Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome

March 28, 2024 updated by: Hospital de Clinicas de Porto Alegre

The Polycystic Ovarian Syndrome (PCOS) is a common disorder related to ovulation problems. Clomiphene citrate (CC) is the drug of first choice for this condition. Nevertheless, CC has a detrimental effect over uterine receptivity.

Raloxifene is a Selective Estrogen Receptor Modulator, that does not have a detrimental effect over the endometrium, and also increase the serum levels of FSH, thus, inducting ovulation.

The objective of this study is to compare the ovulation rate in PCOS patients between clomiphene citrate and raloxifene in a double blind randomized trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

-Introduction The Polycystic Ovarian Syndrome (PCOS) is a frequent endocrine among women in reproductive ages, with a prevalence of 10%. In 2003, a consensus among the European and American Society of Human Reproduction (ESRHE and ASRM) defined that PCOS is a ovarian disfunction which present at least 2 out of 3 criteria: oligomenorrhea or anovulation; clinical or laboratorial signs of hyperandrogenism and polycystic ovaries on ultrasound; other causes, such as congenital adrenal hyperplasia, androgen secretory tumors, Cushing syndrome and hyperprolactinemia must be rule out.

Patients with PCOS who desire to became pregnant need, in their majority, induction of ovulation. Traditionally, clomiphene citrate, an estrogen receptor agonist, is the most used drug for this type of anovulation. The mechanism of action of clomiphene is related to a negative feedback to the endogenous estrogen, resulting in a higher amplitude of gonadotrophin surges, i.e., luteinizing hormone(LH) and follicle stimulating hormone(FSH). Nevertheless, recent studies have been shown that clomiphene citrate has a deleterious effect in the endometrium. The markers of uterine receptivity, among them, the integrin beta3 subunit, has its expression diminished, which implicate in a reduced fecundation rate.

The raloxifene is a selective estrogen receptor modulator. It has an agonist and antagonist activity over different organs. The daily therapy with raloxifene increase bone density, reduce cholesterol serum concentrations (LDL) and do not stimulate the endometrium in post-menopausal women (Delmas PD et al., 1997). Recent studies have shown that this drug is safe in healthy pre-menopausal women (Baker VL et al., 1998). A daily dosi of 100mg per 28 days, beginning on the 3rd day of the cycle, has shown that FSH and LH levels were not affected when compared to controls during the menstrual cycle. However, women who had received 100mg of raloxifene had a 31% increase in their FSH serum levels during the follicular phase, when compared to controls. An increase to 200mg did not increase FSH levels (Baker VL et al, 1998). Furthermore, it has been shown that raloxifene significantly increase the in vitro expression of αvβ3 integrin, suggesting a beneficial effect over the endometrium in relation to clomiphene (Lessey BA, personal communication, 2006).

-Objective To compare the ovulation rate between raloxifene and clomiphene among women with polycystic ovarian syndrome.

To identify the endometrial alterations compatible with ovulations, i.e., secretory endometrium, through endometrial biopsy between the women who used raloxifene or clomiphene.

-Patients and Methods

Patients with the diagnosis of polycystic ovarian syndrome (because of infertility or hirsutism) who had a consultation at outpatient clinic of Hospital de Clínicas de Porto Alegre will be invited to participate in the study, after signing the informed consent. A standard interview will be performed. In the first consultation, the laboratorial exams will reviewed: total testosterone, 17 OH-progesterone, fasting glucose, TSH, prolactin. After the interview, the patient will be randomized for one of the treatments:

100mg of clomiphene or 100mg of raloxifene from day 3 of the menstrual cycle, for 5 days. Menstruation will be induced with 10mg of oral medroxyprogesterone per 10 days. On day 10, urinary LH will be collected daily along with endovaginal ultrasound for assessing follicular development. On post-ovulatory day 8~10, progesterone levels will be measured from blood. An endometrial biopsy on day 8~10 post-ovulation will be performed in those patients who do not wish to became pregnant. The endometrial biopsy will divided into 2 parts and kept in liquid nitrogen and formol for immunohistochemistry and histological analysis respectively.

Sample size and statistical analysis

Ethical aspects

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
        • Hospital de Clínicas de Porto Alegre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 36 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • All patients with polycystic ovarian syndrome will be invited to participate in the study. The PCOS criteria are according to modified Rotterdam criteria (7); i.e., oligoovulation defined as < 6 menstrual periods per year, signs of clinical hyperandrogenism (Ferriman and Gallwey >8) or laboratorial (total Testosterone >=0.81 ng/dL) or polycystic ovary > 10cm3.

Furthermore, all patients with infertility diagnosis based solely on ovulation factor will included in the protocol

  • Age >18 years old and <= 38 years old.
  • No endometriosis on laparoscopy

Exclusion Criteria:

  • Not willing to participate in the study
  • use of IUD or contraceptive pill within 2 months before the study.
  • Hyperprolactinemia (>20ng/mL)
  • Abnormal serum levels of TSH(normal range:0.4-40 mUI/mL).
  • High 17-OH progesterone (>=4.9ng/mL)
  • Endometriosis
  • Known allergy to clomiphene or raloxifene

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Clomiphene
Uso of 100mg of clomiphene citrate during days 5-9 of the menstrual cycle
Drug: clomiphene citrate
100mg PO on days 5-9 of the menstrual cycle
Other Names:
  • Clomid
Experimental: Raloxifene
Use of 100mg of raloxifene during days 5-9 of the menstrual cycle
Drug: raloxifene
100mg PO on days 5-9 of the menstrual cycle
Other Names:
  • Evista

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Ovulation Detected by Ultrasound
Time Frame: cycle day 14-20
Ovulation detected by ultrasound was defined as the percentage of a participants with ovulation detected by ultrasound, defined as the dominant follicle and its subsequent collapse. If a dominant follicle was not observed by day 21 after menses, the ovulation induction was considered to be a failure.
cycle day 14-20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Levels of Progesterone
Time Frame: 8-10 days after ovulation
The level of serum progesterone that indicated ovulation was considered to be 3 ng/mL or greater, on days 8 to 10 after ovulation.
8-10 days after ovulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Clinicas de Porto Alegre

Investigators

  • Principal Investigator: Ricardo F Savaris, MD, PhD, Hospital de Clínicas de Porto Alegre
  • Study Chair: Helena Corleta, MD, PhD, Hospital de Clínicas de Porto Alegre
  • Study Director: Bruce A Lessey, MD, PhD, Greenville Hospital System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

January 26, 2007

First Submitted That Met QC Criteria

January 26, 2007

First Posted (Estimated)

January 29, 2007

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RACLO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Polycystic Ovary Syndrome

Clinical Trials on clomiphene citrate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe