Topical Estriol for Vaginal Health

Study Overview
=================
Brief Summary
-----------------
The purpose of this Phase I study is to investigate and document the effects of local treatment with a topical estriol cream on the vaginal environment of pre-menopausal women.

Detailed Description
-----------------
There is evidence from human studies that estrogen can give rise to health-promoting changes in the vaginal environment in addition to affecting the thickness of the vaginal epithelium. The purpose of the proposed study is to take the first steps in testing the effects of local estrogen treatment on vaginal health parameters in humans. We have chosen an estriol product because, in comparison with estrone (E1) and estradiol (E2), estriol (E3) is generally considered to be a weak estrogen. The duration of estriol's interaction with the estrogen receptor is quick and exhibits rapid metabolic clearance. We have chosen a topical route of administration because it appears to result in fewer systemic effects than oral administration, while allowing us to concentrate treatment locally in the areas we wish to affect. Our primary goal is to test whether or not topically applied estrogen results in significant thickening and maturation of the vaginal epithelium. Our secondary goal is to measure the treatment's effects on other parameters of the vagina, such as Lactobacillus colonization and vaginal pH. If estrogen cream does indeed affect the vaginal environment in pre-menopausal women as it does in post-menopausal women, further study would be indicated to determine whether estrogen cream in the vagina decreases risk of infection in pre-menopausal women.

Official Title
-----------------
Topical Estriol for Vaginal Health

Conditions
-----------------
Vaginal Health

Intervention / Treatment
-----------------
* Drug: estriol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In generally good health Between the ages of 18 and 40 Report regular, consistent menstrual cycles with duration between 25 and 35 days' duration Agree not to initiate hormonal contraception or other systemic or vaginal hormonal treatments during the course of the study Agree to refrain from vaginal douching and use of spermicides, spermicide-treated condoms, diaphragms, cervical caps, vaginal hygiene treatments and other vaginal products during the course of the study except as explicitly allowed under study protocol. Not attempting to get pregnant (and, if sexually active, using an allowed effective contraceptive - i.e., sterilization or male condoms) Exclusion Criteria: Has been informed by a health practitioner that she should avoid estrogen treatments Does not meet one or more of the above inclusion criteria Is currently pregnant Is currently lactating Has IUD in place Has diabetes that is controlled with medication Has menstrual bleeding that usually exceeds 7 days' duration Has used hormonal contraception or other systemic or vaginal hormonal treatment during the past three months Has received systemic antibiotic treatment since the start of bleeding in her current menstrual period Has known history of diagnosis of HIV infection Screens positive for gonorrhea, Chlamydia, or trichomonas Has evidence of high-grade dysplasia or cervical cancer on visual examination or Pap smear Has active genital Herpes lesions Has any of the following: Known, past or suspected breast cancer; Known or suspected estrogen-dependent malignant or pre-malignant tumours (e.g endometrial cancer); History of endometrial hyperplasia; Undiagnosed or abnormal genital bleeding; Previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism); Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction); Acute liver disease, or a history of liver disease where liver function tests have failed to return to normal; Liver disorders such as adenomas; Symptomatic gallstones or gallbladder disease (cholecystitis); Hypertriglyceridemia; Vascular disease associated with lupus erythematosus; Known hypersensitivity to estriol (estrogen E3) or the inactive substances in the study product; Porphyria Presents any other history or condition that provider, in his or her best discretion, feels should rule out study participation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1Topical estriol cream<br> | Drug: estriol<br>* 4 ml vaginal cream (1.0 mg estriol/1 ml cream), 3 days/week for approximately 2 months.<br>|
| Placebo Comparator: 2Placebo cream<br> | Drug: Placebo<br>* Placebo cream<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in thickness of the vaginal epithelium |  | Pre and post treatment luteal and follicular phases | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other vaginal parameters including Lactobacillus colonization and vaginal pH |  | Pre and post treatment follicular and luteal phases | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
estrogen, estriol, cream, vagina, infection prevention