study of Caruso et al. [19] used: T0: Baseline, T1: Before the cross-over, T2: within one week from the end of the study.

Sequence A presents the following phases: on demand → washout → daily. While Sequence B presents the following phases: washout → daily → on demand.

Chedraui P, Pérez-López FR, Sánchez H, et al. Assessment of sexual function of mid-aged ecuadorian women with the 6-item female sexual function index. Maturitas. 2012;71(4):407–412. doi: 10.1016/j.maturitas.2012.01.013.

 PubMed Web of Science ®Google Scholar

Laganà AS, Basile F, Stojanovska L, et al. Effects of a new vaginal cream containing visnadine, prenylflavonoids and bovine colostrum on vaginal health index score and female sexual function index in post-menopausal sexually active women affected by vaginal dryness: a pilot study. Maturitas. 2017;100:123. doi: 10.1016/j.maturitas.2017.03.265.

 Google Scholar

Caputo A, Natoli A, Radice R, et al. Efficacy of an intimate oil solution containing visnadine in women self-reporting sexual symptoms. Minerva Gynecol. 2018;70(4):490–492.

 PubMedGoogle Scholar

Laganà AS, Vitale SG, Stojanovska L, et al. Preliminary results of a single-arm pilot study to assess the safety and efficacy of visnadine, prenylflavonoids and bovine colostrum in postmenopausal sexually ­active women affected by vulvovaginal atrophy. Maturitas. 2018;109:78–80. doi: 10.1016/j.maturitas.2017.12.015.

 PubMed Web of Science ®Google Scholar

Sparavigna A, Caputo A, Natoli A, et al. A randomized single-blind placebo-controlled study of a visnadine emulgel formulation on healthy postmenopausal women. Minerva Ginecol. 2019;71(5):353–358. doi: 10.23736/S0026-4784.19.04398-3.

 PubMed Web of Science ®Google Scholar

Caputo A, Sparavigna A, Natoli A, et al. An open trial of a visnadine emulgel topical application in postmenopausal superficial dyspareunia: daily vs. on-demand use. Minerva Ginecol. 2020;72(1):59–60. doi: 10.23736/S0026-4784.19.04402-2.

 PubMed Web of Science ®Google Scholar

Chaikittisilpa S, Orprayoon N. Effects of visnadine, ethyl ximeninate, Coleus Barbatus and Millet in Emulgel on Sexual Function in Postmenopausal Women (NCT04579991). Available athttps://classic.clinicaltrials.gov/ct2/show/NCT04579991?term=NCT04579991&draw=2&rank=1.

 Google Scholar

Bernorio R, Piloni S, Mori G, et al. Efficacy and tolerability of a spray formulation containing visnadine in women self-reporting sexual symptoms: a randomized double-blind placebo-controlled pilot study. J Endocrinol Invest. 2018;41(6):729–737. doi: 10.1007/s40618-017-0801-0.

 PubMed Web of Science ®Google Scholar

Caruso S, Mauro D, Cariola M, et al. Randomized crossover study investigating daily versus on-demand vulvar visnadine spray in women affected by female sexual arousal disorder. Gynecol Endocrinol. 2018;34(2):110–114. doi: 10.1080/09513590.2017.1354366.

 PubMed Web of Science ®Google Scholar

Data availability statement

Not applicable as this was a systematic review and meta-analysis of publications found in the literature.