There are a variety of medical factors that can compromise the pathophysiology of optimal sexual function. One’s inability to ejaculate can be the result of an interruption of the nerve supply to the genitals, which is often observed following traumatic surgical injury to the lumbar sympathetic ganglia, abdominoperitoneal surgery, or a lumber sympatectomy [39]. Other physiological causes of a male’s inability to ejaculate can be related to other surgical procedures including prostatectomy or any type of genitourinary interventions. As ejaculation is controlled by the autonomic nervous system involving the hypogastric (sympathetic) and pudendal (parasympathetic) nerves, there are several neurodegenerative diseases (e.g., multiple sclerosis, diabetic neuropathy, alcoholic neuropathy) that can result in an inability to ejaculate [40]. In addition, there is age-related loss of fast-conducting peripheral sensory nerves as well as decreased steroid secretion associated with aging that are possible physiological factors which may increase delayed ejaculation in men over 50 years of age [40]. Furthermore, neurological disorders that involve the lumbosacral spine or pain and paresthesia stemming from the external genitalia can affect a man’s ability to orgasm (i.e., pelvic pain syndrome).

Premature ejaculation in men is thought to rarely have a physical cause. Rather premature ejaculation can be the result of psychological factors. Nevertheless, neurological disorders, prostatitis (inflammation of the prostate), or urethritis (inflammation of the urethra), are all plausible causes of premature ejaculation. It follows that once a physician has identified the etiology of a patients premature ejaculation, treating the underlying cause can alleviate this specific sexual disorder. Research indicates that there are a variety of cases in which premature (early) ejaculation is reversible. In particular, several medical conditions (e.g., prostatitis, hyperthyroidism), when treated, can lead to ejaculatory latencies at baseline [41].

If there is a medical condition that compromises a man’s ability to have adequate blood pressure to carry blood to the penis, or if there are any “leaks” in the penile venous system caused by a medical condition, then erectile dysfunction can occur. In addition, for a male to sustain an erection, adequate levels of testosterone are required. In relation, the process of clitoral swelling and vaginal lubrication directly relies upon adequate blood flow to the vaginal area. In the event that a medical condition impedes this process, a woman’s ability to become aroused during sexual activity is compromised [42]. Accordingly, physicians must take a thorough medical and sexual history, conduct physical examination of the organ systems, and request laboratory examinations in order to determine whether or not a medical condition is responsible for a sexual disorder pertaining to arousal. At the same time, the physician must also factor in psychological and cultural considerations that may be contributing to low sexual arousal.

There are a variety of surgical and gynecological interventions like hysterectomy, ileostomy and mastectomy that can significantly affect body image and lead to women feeling less feminine and sexual. Furthermore, decreased blood flow to the pelvic region following surgery involving the pelvic floor, abdomen, bladder, and genitals, or medical conditions like diabetes or atherosclerosis, can directly and indirectly impair sexual desire. Relatedly, sexual desire and interest disorders in both genders are related to altered hormonal levels. Specifically, decreased sex drive and absence of sexual fantasies have been observed to be the result of decreased estrogen, with the mechanism for estrogen’s effect on sex drive thought to be indirect, by enhancing mood, vasomotor symptoms, and genital atrophy. Conversely, other studies have demonstrated that progesterone (another female hormone) might negatively impact sexual desire by affecting mood and the availability of androgens (sex hormones). Androgens are presumed to influence sexual function in both genders through their effects on sexual motivation and desire. Low testosterone levels have been correlated with sexual infrequency and reduced libido as well. Hypogonadism is another medical condition identified to influence sexual desire in men [2]. Lastly, excess of prolactin, a hormone in adults that regulates the behavioral aspects of reproduction and infant care, can lead to diminished libido in both males and females [16, 24].

Genito-pelvic pain/penetration disorder can have a variety of pathophysiological causes. Of note, as pelvic floor symptoms are implicated in this disorder, the probability of a comorbid medical disorder that impacts the pelvic floor or reproductive organs is quite high, with interstitial cystitis, constipation, vaginal infection, endometriosis, and irritable bowel disorder being common differentials to consider [2]. In general, pain during intercourse has the potential to significantly affect an individual’s ability to experience pleasure during sex, and in several instances can result in anxiety and depression, which may in turn deter and discourage the person from sexual activity. Pain during sexual intercourse can have several causes. When viral or vaginal fungal infections are present in women, pain is often reported during sexual activity. If there is a fibroid growth in the female reproductive tract, pain may be located in the uterus. The presence of infections of the ovaries or prior surgeries can also leave scar tissue, which can also lead to pain. In addition, there are a significant amount of gynecological medical conditions that have shown to be responsible for pain before, during, or after intercourse. Cystitis, which is inflammation of the bladder, can lead to painful sex, and women should try to urinate immediately after intercourse to avoid urinary tract infections. Vaginitis is a condition that refers to the inflammation of vaginal tissue and its causes may be due to irritants or bacteria. Women who experience this condition secondary to pelvic inflammatory disease usually complain of painful intercourse and treatment of the underlying cause is necessary to eradicate pain. Urethritis is inflammation of the urethra due to urinary tract infection, which can result in painful sex. Like cystitis, treatment (e.g., antibiotics) of underlying cause should alleviate any pain. Genital Herpes can cause herpetic lesions, which may lead to discomfort and pain during intercourse. Genital warts caused by the human papilloma virus can make sexual activity painful depending on the location. In the case of endometriosis, there is abnormal uterine tissue growth in distinct parts of the body (ovaries are the most common site). Endometriosis can lead to abnormal bleeding, inflammation, scarring, pain, fatigue, and infertility. The pain can usually manifest when the uterus contracts during orgasm. Cystocele is a condition that occurs when the bladder bulges or herniates into a woman’s vagina, which leads to painful intercourse. Uterine prolapse occurs when the uterus falls or “slides” from its normal position into the vaginal canal; the resulting shift in position may lead to painful intercourse. Lastly, rectal disease (i.e., cancer) often leads to complications such as pain that occurs due to the close proximity of the rectum (posterior) to the vagina.

In regards to male erectile disorder, endothelial dysfunction continues to gain increasing notoriety as a primary etiological consideration as to the pathogenesis of atherosclerosis [43]. Atherosclerosis has been identified as the most common cause of vasculogenic erectile dysfunction, particularly in older men. As such, it is frequently considered another manifestation of vascular disease. Hence, the risk factors for the development of endothelial dysfunction leading to coronary artery disease, for example, are similar to the risk factor leading to vasculogenic erectile dysfunction. Men who have underlying diseases leading to vascular abnormalities, including diabetes, have dysfunctional neurogenic and endothelium-dependent penile smooth muscle relaxation that result in erectile dysfunction. At the cellular level, impairment of the l-arginine NO pathway at a number of sites is plausible. As the precise mechanisms have not been clearly defined, endothelial damage can either decrease basal release of NO, or may lead to increased breakdown. Furthermore, eNOS activity may be attenuated by accumulation of NOS inhibitors. In addition to endothelial alterations, vascular smooth muscle cells appear to have a blunted response to nitric oxide. Endothelial function is also possibly related to microalbuminuria, which seems to influence endothelium-dependent and independent vasodilation. Men who have type 2 diabetes mellitus have documented impairment in vasodilation in response to both endothelium-dependent and -independent agonists and increased generation of reactive oxygen species that damage endothelial cells either directly or indirectly via effects on lipid peroxidation and by scavenging nitric oxide to produce peroxynitrite (which is a potent oxidant). There are a variety of other mechanisms that can lead to endothelial dysfunction, including decreased release of acetylcholine by cholinergic nerves, peripheral and autonomic neuropathy, and sparse penile noradrenergic nervous innervation [44]. Endothelial dysfunction has been identified as a possible risk factor for sexual dysfunction in woman as well [33].

There is a significantly high prevalence rate of erectile dysfunction in men who have underlying cardiovascular diseases. Men with chronic cardiovascular diseases commonly experience decreased libido and decreased frequency of sexual activity, as well as erectile dysfunction. In addition, there are a number of medical risk factors common to the development of coronary artery disease, heart failure, and erectile dysfunction including diabetes mellitus, hypertension, smoking, and dyslipidemia. Many patients with coronary atherosclerosis (arteries diseased by cholesterol plaque buildup) have great likelihoods of having diseased arteries outside of the heart. In the case that the arteries supplying blood to the penis are sufficiently diseased, adequate achievement or maintenance of an erection is frequently prevented, often termed “penile angina.” Moreover, potential changes in the pudendal arteries in the penis, stenoses of the common iliac, the hypogastric artery , which supplies the inguinal region with blood in men with peripheral atherosclerosis can lead to erectile dysfunction. For women, high blood pressure and heart disease are also systemic conditions that may be responsible for diminishing sexual arousal. Sexual frigidity and dissatisfaction leading to sexual dysfunction, at least for a prolonged period of time, has also been reported in women after myocardial infarction [48, 49]. Endocrine diseases like hypothyroidism, diabetes, and hyperprolactinemia can also affect a woman’s ability to achieve an orgasm [16].

As previously mentioned, in order for a man to achieve an erection, he must have healthy nerves and blood vessels. For males, diabetes often causes hardening and narrowing of the blood vessels that supply the erectile tissue of the penis, which then directly hampers the process of achieving an erection. Diabetes may also damage the nerves that innervate erectile tissue and the penis can also be less firm during an erection.

Males with a medical history significant for prostate cancer, or who have received surgical and medical intervention for the treatment of prostate cancer, can develop erectile dysfunction. In the presence of a cancerous prostate , nerve impulses are impeded as well as blood flow to the penis, which subsequently leads to erectile dysfunction. In fact, erectile difficulties can indeed be one of the first signs of prostate cancer. Other distinct treatments for eradicating prostatic cancer can result in erectile dysfunction. For example, a radical prostatectomy that completely removes the prostate runs the risk of destroying nervous tissue that surrounds the prostate, which aids the male’s ability to achieve an erection. While surgeons strive to preserve the nerve bundles surrounding the prostate, surgical intervention frequently runs the risk of damaging and severing nerve bundles, which can compromise their integrity and function. Radiation therapy may also result in erectile dysfunction by directly damaging arteries that carry blood to the penis or lead to the formation of scar tissue (fibrosis) near the prostate, which then affects blood flow to the penile tissue. Erectile dysfunction that stems from radiation therapy usually does not develop as rapidly as a radical prostatectomy, and is often not apparent for years.

When a patient sustains a spinal cord injury , it can impede or reduce nerve impulses from the brain to the penis and erectile dysfunction may range from partial to complete. In addition, pelvic injuries also result in harm to nerves that innervate the penis and lead to erectile dysfunction. A collection of studies has shed light on the possibility that frequent bicycling may lead to erectile difficulties, as it is hypothesized that the bicycle seat compresses the path of blood to the penis. Multiple sclerosis is another neurological disorder, where cells of the body’s immune system attack the outer insulating the nerve sheath of axons, thereby causing the production of scar tissue in random spots through out the central nervous system. Consequentially, the fibrotic tissue formed can then interfere and affect the propagation of nerve impulses to the penis thereby causing erectile dysfunction. Further concern is warranted in cases of a suspected neurodegenerative process or movement disorder. In particular, there are a wide range of neurodegenerative disorders (e.g., Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis) and movement disorders (e.g., Dementia with Lewy Bodies, multiple systems atrophy, corticobasal degeneration, progressive supranuclear palsy, Huntington’s disease), also known as “Parkinson’s plus” disorders, that may result in compromised autonomic function, pain, sensory-motor disruption, or sleep disturbance [50]. In addition, the presence of sexual dysfunction may be secondary by medication regimens used in the management of neurodegenerative diseases and movement disorders. Table 22-2 provides a general overview of the epidemiology of sexual disorders or dysfunction related to neurological dysfunction and offers treatment recommendations for each etiology.

Peyronie’s disease is characterized by the presence of hardened and calcified tissue (plaque) in the tunica albuginea of the penis. This sheath encompasses the spongy tissue of the penis. Peyronie’s disease has three main symptoms: lumps present in the penis, pain, and curvature of the penis during erection. While not all causes of Peyronie’s disease are known, physicians agree that sudden trauma to the penis or vigorous sexual activity can lead to this condition. Peyronie’s disease itself can lead to psychological or physical erectile dysfunction [51].

Sexual dysfunctions as a whole are a variety of rather heterogeneous disorders that are characterized by a clinically significant disturbance in an individual’s ability to respond sexually or experience sexual pleasure [2]. There are several of cases where a patient may have multiple sexual disorders due to a medical condition, as a variety of medical conditions often lead to sexual dysfunction and responsiveness across the sexual disorders. As has already been discussed, with the introduction of the DSM-5, a sexual dysfunction diagnosis requires the treating clinician to rule out a multitude of problems that could be better explained by a nonsexual psychiatric disorder, by the direct and indirect effects of a specific substance, by a medical condition, or by profound interpersonal and psychosocial stress [2]. Accordingly, when sexual dysfunction is better explained by a medical condition, then an individual cannot receive a psychiatric diagnosis as outlined in DSM-5. With that said, there are a variety of medical conditions that would cause or result in sexual disorders as characterized in the DSM-5.

For example, in the cases of sexual disorders pertaining to desire or sexual interest (e.g., female sexual interest/arousal disorder, male hypoactive sexual desire disorder), there are a variety of chronic illnesses and medical conditions known to affect these disorders [22]. In the event that chronic illnesses deplete a patient’s energy or compel the patient to adapt and make life long adjustments, depression and anxiety can follow, which in turn can affect sexual drive. According to Sadock, sexual arousal disorders surround the focus, intensity, and duration of sexual activity in which individuals engage [16]. In the event that sexual stimulation is inadequate in focus, intensity, or duration, the diagnosis of an arousal disorder in men or women should not be made. In short, two factors that can influence sexual arousal in females are insufficient vaginal lubrication and clitoral swelling, while a man may be unable to attain or maintain an adequate erection, both of which can be heavily influenced by comorbid medical conditions.

The DSM-5 diagnostic criteria for female orgasmic disorder requires the presence of either (a) marked delay in, marked infrequency of, or absence of orgasm, or (b) markedly reduced intensity of orgasmic sensation on almost all or all (~75%–100%) of occasions of sexual activity. In the majority of cases, this condition is the result of sexual inexperience in either one or both partners, often stemming from a lack of adequate clitoral or vaginal stimulation. However, a multitude of psychological factors, chronic physical conditions, or medications can result in symptoms consistent with female orgasmic disorder. For all intensive purposes, the treating physician must determine the cause of this particular sexual disorder. If a medical etiology is identified, treating that condition may restore orgasmic sensation.