Hormonally induced changes in the vaginal flora associated with menopause are thought to play an important part in the recurrence of urinary tract infections in older women.
Approximately 10 to 15 percent of women over 60 years of age have frequent urinary tract infections. Recurrent urinary tract infections can potentially lead to an increase in urinary incontinence (UI). This can be quite a distressing problem and ongoing problem in the menopausal population who is estrogen deficient. Prior to the onset of menopause when hormone levels are optimal, the glycogen content of vaginal tissues is increased in the presence of estrogen and there is a more acidic environment created which allows lactobacillus, an important organism for preventing vaginal infection to be the most predominant bacterium present in the vagina. Lactobacillus, which produces lactic acid from glycogen and maintains a low vaginal pH, inhibits the growth of many bacteria which cause UTI. Some strains of lactobacillus produce hydrogen peroxide, which may prevent certain UTI provoking bacteria from colonizing the vagina. In addition there are certain unique aspects to the cell walls of the lactobacillus organism that have been shown to prevent the attachment of specific bacteria (E. Coli) to the walls of the urinary tract. Thus, through one or more of these mechanisms, the loss of lactobacillus colonization and the associated atrophy of the vaginal mucosa that normally occurs after menopause may increase the likelihood of recurrent urinary infections. After menopause, however, the vaginal pH increases, lactobacilli disappear from the vaginal flora, and the vagina is predominantly colonized by most bacteria which are the most common causes of urinary tract infections in women. Such colonization presumably accounts in part for the increased susceptibility of these women to urinary tract infections.
Estrogen replacement with either a topically applied vaginal cream or an orally administered agent restores a more healthy viable state to the now atrophic vaginal, urethral, and mucosa of the bladder. Estrogen replacement also lowers the vaginal pH; and may reduce the occurrence of urinary tract infections.
Estrogen deficiency is a major contributor to the pathogenesis of recurrent urinary tract infections in postmenopausal women and show that prolonged estrogen replacement with a topically applied vaginal cream safely and effectively prevents urinary tract infections in these patients. This preventive approach can be considered an alternative to the use of long-term low-dose antibiotics. Topical/intra-vaginal estrogen may be particularly useful in patients in whom the prolonged use of antibiotics induces side effects, allergic reactions, drug interactions, or the emergence of multidrug-resistant microorganisms.
Multiple clinical trials have shown that intra-vaginal estrogen replacement specifically intra-vaginal estriol is extremely effective in reducing the incidence of urinary tract infections in postmenopausal women with recurrent urinary tract infections. Vaginal estriol has been shown to relieve local, vaginal and urinary tract symptoms with minimal to no systemic effects. In summary, estriol is administered topically/intravaginally does not increase the risk of hormone-dependent cancers of the breast or endometrium (uterus).
Estriol has a high relative binding affinity (RBA) for estrogen receptors in the bladder and vaginal tissue. Because of the high binding affinity in the vaginal tissue and bladder, estriol has a stronger and more beneficial effect in these tissues. More importantly estriol has a weak binding affinity for estrogen receptors in the uterus and breast tissue and because of the low RBA for the ER in the uterus and breast, estriol exerts only a weak effect in these tissues.
There are numerous estrogen replacement options available for vaginal application in the form of creams, gels, tablets and estrogen containing rings. The most common estrogens contained within the creams/gels are estradiol (E2) and estriol (E3) and tablets contain estradiol. (E2). The vaginal rings are small silicone vaginal rings impregnated with estradiol.
Escherichia coli, a common urinary tract infection pathogen, can flourish in an environment of increased pH like that which exists in menopausal women who are estrogen deficient and have developed vaginal atrophy. Multiple studies looking at vaginal pH and the recurrence of UTI compared women using topical estrogen vaginal cream for 2-4 months with a no treatment and results showed the treatment group had a significant decrease in pH (more acidic) whereas no change was noted in the pH of the nontreatment group. It appears that the decrease in vaginal pH may support an association between preventing recurrence of UTIs if the vaginal pH is more acidic.