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

July 8, 2009 updated by: Lawson Health Research Institute
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

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

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4V2
        • Lawson Health Research Institute

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

35 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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

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: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Human genome array

Secondary Outcome Measures

Outcome Measure
Denaturing gradient gel electrophoresis

Collaborators and Investigators

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

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Gregor Reid, PhD, MBA, Lawson Health Research Institute and The University of Western Ontario

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

March 1, 2006

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

February 1, 2007

Study Registration Dates

First Submitted

April 24, 2006

First Submitted That Met QC Criteria

April 24, 2006

First Posted (Estimate)

April 26, 2006

Study Record Updates

Last Update Posted (Estimate)

July 9, 2009

Last Update Submitted That Met QC Criteria

July 8, 2009

Last Verified

July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-06-710
  • GR12198E

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.

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