Despite the higher prevalence in certain racial or ethnic groups, diabetes is everywhere in America. The most rapid increase in diabetes prevalence in the last decade has been among adolescents. Historically, children and adolescents with hyperglycemia have been diagnosed with type 1 diabetes, a result of the body being unable to produce adequate amounts of insulin. However, it is now estimated that as many as 46% of juvenile-onset cases of diabetes are type 2, although cases of both types have increased significantly since 2000 [12]. Furthermore, it has been predicted that children born in this millennium will have a one in three chance of developing diabetes in their lifetime; among high-risk groups, the estimate is as high as one in two [13].

All adults older than 45 years of age should be screened for type 2 diabetes every three years or every three years if they have any risk factors [3]. In addition, individuals of any age who are at risk for or are suspect of having diabetes should be screened. Established risk factors for type 2 diabetes include [16]:

Human sexuality is increasingly recognized as an important aspect of an individual's health and quality of life throughout the lifespan. Sexual activity has been associated with health benefits and longevity [18]. However, older adults engaging in sexual activity has long been a taboo, allowing for the perpetuation of myths regarding sexuality later in life. In fact, a regular sex life can continue throughout life. Data derived from the National Social Life, Health, and Aging Project indicate that more than half of individuals 75 to 85 years of age are sexually active, and physical health is significantly correlated with sexual activity and many aspects of sexual function, regardless of age [18].

In order to understand sexual dysfunction in patients with diabetes, it is important to have a solid comprehension of the normal functioning of the male and female reproductive systems. In theory, men and women experience similar physiologic changes (i.e., vasodilation) in response to sexual arousal. However, men are believed to follow a general linear pattern during sexual activity: excitement, arousal, plateau, orgasm, and resolution. Women, on the other hand, are thought to follow a non-linear model of sexual response including emotional intimacy, sexual stimuli, and emotional and physical satisfaction [19].

Diabetes can impact all areas of sexual function due to the presence of vascular impairments, endothelial dysfunction, neurologic derangements, and hormonal changes [1]. The exact cause of sexual dysfunction can be difficult to elucidate and is most likely a result of a combination of these factors.

In women, estrogen acts as a vasoprotector, which diminishes the effects of atherosclerotic disease on female sexuality in the childbearing years. However, as estrogen levels drop, often during perimenopause and menopause, arterial blood flow to the pelvis may be compromised. This is termed clitoral and vaginal vascular insufficiency syndrome and may cause delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse, diminished vaginal sensation, diminished vaginal orgasm, and diminished clitoral sensation or orgasm [26,27]. There is some evidence that hormone replacement therapy in postmenopausal women increases clitoral blood flow, but this must be weighed against the possible risks associated with the therapy [28].

Individuals with diabetes (particularly type 2) tend to be overweight or obese, and this may be a confounding factor for patients experiencing sexual dysfunction. Vascular, endothelial, neurogenic, endocrine, and psychologic factors may all play a role [32]. Obesity and sexuality is a prevailing area of study for researchers, although many studies have been small in scale and focus primarily on the obese male with erectile dysfunction or obese women awaiting bariatric surgery. One study of 12,364 French men and women between 18 and 69 years of age revealed that obese men and women were at a greater risk of negative sexual outcomes than their nonobese counterparts [33]. The research uncovered the fact that obese women were 30% less likely to report a sexual partner in the previous 12 months than women of a healthy weight. Obese men were 70% less likely to report more than one partner in the same time period and greater than 2.6 times more likely to report erectile dysfunction than their nonobese counterparts [33]. However, the study did not determine the cause of sexual inactivity/dysfunction, and the actual etiology may be physical or psychologic (or both) in nature. When an individual views him/herself as visually unappealing, the emotion may be internalized and result in sexual avoidance, even when the individual is in a committed relationship [32].

The first step in addressing sexual dysfunction in most patients is to make changes in one's lifestyle, particularly for women, for whom pharmacologic and surgical options are limited. This includes obtaining adequate rest, engaging in effective stress management techniques, and regular exercise [38]. Regular physical activity is protective against the development of sexual problems in patients with diabetes [36,39]. Weight loss may also be helpful for some patients. In fact, obesity nearly doubles the risk of erectile dysfunction, and even modest improvement in weight may result in better sexual functioning [36]. Smoking is associated with an increase in the risk of erectile dysfunction, and given the implications of smoking for all patients, cessation should be encouraged.

Sildenafil, marketed in the United States as Viagra, is typically given in tablet form in dosages ranging from 20 mg to 100 mg [45,46]. The usual dose is 50 mg taken one hour (range: 30 minutes to four hours) before sexual activity. Sildenafil acts to increase the effect of nitric oxide by inhibiting phosphodiesterase-5, which is responsible for degradation of cyclic guanosine monophosphate in the corpus cavernosum [45]. When sexual stimulation produces local release of nitric oxide, inhibition of phosphodiesterase-5 by sildenafil causes increased levels of cyclic guanosine monophosphate in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood. The medication is only effective in the presence of sexual stimulation. The effect of sildenafil on sexual arousal in women has been studied but is unclear, and data from clinical trials are limited.

The most common adverse reactions are headache and dyspepsia [46]. Other less common side effects include flushing, insomnia, diarrhea, myalgia, epistaxis, dyspnea, abnormal vision (e.g., color changes, light sensitivity, blurred vision), pyrexia, erythema, paresthesia, nasal congestion, and increased liver enzymes [46]. In rare cases, myocardial infarction, hemorrhage, and transient ischemic attack have been reported [45,46]. If severe reactions or vision or hearing changes develop, the patient should be advised to contact his healthcare provider as soon as possible.

Vardenafil acts by increasing cyclic guanosine monophosphate levels, prolonging smooth muscle relaxation, and promoting blood flow into the corpus cavernosum [45]. Potential adverse reactions include headache, dizziness, flushing, decrease or loss of hearing, tinnitus, rhinitis, sinusitis, dyspepsia, nausea, back pain, and flu-like symptoms [46]. A transient decrease in supine blood pressure may also occur. Possible drug-drug interactions have been noted with alpha-blockers, nitrates, antiarrhythmics (e.g., quinidine, procainamide, amiodarone, sotalol), erythromycin, indinavir, itraconazole, ketoconazole, and ritonavir [45]. As with sildenafil, high-fat meals may reduce peak drug levels.

Tadalafil, which is sold as Cialis in the United States, is available in enteric-coated tablets. The typical dose is 10 mg daily taken at least 30 minutes prior to sexual activity, which is titrated to a greater dose as needed [45,46]. Creatinine clearance must be assessed by the healthcare provider prior to initiating the medication. Unlike the other medications, tadalafil may improve erectile function for up to 36 hours after a single dose [46].

In 2009, flibanserin was submitted for approval by the U.S. Food and Drug Administration (FDA) for the treatment of hypoactive sexual desire disorder in women. This medication acts by blocking serotonin, which has been shown to inhibit sexual function. Post hoc analysis of data from studies of flibanserin's antidepressant properties found that the agent significantly improved self-reported sexual function, although this was not replicated in later direct studies [50,51]. The difference could be partly attributed to the different populations studied (i.e., the general public compared to women with major depressive disorder). In 2010, the FDA's Reproductive Health Drugs Advisory Committee voted that flibanserin was not significantly more effective than placebo and that the potential benefits did not outweigh the risk of adverse events [51]. In 2013, the FDA again denied approval of flibanserin after the pharmaceutical company resubmitted a new drug application with data from 14 additional clinical trials; the same reasons for denial were cited [52]. However, after additional data were provided, in 2015 the FDA approved flibanserin to treat hypoactive sexual desire disorder in premenopausal women [53]. The drug includes a boxed warning due to an increased risk for severe hypotension and syncope when taken along with alcohol. One 100-mg tablet is taken daily at bedtime [46].

When used to treat sexual dysfunction in individuals with diabetes, topical testosterone may decrease glucose levels and alter symptoms of hypoglycemia. Patients should be advised to report this and other possible side effects, including priapism, nausea and vomiting, changes in skin color, ankle edema, or sudden weight gain, to their care provider. In addition, patients' female partners should be monitored for signs of virilization, such as acne or changes in body hair distribution.

Estrogen plays an important role in normal female sexual functioning by maintaining the integrity of the female genital tissue, and low estrogen levels can create an excessively sensitive vaginal environment, whereby touch that was once pleasurable becomes annoying, painful, or irritating [19]. Low levels of serum estrogen can also cause vaginal wall atrophy, thinning of the vaginal mucosa, and an elevated pH level, which leads to changes in the vaginal flora and increases the risk for vaginal and urinary tract infections [32]. The major cause of low estrogen levels is menopause, and most women will experience a change in sexual function during this period [27]. Sexual complaints have been associated with serum estrogen levels less than 50 pg/mL.

For patients who do not respond to the first-line therapies of lifestyle change, pharmacotherapy, and/or testosterone replacement, intracavernosal or intraurethral alprostadil may be effective in improving erectile functioning. This second-line therapy consists of the injection of alprostadil, a prostaglandin, into the corpora cavernosa or the insertion of a suppository containing alprostadil into the urethra. The active ingredient is absorbed in to the penile tissue, facilitating smooth muscle relaxation and aiding in tumescence, an effect that lasts approximately 30 to 60 minutes [25]. The dosage should be individualized according to response to dose, etiology of erectile dysfunction, and agent being used [46]. After the initial appointment establishes the correct dose, the patient may self-administer alprostadil 10 to 15 minutes prior to sexual activity up to three times per week, with at least 24 hours between doses. If the medication is administered intraurethrally, the patient should be advised to urinate prior to insertion.

Vacuum pump devices or constrictors are a viable alternative to medication therapy or medication failure. They are non-invasive, have few side effects, and are generally well tolerated [17]. To use, the vacuum tube is lubricated and placed over the penis, with a constriction band situated over the end. A battery- or hand-operated pump is initiated, and a vacuum is produced. Sitting back or lying down may improve the tightness of the seal. For patients with larger abdomens who are unable to visualize the pelvic area, assistance applying the pump may be necessary. When significant tumescence is produced, the band is moved to the base of the penis, the vacuum is released, and the cylinder is removed. The band can safely remain in place for 30 minutes. These devices do not produce a full erection, and the base will remain flaccid; however, sufficient rigidity is obtained for sexual activity in 80% to 90% of cases [25].

The implantation of an inflatable penile prosthesis is a surgical option for the treatment of impotence in men who have not responded to first- or second-line therapies [17]. The prostheses are implanted by a urologist as a pair and are made primarily of a silicone polymer. The three main types of prostheses are malleable, inflatable, and mechanical [25]. The cost varies significantly based on the type of prosthesis selected.

Sexual intimacy is a taboo subject in many cultures, and men and women may feel uncomfortable discussing it, even with healthcare providers [32]. In addition, some patients are less engaged in discussing health issues, particularly conditions like diabetes, depression, or sexual dysfunction. However, if left untreated, diabetes and sexual dysfunction can have significant negative ramifications on mental and physical health. This is an important consideration, as psychologic stress can exacerbate existing issues, including sexual dysfunction, leading to a cycle of despair and dysfunction. In one study, men and women with diabetes and sexual dysfunction reported more depressive symptoms than those without sexual dysfunction [60]. Emotional factors that may interfere with sexual arousal, causing or worsening sexual dysfunction, include [61]:

In addition to the organic impact of depression on sexual arousal and function, the medications used to treat depression can also cause impaired sexual response [27,65]. Antidepressants associated with the greatest rates of sexual side effects include selective serotonin reuptake inhibitors (e.g., paroxetine, sertraline), serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), tricyclic antidepressants (e.g., amitriptyline, clomipramine), and monoamine oxidase inhibitors (e.g., isocarboxazid) [66]. If possible, antidepressants with fewer sexual side effects, such as bupropion, should be selected for patients with diabetes.

Often, patients experiencing sexual dysfunction may be angry, anxious, or self-loathing. These types of feelings make it difficult for the individual to clearly communicate with his or her significant other. If relationship problems are present, referral to a counselor, therapist, or psychologist for individual and couple's counseling is indicated. The couple may also be provided with techniques to improve their sexual relationship, including [32]: