Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array
Information source: Lawson Health Research Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Estrogen Replacement Therapy
Intervention: Premarin (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Lawson Health Research Institute Official(s) and/or principal investigator(s): Gregor Reid, PhD, MBA, Principal Investigator, Affiliation: Lawson Health Research Institute and The University of Western Ontario
Summary
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.
Clinical Details
Official title: Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: Human genome array
Secondary outcome: Denaturing gradient gel electrophoresis
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).
Eligibility
Minimum age: 35 Years.
Maximum age: 95 Years.
Gender(s): Female.
Criteria:
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
Locations and Contacts
Lawson Health Research Institute, London, Ontario N6A 4V2, Canada
Additional Information
Related publications: McGregor JA, French JI, Seo K. Premature rupture of membranes and bacterial vaginosis. Am J Obstet Gynecol. 1993 Aug;169(2 Pt 2):463-6. Review. Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 1994 Jan 29;308(6924):295-8. Chaim W, Mazor M, Leiberman JR. The relationship between bacterial vaginosis and preterm birth. A review. Arch Gynecol Obstet. 1997;259(2):51-8. Review. Sewankambo N, Gray RH, Wawer MJ, Paxton L, McNaim D, Wabwire-Mangen F, Serwadda D, Li C, Kiwanuka N, Hillier SL, Rabe L, Gaydos CA, Quinn TC, Konde-Lule J. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet. 1997 Aug 23;350(9077):546-50. Erratum in: Lancet 1997 Oct 4;350(9083):1036. Taha TE, Gray RH, Kumwenda NI, Hoover DR, Mtimavalye LA, Liomba GN, Chiphangwi JD, Dallabetta GA, Miotti PG. HIV infection and disturbances of vaginal flora during pregnancy. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Jan 1;20(1):52-9. Kalman S, Mitchell W, Marathe R, Lammel C, Fan J, Hyman RW, Olinger L, Grimwood J, Davis RW, Stephens RS. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat Genet. 1999 Apr;21(4):385-9. Patrick DM, Dawar M, Cook DA, Krajden M, Ng HC, Rekart ML. Antenatal seroprevalence of herpes simplex virus type 2 (HSV-2) in Canadian women: HSV-2 prevalence increases throughout the reproductive years. Sex Transm Dis. 2001 Jul;28(7):424-8. Wiesenfeld HC, Hillier SL, Krohn MA, Landers DV, Sweet RL. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis. 2003 Mar 1;36(5):663-8. Epub 2003 Feb 7. Cherpes TL, Meyn LA, Krohn MA, Hillier SL. Risk factors for infection with herpes simplex virus type 2: role of smoking, douching, uncircumcised males, and vaginal flora. Sex Transm Dis. 2003 May;30(5):405-10. Devillard E, Burton JP, Hammond JA, Lam D, Reid G. Novel insight into the vaginal microflora in postmenopausal women under hormone replacement therapy as analyzed by PCR-denaturing gradient gel electrophoresis. Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10;117(1):76-81. Burton JP, Reid G. Evaluation of the bacterial vaginal flora of 20 postmenopausal women by direct (Nugent score) and molecular (polymerase chain reaction and denaturing gradient gel electrophoresis) techniques. J Infect Dis. 2002 Dec 15;186(12):1770-80. Epub 2002 Nov 22. Heinemann C, Reid G. Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy. Can J Microbiol. 2005 Sep;51(9):777-81. Notterman DA, Alon U, Sierk AJ, Levine AJ. Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays. Cancer Res. 2001 Apr 1;61(7):3124-30. Habis AH, Vernon SD, Lee DR, Verma M, Unger ER. Molecular quality of exfoliated cervical cells: implications for molecular epidemiology and biomarker discovery. Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):492-6. Chen B, Wen Y, Zhang Z, Guo Y, Warrington JA, Polan ML. Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women. Hum Reprod. 2006 Jan;21(1):22-9. Epub 2005 Aug 26.
Starting date: March 2006
Last updated: July 8, 2009
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