Aromatase Inhibitor Effects on Ovarian Function During the Follicular and Early Luteal Phase in Women

NCT01046578 | Completed Phase 4

• 1 other identifier: WHIRL-08-1200
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

A single center, open label randomized clinical trial designed to examine ovarian follicular dynamics following attempted atresia induction during the late follicular and early luteal phase of the menstrual cycle using an aromatase inhibitor. We hypothesize that administration of an aromatase inhibitor (AI) at biologically important times of the natural menstrual cycle will cause ovulatory failure in women with preovulatory follicles and failure of luteogenesis in women who have recently ovulated. It is proposed that atresia of the dominant follicle and formation of anovulatory structures will be associated with arrested endometrial development and a shortened interval to menstrual bleeding (3 days). We anticipate that this will provide us with information to facilitate the development of a new method for emergency contraception and a greater understanding of human folliculogenesis. The rationale for the proposed research project is based on the ovarian synchronization concepts developed and documented in the bovine model in the Reproductive Science and Medicine Research group at the University of Saskatchewan combined with novel human ovarian wave concepts of folliculogenesis first elucidated in the Women's Health Imaging Research Laboratory (WHIRL) in the Department of Obstetrics, Gynecology and Reproductive Sciences.

Conditions

Fertility

Keywords

Folliculogenesis; Letrozole; Aromatase Inhibitor; Estrogen

Outcome Measures

Primary Outcomes (1)

• fate of the dominant follicle or luteal structure

  40-45 days

Secondary Outcomes (3)

• interval to follicle wave emergence, and interval to selection of a dominant follicle

  40-45 days

• endometrial thickness/pattern

  40-45 days

• ultrasonographic image attributes of follicular structures that develop after administration of treatment

  ongoing

Study Arms (7)

Single Dose 12mm follicle

EXPERIMENTAL

Single dose (20mg) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated at follicle diameter of 12 mm

Drug: Letrozole

Single Dose 18mm follicle

EXPERIMENTAL

Single dose (20mg) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated at follicle diameter of 18 mm

Drug: Letrozole

Single Dose Post Ovulation

EXPERIMENTAL

Single dose (20mg) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated 24-48 post ovulation

Drug: Letrozole

Multi Dose 12mm follicle

EXPERIMENTAL

Multi dose (2.5mg/day for 5 days) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated at follicle diameter of 12 mm

Drug: Letrozole

Multi Dose 18mm follicle

EXPERIMENTAL

Multi dose (2.5mg/day for 5 days) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated at follicle diameter of 18 mm

Drug: Letrozole

Multi Dose Post Ovulation

EXPERIMENTAL

Multi dose (2.5mg/day for 5 days) of an aromatase inhibitor (Letrozole/Femara(TM); n = 10) initiated 24-48 hours post ovulation

Drug: Letrozole

Control

NO INTERVENTION

No intervention given, followed for course of study on a natural cycle

Interventions

Letrozole DRUG

20 mg, one tablet a day for one day, starting on the day the dominant follicle reaches 12 mm in diameter

Also known as: Femara (TM)

Single Dose 12mm follicle

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female subjects of childbearing potential with normal reproductive function;
• Women between 18 and 35 years of age;
• Normal Body Mass Index (18-30);
• Are naïve to OC or have discontinued OC at least 2 months prior to study entry;
• Subject has signed the informed consent form;
• Subject is in good general health as confirmed by medical history and physical examination

You may not qualify if:

• Irregular menstrual cycles;
• Any contraindication for oral contraception use;
• Known hypersensitivity to Letrozole and co-administered medications;
• Evidence of Polycystic Ovary Syndrome (PCOS) or Endometriosis;
• History of pituitary tumor;
• Pregnancy (suspected or diagnosed) or lactation;
• HIV, HBV, HCV infection;
• Vaginal infection;
• Abnormal ECG;
• Abnormal lab tests for blood profile, liver function and renal function;
• Uncontrolled diabetes and blood pressure;
• History or suspicion of alcohol or drug abuse;
• History of severe mental disorders;
• Participation in an investigational drug trial in the 30 days prior to selection;
• A subject who exhibits a disorder that is a contraindication to steroid hormonal therapy, including, for example, the following conditions:

Sponsors & Collaborators

• University of Saskatchewan: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Related Publications (1)

• Allaway HC, Chizen DR, Adams GP, Pierson RA. Effects of a single 20 mg dose of letrozole on ovarian function post dominant follicle selection: an exploratory randomized controlled trial. J Ovarian Res. 2017 Jan 21;10(1):6. doi: 10.1186/s13048-017-0303-x.

  PMID: 28107821 DERIVED

MeSH Terms

Interventions

Letrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roger A Pierson, PhD

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

• Donna R Chizen, MD

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: January 12, 2010
• Study Start: January 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: November 28, 2016

Record last verified: 2016-11

Locations

CA (1)