Oxytocin
Vaginal Gel

Oxytocin is a nano-peptide (nine amino acids) hormone secreted by the posterior pituitary. Oxytocin acts both peripherally and in the brain.

Oxytocin is secreted by both males and females during orgasm and many consider it as the hormone of desire, social recognition and bonding.

Estrogen is known to increase the number of oxytocin receptors and to increase the release of oxytocin; this was demonstrated by Burbach and colleagues¹ who studied the effect of 17β-estradiol on the activity of the oxytocin gene promoter, in vivo oxytocin messenger RNA and peptide levels in rats and reached this conclusion. Mohr and Schmitz² also showed that the rat oxytocin gene harbors two functional estrogen-responsive elements near the transcription initiation site, one of which is conserved in the respective gene in humans, while Mitchell and colleagues³ studied plasma concentration levels in six women throughout the complete menstrual cycle and found a significant elevation in circulating oxytocin concentration associated with peak levels of luteinizing hormone which is known to be stimulated by estrogen

Oxytocin improves cell growth depending on time and dose, and this is different to the effect of hormonal therapy. Also, oxytocin receptor expression was increased as well as caveolin-1, and hence cell proliferation⁴.

Kallak and Uvnäs-Moberg⁵ found that oxytocin stimulates cell proliferation, in vivo and in vitro, supporting the role of oxytocin signaling in cell proliferation. These findings suggest that an increase in cell proliferation is one of the mechanisms of action by which local oxytocin increases vaginal thickness and relieves vaginal symptoms in postmenopausal vaginal atrophy.

Oxytocin also increases the rate of wound healing, mucosal blood flow and transport of nutrients as well as stimulation of secretion of several growth factors and induction of mitosis in several cell types.^5,6

Oxytocin gel has been studied for the treatment of:

• Restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis.⁷
• Postmenopausal Vaginal Atrophy^8,9,10

In Cases Of Postmenopausal Atrophic Vaginitis Jonasson and co-workers⁷ conducted a 7-day pilot study involving 20 patients equally divided into two groups and found 70% (seven out of ten cases) normalization of the vaginal epithelium on examination

in the oxytocin group (p = 0.003), and a difference approaching significance in the morphological appearance of the vaginal mucosa as compared to the placebo group (p = 0.07);

Al-Saqi and co-workers⁸ conducted a double-blind, randomized, controlled trial to test the effectiveness on postmenopausal vaginal atrophy of vaginal oxytocin gel in two different concentrations, 400 IU (24 cases of which 17 cases completed the study), and 100 IU (24 cases of which 23 cases completed the study), versus placebo (16 cases of which 14 cases completed the study), for 7 weeks. In their study, women had increased superficial cells and maturation value of the vagina, in addition to a significant improvement in symptoms with the 400 IU dose (53% of women had improvement and this was highly significant compared with placebo), while the lower dose (100 IU) was more effective for pH, dyspareunia and the scores of vaginal atrophy by histological evaluation.

Al-Saqi and colleagues⁹ conducted a larger double-blind, randomized, controlled trial involving 68 patients divided into 33 patients receiving 600 IU vagitocin gel and 35 receiving placebo daily in the first 2 weeks, and then twice weekly for another 10 weeks. All cases were followed up for four to five visits by vaginal smears at each visit and vaginal biopsy in 20 of the women both pre- and post-treatment. They found an increase in the proportion of superficial vaginal cells in the first 2 weeks (p = 0.04), a high difference in the maturation value in the first 12 weeks (p = 0.01), and a significant reduction in the scores of atrophy according to the histological parameter at 12 weeks (p < 0.04), all in favor of the vagitocin group. Based on their findings, they concluded that daily vagitocin administration improved vaginal atrophy both cytologically and histologically; the treatment was less effective when the vagitocin was used twice weekly.

Torkey¹⁰ conducted a randomized controlled trial to test the effectiveness of topical 600IU oxytocin gel to improve vaginal atrophy in postmenopausal women. A total of 140 postmenopausal women presenting with vaginal atrophy and who satisfied the inclusion and exclusion criteria were randomized into two groups each of 70 patients; they received intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level, visual, colposcopic and histological vaginal examination were performed before and after treatment. Forty-seven out of 70 women in the oxytocin gel group improved after treatment and none in the placebo group (p = 0.001). Forty-five participants in the oxytocin group and seven in the placebo group reported relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group and seven in the placebo group reported relief of soreness (p = 0.001). Torkey concluded that Oxytocin gel is useful in the restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis.

Torkey¹⁰ also showed that the level of serum estrogen was not elevated after treatment with oxytocin vaginal gel, indicating that the mechanism of improved vaginal mucosa is not related to estradiol but oxytocin, and there were no side-effects for the applied treatments. Jonasson and colleagues7 also showed no significant difference in the circulating estradiol level in both groups. Thus, the effect of oxytocin is most likely exerted locally in the vagina and does not seem to be mediated by estrogen.