Ignite Creation Date:
2024-05-05 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00427700
Status:
COMPLETED
Last Update Posted:
2024-04-11
First Post:
2007-01-26
Brief Title:
Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome
Sponsor:
Hospital de Clinicas de Porto Alegre
Organization:
Hospital de Clinicas de Porto Alegre
Study Overview
Official Title:
Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
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 ie luteinizing hormoneLH and follicle stimulating hormoneFSH 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 ie 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 810 progesterone levels will be measured from blood An endometrial biopsy on day 810 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
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 ie luteinizing hormoneLH and follicle stimulating hormoneFSH 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 ie 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 810 progesterone levels will be measured from blood An endometrial biopsy on day 810 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None