Hi, Overacive bladder is a very common occurance in women, and blood tests are standard to rule out things like diabetes before treatment of OAB. Read below about OAB:
Management of Overactive Bladder in Women
The prevalence of overactive bladder (OAB) in women aged 40-44 is estimated to be about 9%. The problem increases in scope along with the aging population, however, affecting more than 30% of women over age 75.1 Individuals with OAB report having to urinate eight or more times in a 24 hour period, to include two to three times at night. They often feel an urgency that makes it difficult to get to a toilet on time and may experience episodes of urinary incontinence.
Overactive bladder usually indicates overactivity of the detrusor muscle of the bladder and is idiopathic in nature, but it can exist secondary to other urinary dysfunctions or cormorbid conditions, particularly in elderly patients. While OAB does not usually progress to more serious urinary or renal complications, it does adversely affect self esteem and quality of life, and is associated with an increased risk of fracture in older patients.1
Bladder Function
The process of urination requires the coordinated effort of the nervous system, the bladder, and sphincter muscles. As the bladder fills, sensory afferent activity from the bladder and urethra signal the spinal cord via the pelvic nerve. The resulting increase in sympathetic tone inhibits bladder parasympathetic motor nerves and triggers bladder and urethra contractions.
The role of neurotransmitters in the process is not yet completely understood, but in animal models, glutamate functions as an excitatory neurotransmitter in pathways controlling the lower urinary tract. Animal models have also shown that serotonergic activity appears to facilitate urine storage by enhancing the sympathetic reflex pathway and inhibiting the parasympathetic nerves that relax sphincter muscles. Dopamine may have a role in both storing and releasing urine—dopamine D1 receptors appear to suppress bladder activity, while D2 receptors prompt voiding.1
M2 and M3 muscarinic receptors are the most common subtype found in the bladder, but the M3 subtype is isolated in the urinary tract smooth muscle and is thought to play a key role in bladder muscle activity. Acetylcholine is the predominant peripheral neurotransmitter associated with bladder contraction, interacting primarily with the M3 muscarinic receptors to facilitate contraction of the detrusor muscle.1
Diagnosis
As OAB is a cluster of symptoms and not a disease, a complete physical is needed to rule out comorbid conditions and any neurological, abdominal, gynecological, or rectal abnormalities that may be contributing factors. The clinician is advised to review all prescription and over-the-counter medications that the patient is using to identify those known to exacerbate urinary incontinence (including diuretics and alpha-blockers) and those—like tricyclic antidepressants— that may contribute to urinary retention. A urine culture may be warranted based on the results of the initial urinalysis; diagnosis depends on first ruling out known pathologies—including infection, bladder calculi, or bladder cancer—that could account for the symptoms.
Some medical conditions that affect the diagnosis of OAB:2
Neurological diseases
stroke, Alzheimer’s disease, Parkinson’s disease
Cardiovascular disease
congestive heart failure, venous insufficiency
Endocrine disorders
diabetes, hypothyroidism
Urological disorders
UTI, interstitial cystitis, bladder calculi, urethral obstruction
A voiding assessment tool, similar to the kind used to assess lower urinary tract symptoms in men with BPH, can facilitate the diagnosis by gauging the number and severity of symptoms and helping to distinguish between OAB and stress urinary incontinence. Depending on symptoms and presentation, it may be helpful to have the patient complete a three-day bladder diary to catalog fluid consumption, voiding pattern, number of incontinence episodes, and presence of possible irritating factors like caffeine intake.
Non-pharmacologic treatment
Behavior therapy—either alone or in combination with drug therapy—is usually indicated in treatment of OAB. Patients with voiding problems will benefit from learning steps to make them more aware of lower urinary tract function. Strategies to consider:
A bladder, or voiding, diary requires the patient to track when, how often and where the urge to urinate occurs. Such a record can help solidify the diagnosis of OAB as well as make the patient more aware of events that trigger symptoms.
Kegel exercises (also recommended to women after childbirth) strengthen the pelvic floor, developing muscles better able to inhibit involuntary detrusor contractions. Done correctly on a daily basis, women can expect to see some improvement in about six weeks.
Fluid management may be effective, particularly for women who consume a large volume of fluid (>2400 cc)—especially caffeinated beverages— throughout the day. (Patients should be cautioned, however, against radically restricting fluid intake in an effort to reduce urine production.)
Timed voiding uses information collected in the voiding diary to prompt patients to anticipate when they will need to void and to do so before urgency sets in.
“Bladder training” is a collective term that combines these strategies. This type of behavioral treatment has been associated with a significant reduction in urinary incontinence in cognitively-intact women with OAB. A 2002 study of 222 women aged 55 to 92 with urge incontinence found that behavioral training was associated with a 69% reduction in the number of incontinence episodes.3 An earlier study produced similar findings, showing bladder training associated with 57% reduction in incontinence episodes in older women.4
Pharmacologic treatment
Anticholinergic drugs—those that interfere with the ability of acetylcholine to facilitate bladder contraction— have the highest level of proven efficacy in the treatment of overactive bladder. These drugs target the M2 and M3 muscarinic receptors in the bladder, but also affect to varying degrees muscarinic receptors in other parts of the body, including the salivary glands. Inhibition of saliva production (and the resulting dry mouth) is the most common side effect of anticholinergic drugs. Constipation, headache, blurred vision, and dizziness are additional side effects associated with the use of this type of medication.
A 2003 review of 32 studies that assessed the effectiveness of anticholinergic medication in the treatment of overactive bladder found a significant benefit of drug therapy vs placebo, although some of the studies measured a high placebo effect.5 Oxybutynin and tolterodine are the drugs most commonly prescribed in the US for overactive bladder.
Oxybutynin manages symptoms by suppressing involuntary bladder contractions and inhibiting smooth muscle spasms. It is metabolized in the liver and intestinal wall and has a half-life of 2-3 hours. The immediate-release formula has been shown to reduce incontinence episodes by about 50%.1 The extended-release formula is absorbed via the colon and produces a steady plasma concentration with less formation of the N-desethyloxybutynin metabolite associated with reduced saliva production. Studies show that extended-release oxybutynin reduces episodes of urge incontinence by about 70%.1
The transdermal patch formula bypasses liver and intestinal metabolism and produces a steady plasma concentration from the first application. A comparison of extended-release and transdermal forms of oxybutynin in 13 healthy subjects found that the transdermal patch had less of a detrimental effect on saliva production.6 The difference is likely due to how the drug is metabolized. In those taking the oral dose, plasma concentration of the N-desethyloxybutynin metabolite was four times higher than that of the original compound, oxybutynin. On the other hand, there was a lower ratio of metabolite to original compound in those using the transdermal patch. The lower proportion of active N-desethyloxybutynin metabolite translates to less impact on saliva production. During safety and efficacy studies, local skin erythema was the most common side effect associated with the use of the patch.7
Tolterodine is also a muscarinic antagonist available in short-acting and extended release formulas. This drug is metabolized in the liver and has a half life of 2-3 hours. It has an efficacy and safety profile similar to that of oxybutynin, but is associated in some trials with a lower incidence of dry mouth. A 12-week trial of extended-release tolterodine vs placebo showed significantly less urgency (p<.001), and those receiving tolterodine were six times more likely than those receiving placebo to report that they could delay urination without incontinence.8 As with oxybutynin, extended-release tolterodine appears to produce fewer side effects when compared with the short-acting formula.
In 2004, three additional antimuscarinic agents—darifenacin, solifenacin, and trospium—received FDA approval for use in treating overactive bladder.
Darifenacin hydrobromide is an extended-release antimuscarinic agent that is selective for M3 receptors. Peak plasma concentration is reached approximately 7 hours after administration. Metabolism is mediated by cytochrome P450 enzyme CYP2D6 and CYP3A4. Use is contraindicated in patients with urinary retention, gastric retention, and uncontrolled narrow angle glaucoma, and should be used with caution by patients with impaired renal and hepatic function.
Solifenacin is selective for the M3 receptor. Peak plasma concentration is reached in 3 to 6 hours after administration. Metabolism occurs primarily in the liver. Solifenacin is a CYP3A4 substrate, so its pharmacokinetics may be altered if used in combination with drugs that are either inducers or inhibitors of CYP3A4. This medication should be used with caution in patients with impaired renal or hepatic function, and use is contraindicated with significant bladder outflow obstruction and narrow angle glaucoma.
Trospium chloride is a quaternary ammonium compound that has nonspecific affinity for muscarinic receptors. It reaches peak plasma concentration 5 to 6 hours after administration; rate of absorption is reduced when taken with a high-fat meal. This medication is not associated with significant interaction with P450 isoenzyme substrates. Use is contraindicated in patients with urinary retention, gastric retention, and uncontrolled narrow angle glaucoma, and should be used with caution by patients with impaired renal and hepatic function.
A meta-analysis by Chapple et al assessed the overall safety and efficacy profiles of currently available antimuscarinic agents. Analysis of the findings of 56 studies found the medications to be generally effective and well tolerated.9 In summary:
All medications significantly improved symptoms when compared with placebo; for some symptoms, the rate of response tended to be dose dependent.
Use of all medications was associated with tolerable adverse event profiles, with the exception of oxybutytin IR (immediate release), which was associated with a 40% greater rate of treatment withdrawal due to adverse events.
The most commonly reported adverse event was dry mouth; there were differences among drugs and doses in the rate and type of reported adverse event. Other adverse events that were reported—but were not universally significant to all the medications—included blurred vision, constipation, dyspepsia, nausea and vomiting.
Combination treatment
Treatment for OAB depends on symptom profile, underlying cause if identified, and patient preference. In most cases of idiopathic OAB, a combination of both behavior therapy techniques and medication optimizes the chance of treatment success. (The increased awareness gained by bladder education may in part account for the high placebo effect seen in trials of medications designed to treat overactive bladder and urinary incontinence.1)
To study the effects of combination therapy on incidence of urge incontinence, Burgio et al. randomized 197 women aged ≥ 55 with a history of urge incontinence to behavior therapy, drug treatment or control. After 8 weeks of treatment, those who were not satisfied with their outcome were given access to both behavior therapy and medication. Eight women crossed over from behavior treatment alone to combination treatment, boosting treatment success (reduction in incontinence episodes) from a mean 55.7% to 88.5% (p=.034). Twenty-seven women crossed from drug treatment alone to combination treatment; they showed a mean improvement from 72.7% reduction in episodes to 84.3% (p=.001).10
What is the role for hormone replacement therapy (HRT)?
Estrogen, either as a topical or oral formula, is sometimes prescribed to counteract urinary urgency in postmenopausal women, but there are sparse data to support the efficacy of this application. There is some evidence that estradiol reduces the intensity and frequency of spontaneous detrusor contractions and may help preserve the sensory threshold of the bladder.11 However, a recent analysis of Nurses’ Health Study data found that women taking supplemental estrogen, either alone or in combination with progestin, were significantly more likely than women who never used HRT to experience incontinence.12 The mechanism for these findings is not clear; the authors speculate that agents that act as estrogen receptor agonists may have a detrimental effect on the muscles that provide pelvic support, which would increase the risk of stress incontinence, or HRT may have some type of adverse effect on bladder control at the neurologic level, raising the risk of urge incontinence.
