Study of Oxytocin to Treat Vaginal Atrophy in Postmenopausal Women
Up to 50% of all postmenopausal women, experience vaginal dryness, irritation, burning, itching or discomfort, which often make sex to become difficult or painful. These symptoms combined are known as vaginal atrophy. Vaginal atrophy is a consequence of the lining tissue of the vagina becoming thinner, drier, and less elastic due to the lack of estrogen. In addition, vaginal atrophy is associated with an increased pH, which creates an environment more susceptible to infections. The mucosal epithelium shows signs of severe atrophy and cytological examination demonstrate increased number of the basal and parabasal cells and reduced number of superficial cells.
Estrogen treatment either as hormone replacement therapy or topical application is a common treatment for vaginal atrophy. However, some women experience adverse reactions such as uterine bleeding, perineal pain and breast pain and many women are also reluctant to use estrogens due to a general negative view to this topic in the society.
Oxytocin is a peptide hormone, which is normally released into the circulation via the pituitary. The most well known effects of oxytocin are its roles in female reproduction such as facilitation of birth and breast feeding. In addition, oxytocin has in vitro been shown to exert positive effects on the proliferation of human vaginal mucosal cells from postmenopausal women.
Considering the stimulatory effects of oxytocin on vaginal mucosal cell proliferation, topical application of oxytocin to the vaginal mucosa may be an approach to treat vaginal atrophy. In one previous placebo-controlled study on 20 postmenopausal women suffering from vaginal atrophy, a gel containing oxytocin for topical intra-vaginal administration was applied daily for seven days. The results indicated that for subjects receiving topical oxytocin the vaginal atrophy assessed by histological examination was reversed after treatment. A similar effect was not seen in the placebo group, which indicated a difference between placebo and active treatment. However, the limited number of exposed subjects in this pilot study necessitates a larger study in order to generate conclusive proof of concept data for the effects of oxytocin on vaginal atrophy.
Due to the limitations of estrogens in the treatment of vaginal atrophy, many postmenopausal women are left without an effective remedy. Hence, there is a need for alternative non-estrogenic treatments of this indication. The present study is aiming to investigate the efficacy of topical oxytocin in the treatment of vaginal atrophy.
The main objective of this study is to investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Double-blind, Placebo Controlled Multi-centre Study to Evaluate the Effects of Topical Oxytocin on Vaginal Atrophy in Postmenopausal Women|
- The Maturation Value (MV) [ Time Frame: 12 weeks of oxytocin treatment as compared to placebo ] [ Designated as safety issue: No ]The MV describes the change in percentage of superficial cells (Meisels A. The Maturation Value. Acta Cytol. 1967, Jul-Aug;11(4):249)
- Vaginal Atrophy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Atrophy in histological biopsies is assessed by a 4-grade scale
- Quality of Life [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]Using a standardized QoL form
- The Maturation Value [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Same as primary outcome but after 2 weeks treatment
- Vaginal pH [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]
- Concentration of Oxytocin in serum [ Time Frame: 0-60 min after drug admin. ] [ Designated as safety issue: Yes ]The purpose of the evaluation is only to evaluate the systemic uptake. No other PK variables than the concentration are calculated.
- Clinician evaluation of vaginal mucosal appearance [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]Evaluation of seven different features, where every feature is assessed by a 4-grade scale.
- Laboratory assessments [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: Yes ]Clinical Chemistry, Haematology, Urine analysis, Cervical cytology,Endometrial Histology
- Concentration of 17 beta-estradiol in serum [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Vital signs [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: Yes ]Heart rate and blood pressure
|Study Start Date:||August 2010|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
|Experimental: Oxytocin, Intravaginal administration||
Gel for intravaginal use, 600 IU once per day for 2 weeks followed by 600 IU twice a week for ten weeks
|Placebo Comparator: Placebo, Intravaginal administration||
Gel for intravaginal use of identical appearance as active substance, once per day for two weeks followed by twice a week for ten weeks
|Karolinska University Hospital-Huddinge|
|Huddinge, Sweden, SE-141 86|
|Uppsala University Hospital|
|Uppsala, Sweden, SE-751 85|
|Northwick Park & St Marks Hospital NHS Trust|
|Harrow Middlesex, United Kingdom, HA1 3UJ|