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Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array

This study has been completed.
Sponsor:
Information provided by:
Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00318318
First received: April 24, 2006
Last updated: July 8, 2009
Last verified: July 2009

April 24, 2006
July 8, 2009
March 2006
December 2006   (final data collection date for primary outcome measure)
Human genome array
Same as current
Complete list of historical versions of study NCT00318318 on ClinicalTrials.gov Archive Site
Denaturing gradient gel electrophoresis
Same as current
Not Provided
Not Provided
 
Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array
Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array

The purpose of this study is to assess the immunological status of patients using Premarin. Premarin use is associated with an enhanced immune status, and possibly even some anti-cancer effect. The researchers will compare the use of Premarin with those not using hormone replacement therapy (HRT) to track the effects of Premarin in reducing the risk of infection and swelling.

In recent times, adverse publicity has affected the sales of hormone replacement therapies and the perception of women as to whether or not HRTs should be taken. While a number of brands are available, those from Wyeth are the market leaders. Previous studies by our group have shown an advantage of Premarin, a natural conjugated equine estrogen, in fostering recovery of the Lactobacillus flora in the vagina. These organisms have been shown to help protect the host from urinary and vaginal infections. In the present proposal, we aim to further examine the beneficial effects of Premarin through the use of a human genome array technology.

New microarrays allow measurements to be made of 38,000 or more gene expressions on a single sample. We have recently used an Affymetrix array to examine up and down regulation of vaginal genes from a healthy premenopausal woman before and after administration of a probiotic. Somewhat to our surprise, we noted that over 9,000 genes were expressed and major down regulation occurred in cancer and other genes such as inflammatory cytokines. This was especially interesting as it showed that vaginal treatment could influence genes associated with, for example, the intestine. The array provided data or relevance to estrogen replacement therapy, namely the ability to detect and examine changes in estrogen associated factors.

In short, this system can examine changes to inflammation and host defenses. Based upon the findings of Raz and others (1993), it is likely that Premarin down regulates inflammation, either directly or via an alteration of the vaginal environment resulting in restoration of lactobacilli. Another benefit of the restoration of lactobacilli is that these organisms have anti-cancer properties.

The increased prevalence after menopause of urogenital (bladder and vaginal) infections and complications can be counteracted to some extent by restoration of the normal vaginal microbiota. These infections are extremely common, and treatment with antibiotics and antifungals is compromised by rapid rises in drug resistance (up to 30% for fluoroquinolones in some countries and a doubling of resistance to trimethoprim-sulfamethoxazole). BV has been associated with increased risk of preterm labour (McGregor et al. 1993; Hay et al. 1994; Chaim et al. 1997) and sexually transmitted diseases including HIV, herpes simplex virus, gonorrhea and Chlamydia (Sewankambo et al. 1997; Taha et al. 1998; Olinger et al. 1999; Wiesenfeld et al. 2003; Cherpes et al. 2003). Notably, 35-50% of patients and around 50% of UTI patients suffer a recurrence of infection within 3 months. Post-menopausal women have low levels of lactobacilli and high numbers of pathogens, while 100% of those receiving Premarin are colonized by lactobacilli (Burton et al. 2003; Devillard et al. 2004; Heinemann & Reid, 2005).

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Healthy
  • Estrogen Replacement Therapy
Drug: Premarin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
February 2007
December 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Women taking oral Premarin at least for the last month with no urogenital anatomical abnormalities.
  • Women not taking HRT for at least one month with no urogenital anatomical abnormalities (controls).

Exclusion Criteria:

  • Males.
  • Subjects who are not menopausal.
  • Less than 35 years of age.
  • Subjects with recurrent sexually transmitted disease.
  • Subjects with abnormal renal function (serum creatinine >110umol/l, upper limit 90umol/l) or pyelonephritis.
  • Subjects receiving prednisone or immunosuppressive drugs,
  • Subjects who need to be treated for any urogenital infection or with any antimicrobial therapy.
  • Personal history of known or suspected estrogen-dependent neoplasia such as breast or endometrial cancer.
  • Undiagnosed abnormal vaginal bleeding.
  • Active hepatic dysfunction or disease, especially of the obstructive type.
  • Active thrombophlebitis, thrombosis or thromboembolic disorders.
  • Endometrial hyperplasia.
  • Subjects on anticoagulants, antidiabetic and antihypertensive agents
Female
35 Years to 95 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00318318
R-06-710, GR12198E
No
Dr. G. Reid, Lawson Health Research Institute
Lawson Health Research Institute
Not Provided
Principal Investigator: Gregor Reid, PhD, MBA Lawson Health Research Institute and The University of Western Ontario
Lawson Health Research Institute
July 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP