Parkinson’s Diseases involves motor system, mental, cognitive and autonomic functions, and is clinically characterized by motor and non motor impairment. Among the latter, the sexual dysfunction are frequent, impairing quality of life and welfare, but are often overlooked for various reasons, including: reluctance of patients in dealing with sexual problems, lack of awareness about the possible relationship between Parkinson’s Diseases and sexual dysfunction, omission of sexual anamnesis.

Moreover, another aspect to take into account is the relationship between Parkinson’s Diseases and sexual hormones. Indeed, hormones affect the dopamine system and may have a neuroprotective function and effects on symptoms of the disease with implications for clinical practice. Sexual dysfunction in Parkinson’s Diseases can result from alterations in motor, mental or cognitive disease-specific functions and involve both the desire and the sexual arousal. Sexual dysfunction is more common in patients with Parkinson’s Diseases compared with controls of the same age and is more common in men than women. It was observed alteration also in excitement because of the interference of motor impairments and other non motor disorders on sexual activity (sialorrhea, seborrhea, bradykinesia, akinesia, etc.). Motor disorders of Parkinson’s Diseases (bradykinesia, rigidity, tremor, immobility in bed, difficulty in movements of the fingers and hands) can alter the physical contact between partners and make sexual intercourse very difficult. This leads the patient to have a more passive role with the sexual partners and to require a patient with a more active role. Some events such as sweating, drooling, disorders of posture, and tremor make patients less attractive, while hypomimia could be interpreted by the partner as a lack of feeling or desire.

Sleep and nocturnal disturbances, such as Rapid eye movement behaviour disorders, can lead to separation of the bed, which further decrease the opportunities for intimate contact. Moreover, the presence of depression, anxiety, apathy, often present, may also lead to reduced function and sexual satisfaction. Finally, several drugs can cause either hyposexuality or hypersexuality. For example, libido seems to rise after dopaminergic therapy: L-Dopa in 8% of patients is used to restore sexual activity and in 1% of patients induces hypersexuality ; the dopamine agonists may induce hypersexuality in 3% of patients, and apomorphine and ropinirole probably have an effect on stimulation of D2 receptors of preoptic area with an increase of oxytocin at the lumbosacral spinal level, which cause erectogenic stimuli. Parkinson’s Diseases can interfere with sexuality through a more specific mechanism. Indeed, the dopaminergic system (mesodiencephalon and spinal cord) is crucial in sexual desire and excitement : dopamine acts on preoptic area, medial accumbens nucleus, and spinal cord. Alterations of the prefrontal cortex (whose function is modulated by dopamine) are frequently associated with apathy syndrome, characterized by lack of motivation that involves sexual desire, leading to deficiency of excitement and difficulty achieving orgasm.

The degeneration of dopaminergic neurons also determines the impairment of these neural systems. Finally, neuropathological data suggest that brain structures involved in sexual behaviour are also early affected in Parkinson’s Diseases. Actually there is an increasing body of evidence supporting the existence of lateralized brain asymmetries in the regulation of neuroendocrine, reproductive and sexual functions. For instance, there is more gonadotropin-releasing hormone in the right ventromedial hypothalamus than in the left in experimental models. The secretion of this hormone is stimulated by dopamine which, conversely, stimulates the secretion of luteinizing hormone. Luteinizing hormone regulates the synthesis of steroids hormones, such as testosterone. This hormone, either directly or through its metabolic products, has inhibitory effects on the secretion and release of Common gonadotropin-releasing hormone and it directly inhibits the secretion and release of gonadotropins. Prolactin, which is inhibited by dopamine, is also a potent inhibitor of Common gonadotropin-releasing hormone secretion and then indirectly inhibits Luteinizing hormone and testosterone secretion. A dopaminergic deficit has been demonstrated in the hypothalamus of Parkinson’s Diseases patients. Thus, Parkinson’s Diseases and dopaminergic medication may influence hypothalamic and pituitary function. However, Parkinson’s Diseases patients do not seem to differ from healthy elderly in gonadotropic hormones and testosterone levels. Unfortunately, the few studies that assessed endocrine functioning in Parkinson’s Diseases have not considered disease asymmetry and thus neglected the relevance of neuroendocrine asymmetry. Nevertheless, alterations in the concentrations of serum testosterone can be considered a possible cause of sexual dysfunction in patients with Parkinson’s Diseases. A reduced availability of testosterone is found in 20-25% of Parkinson’s Diseases and it can cause depression, fatigue, anxiety, lack of energy and decreased libido, which may be resolved with adequate hormone replacement therapy. In Parkinson’s Diseases patients there is a significant inverse correlation between free testosterone levels and apathy, although there are still controversies on the practical relevance of this issue. It was reported, however, that testosterone therapy in patients with reduced serum levels improves motor and non-motor disorders. Indeed, testosterone can improve writing, tremor, stride length, the ability to cut food, for the latter, testosterone may improve depression, anxiety, libido, sexual dysfunction, all disorders that are often resistant to antiparkinsonian therapy.

Cognitive functioning, in spite of its close relationship with age and mood, was also associated with sexual dysfunction. Of note, the right prefrontal cortex is particularly important for the emotional responses of sexuality. Furthermore, changes in androgen levels in older men modulate, at least in part, the cognitive changes of aging. Fatigue is an additional problem in Parkinson’s Diseases and it is frequently related to major depression, sleep disorder, cognitive impairment, comorbidities, and testosterone deficiency.sexual dysfunction in male Parkinson’s Diseases are erectile dysfunction, sexual dissatisfaction, premature ejaculation, anorgasmia. Other issues of sexuality are hypersexuality and paraphilias. Almost all the partners of young patients (<60 years) are sexually dissatisfied. It is estimated that about 60% of patients report sexual dysfunction. It is interesting to note that erectile dysfunction is associated with an increased risk of developing Parkinson’s Diseases; indeed, the presence of erectile dysfunction, anosmia and constipation can help identifying those at risk of developing Parkinson’s Diseases. Erectile dysfunction is certainly one of the most common non motor symptoms in Parkinson’s Diseases, but it also easily diagnosed and is currently well controlled with therapy. Several therapeutic aids are useful for treatment. The first is the use of dopamine agonists. If there is no adequate effectiveness, inhibitors of phosphodiesterase type 5 (tadalafil, vardenafil, sildenafil) are extremely effective. Phosphodiesterase type 5 (PDE 5) enzymes are highly concentrated at the level of visceral smooth muscle where reduce cyclic adenosine monophosphate guanosine (cyclic guanosine monophosphate), the second messenger of nitric oxide, involved in the relaxation of vascular smooth muscle. This pathway is essential for vasodilatation in the corpus cavernosum. Sildenafil, tadalafil and vardenafil can sometimes cause mild and transient side effects: headache, flushing, dyspepsia, rhinitis, abnormal vision, back pain and myalgia. Apomorphine is indicated in patients with orthostatic hypotension in which Parkinson’s DiseasesE inhibitors are contraindicated. Hypersexuality is one of the possible manifestations of the disorder of impulse control, which affects about 5% of Parkinson’s Diseases patients. This dysfunction is more frequent in patients taking dopamine agonists or IMAO-B, in those with a history of mood disorders, anxiety, irritability or aggressiveness, impulsivity, alcohol or drug abuse. When hypersexuality is associated with mild cognitive impairment, the use of acetylcholinesterase inhibitors may be therapeutical. Parkinson’s Diseases-related sexual dysfunction, which has been suggested as a result of central and autonomic dysfunction compounded by defective motor skills, reduces self-esteem so that comorbid psychiatric states like anxiety and depression are rather common in these patients. However, it has received scant attention both in clinical context and in research. Sexual dysfunction in Parkinson’s Diseases is often underrecognized and undertreated. However, some studies have shown that, in both genders, sexual difficulties in getting aroused and decreased desire are highly frequent in Parkinson’s Diseases. In addition, decreased sexual desire in patients with Parkinson’s Diseases correlates with reduced general satisfaction from life. Although erectile dysfunction and premature ejaculation have been pointed out as the main causes of higher levels of sexual dissatisfaction, men with Parkinson’s Diseases may have lack of drive and interest in sex even thought they are still potent. Studies about sexual dysfunction are incomplete and contradictory. Some authors have already considered some variables when assessing sexual dysfunction in Parkinson’s Diseases such as age, stage and disease duration and severity, impact in activities of daily living, and quality of life. However, many variables, such as psychiatric disorders, cognition, fatigue, apathy, sleep disorders, drug therapy, and personal relationships have been neglected. Data regarding sexual dysfunction in Parkinson’s Diseases are scarce; nevertheless, the prevalence of sexual problems in Parkinson’s Diseases seems to be higher than in the general population. Lindau et al. have recently published the results of a community-based survey assessing sexual life in more than 3,000 elderly. The most important factors in the development of sexual dysfunction were aging and female gender. Among women, low desire was the most prevalent sexual problem, while erectile dysfunction was the most prevalent one among men. In Parkinson’s Diseases, decreased interest in sex was associated with aging and female gender, too. However, depression seems to be the most important predictor of loss libido. The relationship between depressive disorders and sexual disorders is well established. The largest study assessing the prevalence of sexual dysfunction in depressed patients showed that 52.8% of untreated patients reported decreased libido. Lipe et al reported a study in which the sexual function of a group of male Parkinson’s disease patients was compared with a group of patients with arthritis. Sexual problems were found to increase in relation to disease severity and depression in both groups; moreover, the two groups were similar in all measured aspects of sexual functioning, with the exception of more arousal dysfunctions in the Parkinson’s Diseases group. Interestingly, a recent study has reported hypersexuality as a complication of levodopa treatment in Parkinson’s Diseases. The general lack of professionals’ interest in sexual function in Parkinson’s disease may relate to two main assumptions, neither of which is warranted. First, Parkinson’s disease is not generally assumed to be associated with physiological dysfunction or neuronal damage that would interfere with the sexual response. Autonomic dysfunction affecting the urogenital system is, however, found in some patients with idiopathic Parkinson’s disease, whereas in patients with Parkinsonism, especially in multiple system atrophy, such autonomic dysfunction may be the main problem. Second, there may be an implicit assumption that patients with Parkinson’s disease, being generally middle-aged or elderly, are not interested or have a diminishing interest in sex. While the frequency of sexual intercourse may diminish with age, this does not mean that sexuality plays no role in the lives of the elderly. This assumption also ignores the significant proportion of cases with early onset Parkinson’s disease who develop the disease in early or mid-adulthood when reduced sexual activity is not the norm. While autonomic nervous system involvement may be a possible cause of primary sexual dysfunction in some patients with Parkinson’s disease, many other factors may lead or contribute to secondary sexual dysfunction, either in the patient, their partner or both. The motor symptoms of Parkinson’s disease may make the act of sexual intercourse difficult. Fatigue may also play a role.

Anti-Parkinsonian medication may have some effect on both libido and the sexual response. The hypersexuality reported in some patients may be a problem, whereas the desire of an increasing in frequency of sexual intercourse is not shared by both partners. Diminishing physical capacity may necessitate the patient taking a more passive role. In addition, because of drug regimes, motor function for many patients is at its best in the morning and worst at night. A shift in the pattern of sexual activity may therefore be desirable to take advantage of the optimum motor status of the patient. Difficulties may develop in couples who do not want to try, or are unwilling to make, such adaptive changes in sexual behaviour, either in its timing, or in the roles played by individual partners. Furthermore, if the patient’s movement disorder is disruptive at night, the couple may take sleeping in separate beds or even in separate rooms, thus decreasing the opportunity for spontaneous sexual contact. In conclusion, the disturbance of sexual function in Parkinson’s Diseases is a complex phenomenon resulting from the interaction of several factors: neurodegeneration areas of central and autonomic nervous system involved in sexual function, mental and physical impairment and disability homeostasis generated by the disease, sexual side effects of drug therapy, altered relationship dynamics with their partner, and comorbidities such as dyslipidemia, hypertension, diabetes, hypogonadism and depression.

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