Full text of DOI:10.1007/PL00004040

Int Urogynecol J (2001) 12:332–336
ß 2001 Springer-Verlag London Limited
International
Urogynecology
Journal
Original Article
Does the Menopause Influence the Risk of Bacteriuria?
A. Hextall, R. Hooper, L. Cardozo, C. Stringer and R. Workman
King’s College Hospital, London, UK
Abstract: The objective of this study was to test the
hypothesis that the risk of bacteriuria is increased as a
result of estrogen deprivation following the menopause.
All midstream urine samples (MSU) sent to the King’s
College Hospital department of microbiology by general
practitioners in 1997 were assessed. Bacteriuria was
diagnosed when the bacterial count was >105 organisms/
ml. Logistic regression analysis was performed to
investigate the effects of age and sex on the likelihood
of having a positive result. Non-linear effects of age
were investigated, with interest focusing in particlar on
the time around the menopause. There were 15 392 MSU
samples analyzed; 11 811 (77%) were from women and
3581 (23%) from men. In both sexes the proportion of
positive results increased with increasing age
(P<0.0001). The specimens taken from women were
significantly more likely to be positive than those taken
from a man of the same age (P<0.0001). In women there
was no evidence of any non-linear relationship between
age and the log odds of a positive result. A plot of the
proportion of positive results versus age did not suggest
any departure from a linear relationship at or following
the menopause. In conclusion, the increased risk of
bacteriuria which occurs as women get older appears to
happen gradually as a result of the aging process, rather
than as the result of pathophysiological changes in the
urogenital tract that take place at or following the
menopause.
Introduction
Urinary tract infections (UTI) occur in women of all
ages, with at least 20%–30% of the female population
being affected at some time [1]. Risk factors include
sexual intercourse, the use of the diaphragm for
contraception, previous urinary tract infection, and
lower urinary tract dysfunction such as ureteric reflux
or impaired bladder emptying [2]. Elderly women are
thought to be particularly likely to develop bacteriuria,
with a reported prevalence of 20% in community-
dwelling women and sometimes over 50% in institutio-
nalized patients [3,4]. However, it is at present unclear if
the increased risk of UTI which occurs as women get
older is a result of the aging process or of the
pathophysiological changes that occur in the urogenital
tract as a result of estrogen deficiency following the
menopause.
Materials and Methods
All midstream urine samples (MSU) sent from the
community by general practitioners (GP) in 1997 were
assessed. The indication for urine culture was deter-
mined on an individual basis and therefore not available
for analysis. Bacteriuria was diagnosed when the urinary
bacterial count was >105 organisms/ml. Samples with a
mixed growth of organisms were classified as not
infected, in line with departmental policy. Each result
was entered on to a computerized database which
included details of the patient’s age, sex, and the
infecting organism. Logistic regression analysis was
performed to investigate the relationship between age
and the likelihood of having a positive (infected) MSU
result, and to compare the results for men and for
women. Changes in the rate of bacteriuria occurring at
Keywords: Estrogen; Menopause; Urinary tract infec-
tion
Correspondence and offprint requests to: Professor Linda Cardozo, 8
Devonshire Place, London W1N 1PB, UK. Tel: +44 207 346 3568;
Fax: +44 207 346 3449; Email: lcardozo@compuserve.com

Menopause and Risk of Bacteriuria
333
around the time of the menopause were investigated by
looking for a non-linear (more specifically, a quadratic)
relationship between age and the log odds of a positive
result. Among positive MSU results from female
subjects, the proportions due to particular infecting
organisms were analyzed in the same way to try and
establish if the menopause led to a change in the
bacterial flora of infected urine.
Results
All 15.392 MSU samples sent from the community-
based general practices from 1 January 97 to 31
December 97 inclusive were analyzed; 11.811 (77%)
were from women and 3581 (23%) from men. The
number of samples sent from patients in each age group
is shown in Fig. 1. A logistic regression analysis looking
Fig. 1. The number of urine samples sent from patients in each age group.
Fig. 2. Proportion of samples that were positive, by subject’s age. The proportions for females are calculated and plotted at each year of age. For
males, from whom there were fewer samples, the proportion plotted at a given age is calculated over a 3-year interval around that age.

334
A. Hextall et al.
Fig. 3. Proportions of the more common organisms in positive samples from female subjects. The proportion plotted at a given age is calculated
over a 7-year age interval around that age. 69% of infections were caused by E. coli, and this proportion did not change significantly with age.
This has been left off the graph in order to allow increased resolution at proportions below 20%.
at the effects of age and sex found a significant linear between age and the log odds. If the quadratic term was
not significant, a linear relationship was tried instead.
effect of age (w2 = 179.4, P<0.0001) which did not differ
between males and females (interaction w2 = 0.02,
The only organism for which the quadratic term
approached significance was Klebsiella (w2 = 3.60,
P = 0.88). However, there was a significant main effect
of sex (w2 = 170.9, P<0.0001): a specimen from a
P = 0.058), which appeared to account for a constant
proportion of infections at ages below 50, and a steadily
increasing proportion as age increased above 50 (Fig. 3).
The proportion of infections caused by Enterococcus
decreased with increasing age (w2 = 28.0, P<0.0001),
whereas Proteus was responsible for a steadily increas-
ing proportion of infections (w2 = 6.89, P = 0.009)
(Fig. 2). The proportion of positive results due to E.
coli did not vary with age (w2 = 1.28, P = 0.26).
woman was more likely to be positive than one from a
man of the same age (Fig. 2).
However, when non-linear effects of age were also
considered they were found to differ between men and
women (interaction w2 = 8.95, P = 0.003). In women,
there was no evidence of any non-linear relationship
between age and the log odds of a positive result (w2 =
0.79, P = 0.37). A plot of the proportion of positive
results did not suggest any departure from a linear
relationship at or following the menopause. In men there
was a significant non-linear relationship between age and
the log odds of a positive result (w2 = 14.4, P = 0.0001).
Over the first 15–20 years of life the proportion of
positive MSU results fell steadily, but thereafter
increased with age.
The organisms that led to positive MSU results in
women were then investigated. Escherichia coli was the
most common overall, accounting for 69.0% of
infections. Enterococcus accounted for 8.5%, Proteus
for 7.6% and Klebsiella for 6.1%. No other genus
accounted for more than 2% of infections.The propor-
tions of each of E. coli, Enterococcus, Proteus and
Klebsiella in positive results from women were analyzed
Discussion
The female lower urinary and genital tracts have a
common embryological origin, both arising from the
primitive urogenital sinus. Estrogen receptors have been
located in the vagina, urethra and trigone of the bladder
in areas that have undergone squamous metaplasia [5,6].
The urogenital tract is therefore sensitive to fluctuations
in the circulating level of sex steroids. Estrogen levels
fall following the menopause, and as a result changes in
the vaginal flora occur which are thought to place
women at an increased risk of bacteriuria. There is a
decrease in vaginal pH, a reduction in the number of
using logistic regression to fit a quadratic relationship lactobacilli and an increase in colonization by fecal

Menopause and Risk of Bacteriuria
335
Table 1. Randomized studies of oestrogen for recurrent urinary tract infection
Study
Study group
Type of
estrogen
Route of
delivery
Duration of therapy
5 months
Results
Kjaergaard et al. 1990 21 postmenopausal women
with recurrent cystitis
10 active group
Estradiol
Vaginal tablets
Number of positive cultures
not statistically different
between the two groups.
11 placebo
Kirkengen et al. 1992
40 postmenopausal women
with recurrent UTIs
20 active group
Estriol
Oral
12 weeks
Both estriol and placebo
significantly reduced the
incidence of UTIs (P<0.05).
After 12 weeks oestriol was
significantly more effective
than placebo (P<0.05)
20 placebo
Raz & Stamm 1993
93 postmenopausal women
with recurrent UTIs
50 active group
Estriol
Vaginal cream
8 months
Significant reduction in the
incidence of UTIs in the
group given estriol
compared to placebo
(P<0.001).
43 placebo
Cardozo et al . 1998
Eriksen 1999
72 postmenopausal women
with recurrent UTIs
36 active group
Estriol
Oral
6-month treatment
Reduction in urinary
period with a further symptoms and incidence of
6 months’ follow-up UTIs in both groups. Estriol
no better than placebo
36 placebo
108 women with recurrent
UTIs
53 active group
55 no treatment
Estradiol
Estring
36 weeks for the
active group
36 weeks or until
first recurrence for
the controls
Cumulative likelihood of
remaining free of infection
was 45% in active group
and 20% in control group
(P=0.008)
uropathogens [7]. For this reason, exogenous estrogen although there is some evidence that systemic responses
has been administered both orally and topically to try to acute inflammatory stimuli may be dysregulated in old
and reverse these changes, with the aim of restoring the age [17].
bacterial flora of the genital tract to the premenopausal
If changes in the vaginal flora at or following the
state. However, the five published randomized studies of menopause were really responsible for the increased risk
estrogen replacement for prophylaxis against recurrent of bacteriuria as women get older, we would have
urinary tract infections (summarized in Table 1) have expected to see an acceleration in the number of positive
given conflicting and largely disappointing results, with MSU results with increasing age, starting at the earliest
only two showing that estrogen is better than placebo ages of menopause (and, furthermore, this pattern would
when given for this indication [8–12]. Therefore, it is not have been repeated in male subjects). Instead, what
possible that women are at an increased risk of lower we found was a steady rate of increase in positive MSU
urinary tract infection as they get older because of the results from females (and indeed from males) from early
effects of aging, rather than because of the pathophy- adulthood onwards. The most common infecting
siological changes associated with the menopause and organism was E. coli, which was present in 69% of
consequent estrogen deficiency.
infected samples from females and 49% of infected
There are a number of functional changes in the lower samples from males. The prevalence of E. coli and the
urinary tract which may place women at an increased other organisms shown in Fig. 2 was similar to that
risk of bacteriuria as they get older. Urodynamic studies previously reported by Gru¨neberg [18]. There was in fact
have shown that the urethra and bladder become less a fall in the proportion of positive results due to an
efficient with age [13,14]. Elderly women have a Enterococcus with increasing age in our sample,
reduced urine flow rate, increased urinary residual, a suggesting that colonization of the vagina with bowel
higher first sensation of a desire to void and increased flora was not the main underlying cause for the increase
bladder capacity, although the later may fall in the eighth in the rate of infection as women get older.
and ninth decades [15]. In addition, detrusor pressures at
Longitudinally to determine the changes occurring
urethral opening and closure during voiding fall in perimenopausally in the vaginal and urinary flora of
absolute terms as women become older [16]. Poor community-based women would require a large, ex-
perineal hygiene also becomes more common because of pensive study of probably at least 10 years’ duration. We
an increased risk of urinary or fecal incontinence at a therefore used the microbiological database at King’s
time when catheterization for a variety of reasons is College Hospital as a model for the changes occurring in
more prevalent. There is little evidence to suggest that the population. There are of course some limitations to
impairment of immune and inflammatory responses this approach, which have been recognized. These data
increases susceptibility to infection in elderly women, are cross-sectional rather than longitudinal, and the

336
A. Hextall et al.
10. Raz R, Stamm WE. A controlled trial of intravaginal estriol in
postmenopausal women with recurrent urinary tract infections. N
Engl J Med 1993;329:753–756
11. Cardozo L, Benness C, Abbott D. Low dose oestrogen
prophylaxis for recurrent urinary tract infections in elderly
women. Br J Obstet Gynaecol 1998;105:403–407
12. Eriksen B. A randomised, open, parallel-group study on the
preventive effect of an estradiol-releasing vagial ring (Estring) on
recurrent urinary tract infections in postmenopausal women. Am J
Obstet Gynecol 1999;180:1072–1079
number of patients being affected by urinary symptoms
in each age group is impossible to determine. Some
patients may also have been represented more than once
in the data set. We did not include samples sent from
hospital clinics and wards because of the large number
of specimens taken in specialist units (including
intensive care, liver unit, urology and urogynecology),
which may have skewed the results.
Ideally we would have liked to be able to determine
whether each woman in the sample had reached
menopause, so that we could compare pre- and
postmenopausal women after controlling for age and
other relevant factors (such as treatment with hormone
replacement therapy) using logistic regression. This
information was not available in the present study, so
that we had to use the average age of the menopause (50
years [19]) as a proxy for the onset of estrogen
deficiency. The present uptake of hormone replacement
therapy in the UK and elsewhere in Europe is probably
less than 15% of women aged 40–65 [20,21], with as
many as 40% of women failing to complete 12 months
of treatment even when there is a clear reason to do so
[22]. The use of estrogen replacement in our study
population is therefore unlikely to have had a significant
effect on the results.
In conclusion, bacteriuria becomes more common in
both men and women with increasing age. However, no
specific changes appear to occur in the rate of infection
or the infecting flora at the time of the menopause. It is
therefore unlikely that pathophysiological changes in the
urogenital tract which occur as a result of estrogen
deficiency following the menopause have a significant
impact on the prevalence of bacteriuria in community-
dwelling women.
13. Rud T. Urethral pressure profile in continent women from
childhood to old age. Acta Obstet Gynecol Scand 1980;59:331-
335
14. Malone Lee J. The characterisation of detrusor contractile
function in relation to old age. Br J Urol 1993;72:873–880
15. Collas DM, Malone Lee J. Age-associated changes in detrusor
sensory function in women with lower urinary tract symptoms. Int
Urogynecol J 1996;7:24–29
16. Wagg AS, Lieu PK, Ding YY et al. A urodynamic analysis of age
associated changes in urethral function in women with lower
urinary tract symptoms. J Urol 1996;156:1984–1988
17. Horan MA, Parker SG. Infections, aging and the host response.
In: Horan MA, Little RA, eds. Injury in the aging; Cambridge:
Cambridge University Press, 1998:126–146
18. Gru¨neberg RN. Changes in urinary pathogens and their antibiotic
sensitivities, 1971–1992. J Antimicrob Chemother 1994;33(Suppl
A): 1–8
19. Research on the menopause in the 1990s. Report of a WHO
Scientific Group. Geneva 1996, WHO technical report series 866.
20. Barlow DH, Brockie JA, Rees CMP. Study of general practice
consultations and menopausal problems. Br Med J 1991;302:274–
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21. Wilkes HC, Meade TW. Hormone replacement therapy in general
practice: a survey of doctors in the MRC’s general practice
framework. Br Med J 1991;302:1317–1320
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