Journal of Womens Health, Issues and Care ISSN: 2325-9795

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Research Article, J Womens Health Issues Care Vol: 6 Issue: 1

"Not Yet Classified” Abnormal Uterine Bleeding in Reproductive-age Women

Barbara Grzechocinska, Aleksandra Zygula, Anna Cyganek* and Miroslaw Wielgos
Department of Obstertics and Gynecology, Warsaw Medical University, Warsaw, Poland
Corresponding author : Dr. Anna Cyganek
Department of Obstertics and Gynecology, Warsaw Medical University, Plac Starynkiewicza 1/3, 02-015 Warsaw, Poland
Tel: + 48 602 103 022
FAX: + 48 22-502 21 57
E-mail:
[email protected]
Received: November 23, 2016 Accepted: January 21, 2017 Published: January 27, 2017
Citation: Grzechocinska B, Zygula A, Cyganek A, Wielgos M (2017) ‘‘Not Yet Classified” Abnormal Uterine Bleeding in Reproductive-age Women. J Womens Health, Issues Care 6:1. doi: 10.4172/2325-9795.1000259

Abstract

Objective: Abnormal uterine bleeding (AUB) is a common problem among women in reproductive age. Not always is their cause easy to establish and in those cases not yet classified abnormal uterine bleeding is diagnosed. The aim of this study was the analysis of the clinical and histopathological results of the endometrium evaluation in women with initially diagnose of not yet classified bleeding who had undergone curretage, because of prolongated bleeding.
Methods: The study was conducted among 78 women aged between 21 and 42 years with prolongated uterine bleeding. Not yet classified uterine bleeding diagnose was based on patient history and physical examination. The percentage of the histopathological findings that confirmed the initial diagnose was evaluated and two groups of women, those with normal and abnormal endometrium in the aspects of clinical data (age, parity, BMI (body mass index) and menstruation bleeding pattern were compared.
Results: The initial diagnose of non classified uterine bleeding was confirmed only in 42.3% of women. The further results of abnormal uterine bleeding were as follows: endometrial polyps in 30.8%, hormonal imbalance in 14%, hyperplasia of the endometrium in 6% and endometritis in 4%. The only statistically significant parameter was frequent occurrence of regular than irregular menstrual cycles in a group of women with non classified uterine bleeding.
Conclusion: Histopathological examination of the endometrium enabled to find the cause of bleeding in more than a half of women with initially recognized non classified uterine bleeding. Besides the higher incidence of regular cycles in the group of women with confirmed not yet classified bleeding, no differences depending on age, parity, BMI, length and amount of menstrual bleeding were observed among women with abnormal uterine bleeding.

Keywords: Abnormal uterine bleeding; Curettage; Endometrial polyps; Endometrial hyperplasia; Endometritis; Hormonal disorders

Keywords

Urinary tract infection; Bacteriuria; Estrogen; Postmenopausal women; Antimicrobial prophylaxis; Probiotic lacto bacilli

Urinary Tract Infection

Urinary tract infection (UTI) is a disorder wherein the urinary tract tissues are invaded by microbes. In the primary as well as secondary care setting, UTI is ranked as the second most common medical symptom for experimental antimicrobial treatment [1,2].
UTI is a worldwide problem. It is extremely widespread and, clinically apparent and is very frequent in women. UTI is more prevalent in women than in men [3]. One in five women experience urinary tract infection during her lifetime [4,5].
UTIs can occur due to a multitude of conditions, despite the urinary tract being usually sterile. These infections may be complicated or uncomplicated, and symptomatic or asymptomatic [4-6]. Urinary tract infections are of two types: 1) Simple that occurs in a functionally and structurally normal urinary tract and, 2) Complex occurs in a urinary tract that is not normal or there are other factors present. The risk factors of complex urinary tract infection are the patient factors (male child <12 years, pregnancy, immune-suppression), structural or functional factors (presence of indwelling catheter, chronic retention, bladder outflow obstruction, polycystic kidneys, upper tract calculi, bladder stones) and bacterial factors (nosocomial/multi-resistant organisms) [7].
The perils of UTI include sex, content of moisture in and around the urethra, genetic predisposition (blood group), utilization of spermicidal agents and diaphragm, which come under the purview of behavioral factors, recent sexual intercourse, personal hygiene practices, frequency of urination or birth control pill use, urologic structural abnormalities, reduced lactobacilli concentration in elderly women, nosocomial acquired infections, diabetes, immunesuppression, stone formation hypertension, and instrumentation like catheterization [4,8-10].
Repeated occurrence of UTI is very common in postmenopausal women. It presents as dysuria, which is associated with irritative voiding symptoms such as urinary frequency, urgency and urge incontinence. A major reason of its occurrence is re-infection by the original bacterial isolate in young and otherwise healthy women with no anatomic or functional abnormalities of the urinary tract. Frequency of sexual intercourse is the most potent predictor of UTI in patients marked with recurrent dysuria. In case of individuals with co-morbid conditions or other predisposing factors, recurrent complicated urinary tract infections represent a risk for ascending infection or urosepsis [11].
In a study conducted by Dason et al. [12], the percentage of UTIs that recurred once and twice was 27% and 3% respectively. The UTIs’ recurring nature was mostly as a result of bacterial re-infection or persistence. Persistent infections are characterized by the noneradication of the same bacteria in the urine even after a fortnight of the sensitivity-adjusted treatment. Re-infections are defined as a different organism making its presence felt, the same organism recurring after a fortnight, or an intervening culture which is sterile in nature.

Micro Organisms and Urinary Tract Infection

UTI is mostly caused due to normal bacterial flora which enters the urinary tract via the urethra from bowel, vagina, or perineum. It must be kept in mind that it is not the presence of micro organism that leads to urinary tract infection symptoms, but the expression of organism virulence factors. This expression allows micro organism adherence to urethra and perineum followed by its movement into the bladder and capture of the urothelium that leads to the symptoms other than the inflammatory response [7].
The uropathogenic bacteria may resist against host defenses, adhere and grow causing infection of the urinary tract. Despite several antibacterial factors like pH, osmolarity, urea concentration, organic acids, urine salt content, urinary inhibitors to bacterial adherence (Tamm-Horsfall protein), low-molecular-weight oligosaccharides, bladder mucopolysaccharide, secretory IgA, and lactoferrin, some bacteria may colonize to cause infection [3,8].
Gram negative bacteria such as- E.coli and Klebsiella spp. have been reported as the most common UTI causing organisms [1-3,13- 15]. E. coli causes around 70-95% upper and lower UTI [16].
E. coli is the cause for 80–85% of community-acquired UTI, while Staphylococcus saprophyticus accounts for 5–10% urinary tract infections [17]. In very rare cases UTI is caused due to viral or fungal infections [13].
Urinary tract infections associated to healthcare involve wide range of pathogens like: E. coli -27%, Klebsiella and Pseudomonas -11%, fungal pathogen, Candida albicans -9%, and Enterococcus -7% [14,15,18]. Staphylococcus aureus causes urinary tract infections that occurs secondary to blood-borne infections [19]. Mycoplasma genitalium and Chlamydia trachomatis only infect the urethra, not the bladder. So infections caused by these are categorized as a urethritis rather than UTI.
The healthy urinary tract is normally able to resist bacterial infections. A reservoir for pathogenic bacteria e.g. E. coli is the large intestine and perinea area. It has been demonstrated in various studies that women susceptible to UTIs have epithelial cells, equipped with additional receptors for drawing uropathogenic bacteria, compared with the controls [5,16,20]. Generally UTI is caused by E. coli, which is increasing at an alarming rate in resistance of E.coli in UTI [1]. According to Behzadi, et al. [3] uropathogenic E. coli was the most commonly found bacteria across seasons during the 2-year study period. With regard to E.coli infections, women are particularly vulnerable. There is a significant association between female gender and urinary tract infection s caused by E.coli (p< 0.05) calculated using χ2 test. Klebsiella pneumoniae is found to be the second most common uropathogenic agent [3]. Gram negative bacteria of E. coli and K. Pneumonia are the bacterial agents which invariably cause UTI, according to various studies [1]. Streptococcus spp, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterococci were the third pathogens to cause urinary tract infection. Presence of coliforms and Enterococcus spp. in high numbers on the perineum may be a reason for the occurrence of UTI [3].
In the absence of any symptom to indicate the presence of asymptomatic bacteriuria (ASB) it can be characterized by the existence of positive urine culture. It is more common in the elderly and may cause urinary tract abnormalities [7]. Epidemiologically around 15%- 20% of women of age 65-70 year and 20% -50% of women of age >80 years old suffer from bacteriuria [21]. More often bacteriuria occurs in functionally impaired women; persistent bacteriuria occurs in nursing home residents, and transient bacteriuria in young, and healthy postmenopausal women. Bacteriuria is asymptomatic in a majority of elderly women and their treatment with antibiotics is not recommended [22].

Urinary Tract Infection and Post-Menopausal Women

The incidence of symptomatic UTI increases dramatically with age and remains high in women throughout their adult life. Urinary tract infections are the most common infection in postmenopausal women. Postmenopausal women may be at increased risk for UTI given their increased incidence of cystocele and high volumes of postvoid residual urine.
It is estimated that the incidence of UTI in postmenopausal women ranges from 4%-15%. The clinical presentation of UTI is different in postmenopausal older women compared with younger women. Symptoms like frequency, dysuria, hematuria, and fever are not reported by postmenopausal women, but they are likely to report flank pain experienced by them. Also, the elements of risk associated with symptomatic UTI in postmenopausal women are poorly described except for in the history of UTI [23].
In postmenopausal women mechanical or physiologic factors that affect bladder emptying are major factors for the cause of UTI. Other aspects of UTI in postmenopausal age group are cystocoele, urinary incontinence and large post void residual volumes, atrophic vaginitis, and a history of urinary tract infections prior to menopause.
Annually, about 150 million UTI cases are reported all over the world. In the United States, UTI accounts for 16 billion dollars in direct health care costs. The prevalence of UTIs increases with age in women. Ten to 15% of women between the ages of 65 and 70 suffer from Bacteriuria [24].
Postmenopausal women are also affected by recurrent UTI which is defined as ≥ 3 UTI per year or ≥ 2 urinary tract infections per half year [25]. Among women, there are three categories of recurrent UTI. They are classified according to age: 1) premenopausal women, 2) postmenopausal women in the age group of 50-70 years, who are neither institutionary tract infectiononalized nor catheterized and 3) elderly institutionalized women, who may be catheterized [21]. In postmenopausal women, lack of estrogen, non-secretor status, a history of urinary tract infection in the premenopausal period, incontinence, presence of a cystocele, and postvoid residual urine appears to be the key aspects liable for recurrence of UTI [16].

Risk Factors for Urinary Tract Infection in Postmenopausal Women

Jackson et al. [26] conducted a prospective cohort study in 1017 postmenopausal women aged 55 to 75 years to describe the incidence of and risk factors associated with UTI after menopause. Insulin treated diabetes is a potential risk factor for incident acute cystitis among postmenopausal women, while a lifetime history of UTI was the strongest predictor. The aging process in postmenopausal women, contributes to occurrence of issues in lower urogenital tissue that also includes UTI [27].
In a case-control study by Raz et al. [21] 149 postmenopausal women with a history of repeated occurrence of UTI were compared with 53 women with no history of UTI. The risk factors in healthy non institutionalized and non catheterized women were observed. Three urological factors viz. incontinence, presence of a cystocele and post voiding residual volume were strongly associated with recurrent infection in the urinary tract. Multivariate analysis has shown that urinary incontinence, non-secretor status, a history of UTI before menopause was strongly related to recurrent UTI in postmenopausal women [27].
Jackson et al. [26] explained incidence as well as risk factors for acute cystitis among diabetic and non-diabetic postmenopausal women in a similar way. The effect of estrogens on these women was also discussed. The incidence of urinary tract infection was 0.07 people per year. Insulin-dependent diabetes mellitus and a lifetime history of urinary tract infection were independent prediction of infection. History of use of vaginal estrogen cream in recent months and history of occurrence of kidney stones were associated with urinary tract infection at a borderline [21]. After multivariable adjustment sexual activity, parity, postcoital urination, postvoid residual bladder, urinary incontinence, vaginal dryness, vaginal bacterial flora, use of cranberry juice and volume were not associated with incidence of acute cystitis [21]. In older institutionalized women, the major concerns associated with UTI were urine catheterization and functional status deterioration. Catheterization increases the possibility of infection in urinary tract [21].
Genitourinary syndrome of menopause (GSM) is a recent term describing various menopausal signs and symptoms associated with physical changes of the vagina, vulva, and lower urinary tract. The GSM not only includes genital symptoms and sexual symptoms, but also urinary symptoms such as dysuria, urgency, and recurrent urinary tract infections. There is a dramatic increase in the incidence of UTI in elderly women. Risk factors due to UTI vary among premenopausal and postmenopausal women. Repeated occurrence of UTI in elderly women leads to anatomic changes like cystocele, increased residual urine and diabetes [28].
History of UTI, sexual activity, treated diabetes, and incontinence are associated with a higher risk of UTI. Prevention of UTI in postmenopausal women is paramount. Use of indwelling urinary catheters is considered to be a major risk factor for UTI and should be limited. It is one of the most important preventive strategies. Careful catheter care reduces infection rates, but the best approach is to avoid catheterization. The therapeutic role of oral estrogen is still uncertain However, topical oestrogen therapy in postmenopausal women lower intravaginal pH, allowing increase in lactobacilli, colonisation that replace the more pathogenic Gram-negative organisms colonizing [29,30].
Bacteriuria
The phenomenon of increased mortality rates among individuals who belong to the senior age bracket is due to Bacteriuria. Studies have shown that reduced longevity is linked with UTI among Greek and American patients [31,32]. Nordestam, et al. [32] examined patients of advanced age, and compared their longevity, keeping in mind bacteriuria [32]. Rise in mortality in relation to bacteriuria was not observed among healthy individuals. With regard to Bacteriuria appearing as a mortality risk factor, it did not seem to be the case. Bacteriuria was associated with increased mortality in patients with concomitant disease, but it is not the cause [21].
Estrogen
Estrogen deficiency is another important factor in postmenopausal women for the bacteriuria development. Women in the postmenopausal stage showed genitourinary symptoms; 50% exhibited genitourinary disorders, and urinary incontinence was seen among 29% [33].
A noteworthy reduction in estrogen secretion by ovary is observed in postmenopause, which is a development that is often linked to vaginal atrophy. Clinical manifestations are marked by vaginal, itching, dryness, dyspareunia, and urinary incontinence [34].
Estrogen stimulates of lactobacillus the proliferation in vaginal epithelium, decreases pH, and keeps at bay Enterobacteriaceae vaginal colonization that is the main pathogen present in the urinary tract [35].
If the estrogen is absent, the volume of the vaginal muscles decreases, that results in the slackness of ligaments that hold the uteric pelvic floor and bladder, leading to the development of internal genitalia prolapse.
Raz and Stamm [36] conducted a randomized, double-blind, placebo-controlled study and reported the dramatic effect of vaginal estriol treatment on women in the postmenopausal stage suffering from recurring UTI. Prevalence of UTI among women administered vaginal estriol decreased to 0.5 episodes per year in comparison with 5.9 episodes per year in women receiving placebo. Also, after 1 month of treatment lactobacillus appeared across a little more than half of the group treated with estrogen and none in the group which received placebo treatment. The vaginal pH was also reduced from 5.5 ± 0.7 prior treatment to 3.6 ± 1.0 post treatment. Similar results were obtained from another study, in which the women receiving estradiol-vaginal ring showed a marked decrease in urogenital symptoms (dyspareunia and urge, vaginal dryness, and stress incontinence) after 9 months of study. Additionally, 45% women administered estradiol were still free of UTI, while only 20% women treated with placebo were still free of UTI [37]. There was another research that displayed contradicting results where estriolcontaining vaginal pessaries appeared to have reduced effectiveness in comparison with oral nitrofurantoin macrocrystals use in relation to effectively countering or preventing bacteriuria among women in the postmenopausal stage. Estriol-containing vaginal pessaries could not also restore vaginal lactobacilli and decrease vaginal pH in women in the postmenopausal stage [35].
Frequency of UTI after treatment with hormonal therapy was assessed by Brown et al. [38] in a randomized, blinded trial of 2,763 postmenopausal women in the age group of 44 and 79 years. Frequency of UTI was higher in the group receiving hormone treatment, even though the difference was statistically insignificant. Jackson et al. [26] did not perceive oral or vagina estrogen as a factor that protects against the recurrence of UTI.
Hence, the efficacy of estrogen in the prevention of urinary tract infection in postmenopausal women with recurrent infections remains questionable. Currently, estrogen is mainly recommended for women in the postmenopausal stage, specifically for those afflicted with multidrug-resistant uropathogens, and among those whose symptoms are linked to atrophic vaginitis [39].
Environmental or life style factors involved or its role in postmenopausal UTI
There are various environmental and life style factors involved in UTI. It is important to determine which factors are contributing to UTI occurrence in post-menopausal women. Lifestyle factors include diet, clothing, hygiene, etc. High sugar diet and processed foods increases the susceptibility of UTI. Food intolerances may cause symptoms that mimic UTI. Uncomfortable clothing, tight fitting, non-cotton underwear increase the risk of UTI. Delay in urination or holding of urine for long time should be avoided as it can contribute to UTI. Stress increases the risk of UTI due to its impact on immune system. Environmental factors include infections by pathogens such as E.coli, Enterococcus faecalis, Enterobacter species, Staphylococcus saprophyticus, Kleibsiella pneumoniae, Proteus mirabilis, and Pseudomonas species [40,41].
Other factors
Urological factors including urinary incontinence, presence of cystocele and post voiding residual volume, along with previous UTI and non-secretor status, are associated with recurrent UTI.
In a case-control study by Foxman et al. [42], the part played by health behavior, and sexual and medical history in healthy women between the ages of 40 to 65, with regard to UTI risk, was investigated. It was noticed that sexual activity was not linked with UTI infection acquisition in the group, while UTI history in the past year, exposure to cold, use of antibiotics in the previous two weeks, and urine loss were positively associated with UTI [21].

Treatment and Management

The vaginal health can be improved using various modalities such as vaginal cream, vaginal pessary, estradiol–vaginal ring, etc. Different forms of estrogen and estrogen combined with antibiotic therapy may be practiced everyday in order to obtain the optimal solution for urinary tract infection. It is important that every physician treats each patient as an individual provides best care to them. Cystoscopy along with external genitalia inspection is recommended in order to remove leukoplakia. The estrogen deficiency may cause bacteriuria. Estrogen helps in the proliferation of lactobacillus in the vaginal epithelium, lowering the pH, and thereby preventing vaginal colonization of Enterobacteriaceae in the vagina, the main pathogens in the urinary tract [43].
In postmenopausal women estrogen therapy promotes resistance to urinary tract infections by altering lower urinary tract mucosal defense mechanisms [44]. In postmenopausal women, topical vaginal estrogen cream reduces recurrence of urinary tract infection. However; the use of vaginal estrogen from pessaries was not found as useful as a low dose of antibiotic (Table 1) [45].
Table 1: Available treatments for UTI in post-menopausal women.
In postmenopausal patients’ first vaginal substiturinary tract infection of estriol must be started. In patients with recurrent urinary tract infection oral or parenteral immunoprophylaxis is an additional option. Specific plant combinations, cranberry products, or probiotics may also be used [25]. Vaginal prophylaxis with estriol has shown its positive effect with no serious gynecological adverse effects. Prevention of recurrent urinary tract infection with cranberries has shown increasing evidence; however, the exact mode of this therapy is still undefined. The other promising modalities include phytotherapeutics, urine acidification, mannose that influence bacterial intestinal and vaginal flora [46].
Kaisan et al. [47] studied prophylactic potential of the use of estriol in the treatment of urinary infections in postmenopausal women suffering from type 2 diabetes mellitus (DM) and asymptomatic bacteriuria. They observed that administration of the local estriol can effectively prevent and treat UTI in postmenopausal females.
Continuous antibiotic prophylaxis or postcoital prophylaxis is most effective in recurrent UTI prevention. First line drugs available for the treatment of UTI are Nitrofurantoin, trimethoprim, and fosfomycin trometamol. Antibiotic prophylaxis reduces uropathogens in the gut or vaginal flora and also reduces bacterial „fitness”. The frequency of recurrent UTI can be reduced by 90%. As per European Association of Urology guidelines, antimicrobial prophylaxis should be considered only after counseling due to possible unfavourable events and the concern of selecting resistant pathogens.25 Continuous long term prophylaxis (LP) with single postcoital doses or low dose antibiotics may lower the rate of recurrent UTi to as low as 5% [46].
Turner et al. [48] demonstrated the sensitivity of dipstick urinalysis in postmenopausal women with irritative bladder symptoms. Palou et al. [49] conducted a multicenter, randomized, prospective and controlled study between two short antibiotic regimes: fosfomycin trometamol and ciprofloxacin in terms of eradication of bacteria in postmenopausal women with uncomplicated acute cystitis who complete the full course of antibiotic treatment. The fosfomycin trometamol and ciprofloxacin have a comparable efficacy profile in postmenopausal women for the treatment of lower tract urinary infection.
Hormonal replacement therapy may minimize physiological changes that occur during menopause, which leads to genitourinary symptoms and UTI. However it is uncertain whether this therapy is suitable for the prevention of recurrent UTI in postmenopausal women [23].
Treatment of UTI in healthy women in the postmenopausal stage is similar to that of women in the premenopausal stage. Controlled studies conducted for short-term therapy among postmenopausal women was not documented properly as it was done in the case of studies conducted among younger women. Raz and Rozenfeld in their research on women in the postmenopausal stage with uncomplicated UTI reported that ofloxacin, 200 mg once daily for 3 days [50] was more effective than a 7 day course of cephalexin, 500 mg four times daily, in both short and long-term follow-up. Similar results were obtained in another study that included 183 postmenopausal women of 65 years of age with acute uncomplicated UTI treated with ciprofloxacin 250 mg twice daily [21]. In another study, the bacterial eradication rate was high and the bacterial resistance rate to ciprofloxacin was low [51].
Antibiotics should not be used for the treatment of elderly women with asymptomatic bacteriuria [21]. The optimal antimicrobial dose and period of treatment in elderly women is similar to those suggested for young postmenopausal women [21].
Vaginal estrogen could be administered for prevention of UTI. Incidence of UTI among women in the premenopausal stage is not reduced by oral estrogen. Cranberry and probiotic lacto bacilli are the alternative methods used to avert the recurrence of UTI in postmenopausal women. Antimicrobial prophylaxis may be conducted among premenopausal women as is usually recommended [21].

Conclusion

Most prevalent bacterial infections present in the society and health care setting is the urinary tract infections. In spite of the increased incidence of bacteriuria among elderly women, the majority of the research on urinary tract infection has been conducted in young women. Bacteriuria is very frequently observed in healthy postmenopausal women as well as institutionalized women. Bacteriuria in women of advanced age is linked with higher rates of mortality; but mostly bacteriuria is asymptomatic and does not cause death. Estrogen deficiency may lead to the development of bacteriuria.
Multidrug-resistant uropathogens are growing at an alarming rate. Normal flora restoration with lactobacilli using probiotics is an alternative strategy. Another option may be competitive compound use, which inhibits bacteria attachment to the uroepithelium. However, either of the two methods have not reported any results which could be termed as conclusive. Proanthocyanidin is present in cranberries which could prevent E. coli uropathogen colonization in the vaginal mucosa, and decrease bacteriuria frequency
There is a relation between bacteriuria and diabetes or sexual intercourse. The role of estrogen (vaginal or oral) along with probiotics and lactobacilli use continues to remain questionable. Further randomized studies on a large scale are required to define as well as ascertain the explicit function of estrogen therapy, lactobacilli, probiotics, and other techniques to reduce the use of antibiotics.

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