The tone of the urethra and bladder neck is maintained in large part by α-adrenergic activity from the sympathetic nervous system. For this reason, many pharmacologic agents are used with varying degrees of success to treat stress incontinence. These drugs include imipramine (which has a concomitant relaxing effect on the detrusor), ephedrine, pseudoephedrine, phenylpropanolamine, and norepinephrine. Many of these compounds increase vascular tone and may, therefore, lead to problems with hypertension, a condition that afﬂicts many postmenopausal women with stress incontinence. There is an increased risk for hemorrhagic cerebral vascular accident in women taking phenylpropanolamine, and while the risk is very low, it is not possible to predict who is at risk for this complication (57). The use of these agents in the treatment of stress urinary incontinence appears to be more limited than originally thought (58). No drugs are cleared by the FDA to treat stress incontinence.
Based on a biologic rationale, it was thought that estrogen could effectively treat urinary incontinence, given the presence of estrogen receptors in the bladder, urethra, and levator muscles.
In early uncontrolled case series, women using various estrogen preparations experienced less incontinence. However, in several large randomized trials, women assigned to receive estrogen and progesterone did not have less leakage, and were more likely to experience the onset of incontinence or worsening of baseline symptoms (59). In over 23,000 women enrolled in the Women’s Health Initiative double-blind, placebo-controlled, randomized clinical trial, use of menopausal hormone therapy (conjugated estrogen alone in women with a prior hysterectomy, conjugated estrogen and medroxyprogesterone acetate in women with a uterus) increased the incidence of all types of urinary incontinence at 1 year among women who were continent at baseline (60). Among women who reported urinary incontinence at baseline, both frequency and severity of incontinence worsened at 1 year in women taking either hormone preparation compared with those in the placebo group. Thus, conjugated estrogen with or without progestin should not be prescribed for the prevention or relief of urinary incontinence.
The drugs used for treating detrusor overactivity can be grouped into different categories according to their pharmacologic characteristics; these drugs are anticholinergic agents that exert their effects on the bladder by blocking the activity of acetylcholine at muscarinic receptor sites. All of these drugs have side effects, the most common of which are dry mouth resulting from decreased saliva production, increased heart rate because of vagal blockade, feelings of constipation resulting from decreased gastrointestinal motility, and occasionally, blurred vision caused by blockade of the sphincter of the iris and the ciliary muscle of the lens of the eye.
Medications commonly used to treat these conditions are listed in Table 26.9. The introduction of several new drugs for overactive bladder resulted in significant attention being given to urinary incontinence in the media.
The newer drugs have some advantages over oxybutynin, which was available for decades. These advantages include once-(or sometimes twice-) daily dosing, rather than three to four times per day and, to some degree, a less severe side-effect profile. The latter results from changes in the delivery system and to more selectivity of muscarinic receptors (so that, for example, the bladder may be targeted more than the salivary glands). In addition, quaternary amines (such as trospium chloride) are not distributed into the central nervous system because of their large molecular size and hydrophilicity. The primary disadvantage of the newer agents is cost.