Estrogen, Bladder Hurdles & Conservative Therapy

Estrogen plays an important role regulating physiological functions in the female. This hormone promotes breast development during adolescence and influences the menstrual cycle, but as estrogen levels decrease around menopause, there can be adverse consequences for the lower urinary tract. Urgency, overactive bladder, urinary incontinence and urinary tract infections comprise some of these 'bladder hurdles.'  

The purpose of this article is to help the reader understand the physiological mechanism behind estrogen depletion and lower urinary tract symptoms (LUTS) and the efficacy behind medical and conservative treatment options. Physicians and therapists working together as a team can significantly improve bladder hurdles related to menopause. Improved awareness surrounding treatment options, a team approach, and early intervention will increase the probability of the least invasive, most effective and inexpensive treatment options for these bladder conditions. Patients playing an active role in their care with symptom reporting and adhering to home programs will make this conservative team approach possible. 

URGENCY

Urgency is a sudden onset of needing to 'pee.' The sensation of bladder filling should gradually increase over time; the first sensation of bladder filling is usually perceived around 100 mL, consideration of finding a bathroom happens about 250 mL and the typical bladder capacity when full is about 400-600 mL. 

Urgency is often associated with frequency. The typical voiding interval is about 2-4 hours and the average person urinates 7 times per day. When a patient complains of urinary urgency (with or without urinary incontinence), frequency, and nocturia (night time voiding), they may receive a diagnosis of overactive bladder (OAB). It is estimated that 21% of women display signs of OAB and the prevalence rises to about 35% in women over 35 years of age (Chen, et al, 2001).

Urgency associated with decreased estrogen levels have been confirmed in breast cancer patients receiving hormone therapy and animal studies. The incidence of OAB in young breast cancer patients was about 1.4%, but increased 14-fold when given estrogen depriving therapies. Lowering estrogen levels in rats showed to induce urinary frequency and impair voiding ability (Cheng et al, 2017). 

MEDICAL TREATMENT:

Cheng and colleagues propose that local estrogen therapy may be beneficial for reducing OAB symptoms (it is important to note, however, that patients and oncologists may be leery of prescribing topical hormones in estrogen-fed cancer cases). 

Tricyclic anti-depressants, such as Elavil, can reduce urgency; by acting as an anti-cholinergic, these drugs can relax the bladder (encourage filling), decrease the intensity of bladder contractions (calm detrusor instability leading to aberrant signals to void) and delay the desire to void. These drugs are commonly prescribed for people with interstitial cystitis (IC) who have pain associated with bladder filling and thus, higher frequency. Furthermore, the anti-histamine effects of some tricyclic anti-depressants decrease inflammation of the bladder lining and can affect pain neurotransmitters. 

Please see the urge urinary incontinence section for a table comparing the effectiveness and side effects of anti-cholinergic and adrenoceptor agonist medications. 

On the flip side, it is also important that physicians are doing a full medication review to screen for drugs that could cause urgency; these include blood-pressure medications, anti-depressants (yup, some actually cause urgency), diuretics and sleeping pills. These medications may be necessary and life-saving, but considering dose and timing of the medication can make a considerable difference. Sometimes it can be difficult to decipher if urgency is due to medications or modifiable factors like lifestyle and behavior;  a thorough subjective interview can help weed out other variables.

CONSERVATIVE THERAPY:

Pelvic rehabilitation can make a significant difference in reducing urgency symptoms. Here are just a few tools in the therapist's treatment bag: 

• Bladder retraining: Investigating a bladder diary at initial eval will help to identify bladder habits and irritants (both consumable liquid and environmental cues). A bladder diary also serves as an important tool for awareness training. Therapists teach gaiting and distraction techniques to encourage proper feedback loops between the bladder and brain re-establishing cortical control.

• Behavioral modification: Identifying bladder irritants such as caffeine, carbonation, cocktails and citrus can help council our patients to make healthier dietary bladder choices.

• Orthopedic evaluation: Anatomical structures related to the bladder can cause irritation leading to urgency and frequency. A few common explanations are an overactive pelvic floor irritating the pudendal nerve, restricted fascia around the hip flexor muscles, a tender point over anterior pubococcygeus, or spasm of the pyramidalis muscle leading to detrusor instability. An experienced therapist can help assess for this.

• Any array of manual therapy techniques as well as individualized prescriptive exercise will be prescribed to deter any irritating factors and help calm the bladder.

STRESS URINARY INCONTINENCE

Stress urinary incontinence is the involuntary leakage of urine during episodes of increased intra-abdominal pressure like laughing, coughing, sneezing or lifting due to urethral sphincter failure. Approximately 44 - 57% of middle-aged and postmenopausal women (40 to 60 years old), and 75% of elderly women (aged ≥75 years) experience stress urinary incontinence (Quaseem et al, 2014).  We often think about SUI as a purely mechanical problem, but estrogen also plays a role; estrogen receptors exist along the length of the urinary tract, urethra and vagina. A lack of estrogen can also impact structures providing support like the pelvic floor muscles, abdominal ligaments, fascia and connective tissue. Estrogen increases vascular and collagen support to these areas making them more plump, lubricated and supportive (Augoulea et al, 2017). 

MEDICAL TREATMENT

Unlike urgency, the American Collage of Physicians does not recommend pharmaceuticals for stress urinary incontinence (SUI). Hormone therapy is a different story, however HOW they are delivered is important to consider. The evidence does not support topical estrogen (creams), estradiol implants were no better than placebo, and transdermal patches actually worsened SUI. Vaginal estrogen improved SUI the most (Qaseem et al, 2014). Furthermore, the use of vaginal estrogen improved with pelvic floor muscle training. 

CONSERVATIVE THERAPY

The American College of Physicians strongly recommends pelvic floor rehab as the best preliminary form of treatment for SUI. High-quality evidence supports pelvic floor muscle retraining. Internal EMG biofeedback is also a helpful adjunct for people with decreased pelvic floor awareness. Vaginal cones and trendy 'jade eggs' are gaining popularity, but currently there is insufficient evidence to support these devices. 

URGE URINARY INCONTINENCE

Urge urinary incontinence (UUI) is the involuntary loss of urine associated with sudden onset of bladder urgency.  How is estrogen involved? Estrogen receptors are present in the smooth muscle of the bladder and urethra, peripheral nerves, and central nervous system.(Cheng et al, 2017). The presence of estrogen may help protect the lining of the urethra, assist with blood flow, maintain urethral pressure and relax the bladder to allow for filling. 

MEDICAL TREATMENT:

One might think that if estrogen can decrease urgency and maintain continence that oral or systemic estrogen therapy might work, however, research has shown that it actually increases the risk of UUI and that local estrogen may be more effective (Cheng et al, 2017).

Other drugs such as anti-cholinergics and adrenoceptor agonists are more common, however, the side effects often make them unsafe or people may not be able to tolerate them. For example, Oxybutinin is a common antimuscarinic or anti-cholinergic medication whose side effects may include dry mouth and insomnia, but also this year Oxybutinin was shown to be linked to dementia in older patients. Other risks of some anti-cholinergic medications include hallucinations and dizziness. Another useful medication is Mirabegron which is an adrenoreceptor agonist; side effects of it do include gastrointestinal disorders. It is important to note that constipation can actually make urgency and incontinence worse. Other non-surgical options may include Botox or electrical stimulation of nerves such as the tibial nerve.  It is for this reason, however, that the American College of Physicians recommends pharmacologic treatment in women with UUI only if bladder training was unsuccessful, therefor, bladder retraining ought to be the first line of approach for management with urge urinary incontinence.

For a fabulous table summarizing the research about pharmacological interventions for UUI specifically look here. 

CONSERVATIVE THERAPY

I would like to point out that bladder retraining alone has low-grade evidence and comes with weak recommendations, however, pelvic floor muscle training with bladder retraining improved urinary incontinence more than the anti-cholinergic drug Tolterodine alone. In my own practice, bladder retraining made a considerable enough difference to enable physicians to ween patient from medications.  When I teach continuing education courses, I encourage whomever is providing the bladder retraining (urology clinics, incontinence nurses and therapists) to perform a complete bladder diary analysis, give time for a  thorough patient interview, and provide personalized lifestyle modification suggestions. Handouts to improve patient carry-over are highly recommended. 

I believe that an internal assessment of pelvic floor musculature (more than biofeedback alone) is incredibly important in determining potential contributing factors for LUTS symptoms. Occasionally, overactive pelvic floor muscles can irritate the pudendal nerve causing urge sensations; in this case lengthening would be important prior to strengthening. Furthermore, a significant portion of women are not able to perform an appropriate pelvic floor muscle contraction with verbal cuing and may even be working against themselves worsening incontinence symptoms.

CONCLUSIONS

In conclusion, estrogen plays an important role in bladder function. Multiple treatment options are available including hormone therapy, pharmaceuticals, surgery, Botox, E-Stim, bladder retraining, pelvic floor muscle training, manual therapy and exercise. Pelvic rehabilitation is a relatively new, well-researched and growing area of conservative management. With early intervention, a team approach and patient buy-in, we can help improve urgency, frequency and urinary incontinence in our female clients making them feel more empowered in life and at a more affordable price!

- Article written by Susannah Haarmann, PT, WCS, CLT

Susannah is a board-certified Women's Clinical Specialist by the American Physical Therapy Association. She is a private practice owner in Asheville, North Carolina, teaches nationally in pelvic health and internationally in breast oncology rehabilitation. Susannah is an advocate of conservative treatment for pelvic health conditions and writes handouts for practitioners to improve patient literacy.

REFERENCES:

Augoulea, A., Sioutis, D., Rizos, D., Panoulis, C., Triantafyllou, N., Armeni, E., Deligeoroglou, E., Chrelias, C., Creatsa, M., Liapis, A. and Lambrinoudaki, I. (2017), Stress urinary incontinence and endogenous sex steroids in postmenopausal women. Neurourol. Urodynam., 36: 121–125. doi:10.1002/nau.22885

Chen YC, Ng SC, Chen SL, et al. Overactive bladder in Taiwanese women: re-analysis of epidemiological database of community from 1999 to 2001. Neurourol Urodyn 2012; 31:56–59.

Cheng CL, Li JR, Lin CH, Groat W., Positive association of female overactive bladder symptoms and estrogen deprivation: A nationwide population-based cohort study in Taiwan. Medicine (Baltimore) 2016 Jul; 95(28): e4107. Published online 2016 Jul 18. doi: 10.1097/MD.0000000000004107

Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD, Shekelle P, et al. Nonsurgical Management of Urinary Incontinence in Women: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014;161:429–440. doi: 10.7326/M13-2410