Home
Search
Study Topics
Glossary
|
|
|
|
|
|
Sponsors and Collaborators: |
Hospital de Clinicas de Porto Alegre Greenville Hospital Center of Women's Medicine |
---|---|
Information provided by: | Hospital de Clinicas de Porto Alegre |
ClinicalTrials.gov Identifier: | NCT00427700 |
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.
Condition | Intervention | Phase |
---|---|---|
Polycystic Ovary Syndrome |
Drug: clomiphene citrate Drug: raloxifene |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome |
Estimated Enrollment: | 80 |
Study Start Date: | August 2008 |
Estimated Study Completion Date: | August 2009 |
Estimated Primary Completion Date: | August 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1: Active Comparator
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 mnestrual cycle
|
2: Experimental
Use of 100mg of raloxifene during days 5-9 of the menstrual cycle
|
Drug: raloxifene
100mg PO on days 5-9 of the mnestrual cycle
|
-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 polycystics 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-menopausic women (Delmas PD et al., 1997). Recent studies have shown that this drug is safe in healthy pre-menopausic 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
Ages Eligible for Study: | 18 Years to 38 Years |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Furthermore, all patients with infertility diagnosis based solely on ovulation factor will included in the protocol
Exclusion Criteria:
Contact: Eduardo P Passos, MD, PhD | 55 51 99810169 | epp@via-rs.net |
Brazil, Rio Grande do Sul | |
Hospital de Clínicas de Porto Alegre | Recruiting |
Porto Alegre, Rio Grande do Sul, Brazil, 90035-003 | |
Contact: Ricardo F Savaris, MD, PhD 55 51 21018405 rsavaris@hcpa.ufrgs.br | |
Contact: Eduardo P Passos, MD, PhD 55 51 99810169 epp@via-rs.net | |
Principal Investigator: Ricardo F Savaris, MD, PhD | |
Sub-Investigator: Eduardo P Passos, MD, PhD | |
Sub-Investigator: Helena Corleta, MD, PhD |
Principal Investigator: | Ricardo F Savaris, MD, PhD | Hospital de Clínicas de Porto Alegre |
Study Chair: | Eduardo P Passos, 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 |
Responsible Party: | HCPA-UFRGS ( Ricardo Francalacci Savaris ) |
Study ID Numbers: | RACLO |
Study First Received: | January 26, 2007 |
Last Updated: | December 26, 2008 |
ClinicalTrials.gov Identifier: | NCT00427700 |
Health Authority: | Brazil: Ministry of Health |
Polycystic Ovary Syndrome clomiphene citrate Raloxifene |
Polycystic ovarian syndrome Genital Diseases, Female Raloxifene Gonadal Disorders Citric Acid Polycystic Ovary Syndrome |
Clomiphene Endocrine System Diseases Endocrinopathy Ovarian Diseases Cysts Ovarian Cysts |
Syndrome Estrogen Antagonists Disease Anticoagulants Molecular Mechanisms of Pharmacological Action Hormone Antagonists Physiological Effects of Drugs Hematologic Agents Hormones, Hormone Substitutes, and Hormone Antagonists Bone Density Conservation Agents Reproductive Control Agents |
Selective Estrogen Receptor Modulators Pharmacologic Actions Adnexal Diseases Estrogen Receptor Modulators Neoplasms Pathologic Processes Fertility Agents, Female Therapeutic Uses Fertility Agents Chelating Agents |