Administration of Oral Contraceptives at Different Times of the Follicular Phase of the Menstrual Cycle
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Follicular Profiles After Administration of Oral Contraceptives at Different Times of the Follicular Phase of the Menstrual Cycle|
- follicle growth
- estradiol concentration
- LH concentration
- endometrial development
|Study Start Date:||February 2002|
|Estimated Study Completion Date:||December 2002|
This study is a single-centre, randomized, open-label, double-controlled protocol to study the patterns of ovarian follicular growth and regression in women administered 0.15mg desogestrel /0.03mg ethinyl estradiol at different stages of the follicular phase of the menstrual cycle.
We tracked the growth and regression of dominant follicles after administration of OC by means of highly sophisticated transvaginal ultrasonography and computerized image analysis techniques. The extremely high resolution ultrasonography of the ovarian follicles and the computer-assisted image analysis are unique to the Women’s Health Imaging Research Laboratory (WHIRL) at the University of Saskatchewan. The synergyne (© R.A. Pierson) image analysis program was developed in the WHIRL and has the ability to allow assessment of the physiologic status of follicles as small as 6 to 10 mm. This unique protocol will allow us to characterize patterns of follicular growth and atresia under the suppressive effects of oral contraception, as well as the assessment of anovulatory follicles which may develop when OCs are administered at advanced stages of follicular development.
The working hypothesis is that the administration of monophasic OCs prior to and during the time of physiologic selection of the dominant follicle will prevent the development of an ovulatory follicle (selection occurs when the dominant follicle reaches 10mm [Baerwald & Pierson, unpublished data]). In addition, we hypothesize that administration of OCs after selection of the dominant follicle, at more advanced stages of follicular development will result in 1 of 4 scenarios: 1.) Ovulation of the dominant follicle, 2.) Regression of the dominant follicle, 3). Formation of a Hemorrhagic Anovulatory follicle (HAF) or Luteinized Unruptured Follicle (LUF), or 4.) Formation of a follicular cyst. We hypothesize that atresia of dominant follicles and formation of anovulatory follicular structures will be associated with limited endometrial development. In testing these hypotheses, we will determine if OCs can safely and effectively be administered at any time during the follicular phase of the menstrual cycle.
This study will evaluate the ovarian and uterine responses to administration of a combined dose of 0.15mg desogestrel /0.03mg ethinyl estradiol at 1 of 3 different stages of the follicular phase of the menstrual cycle. The objectives of the trial are to:
- Develop new and more user-friendly administration schemes for OC use;
- Use the administration of OCs at different stages of follicular development in women as a model for studying follicular atresia;
- Assess the differences in kinetics, physiologic status (state of viability or atresia), and ultrasonographic image attributes of follicles which grow, regress, ovulate, or form anovulatory follicular structures after the administration of exogenous steroid hormones;
- Assess endometrial response to ovarian suppression by ultrasonographic evaluation of endometrial thickness and endometrial pattern.
After screening measurements confirm subject eligibility, subjects will be randomized to initiate OC therapy at one of three different times of the menstrual cycle:
Experimental Group #1: receives OCs when the dominant follicle reaches 10mm Experimental Group #2: receives OCs when the dominant follicle reaches 14mm Experimental Group #3: receives OCs when the dominant follicle reaches 18mm
Fifteen women will be randomized to each of the 3 experimental groups in a stratified design scheme. Data collected from an ongoing OC trial (BMC# 2000-169) will serve as OC control data (n=15). Data collected from a previous study (BMC# 1988-80) will serve as natural cycle control data (n=60).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00204438
|Ob-Gyn Royal University Hospital|
|Saskatoon, Saskatchewan, Canada, S7N 0W8|
|Principal Investigator:||Roger A Pierson, MS PhD||University of Saskatchewan|