Urologic Complications in Diabetes

Abstract

Urologic complications such as bladder and sexual dysfunction among men and women with diabetes have received relatively little attention. This is despite emerging evidence that demonstrates that urologic complications increase with age in the general population and are more common in individuals with diabetes compared to those without diabetes. Here we summarize the latest information about the epidemiology of urologic complications in the setting of diabetes and the most recent findings regarding pathophysiology. In addition, we identify knowledge gaps and need for future funding to address these gaps that will reduce the burden of urologic complications in diabetes and optimize quality of life for all individuals affected by it.

INTRODUCTION

Urologic complications among men and women with diabetes have received relatively little attention. Diabetes impacts the function and structure of the lower urinary tract including the bladder and prostate, which can lead to complications such as urinary incontinence and lower urinary tract symptoms (LUTS). Diabetes has also been implicated in significant detriments to male and female sexual function. Although urologic complications increase with age in the general population, urologic complications are even more common in individuals with diabetes compared to those with normal glucose. It has been estimated that risk of urologic complications is increased 25% to threefold in men and about 50% to 200% in women among those with diabetes compared to those with normal glucose.¹ It appears that urologic complications among those with diabetes may be even more common than widely recognized microvascular complications such as retinopathy, neuropathy, or nephropathy.¹

BLADDER DYSFUNCTION IN MEN

Epidemiology

In men, lower urinary tract symptoms (LUTS) are common, age-related complaints that are most often attributed to the histologic enlargement of the prostate also known as benign prostatic hyperplasia (BPH).² BPH is the most common benign neoplasm in American men and primarily manifests clinically as the progressive development of LUTS that are variably comprised of obstructive voiding symptoms: urinary hesitancy, delay in initiating micturition, intermittency, involuntary interruption of voiding, weak urinary stream, straining to void, sensation of incomplete emptying, and terminal dribbling; and bladder storage symptoms: frequency, nocturia, urgency, incontinence, bladder pain or dysuria.³ Similar urinary symptoms, however, may also result in diabetes from bladder dysfunction due to denervation and poor detrusor contractility and/or detrusor overactivity resulting from microvascular complications, which increase hyperactivity of the detrusor.² These LUTS attributed to bladder dysfunction have also been described in the literature as diabetic cystopathy. The failure to differentiate symptoms due to BPH from those due to LUTS/diabetic cystopathy in men with diabetes has contributed to the confusing evidence in the literature.⁴ The mainstay of LUTS measurement in clinical practice and research is the American Urological Association Symptom Index (AUASI) a standardized, validated, 7-item self-reported index of LUTS in men that queries the severity of LUTS over the last 4 weeks on a scale of 0–5. Men are typically classified as having mild, moderate, or severe symptoms based on their summed AUASI scores, with mild symptom scores ranging from 0–7, moderate symptoms from 8–19, and severe symptom scores ≥20.⁵

Several epidemiologic studies that have examined the association between LUTS and self-reported history of diabetes suggest that LUTS may occur more frequently among men with diabetes, with an estimated 25% to threefold increased risk of LUTS in men with diabetes. In a cross-sectional evaluation of two population-based cohorts, men with diabetes were 1.28 times more likely to report moderate to severe LUTS compared to their non-diabetic counterparts after adjustment for age (95%CI=1.03, 1.95).⁶ Similar findings were observed in a study using National Health and Nutrition Examination Survey (NHANES) data which demonstrated that a history of diabetes was positively associated with LUTS (OR=1.67, 95%CI=0.72,3.86). In the same study odds of LUTS increased with increasing glycosylated hemoglobin levels (p-trend=0.005).⁷ In addition, in the Baltimore Longitudinal Study of Aging (BLSA), it was noted that men with elevated fasting glucose (more than 110 ng/mL) were 2.5-fold and diabetic men (fasting glucose levels ≥126 ng/mL and/or history of treatment with insulin or oral hypoglycemic agents) threefold more likely to have LUTS than men without diabetes.⁸ In an ancillary study of urologic complications (UroEDIC) in the Diabetes Control and Complications Trial (DCCT) and its observational follow up, the Epidemiology of Diabetes Intervention and Complications (EDIC) study, randomization to intensive versus conventional treatment for type 1 diabetes (T1D) in the DCCT did not reduce the risk of having moderate to severe LUTS.⁹ These men were relatively younger on average than the population of males that typically experience an increase in the frequency of LUTS and management of diabetes was very good among men assigned to usual care, which might have affected the ability to detect an effect of intensive treatment on LUTS.⁹

Studies that have incorporated more objective measures of BPH as well as LUTS as the outcomes have reported mixed results. In the Massachusetts Male Aging Study, men with diabetes were 1.5 (0.8–2.7) times more likely to be diagnosed with clinical BPH (defined as BPH surgery or LUTS),¹⁰ whereas a decreased risk of BPH and increased risk of LUTS was observed among diabetic men in the California Men’s Health Study.⁹ Finally, in a prospective cohort study examining the influence of diabetes on the progression of BPH markers, diabetic men reported a larger increase in the AUASI score than did non-diabetic men.¹¹ However, there were no differences in change of prostate volume or PSA suggesting, perhaps, that the presence of diabetes may be less directly associated with prostate growth and more closely associated with bladder dysfunction due to the diabetes itself.¹¹ As there is clinical overlap between the presence of BPH and LUTS with LUTS being the primary manifestation of BPH, the conditions can be manifestations of different pathophysiological pathways mediated through hormonal, environmental, genetic, neuropathic and (micro) vascular influences, particularly in the diabetic patient.¹²

Pathophysiology

Diabetes may potentially influence BPH through several mechanisms. First, insulin may influence BPH risk directly by increasing the transcription of genes involved in sex hormone metabolism or indirectly through altered hormone metabolism as a result of obesity.⁷ Accumulating data suggest that inflammation may play an important role in the development and progression of BPH and accompanying LUTS. It has been suggested that inflammatory mediators may contribute to prostatic epithelial and stromal cell growth both directly, through growth induction via cytokines that stimulate production of prostatic growth factors, and indirectly through decreases in prostate cell death via downregulation of prostate cell apoptosis.¹³ Second, while the trophic effect of increased insulin concentrations secondary to insulin resistance might induce an enlarged prostate, high insulin levels may in turn, increase sympathetic nerve activity, which probably contributes to an increase of prostate smooth muscle tone.⁷ Additionally, hyperglycemia itself may play a role by increasing cystolic-free calcium in smooth muscle cells as well as in neural tissue, thus leading to sympathetic nervous system activation. This would coincide with observations of increased LUTS severity in men with elevated post load glucose concentration as well as with a higher percentage of glycosylated hemoglobin compared with men with lower levels.¹⁴ Third, diabetes may precipitate urinary storage symptoms through neurologic mechanisms that are completely independent of any potential links with BPH. This dysfunction typically involves autonomic neuropathy leading to functional parasympathetic and possibly sympathetic denervation of the detrusor.²

Knowledge Gaps

Overall, these data suggest that diabetes increases the risks of BPH and LUTS and support the concept that BPH and LUTS to some extent may be preventable disorders associated with modifiable exposures, challenging researchers and practitioners to revisit traditional paradigms of diagnosis and treatment. Although LUTS are the primary clinical manifestation of BPH, they also represent a syndrome generated by a host of bladder-related etiologies that may or may not coexist with true pathological BPH. Distinguishing BPH-associated LUTS from non-BPH-LUTS may reveal patterns by which diabetes influences BPH and LUTS phenotypes, suggest new methods for diagnosis, and allow more precise tailoring of treatments. Regardless of etiology, the prevention of BPH and LUTS is of substantial import to public health. Current disease trends in the United States suggest that, as the population ages, diabetes, BPH, and LUTS will markedly increase in prevalence and place substantial strains on finite healthcare resources. Currently no data exist to demonstrate the feasibility and/or effectiveness of diabetes treatment for prevention of BPH/LUTS. Future research is therefore needed to identify the magnitude of onset and progression of BPH/LUTS associated with diabetes, elucidate mechanisms by which diabetes exerts its effects on BPH/LUTS, and identify the most effective treatment and prevention strategies for BPH/LUTS associated with diabetes to reduce the psychosocial, medical, and economic costs of these highly prevalent and chronic disorders affecting men.

MALE SEXUAL DYSFUNCTION

Epidemiology

Male sexual dysfunction can involve physiological and psychological problems with erections, ejaculation, libido, and orgasm. Most available data on sexual dysfunction in patients with diabetes pertains to erectile dysfunction (ED). The 2009 International Consultation on Sexual Dysfunctions defines ED as: “a man’s consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual activity.”¹⁵ The mainstay of sexual dysfunction measurement in clinical practice, outcomes research, and clinical trials is the International Index of Erectile Function (IIEF).¹⁶ The IIEF assesses five domains of male sexual function, including desire, erectile function, orgasm, intercourse satisfaction, and overall satisfaction. Validated cut-off scores for the erectile function domain of the original IIEF (IIEF-EF) have been developed to stratify severity of ED.¹⁷ The IIEF is considered the gold standard for patient-based assessment of male sexual function by the International Society for Sexual Medicine.¹⁵

ED is prevalent among men with diabetes.^18–20 Estimates have ranged from 23% to 61.8%.^18–20 In the Health Professionals Follow up Study (HPFS) cohort of 31,027 men, the prevalence of ED among men with diabetes (45.8%) was almost double that of men without diabetes (24.1%). Men with type 1 diabetes more often reported having poor or very poor erections (61.8%) compared to men with type 2 diabetes (46.2%).¹⁹ Of men with type 1 diabetes in the DCCT/EDIC, 46% reported ED.²¹ Researchers using the Massachusetts Male Aging study reported an ED incidence of 51/1000 person-years among men aged 40–69 with diabetes (95%CI 31.7–81.2/1000 person-years),²² approximately double the incidence rate of ED among men aged 40–69 without diabetes, 24.8 cases per 1,000 person-years (95% CI 21.4–28.7/1000 person-years). An analysis of the NHANES based on 2,126 male participants from 2001–2002, showed that men with diabetes had nearly 3 times increased odds (OR [95%CI] 2.91 [1.47–5.73]) of reporting ED compared to men without diabetes.²³ Similarly, in results from the Boston Area Community Health (BACH) survey assessing 2301 men aged 30–79 of which 293 had diabetes, having diabetes increased the odds of reporting ED 2.96 times (95%CI 1.8–4.86).²⁴ In the DCCT/EDIC study of men with type 1 diabetes, utilizing R-R variation and Vasalva ratios to assess cardiovascular autonomic neuropathy (CAN), it was identified that the prevalence of abnormal CAN at EDIC year was higher in participants with ED or LUTS compared to those without (p<0.0001). After adjusting for risk factors in a multivariable analysis, participants with CAN had 2.65 greater odds of ED and LUTS (95% CI=1.47,4.79).²⁵ This association suggests that CAN may serve as a marker or predictor of the development of ED or LUTS in men with T1D.

Data from clinical trials has informed treatment recommendations for men with diabetes and ED.^20,26–28 Two of the studies were ancillary studies from larger randomized trials looking at ED as a secondary outcome,^20,26 while the others were placebo controlled randomized trials investigating the utility of phosphodiesterase inhibitors in men with diabetes.^27,28 In an ancillary study of the Look Action for Health in Diabetes (Look AHEAD) cohort which examined ED as an outcome, overweight men with type 2 diabetes were randomly assigned to either a diabetes support and education group (control) or to an intensive lifestyle intervention group (intervention) that sought to reduce weight by 7% and increase physical activity.²⁶ The weight loss intervention was mildly helpful in maintaining erectile function but did not appear to improve it. From baseline to one year, 8% of men who underwent the intervention reported worsening ED, 70% stayed the same, 22% improved. In contrast in the control group, 20% reported worsening, 57% stayed the same, 23% improved (P= 0.006).²⁶ In an ancillary study of intensive glycemic therapy on erectile function in men with type 1 diabetes from the DCCT, subjects were treated to conventional versus intensive glycemic therapy. Overall, the risk of ED was directly associated with mean HbA1c levels during the trial. The authors contend that the results support early implementation of intensive insulin therapy in young men with type 1 diabetes.²⁰ In addition to weight loss and glycemic control, primary treatment for ED in men with diabetes may include medical management with erectile aids. Both sildenafil and vardenafil, phosphodiesterase inhibitors used to treat erectile dysfunction, have been shown in randomized trials to be efficacious and well-tolerated for the treatment of ED in men with diabetes.^27,28

Pathophysiology

While the pathophysiology for erectile dysfunction is multifactorial involving psychological, vascular, and hormonal processes,^29–31 early experimental evidence suggests an important role for neuropathy.^32,33 This is mediated through impaired nitric oxide (NO) release and NO-synthase function of nonadrenergic, noncholinergic neurons, decreased smooth muscle relaxation of the corpus cavernosum, impaired sensation of the glans, and abnormal motor function of skeletal muscles participating in erections.³² These occur in conjunction with endothelial cell dysfunction, chronic inflammation and accelerated atherosclerosis, contributing to both ED and increased risk for cardiovascular disease. Animal models of type 1 diabetes exhibit a two-stage neuronal degeneration leading to the ED phenotype. Interestingly, pro erectile NO-containing nitrergic neurons degenerate under experimental diabetes, whereas the opposing adrenergic neurons which mediate vasoconstriction are preserved.³⁴ Associated comorbid conditions, such as aging, hypertension, cardiac disease, obesity, and a lack of exercise, also promote ED in men with diabetes.²³ Finally, chronic illness can produce psychological and relationship difficulties that can compound sexual problems.³⁵

Knowledge Gaps

While several studies have supported significant associations between the presence or absence of type 2 diabetes and ED, much of the evidence that has shed light on the specific characteristics of the diabetes experience related to ED has been completed in the setting of type 1 diabetes.^25,36,37 Longitudinal data defining the burden, impact, and risk reduction strategies among people who have or are at risk for type 2 diabetes using rigorous measures of diabetes factors (i.e., glycemia, neuropathy) and standardized assessments of ED are limited. Unfortunately, no clinically available diagnostic tests have been broadly disseminated to identify autonomic neuropathy of the penile or genital organs, although several promising techniques can measure the sympathetic autonomic innervation of the corpus cavernosum of the penis.³⁸ Though previously cardiovascular autonomic neuropathy (CAN) was diagnosed utilizing cumbersome cardiovascular reflex tests, a recent study from the DCCT/EDIC showed that heart rate variability indices from a standard 12-lead electrocardiogram (ECG) may have an acceptable sensitivity/specificity to be utilized as a measure of CAN.³⁹ These new assessments can be used with increasing frequency in research and clinical settings allowing for further investigations into the relationship between autonomic neuropathy and ED. Further, a minority of studies have reported on the impact of diabetes on other types of sexual dysfunction other than ED.⁴⁰ Additional studies assessing the broad spectrum of sexual dysfunction in men with diabetes are needed. Finally, clinical trial evidence on ED treatment and prevention in men with type 1 or type 2 diabetes is scant. Studies are needed to evaluate the effects of standard diabetes treatment, standard ED treatment, and their combination on ED onset and progression in men with diabetes or prediabetes.

BLADDER DYSFUNCTION IN WOMEN

Epidemiology

In women, LUTS, which include urinary incontinence (UI), bladder storage symptoms, sensory symptoms, and voiding and postmicturition symptoms, are increasingly recognized in those with diabetes.^2,41 Bladder storage symptoms in women include increased daytime urinary frequency, nocturia, urgency, and overactive bladder (OAB) syndrome (i.e., urinary urgency, often accompanied by nocturia and frequency, with or without urgency UI leakage, in the absence of urinary tract infection or other obvious pathology).⁴¹ Sensory symptoms occur during bladder filling and include increased, reduced, or absent bladder sensation. Voiding and postmicturition smptoms include hesitancy, slow stream, intermittency, straining to void, feeling of incomplete bladder emptying, postmicturition leakage, dysuria, and urinary retention. Overall, UI has received by far the greatest amount of attention in the literature on the urologic complications of diabetes. UI is defined as involuntary loss of urine. Several types of UI, which are thought to have different etiologies, are generally distinguished in epidemiologic research: stress UI, defined as involuntary loss of urine with physical exertion, sneezing, or coughing; urgency UI, defined as involuntary loss of urine associated with a strong, sudden desire to void; and mixed UI, defined as involuntary loss of urine associated with both physical exertion, sneezing or coughing, and a strong, sudden desire to void.⁴¹

Estimates of the prevalence of weekly UI, a severity level generally considered clinically significant, range from 24% to 49% in women with type 2 diabetes. Urgency UI is particularly increased among women with diabetes compared to women without diabetes.^42–44 Similar to data on prevalent UI, existing data suggest that UI incidence is higher among women with diabetes versus those with normal glucose levels. For example, in the Nurses’ Health Study (NHS), which examined development of weekly UI over 4 years, the incidence was 11% among women with type 2 diabetes and was almost 40% lower at 7% among women without diabetes.⁴⁵ Although even fewer data on diabetes and incident UI type are available, study findings also suggest that women with diabetes develop urgency UI disproportionately. Studies have considered the odds of UI in relation to specific characteristics of type 2 diabetes, such as duration of diabetes, glycemic control, type of treatment, and presence of complications of diabetes. In the Nurses’ Health Study, the odds of prevalent UI were modestly increased in women with type 2 diabetes for more than 10 years versus less than 5 years (adjusted odds ratio 1.17, 95% CI 1.03–1.33).⁴⁶ Several studies have found strong associations between neuropathy or microvascular complications and odds of UI.^45,47,48 Among women with type 2 diabetes in the NHANES, the odds of prevalent weekly UI were over two-fold higher in those with neuropathic pain.⁴⁷

Currently, all information about UI in type 1 diabetes among women in the United States is derived from the DCCT/EDIC ancillary UroEDIC study. Among these study participants, the prevalence of at least monthly UI during the past year was 38%, and the prevalence of weekly UI was 17%.⁴⁹ The odds of prevalent weekly UI were 30% higher in women with type 1 diabetes in UroEDIC compared with women in the NHANES with fasting glucose <100 mg/dL, although the association was not statistically significant.⁵⁰ Similar to type 2 diabetes, the ratio of stress to urgency UI was lower among women with type 1 diabetes (18.5/8.8) than in women with normal glucose levels (13.4/4.5), and the odds of urgency UI were particularly elevated in women with type 1 diabetes.⁵⁰ When adjusted for clinical covariates (including age, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), 10-year long term mean study HbA1c was associated with increased odds of incident urinary incontinence (OR=1.41, 95% CI 1.07–1.89 per % HbA1c increase).⁵¹ Other longitudinal studies to evaluate whether changes in glycemic control predict changes in UI symptoms have not been conducted.

An analysis using data from the Diabetes Prevention Program (DPP) demonstrated the effectiveness of a low-fat diet and moderate-intensity physical activity intervention for decreasing type 2 diabetes incidence as well as UI prevalence among overweight and obese women at risk of developing type 2 diabetes.⁵² Specifically, UI was measured at the end-of-trial visit using a self-administered questionnaire; the prevalence of weekly UI was significantly lower among women in the lifestyle intervention group compared with women in the groups receiving metformin treatment or placebo (38.3% vs. 48.1% vs. 45.7%, respectively, p=0.001; adjusted OR 0.76, 95% CI 0.61–0.95 comparing lifestyle intervention vs. placebo groups).⁵² In analyses by UI type, the lifestyle intervention appeared to be associated with lower prevalence of weekly stress UI (adjusted OR 0.80, 95% CI 0.64–1.01 comparing lifestyle intervention vs. placebo groups), but not urgency UI. Almost all of the treatment effect was attributable to weight loss.⁵² Additionally, in a 6-year follow-up study of 1,778 women from the DPP, the prevalence of weekly UI had increased across the lifestyle intervention, metformin, and placebo groups, but remained lower in the lifestyle intervention group (46.7% vs. 53.1% vs. 49.9%, respectively, p=0.03), indicating that the beneficial effects of the diet and exercise intervention extended years beyond the end of the trial.⁵³ Overall, these data suggest that weight loss and lifestyle intervention may lower risk of type 2 diabetes onset and promote remission of stress UI. Similarly, data from the Look AHEAD trial suggest that weight loss may be an effective strategy to specifically prevent stress UI in overweight and obese women with type 2 diabetes.⁵³ In the DCCT/UroEDIC study, randomization to conventional versus intensive treatment for type 1 diabetes in the DCCT (mean follow-up 6.5 years) was not associated with prevalence of weekly UI assessed 10 years after the end of the trial (odds ratio 1.24, 95% CI 0.79–1.96).⁴⁹ However, management of diabetes was very good among women assigned to usual care and both groups had similar diabetes control during the decade following the trial, which might have affected the ability to detect an early effect of intensive type 1 diabetes treatment on UI.

Pathophysiology

The precise mechanisms underlying urinary dysfunction in diabetes are not yet understood. However, several mechanisms that might explain a link between diabetes and LUTS have been hypothesized, mainly based on data from animal studies. These mechanisms include diabetic neuropathy and microvascular damage, leading to detrusor muscle and urothelium dysfunction.^12,54 For example, over the long-term, microvascular and neuronal damage resulting from diabetes may compromise innervation of the lower urinary tract and detrusor muscle, leading to the hallmark features of diabetic cystopathy: decreased bladder sensation, decreased detrusor muscle function, increased bladder volume, and overdistention.⁵⁵ This is supported by data from the UroEDIC study which identified in multivariable analysis after adjusting for known risk factors, that a Valsalva ratio ≤1.5, a marker for cardiovascular autonomic neuropathy, was associated with increased odds of contemporaneous urinary incontinence.⁵⁶ In addition, several hypotheses have been proposed to explain increased involuntary detrusor muscle contractions in women with diabetes. For example, experimental studies of rat bladder strips suggest diabetes increases responsiveness of bladder tissue to electrical field stimulation, possibly by promoting changes in membrane lipid composition, increasing neurotransmitter release, increasing calcium-channel activity, or enhancing calcium sensitivity.⁵⁴ Finally, the urothelium, a key sensory organ necessary for proper bladder function, has been shown in animal studies to increase in thickness with longer diabetes duration.¹² Urothelial release of prostaglandins appears to increase in proportion to the increase in urothelium thickness, resulting in increased sensitivity of the bladder smooth muscle, a change which theoretically could promote detrusor overactivity and urinary symptoms.^54,55

Knowledge Gaps

Few studies have collected prospective data on LUTS among women with or without diabetes; thus, relatively little is known regarding the incidence and natural history of LUTS. Another limitation of the U.S. literature on diabetes and LUTS in women is the minority of studies that have reported on LUTS other than UI. Notable exceptions are the BACH survey and the Reproductive Risks of Incontinence Study at Kaiser (RRISK), which have provided information on a broad variety of LUTS in U.S. women.^57,58 Additional studies assessing the broad spectrum of LUTS including overactive bladder as well as the collection of standardized assessments of post void residual volumes to estimate burden of urinary retention in women with diabetes are needed. Clinical trial evidence on UI treatment and prevention in women with type 1 or type 2 diabetes is scant. Further research is needed on the efficacy and safety of behavioral, pharmacological, and surgical treatments for UI in women with diabetes.⁵⁹ In addition, studies are needed to evaluate the effects of standard diabetes treatment, standard UI treatment, and their combination on UI prevalence and incidence in women with diabetes or prediabetes.⁵⁹ Finally, as described for bladder dysfunction in men above, studies elucidating mechanistic underpinnings for urinary dysfunction in diabetes are warranted.

FEMALE SEXUAL DYSFUNCTION

Epidemiology

Female sexual dysfunction (FSD) describes a departure from normal sensation and/or function during sexual activity, and includes dyspareunia, obstructed intercourse, vaginal laxity, and decreased sexual desire, arousal, or orgasm.^41,60 Relatively few studies have focused on sexual dysfunction in women with diabetes. Among existing studies, the majority are limited by small sample sizes, not including control women without diabetes, use of unidimensional measures of sexual function, or focusing on clinic or other nongeneralizable populations.⁶¹ FSD is primarily measured using the Female Sexual Function Index (FSFI), a 19 item multi-dimensional, validated widely used self-report measure that assesses sexual function over the past 4 weeks and provides scale scores across six domains, including sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. FSFI scores range from 2–36, with high scores indicating better sexual function.⁶² The FSFI has been shown to have strong psychometric properties, and to discriminate well between women with and without sexual dysfunction.^61,62 The Reproductive Risk of Incontinence Study in Kaiser follow up (RRISK 2) is one of the largest studies to compare sexual functioning in women with versus without diabetes.⁶¹ In this cross-sectional study of 2,270 women aged 40 to 80 years, including 486 women with diabetes, sexual functioning in the past 3 months was assessed using items derived from the FSFI. Among these women, those with insulin-treated diabetes versus no diabetes had a significantly higher prevalence of difficulty with lubrication (34% versus 19%, p=0.003) and low sexual desire (62% vs. 53%, p=0.04).⁶¹ After adjusting for a variety of potential confounding factors, women with insulin-treated diabetes were significantly more likely than women without diabetes to report difficulty with lubrication (OR 2.37, 95% CI 1.35–4.16) and difficulty with orgasm (OR 1.80, 95% CI 1.01–3.20). In addition, there were non-statistically significantly elevated odds of pain or discomfort with intercourse among women with insulin-treated diabetes versus women without diabetes (OR 1.52, 95% CI 0.76–3.06).⁶¹

Very little is known about sexual dysfunction among women with type 1 diabetes. One study of 424 women with type 1 diabetes (mean age 43 years) in UroEDIC found a 35% prevalence of sexual dysfunction, defined based on a cutoff score of 22.75 on an abbreviated version of the Female Sexual Function Index.⁶³ Common complaints among women meeting the criteria for sexual dysfunction were decreased desire (57%), problems with orgasm (51%), inadequate lubrication (47%), problems with sexual arousal (38%), and pain during intercourse (21%).⁶³ Diabetes related factors such as glycemic control were not related to FSD. The only significant predictors of FSD in this study were depression and marital status suggesting that FSD in diabetes may be more psychogenic in nature; the study did not include a comparison group of women without type 1 diabetes.⁶³

Pathophysiology

Several mechanisms, including psychological factors, diabetes complications and medication use, may explain a higher prevalence of sexual dysfunction in women with diabetes than those without diabetes. Depression, a common condition in adults with diabetes,⁶⁴ was found to be significantly associated with decreased arousal (OR 2.47, 95% CI 1.31–4.66) and inadequate lubrication (OR 2.41, 95% CI 1.33–4.37) in women in UroEDIC with type 1 diabetes.⁶³ Moreover, antidepressant use may lead to new onset or worsening of sexual dysfunction.⁶⁵ Complications of diabetes, such as neurovascular dysfunction leading to suboptimal pelvic blood flow and damage to large sensory fibers, may also contribute to higher frequency of decreased sexual arousal in women with diabetes. This is supported by UroEDIC data which demonstrated that lower R-R variation, a marker of cardiovascular autonomic neuropathy, was associated with increased odds of FSD.⁵⁶ In addition, vaginal infections and decreased vaginal lubrication, which are more common in women with than without diabetes, may contribute to sexual pain. Sexual dysfunction may also occur as an adverse effect of medications used for conditions commonly comorbid with diabetes, such as depression, hypertension, and high cholesterol.⁶⁶

Knowledge Gaps

Much remains to be learned regarding the incidence, prevention, and treatment of sexual dysfunction among women with diabetes. Considering that FSD can have a negative effect on quality of life and partner relationships, the sexual difficulties of women with diabetes warrant more attention in both research and practice. Similar to the annual evaluation of diabetes complications, women with diabetes should also be regularly queried about the presence of depressive symptoms, sexual function, and sexual satisfaction. Although nonpharmacologic and pharmacologic treatment options for sexual dysfunction are available,⁶⁶ their effectiveness or appropriateness specifically among women with diabetes is largely unknown.

SUMMARY

Healthcare providers should be alert for urologic complications among their patients with diabetes because these conditions are prevalent and often unrecognized and, thus, undertreated. As people with diabetes live longer and avoid other diabetes-related complications, urological complications may represent a more significant burden and impact on quality of life, as well as present an opportunity for increased symptom mitigation efforts. Future research is needed to identify mechanisms and effective treatment and prevention strategies to decrease the psychosocial, medical, and economic costs of these chronic disorders in men and women with diabetes.