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

Overview

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).