Table 1 Summary of included studies

Jonasson et al. (2011) [14]

Double-blinded, randomized pilot study.

20

1 mg.

Placebo.

7 days.

Postmenopausal women (at least two years after menopause) who were suffering from symptoms of vaginal atrophy and had not used any estrogen or other hormonal treatments (systemic or topical) during a four-week period prior to the trial.

Women who have an endocrine disease and any other serious illnesses.

Oxytocin normalizes the morphological appearance of the vaginal mucosa and promotes the restoration of the vaginal epithelium.

Al-saqi et al. (2015)

[18]

Double-blinded, randomized controlled trial.

64

400 and 100 IU.

Placebo.

7 weeks.

Women who had objective signs of vaginal atrophy, vaginal pH > 5, endometrial thickness < 4 mm as measured by ultrasound, body mass index (BMI) 30 kg/m², and blood pressure < 150/90 mmHg.

Women with 5% superficial cells in the vaginal smears, plasma FSH levels < 40 IU/L, 17b-estradioL levels 70 pmol/l, or malignant changes in the endometrium.

Oxytocin stimulated the growth of the vaginal epithelium cells, so restoring the atrophic vaginal mucosa.

Al-Saqi et al. (2016)

[19]

Multicentric, double-blinded, randomized controlled trial.

68

600 IU daily for the first two weeks and 600 IU twice a week for ten weeks.

Placebo.

14 weeks.

Women were healthy > 40-year-old women four years or more after natural menopause. The vaginal mucosa should be atrophic (as evaluated clinically), and atrophy should be verifiable by cytological assessment (superficial cells < 5%), vaginal pH > 5. In addition, plasma follicle-stimulating hormone (FSH) levels should be > 40 IU/L, 17b-estradiol levels < 70 pmol/L, and body mass index (BMI) < 29 kg/m².

Patients were excluded if they used any type of estrogen, including phytoestrogens, herbal products with known estrogenic effect, or hormonal intrauterine device, within three months prior to screening. Exclusion criteria also included a history of prior or current malignant illness or endometrial hyperplasia or having systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg at screening. Known or suspected drug or alcohol abuse within the12 months prior to screening.

Intravaginal vagitocin increased the percentage of the superficial cells, the maturation value and histological scores of vaginal atrophy.

Torky et al. (2018)

[15]

Randomized control trial.

140

1 mg (equivalent to 600 IU).

Placebo.

1 month.

Two years after menopause, suffering from symptoms of vaginal atrophy (vaginal dryness, pain, itching, discomfort, or bleeding with intercourse) and did not use any estrogen or other hormonal treatments (systemic or topical) during the last 4 weeks prior to the study. All women were sexually active.

Women with any serious illnesses, malignancy, or history of malignancy, Women with no sign of vaginal atrophy at the assessment examination were excluded.

Oxytocin gel helped in the restoration of the vaginal epithelium.

Abedi et al. (2020)

[17]

Randomized controlled trial.

96

400 IU.

Placebo 400 IU.

8 weeks.

Postmenopausal women aged between 40–50, monogamous with a sexual relationship, whose last menstruation was more than one year prior to the study, and whose score of sexual function was less than 26 according to the Female Sexual Function Index (FSFI).

Women using hormone replacement therapy, having any vaginal bleeding or any breast diseases, using vaginal lubricant, or having any undiagnosed genitalia disorder.

Oxytocin vaginal gel significantly improved vaginal atrophy as well as sexual function.

Jonasson et al. (2020) [16]

Randomized, double-blinded, controlled study.

157

400 IU.

VagiVital (Aqueous Hypromellose-based vaginal gel).

12 weeks.

Females aged 40–65 years who were either postmenopausal or had undergone surgical bilateral oophorectomy, with ≤ 5% superficial cells in vaginal smear cytology, a vaginal pH > 5.0, a body mass index ≤ 32 kg/m2, an endometrial thickness of < 4 mm, and at least one moderate to severe VVA symptom, but who were otherwise in good health and had provided signed informed consent, were considered eligible to participate in the study. In addition, women were to abstain from vaginal sexual activity and the use of vaginal douching within 24 h prior to vaginal pH measurements. Further, women with an intact uterus were required to have an acceptable result from a Pap smear conducted within 6 months prior to the initial dose of study medication.

Women were not permitted to use estrogen alone or estrogen/progestin for any of the following time periods: (a) Vaginal hormonal products (rings, creams, gels, vaginal suppositories) within 12 weeks prior to the screening visit, (b) transdermal estrogen alone or estrogen/progestin products including percutaneous estrogen gels for at least 12 weeks prior to the screening visit, (c) oral estrogen and/or progestin therapy within 12 weeks prior to the screening visit, (d) intrauterine progestin therapy within 12 weeks prior to the screening visit, (e) progestin implants and estrogen alone injectable drug therapy within 12 weeks prior to the screening visit, and (f) estrogen pellet therapy or pregestational injectable drug therapy within 6 months prior to the screening visit.

Significant reductions in the severity of the MBS were seen in both the Aqueous Hypromellose-based vaginal gel and the oxytocin gel groups, but no significant differences in severity reduction were seen between the groups. Both gels were safe and well tolerated.

Zohrabi et al. (2020)

[28]

Randomized controlled trial.

96

400 IU.

Placebo.

8 weeks.

Literate women, age 40–60, at least one year passed from their last menstrual period or the level of FSH > 40 IU, monogamous women with a sexual relationship.

Women with vaginal infection, women who used hormone replacement therapy, any undiagnosed genitalia diseases, smokers’ women, a body mass index of more than 30 kg/m², vaginal bleeding or spotting, any breast diseases with unknown cause, using vaginal lubricant at least 15 days before the intervention.

Oxytocin gel improves the vaginal maturation index and subjective symptoms of vaginal atrophy and reduces the pH of the vagina.