Accepted Manuscript

Title: Association between Pelvic Organ Prolapse and

Climacteric Symptoms in Postmenopausal Women

Authors: Angelo Cagnacci, Federica Palma, Antonella

Napolitano, Anjeza Xholli

PII: S0378-5122(16)30270-5
DOI: http://dx.doi.org/doi:10.1016/j.maturitas.2017.02.011
Reference: MAT 6776

To appear in: Maturitas

Received date: 12-10-2016

Revised date: 4-2-2017
Accepted date: 10-2-2017

Please cite this article as: Cagnacci Angelo, Palma Federica, Napolitano
Antonella, Xholli Anjeza.Association between Pelvic Organ Prolapse
and Climacteric Symptoms in Postmenopausal Women.Maturitas
http://dx.doi.org/10.1016/j.maturitas.2017.02.011

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
Highlights

The association between climacteric symptoms and pelvic organ prolapse was
investigated in a single-center cross-sectional study of 1382 postmenopausal
women.
The Greene Climacteric Scale was used to investigate symptoms.
A higher score on the Greene Climacteric Scale was associated with a higher
prevalence of pelvic organ prolapse.

ASSOCIATION BETWEEN PELVIC ORGAN PROLAPSE AND CLIMACTERIC SYMPTOMS IN

POSTMENOPAUSAL WOMEN

RUNNING TITLE: POP AND CLIMACTERIC SYMPTOMS

Angelo Cagnacci MD PhD, Federica Palma MD, Antonella Napolitano MD, Anjeza Xholli
MD.

Department of Obstetrics, Gynaecology and Paediatrics,

Azienda Policlinico of Modena
Modena, Italy

Corresponding author: Prof. Angelo Cagnacci MD, PhD, Ginecologia ed Ostetricia,

Azienda Sanitaria Universitaria Integrata di Udine, piazza della Misericordia 15, 33100
Udine, Italy.
Tel 39-0432 559635; e-mail: angelo.cagnacci@uniud.it
Abstract
Objective: To evaluate whether climacteric symptoms are related to pelvic organ prolapse
(POP) in postmenopausal women.
Study Design: A cross-sectional investigation was performed of 1382 postmenopausal
women attending an outpatient service for menopause at a university hospital.
Main Outcome Measures: Data regarding climacteric symptoms, as captured by the
Greene Climacteric Scale, and objective POP were retrieved from an electronic database.
Additional data retrieved were age, anthropometric measures, personal and reproductive
history, use of medication or drugs, coffee, smoking, state of anxiety (STAI scale score)
and depression (Zung scale score).
Results: The score on Greene Climacteric Scale was higher (p=0.02) in women with
(n=538) than in those without (n=844) POP (29.613.6 vs. 27.813.; p=0.02). In multiple
logistic regression models, the score was independently related to POP as a whole (OR
1.012; 95%CI 1.003,1.022; p=0.009), and to bladder prolapse (OR 1.011; 95%CI
1.007,1.07; p=0.02) but not to uterus prolapse (OR 1.003; 95%CI 0.99,1.016; p=0.63) or
rectum prolapse (rectocele) (OR 1.004; 95%CI 0.988,1.02; p=0.62).
Conclusions: In postmenopausal women, a higher burden of climacteric symptoms , is
associated with POP. Underlying mechanisms were not assessed and deserve further
investigation.

Keywords: Pelvic Organ Prolapse, Cystocele, Climacteric Symptoms, Menopause, Hot

Flush
1. Introduction
1.1.Background/Rationale
Pelvic organ prolapse (POP) is a multifactorial defects represented by a descent of
bladder, uterus or rectum. Epidemiological evidence indicates that risk factors for POP are
pelvic organ surgery, particularly hysterectomy [1,2], vaginal delivery [3,4], a low socio-
economic class [5], type of job [5], obesity [6] and some diseases such as diabetes [6,7] or
chronic obstructive pulmonary disorders [8]. Rates of POP are high with estimates of 38-
50% affected, and with an 11-19% lifetime risk for undergoing surgery [3,9,10]. In the
future this risk is going to double, as the population ages [11]. POP may affect many
aspects of womans quality of life including her social, psychological, physical, sexual,
body image, sleep and overall well-being [9]. Qualitative and quantitative deficiencies in
pelvic collagen are believed to exist in women with POP [12-14], with data indicating a
global collagen deficiency [14-16].
In the late peri-menopause women suffering from a higher degree of climacteric symptoms
experience an acceleration of collagen turnover, for example in bone [17] leading to an
higher risk of bone fractures [18]. Whether they also experience an increased risk of POP
is presently unknown. This possibility is supported by the recent report showing that
women with a higher degree of climacteric symptoms are at higher risk of urinary
incontinence, of which POP represents a well-recognized risk factor [19].

1.2 Objectives
In this study it was investigated whether in post-menopausal women a higher degree of
climacteric symptoms is associated with an increased risk of POP.

2. Methods
2.1 Study design and setting
Cross - sectional investigation of the data retrospectively extracted from an electronic
database of the menopause outpatient service of our University Hospital. The local ethics
committee and the Institutional Review Board previously approved the anonymous
extraction of the data.
All postmenopausal women who entered into the analysis had previously signed an
informed consent, allowing the anonymous use of their data for scientific purposes. Data of
each single woman were collected and entered into a computer database at the time of
their examination. Subsequently, they were anonymously retrieved for statistical analysis.
Our database included specific information on pelvic floor defects since January 2010.
Accordingly, only first consultancies, performed between January 2010 and December
2015, were considered.

2.2 Participants
Of the 2574 extracted records, 702 were discarded, because the women were in pre-or
peri-menopause (defined as irregular menstrual cycles, up to amenorrhea for less than 12
months, experience of climacteric symptoms, and FSH serum level>30 IU/ml). The other
490 records were discarded due to incomplete data. Hysterectomised women were
excluded whether their FSH values were below 40 IU/L. Accordingly final analysis was
performed on 1382 postmenopausal women (Figure 1). No significant difference was
observed between the group of included women and that of women excluded for
incomplete data.

2.3 Variables and data measurement

Data collection and measured variables were already described in a previous article (19].
Climacteric symptoms were evaluated by the Greenes climacteric scale [19]. The
climacteric scale is composed of 21 items, and it evaluates vasomotor symptoms (two
items), anxiety (six items), depression (five items), somatic symptoms (seven items), and
sexuality (one item). Each item has four options, that range from not at all (0), mild (1),
moderate (2), to severe (3). The sum of the items score is used to obtain the score of the
Greenes climacteric scale as a whole (range 0-63). The scores of the individual sub-
scales for vasomotor symptoms (range, 0 to 6), anxiety (range, 0 to 18), depression
(range, 0 to 15), somatic symptoms (range, 0 to 21), and sexuality (range, 0 to 3) were
also evaluated. Total score and sub-scales scores were extracted and used in the analysis
as numerical data.
The Y-1 form of the State-Trait-Anxiety-Inventory (STAI) had been used to specifically
evaluate the state of anxiety [19], and the Zungs scale (SDS) as well, to specifically
evaluate depression [19]. These scales are made up of 20 questions with 4 possible
answers (score 1-4). Scores range from 20 (best) to 80 (worst). The presence of bladder
(cystocele), uterus, or rectum (rectocele) prolapse was evaluated at the time of
examination, according to the Baden-Walker halfway stratification [20]. Experienced
physicians, trained in evaluating POP performed the examinations. In order to reduce the
inter-observer variability, we decided to analyse only the presence or absence of the
defects, rather than its degree. However sub-analyses were also performed with the
different degrees of the single defects (grade 1 to 4). Additional data retrieved were related
to age, age at menarche, age at menopause, years since menopause, having been
pregnant, number of deliveries, type of menopause (physiological/surgical or
induced/hysterectomy), ever use of hormonal contraceptives (yes/no) current and former
use of menopause hormone therapy (MHT) (no/yes), use of anxiolytics (no/yes), anti-
hypertensive (yes/no) and anti-osteoporotic (yes/no) drugs, smoking (never or ever), use
of coffee (yes/no), marital status (unmarried, married, divorced, or widow), education,
divided into low (primary school), middle (high school), and high (university degree).
Height (in meters) and weight (in kilograms) were obtained from women who were
barefoot and wore light clothes, and the waist circumference was measured on standing
women along the horizontal plane, at the level of the natural waist (narrowest abdominal
circumference). Body mass index was calculated as the ratio of weight in kilograms to the
square of height in meters (BMI; Kg/m2).

2.4 Statistical Methods

Data distribution was assessed and found to be normal allowing use of parametric tests.
The Students t test was used for comparing data of women with and without POP.
Frequencies were compared using contingency tables, and the chi-squared test.
Simple logistic regression analyses were used to relate the dependent variable POP, to
each parameter that had been retrieved by the electronic database. As sub-
analyses,similar simple logistic regression analyses were performed considering bladder,
uterus, or rectum descent, instead of POP, as the dependent variable. Factors emerging
as related to the dependent variable were tested for collinearity, through simple regression
analysis. Collinearity was accepted with a coefficient of regression>07 [19]. Multiple
logistic regression models were constructed with POP as the dependent variable and as
independent determinant all those parameters that at simple logistic analysis were found
to be significantly related (or, more strongly related in the case of collinearity) to POP
(Model 1). Sub-analyses were also separately performed for bladder, uterus or rectum
prolapse as the dependent variable. Among the independent parameters the Greenes
scale score, and not its sub-scales scores, were entered into the logistic regression
models, in order to evaluate the composite burden of the climacteric symptoms. When at
simple logistic regression analysis the Greenes scale score was not related to the
dependent variable, its value was forced into the multiple logistic regression model. For
each multiple logistic regression model the R2 is provided as a measure of the quality of
the model. R2 indicates the proportion of the dependent variables variability that is
explained by the independent variables [19]. Statistical analysis was performed by the
statistical package StatView 5.01 (SAS institute inc. 1998, SAS campus drive, North
Carolina USA). For all parameters, a two - tail p value below 0.05 was considered to be
significant.
All the numerical results are expressed as meanstandard deviation (SD).

3. Results
3.1 Participants and descriptive data
The participating women were all white. 1072 (77.5%) were in physiological menopause
(amenorrhea for at least 12 months, and FSH level >40 IU/ml), 76 (5.5.0%) in surgical
menopause (ovariectomy plus hysterectomy), and 234 (17.0%) were hysterectomized,
with ovary conservation. 465 women (33.7%) had been on MHT for at least 3 months;
either a combination of estrogen plus progestogen therapy (n=322), or estrogen alone
therapy (n=143), whether in physiological or surgical menopause respectively. 844
(61.1%) postmenopausal women did not suffer from POP, while 538 (39.9%) did (Table 1).
A descent of the bladder was present in 503 (36.4%), of the uterus in 155 (11.2%) and of
the rectum in 93 (6.7%) of the women. A combined defect was present in 121 (8.7%) of
the women.

3.2 Characteristics of women with POP

Women with POP had a higher score of the Greenes climacteric scale. They also had an
older age, more years since the menopause, a higher rate of hysterectomy, a higher
prevalence of having been pregnant, a higher number of deliveries, a more frequent
unmarried status, low level of education, and a higher probability of being housewife. In
addition they had a reduced prevalence of using coffee, and smoking (Table 1).

3.3 Climacteric symptoms and POP

In simple logistic regression, the presence of POP was associated positively with the
Greenes scale score for climacteric symptoms, age, years since menopause, number of
deliveries, BMI, waist circumference, whether they have had a hysterectomy, their status
as a housewife, a lower education, and negatively with smoking and use of coffee (Table
2). In multiple logistic regression models, the Greenes climacteric scale score remained
independently associated with POP, along with an older age, number of deliveries, BMI,
having had a hysterectomy and the use of coffee (Table 2).

3.4 Climacteric symptoms and bladder prolapse

In simple logistic regression, the presence of bladder prolapse, but not its degree, was
positively associated with the Greenes score for climacteric symptoms, age, years since
menopause, number of deliveries, BMI, waist circumference, whether they have had a
hysterectomy, their status as a housewife, a lower education, and negatively with the use
of coffee (Table 3).
In multiple logistic regression models, the Greenes climacteric score remained
independently associated with the presence of a bladder prolapse, along with age, number
of deliveries, BMI, having had a hysterectomy, status as a housewife and the use of coffee
(Table 3). The Greenes climacteric score was not associated with the degree of bladder
prolapse.

3.5 Climacteric symptoms and uterus prolapse

In simple logistic regression, the presence of uterus prolapse, but not its degree, was not
associated with the Greenes climacteric scale score. Uterus prolapse was positively
associated with age, years since menopause, BMI, waist circumference, low education
and negatively to be a smoker (Table 4).
In multiple logistic regression models, the Greenes climacteric score was forced into the
analysis, but still it did not emerge as an independent variable related to uterus prolapse
(Table 4).

3.6 Climacteric symptoms and rectum prolapse

In simple logistic regression, the presence of rectum prolapse, but not its degree, was not
associated with the Greenes scale score for climacteric symptoms. Rectum prolapse was
related to age, years since menopause, BMI, waist, hysterectomy, status as a housewife,
and low education (Table 5).
In multiple logistic regression models, the Greenes climacteric score was forced into the
analysis, but still it did not emerge as an independent variable related to rectum prolapse
(Table 5).

4. Discussion
4.1 Key results
Women suffering from pelvic floor defect scored higher in the Greenes climacteric scale
score. In multiple logistic regression analysis the Greenes climacteric scale score was an
independent determinant of POP. No association was found with the degree of POP. POP
severity may change over time and its subjective quantification can increase inter-observer
variance, thus reducing the power of our analysis. Among the different POPs a higher
degree of climacteric symptoms was mainly associated with a higher risk of bladder
prolapse. The risk of uterus or rectum prolapse tended to be increased but not significantly
so. Likely, the lack of significance was due an to insufficient statistical power of our
analysis due to the smaller number of subjects suffering from rectum or uterus than
bladder prolapse.
Pregnancy or number of deliveries represented risk factors for POP, as previously
reported [3,4], particularly of bladder prolapse. Probably, this association also explains the
differences observed between women with and without POP, such as a higher prevalence
of being married, of being a housewife, of having received a lower education, of being non-
smoker and of not being on anti-hypertensives. Indeed, in the multiple logistic regression
models that contained pregnancy and number of deliveries, as independent variables, all
these other factors lost their independent association with POP. Vice-versa, and in
accordance with previous studies, POP remained associated with an advancing age,
adiposity [6], as measured by BMI, and with having performed a hysterectomy [1,2]. The
use of coffee was independently associated with a lower prevalence of POP, and in
particular of bladder prolapse. A statistical association does not mean a cause-effect
relation. However, the reported dose- and gender- related effect of caffeine on collagen
turnover [21,22] and the stimulating properties of caffeine on rat collagen [23,24] indicate
that the role played by caffeine on POP should be further explored.

4.2 Interpretation
The association between climacteric symptoms and POP can be the consequence of
common modifications induced by gonadal steroid withdrawal. Women suffering from
climacteric symptoms might be more sensible to steroid deprivation. This may explain the
reason why women having suffered from intense vasomotor or climacteric symptoms are
at higher risk of cardiovascular disease, osteoporosis and urinary incontinence. Indeed a
higher rate of collagen loss [17] is associated with climacteric symptoms, and this may
have an influence on the risk of osteoporosis [18] and pelvic floor support [12,13]. Some
evidence indicates that climacteric symptoms per se, may contribute to the determination
of postmenopausal diseases. Intense climacteric symptoms are associated with an
increased secretion of cortisol [25]. Elevated cortisol may play a role both in inducing
metabolic modifications implicated in the pathogenesis of cardiovascular diseases [26,27],
and in collagen degradation [28,29], with an implication in the pathogenesis of
osteoporosis and POP. This analysis adds to our previous report on the functional
association between climacteric symptoms and urinary incontinence [19], the clinical
evidence that climacteric symptoms are associated with POP, one of the risk factors for
urinary incontinence.

4.3 Limitations
The present investigation has several limitations. Data were retrospectively retrieved by an
electronic database. The Greenes scale offers a subjective evaluation of the bother
induced by climacteric symptoms without any objective evaluation. There was a lack of
information about family history of POP, personal history of constipation, emphysema and
of instrumental delivery, which may have implications for pelvic floor function. The strength
of the study is in the composite evaluation of climacteric symptoms, and the inclusion of a
physicians evaluation of pelvic floor defects. In order to reduce variability among
observers we limited the analysis only to the presence or absence of a defect, without
evaluating its degree. Besides the limitations, overall, the data seems to indicate that
women with POP have a higher degree of climacteric symptoms.

4.4 Generalizability
The study was made on Caucasian women of a single outpatient centre. Women were not
from general population but they were part of a selected group of women asking for a
medical consultation. Thus, prevalence of POP may be different from that obtained in the
general population, and the results cannot be generalized. In addition women were
relatively young, less than 10 years since their menopause, as a mean, and hence findings
may not be applicable to an older cohort of women.

5. Conclusions
A higher degree of climacteric symptoms is present in women with POP, as previously
reported for preclinical cardiovascular disease [30] and osteoporosis [17,18]. Whether the
endocrine and metabolic modifications associated with climacteric symptoms play any
causative role in favouring POP remains to be determined.

Contributors
All the authors significantly contributed to the study design, data collection and analysis,
discussion of the results and manuscript writing.

Conflict of interest
The authors report no conflict of interest.

Funding
This research did not receive any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.

Ethical approval
The local ethics committee and the Institutional Review Board approved the anonymous
extraction of the data.
Provenance and peer review
This article has undergone peer review.

Acknowledgments
We thank Manuela Bellafronte MD, Marianna Cannoletta MD, and Cecilia Romani MD for
patient management.

References

[1] D. Altman, C. Falconer, S. Cnattingius, F. Granath, Pelvic organ prolapse surgery

following hysterectomy on benign indications, Am. J. Obstet. Gynecol.198 (2008)
572.e1-e6.
[2] K. Cooper, A. Lee, P. Chien, E. Raja, V. Timmaraju, S. Bhattacharya, Outcomes
following hysterectomy or endometrial ablation for heavy menstrual bleeding:
retrospective analysis of hospital episode statistics in Scotland. B.J.O.G. 118 (2011)
1171-1179.
[3] S.L. Hendrix, A. Clark, I. Nygaard, A. Aragaki, V. Barnabei, A. Mc-Tiernan, Pelvic
organ prolapse in the Womens Health Initiative: gravity and gravidity, Am. J. Obstet.
Gynecol. 186 (2002) 1160-1166.
[4] G. Tegerstedt, A. Miedel, M. Maehle-Schmidt, O. Nyren, M. Hammarstrom, Obstetric
risk factors for symptomatic prolapse: a population-based approach. Am. J. Obstet.
Gynecol. 194 (2006) 75-81.
[5] P.J. Woodman, S.E. Swift, A.L. OBoyle, M.T. Valley, D.R. Bland, M.A. Kahn, J.I.
Schaffer, Prevalence of severe pelvic organ prolapse in relation to job description and
socioeconomic status: a multicenter cross-sectional study, Int. Urogynecol. J. Pelvic
Floor Dysfunct. 17 (2006) 340-345.
[6] S. Pandey, S. Bhattacharya, Impact of obesity on gynecology. Womens Health (Lond
Engl). 6 (2010) 107-117.
[7] M. Forsman, A. Iliadou, P. Magnusson, C. Falconer, D. Altman, Diabetes and obesity-
related risks for pelvic reconstructive surgery in a cohort of Swedish twins. Diabetes
Care. 31 (2008) 1997-1999.
[8] S.E. Swift, T. Pound, J.K. Dias, Case-control study of etiologic factors in the
development of severe pelvic organ prolapse. Int. Urogynecol. J. Pelvic Floor
Dysfunct. 12 (2001) 187-192.
[9] C. Ghetti, M.J. Lee, S. Oliphant, M. Okun, J.L. Lowder, Sleep quality in women seeking
care for pelvic organ prolapse. Maturitas 80 (2015) 155-161.
[10] F.J. Smith, C.G. Holman, R.E. Moorin, N. Tsoks, Lifetime risk of undergoing surgery
for pelvic organ prolapse. Obstet Gynecol. 116 (2010):1096.
[11] K.M. Luber, S. Boero, J.Y. Choe, The demographics of pelvic floor disorders: current
observations and future projections. Am J Obstet Gynecol.184 (2001):14961501.
[12] S.R. Jackson, N.C. Avery, J.F. Tarlton, S.D. Eckford, P. Abrams, A.J. Bailey,
Changes in metabolism of collagen in genitourinary prolapse. Lancet. 347 (1996)
16581661.
[13] M.Y. Wong, O.H. Harmanli, M. Agar, V. Dandolu, M.H.T. Grody, Collagen content of
non support tissue in pelvic organ prolapse and stress urinary incontinence. Am. J.
Obstet. Gynecol. 189 (2003) 15971600.
[14] B.H. Chen, Y. Wen, H. Li, M.L. Polan, Collagen metabolism and turnover in women
with stress urinary incontinence and pelvic prolapse. Int. Urogynecol. J. Pelvic Floor
Dysfunct. 13 (2002) 8087.
[15] M.E. Carley, J. Schaffer, Urinary incontinence and pelvic organ prolapse in women
with Marfan or Ehlers Danlos syndrome. Am. J. Obstet. Gynecol. 182 (2000) 1021
1023.
[16] P.A. Norton, J.E. Baker, H.C. Sharp, J.C. Warenski, Genitourinary prolapse and joint
hypermobility in women. Obstet. Gynecol. 85 (1995) 225228.
[17] C.J. Crandall, C.-H. Tseng, S.L. Crawford, R.C. Thurston, E.B. Gold, J.M. Johnston,
G.A. Greendale, Association of menopausal vasomotor symptoms with increased
bone turnover during the menopausal transition. J. Bone Min. Res. 26 (2011) 840
849.
[18] C.J. Crandall, A. Aragaki, J.A. Cauley, J.E. Manson, E. LeBlanc, R. Wallace, J.
Wactawski-Wende, A. LaCroix, M.J. OSullivan, M. Vitolins, N.B. Watts, Associations
of menopausal vasomotor symptoms with fracture incidence. J. Clin. Endocrinol.
Metab. 100 (2015) 524534.
[19] A. Cagnacci, F. Palma, M.M. Carbone, G. Grandi, A. Xholli, Association between
urinary incontinence and climacteric symptoms in postmenopausal women.
Menopause. (2016) DOI: 10.1097/GME.0000000000000727
[20] W.F. Baden, T.A. Walker, H.J. Lindsday, The vaginal profile. Tex. Med. J. 64 (1968)
56-58.
[21] D.R. Lee, J. Lee, M. Rota, J. Lee, H.S. Ahn, S.M. Park, D. Shin, Coffee consumption
and risk of fractures: a systematic review and doseresponse meta-analysis. Bone. 63
(2014) 2028.
[22] H. Hallstrm, H. Melhus, A. Glynn, L. Lind, A.-C. Syvnen, K. Michalsson, Coffee
consumption and CYP1A2 genotype in relation to bone mineral density of the proximal
femur in elderly men and women: a cohort study. Nutr. Metab. 7 (2010) 12.
[23] A.M.S. Reis, L.G.R. Ribeiro, N. de Melo Ocarino, A.M. Goes, R. Serakides,
Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with
caffeine throughout pregnancy. B.M.C. Musculoskeletal Disorders. 16 (2015) 10.
[24] J.F. Folwarczna, M. Pytlik, M. Zych, U. Cegiea, I. Kaczmarczyk-Sedlak, B. Nowinska,
L. Sliwinski, Favorable effect of moderate dose caffeine on the skeletal system in
ovariectomized rats. Mol. Nutr. Food Res. 57 (2013) 17721784.
[25] A. Cagnacci, M. Cannoletta, S. Caretto, R. Zanin, A. Xholli, A. Volpe, Increased
cortisol. A possible link between climacteric symptoms and cardiovascular risk factors.
Menopause. 18 (2011) 273-278.
[26] A. Cagnacci, M. Cannoletta, F. Palma, R. Zanin, A. Xholli, A. Volpe A, Menopausal
symptoms and risk factors for cardiovascular disease in postmenopause.
Climacteric. 15 (2012) 157-162.
[27] A. Cagnacci, F. Palma, C. Romani, A. Xholli, M. Bellafronte, C. Di Carlo, Are
climacteric complaints associated with risk factors of cardiovascular disease in peri-
menopausal women? Gynecol. Endocrinol. 31 (2015) 359-362.
[28] C.Sultan, C. Loire, P. Kern, O. Fenard, A. Terraza, Collagen and steroid hormones.
Ann. Biol. Clin. (Paris). 44 (1986) 285-288.
[29] B. Ambrosi, T. Re, E. Passini, S. Peverelli, A. Sartorio, P. Colombo, Clinical and
preclinical aspects of adrenal Cushing syndrome. Minerva Endocrinol. 20 (1995) 39-
47.
[30] R.C. Thurston, L.H. Kuller, D. Edmundowicz, K.A. Matthews, History of hot flushes
and aortic calcification among postmenopausal women. Menopause 17 (2010) 256-
261.
8. Legends to Figures.
Figure 1. Flow chart of subjects selection.
Table 1. Mean (SD) characteristics of the post-menopausal women without and with
pelvic floor defects.
Variable No defect Pelvic Floor P
(N=844) Defect value
(N=538)
Age (yrs.) 55.4 5.8 56.8 5.5 0.001
Weight (Kg) 66.7 12.0 67.9 12.1 0.07
2
BMI (Kg/m ) 25.9 4.5 26.5 4.6 0.01
Waist (cm) 88.1 12.7 89.4 11.7 0.04
Age at Menarche (yrs.) 12.71.6 12.81.5 0.15
Years since menopause 7.2 6.1 8.5 6.4 0.003
Age at menopause (yrs.) 48.1 5.1 48.3 5.8 0.57
Natural menopause (%) 73.0 69.5 0.108
Hysterectomy (%) 13.9 20.1 0.0005
Pregnancy (%) 89.3 93.6 0.014
N of delivery 2.13 1.2 2.32 1.3 0.007
Smoking (%) 29.8 24.1 0.041
Use of caffeine% 85.3 78.4 0.0009
Use of anxiolytics (%) 9.2 11.1 0.248
Use of anti-hypertensives 51.3 22.6 0.0001
Use of MHT (%) 35.7 32.7 0.252
Married (%) 78.1 80.0 0.375
Unmarried (%) 5.2 1.1 0.0001
Divorced (%) 8.3 8.9 0.697
Widow (%) 8.3 9.3 0.520
Low education(%) 39.0 30.9 0.001
Middle education(%) 55.5 57.5 0.449
High education (%) 5.2 5.9 1.000
Housewife (%) 39.8 51.7 0.0001
Worker (%) 16.8 14.5 0.313
Employee (%) 35.0 26.0 0.0004
Retired (%) 6.9 6.7 0.999
Greenes Scale Score 27.813.1 29.613.6 0.02
STAI (Y - 1) score 47.110.1 46.28.8 0.100
Zung (SDS) score 38.19.9 38.09.1 0.890
STAI (Y-1)= State-Trait Anxiety Inventory Y-1 ; ZUNG (SDS) Self Depression Scale
 Table 2. Odds Ratio (95% confidence interval) by simple logistic regression analyses and
multiple logistic regression model (Model 1) for Pelvic Organ Prolapse (POP).

Variable POP P value POP P value

OR (95%CI) OR (95%CI)
Univariate Model 1*
Multivariate
Greenes score 1.01 (1.002;1.018) 0.02 1.012 (1.003;1.022) 0.009
Age (yrs.) 1.044 (1.02;1.06) 0.04 1.04 (1.01;1.071) 0.0001
Years since Menopause 1.03 (1.015;1.05) 0.003 0.99 (0.96;1.07) 0.585
N. of delivery 1.77(1.17;2.67) 0.007 1.15 (1.04;1.27) 0.004
Body Mass Index (kg/m2) 1.03(1.007;1.056) 0.01 1.05 (1.002;1.10) 0.04
Waist (cm) 1.01 (1,001-1.019) 0.035 0.99 (0.973;1.007) 0.252
Hysterectomy (yes) 1.54 (1.16;2.06) 0.003 1.85 (1.30;2.63) 0.0006
Housewife (yes) 1.603 (1.29;1.99) 0.0001 1.30 (0.95;1.78) 0.10
Low Education (yes) 1.37 (1.09;1.71) 0.005 0.94 (0.68;1.31) 0.733
Smoking (yes) 0.75(0.85;0.96) 0.022 0.861 (0.51;1.14) 0.292
Use of Coffee (yes) 0.627 (0.47;0.82) 0.002 0.65 (0.48;0.88) 0.006
* R squared of the model is 0.05. The model was obtained by entering all the variables
significantly related to the dependent variable by simple logistic regression analysis and
that are reported in the column Univariate.
 Table 3. Odds Ratio (95% confidence interval) by simple logistic regression analyses and
logistic regression model (Model 1) for bladder prolapse.

Variable Bladder Prolapse P value Bladder Prolapse P value

OR (95%CI) OR (95%CI)
Univariate Model 1*
Multivariate
Greenes score 1.008 (1.00;1.017) 0.05 1.011 (1.007;1.07) 0.02
Age (yrs.) 1.042 (1.02;1.06) 0.0001 1.04 (1.009;1.07) 0.001
Years since Menopause 1.03 (1.013;1.05) 0.0001 1.00 (0.973;1.021) 0.99
N.of delivery 1.72(1.13;2.62) 0.015 1.10 (1.03;1.21) 0.043
Body Mass Index (kg/m2) 1.028(1.004;1.053) 0.03 0.99 (1.001;1.10) 0.043
Waist (cm) 1.01 (1,00;1.019) 0.04 0.99 (0.97;1.01) 0.423
Hysterectomy (yes) 1.41 (1.06;1.89) 0.02 1.583 (1.11;2.25) 0.011
Housewife (yes) 1.54 (1.24;1.93) 0.0001 1.38 (1.07;1.78) 0.013
Low Education (yes) 1.26 (1.008;1.58) 0.05 1.003 (0.77;1.29) 0.980
Use of Coffee (yes) 0.573 (0.43;0.76) 0.0001 0.601 (0.44;0.81) 0.001
* R squared of the model is 0.04. The model was obtained by entering all the variables
significantly related to the dependent variable by simple logistic regression analysis and
that are reported in the column Univariate.
 Table 4. Odds Ratio (95% confidence interval) by simple logistic regression analyses and
multiple logistic regression model (Model 1) for uterus prolapse.

Variable Uterus Prolapse P value Uterus Prolapse P value

OR (95%CI) OR (95%CI)
Univariate Model 1*
Multivariate
Greenes score 1.001 (0.99;1.014) 0.85 1.003 (0.99;1.016) 0.637
Age (yrs.) 1.046 (1.01;1.07) 0.002 1.04 (1.00;1.08) 0.052
Years since Menopause 1.025 (1.00;1.05) 0.05 0.997 (0.96;1.032) 0.880
Body Mass Index (Kg/m2) 1.036(1.001;1.073) 0.05 1.023 (0.96;1.09) 0.497
Waist (cm) 1.014 (1,00;1.027) 0.05 1.004 (0.97;1.03) 0.756
Low Education (yes) 1.06(1.08;2.11) 0.016 0.825 (0.52;1.30) 0.410
Smoking (yes) 0.488 (0.31;0.76) 0.0014 0.519 (0.32;0.82) 0.006
* R squared of the model is 0.045. The model was obtained by entering all the variables
significantly related to the dependent variable by simple logistic regression analysis and
that are reported in the column Univariate. The Greenes score was forced into the
analysis.
 Table 5. Odds Ratio (95% confidence interval) by simple logistic regression analyses and
multiple logistic regression model (Model 1) for rectum prolapse.

Variable Rectum Prolapse P value Rectum Prolapse P value

OR (95%CI) OR (95%CI)
Univariate Model 1*
Multivariate
Greenes score 1.006 (0.99;1.021) 0.48 1.004 (0.988;1.02) 0.62
Age (yrs.) 1.048 (1.013;1.08) 0.0076 1.044 (0.987;1.10) 0.13
Years since Menopause 1.04 (1.012;1.07) 0.006 0.995 (0.95;1.04) 0.878
Body Mass Index (kg/m2) 1.055(1.01;1.10) 0.02 1.03 (0.95;1.12) 0.486
Waist (cm) 1.02 (1,002;1.036) 0.03 0.98 (0.96;1.03) 0.820
Hysterectomy (yes) 1.84 (1.13;3.0) 0.015 2.31 (1.30;4.13) 0.005
Housewife (yes) 1.64 (1.07;2.52) 0.022 1.70 (0.68;4.23) 0.25
Low Education (yes) 2.08 (1.36;3.18) 0.0007 1.28 (0.80;2.05) 0.296
* R squared of the model is 0.068. The model was obtained by entering all the variables
significantly related to the dependent variable by simple logistic regression analysis and
that are reported in the column Univariate. The Greenes score was forced into the
analysis.
 TOTAL WOMEN
N=2574

Peri-Menopause
N=702

Incomplete Data
N=490

ANALYSES
N=1382

No Prolapse Pelvic Organ

N=844 Prolapse
N=538

Bladder Prolapse Uterus Prolapse Rectum Prolapse

N=503 N=155 N=93