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

Phase 1
35 Years
95 Years
Not Enrolling
Healthy, Estrogen Replacement Therapy

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Trial Information

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

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

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

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).

Inclusion Criteria:

- Women taking oral Premarin at least for the last month with no urogenital anatomical

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Human genome array

Principal Investigator

Gregor Reid, PhD, MBA

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lawson Health Research Institute and The University of Western Ontario


Canada: Health Canada

Study ID:




Start Date:

March 2006

Completion Date:

February 2007

Related Keywords:

  • Healthy
  • Estrogen Replacement Therapy
  • Premarin,
  • HRT,
  • RNA,
  • Gene Expression.
  • Postmenopausal Women