Beneficial Effects of Oral Premarin Estrogen Replacement Therapy Assessed by Human Genome Array
Condition: Healthy; Estrogen Replacement Therapy
Study type: Interventional
Phase: Phase 1

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.
    

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).
    

Intervention name(s): Premarin
Intervention type(s): Drug
Intervention MeSH terms: Estrogens, Conjugated (USP)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Premarin,; HRT,; RNA,; Gene Expression.; Postmenopausal Women