Do calcium channel blockers cause urinary incontinence? How about other classes of blood pressure medications?

Do calcium channel blockers cause urinary incontinence? How about other classes of blood pressure medications?

Comment by InpharmD Researcher

Calcium channel blockers have been associated with urinary incontinence by impairing bladder contractility. With almost exclusively observational evidence, studies focused on older patients, especially women. Significant correlations were not observed between CCBs and urinary incontinence in case-control studies; however, ACEIs, ARBs, and alpha blockers were shown to increase the incidence of urinary symptoms.

Background

Calcium channel blockers (CCBs) have been associated with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Particularly, dihydropyridines contribute to detrusor underactivity by inhibiting extracellular calcium influx, thereby impairing bladder contraction and exacerbating urinary storage and voiding symptoms. Significant association between CCB use and LUTS, including nocturia, urinary frequency, urgency, and incomplete bladder emptying, have been observed. Studies report that withdrawal of CCBs often led to resolution of these symptoms. Notably, a 2012 population-based study linked CCB monotherapy to an increased incidence of nocturia, while another cross-sectional study from 2013 demonstrated a strong correlation between CCB use and moderate-to-severe LUTS in hypertensive patients. In-vitro investigations further showed that CCBs suppress bladder contractility, reinforcing their potential to worsen LUTS in individuals with pre-existing BPH. Careful patient selection would occur when prescribing CCBs, along with regular monitoring to mitigate potential worsening of LUTS and its associated negative impact on quality of life. [1], [2], [3]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Do calcium channel blockers cause urinary incontinence? How about other classes of blood pressure medications?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-3 for your response.

Associations of commonly-used medications with urinary incontinence in a community-based sample
Design	Population-based, epidemiologic, case-control study N= 5,503
Objective	To examine the association between use of medications and prevalence of urinary incontinence (UI) in gender-specific analyses of a community-based, representative sample
Study Groups	Women with UI (n= 252) Women without UI (n= 2646) Men with UI (n= 100) Men without UI (n= 2023)
Inclusion Criteria	Men and women aged 30-79 residing in Boston, Massachusetts; baseline data collected 2002-2005
Exclusion Criteria	Subjects with genitourinary cancers, prolapsed bladder, bladder prostate surgery, UI surgery, recommendation for catheter use, Parkinson’s disease, and multiple sclerosis
Methods	Patients in the Boston area were recruited for a survey-based study. Urologic symptoms were ascertained in a two-hour, in-person interview. Incontinence was defined as urine leakage occurring weekly or more often. Medications used in the past month were considered 'current use'. Associations of 20+ medications and prevalent UI were examined using multivariable logistic regression with adjustments for known UI risk factors.
Duration	Baseline data collected 2002-2005
Outcome Measures	Primary: Association between medication use and prevalence of UI Secondary: Gender-specific prevalence of UI among medication users
Baseline Characteristics		Women	Men
	UI prevalence	9.0%	4.6%
	Mean age	Older than non-UI women	Older than non-UI men
	Comorbidities Diabetes Cardiac disease High cholesterol Hypertension Obesity Estrogens	15.6% 11.2% 38.1% 41.7% 52% 11.8%	15.7% 17.6% 39.3% 29.9% 35.9% N/A
Results	Medication	Women with UI (n= 252)	Men with UI (n= 100)
	Antihistamines	28.4%	5.9%
	Angiotensin II receptor blockers (ARBs)	22.9%	22.2%
	Angiotensin-converting enzyme (ACE) inhibitors	14%	7.7%
	Beta blockers	12.4%	6%
	Calcium channel blockers	17.8%	5.9%
	Statins	14.7%	5.8%
	Thiazide	14.6%	6.7%
	Loop diuretics	10.7%	19.1%
	Proton-pump inhibitors	20.5%	3%
	Corticosteroids	17.3%	5%
	Per multivariate adjustment, there were significant associations for antihistamines, beta receptor agonists, ARBs, and estrogens with UI among women (all odds ratios [ORs] >1.7), and a borderline-significant association for anticonvulsants (OR 1.75; 95% CI 1.00 to 3.07). Calcium channel blockers were not associated with UI in women (OR 1.29; 95% CI 0.84 to 1.98). Men only showed an associated with anticonvulsants (OR 2.50; 95% CI 1.24 to 5.03) after multivariate adjustments, although ARBs showed borderline significance (OR 2.21; 95% CI 0.96 to 5.10).
Adverse Events	N/A
Study Author Conclusions	Although a cross-sectional analysis cannot determine causality, this analysis suggests certain medications should be further examined in longitudinal analyses of risk to determine their influence on urologic symptoms.
Critique	The study's cross-sectional design limits the ability to determine causality. The large, community-based sample and gender-specific analysis are strengths, but the exclusion of individuals with past urologic disease limits applicability. The study did not consider dose or duration of medication use, which could impact results. Limited power among men due to lower UI prevalence may have affected the ability to detect associations.

References:

Hall SA, Yang M, Gates MA, Steers WD, Tennstedt SL, McKinlay JB. Associations of commonly used medications with urinary incontinence in a community based sample. J Urol. 2012;188(1):183-189. doi:10.1016/j.juro.2012.02.2575

Antihypertensive Drug Class Use and Differential Risk of Urinary Incontinence in Community-Dwelling Older Women
Design	Longitudinal cohort study N= 959
Objective	To evaluate whether self-reported urinary incontinence (UI) in community-dwelling older women is associated with the use of different classes of antihypertensive agents
Study Groups	All participants (n= 959)
Inclusion Criteria	Women aged 72-81 years without baseline urinary incontinence (UI) from the Health, Aging, and Body Composition Study
Exclusion Criteria	Women missing either medication or UI information and those who reported prevalent UI at baseline
Methods	Participants' use of antihypertensives from 10 drug classes was determined during Year 3 in-person interviews. Self-reported UI was assessed at Year 4 visits.
Duration	1997-98 to 2001-02; 4 years
Outcome Measures	Primary: Association between antihypertensive use and self-reported UI Secondary: Dose-response relationship between antihypertensive use and UI
Baseline Characteristics		All participants (n= 959)
	Age, years	73.3 ± 2.8
	Black	441 (46.0%)
	Comorbidities Hypertension Diabetes mellitus Coronary heart disease Cancer	452 (47.1%) 161 (16.8%) 98 (10.2%) 144 (15.0%)
	Number of prescription drugs	3.6 ± 2.7
	Estrogen use	213 (22.2%)
	Bladder antispasmodic use	7 (0.7%)
	Hysterectomy	452 (47.1%)
Results	Medication Use at Year 3	UI (n= 197)	No UI (n= 762)	Adjusted OR (95% CI)
	Any antihypertensive No hypertensives 1 hypertensive medication 2+ hypertensive medications	117 (59.39%) 80 (40.61%) 38 (19.29%) 79 (40.10%)	464 (60.89%) 298 (39.11%) 202 (26.51%) 262 (34.38%)	0.89 (0.63-1.26) Reference 0.69 (0.44-1.08) 1.05 (0.71-1.55)
	Specific antihypertensive classes Beta blockers Peripheral alpha blockers Loop diuretics Thiazide diuretics Potassium-sparing diuretics Calcium channel blockers Angiotensin-converting enzyme inhibitors Angiotensin receptor blockers	27 (13.71) 11 (5.58) 17 (8.63) 50 (25.38) 24 (12.18) 44 (22.34) 35 (17.77) 12 (6.09)	131 (17.19) 11 (1.44) 61 (8.01) 183 (24.02) 70 (9.19) 196 (25.72) 128 (16.80) 51 (6.69)	0.72 (0.45-1.16) 4.47 (1.79-11.21) 0.96 (0.51-1.81) 0.91 (0.57-1.45) 1.48 (0.79-2.76) 0.76 (0.51-1.14) 1.10 (0.70-1.71) 0.88 (0.44-1.76)
	Peripheral alpha blocker (doxazosin, prazosin, terazosin) use was associated with increased odds of urinary incontinence, especially when combined with loop diuretics.
Adverse Events	N/A
Study Author Conclusions	In community-dwelling older women, peripheral alpha blocker use was associated with urinary incontinence, and the odds nearly doubled when used with loop diuretics.
Critique	The study's strengths include its longitudinal design and thorough data collection on medication use. However, reliance on self-reported urinary incontinence and the inability to restrict analyses to only those with hypertension may limit the findings. Additionally, the study's generalizability may be limited due to the specific demographic and geographic characteristics of the sample.

References:

Peron EP, Zheng Y, Perera S, et al. Antihypertensive drug class use and differential risk of urinary incontinence in community-dwelling older women. J Gerontol A Biol Sci Med Sci. 2012;67(12):1373-1378. doi:10.1093/gerona/gls177

Prevalence of commonly prescribed medications potentially contributing to urinary symptoms in a cohort of older patients seeking care for incontinence
Design	Cross-sectional, multicenter, observational study N= 390
Objective	To determine the prevalence of use of medications potentially contributing to urinary symptoms in a clinical cohort of incontinent patients
Study Groups	All patients (n= 390)
Inclusion Criteria	New patients aged 60 years and older seeking care for incontinence in specialized outpatient geriatric incontinence clinics in Quebec, Canada
Exclusion Criteria	Patients with known dementia (Mini-Mental State Exam score ≤24), missing data or incomplete medication information
Methods	Participants were recruited from one of three urology clinics in Quebec, Canada. Medication use was recorded from each patient's medication profile. Lower urinary tract symptoms and severity of incontinence were measured using standardized questionnaires. Increased daytime urinary frequency was defined as passing urine 8 or more times per day. Participants reporting the need to wake up at night more than once to urinate were defined as having nocturia. Participants who reported a feeling of urgency and having to rush to the toilet before passing urine (occasionally, most of the time, or all of the time) were designated as having urinary urgency.
Duration	Not specified
Outcome Measures	Primary: Prevalence of medications potentially contributing to lower urinary tract symptoms Secondary: Associations between specific medication classes and the type and severity of urinary symptoms
Baseline Characteristics		All patients (n= 390)
	Age, years	72.4 ± 6.4
	Female	355 (91%)
	≥3 comorbidities Hypertension Dyslipidemia Diabetes Cardiovascular disease Musculoskeletal disorders	315 (80.7%) 118 (30.3%) 166 (42.6%) 93 (23.8%) 133 (34.1%) 385 (98.7%)
	Polypharmacy (≥5 medications)	244 (62.6%)
	Type of incontinence Urgency Stress Mixed Urgency with impaired emptying Functional	175 (45%) 56 (14.4%) 98 (25%) 16 (4.1%) 45 (11.5%)
	Severity of incontinence Moderate Severe	194 (49.7%) 169 (43.4%)
Results	Medication class	All patients (n= 390)
	Any medication class	236 (60.5%)
	Calcium channel blockers	85 (21.8%)
	Benzodiazepines	68 (17.4%)
	Other centrally active agents*	65 (16.7%)
	ACE inhibitors	56 (14.4%)
	Oral estrogens	50 (12.8%)
	Oral estrogen + progesterone	12 (3.1%)
	NSAIDS	38 (9.7%)
	GABAergic analgesics	11 (2.8%)
	Loop diuretics	7 (1.8%)
	Thiazolinedione hypoglycemic agents	3 (0.8%)
	Alpha blocking antihypertensives	1 (0.3%)
Adverse Events	Not specified
Study Author Conclusions	The prevalence of use of medications potentially causing urinary symptoms is high among incontinent older adults. More research is needed to determine whether de-prescribing these medications results in improved urinary symptoms.
Critique	The study highlights the high prevalence of medication use potentially contributing to urinary symptoms in older adults, which is a significant finding. However, the cross-sectional design limits the ability to establish causality between medication use and urinary symptoms. The exclusion of patients with dementia and those in nursing homes may underestimate the prevalence of medication use. Additionally, the study's reliance on self-reported data may introduce bias. The descriptive design and exclusion up patients without symptoms did not allow for comparisons between women with and without incontinence.

References:

Kashyap M, Tu le M, Tannenbaum C. Prevalence of commonly prescribed medications potentially contributing to urinary symptoms in a cohort of older patients seeking care for incontinence. BMC Geriatr. 2013;13:57. Published 2013 Jun 10. doi:10.1186/1471-2318-13-57