2Neurologist, Haseki Training and Research Hospital, Department of Neurology, Istanbul - Turkey
3Assoc. Prof. Dr., Haseki Training and Research Hospital, Department and Movement Disorders Outpatient Clinic, Istanbul - Turkey
Objective: Due to the complex nature of Parkinson’s disease (PD) and distinct sexual physiologies, male and female patients might have different patterns of sexual dysfunction (SD) in PD. The aim of this study was to assess determinants of SD in female and male patients with PD.
Methods: Seventy nine outpatients with idiopathic PD (46 male, 33 female; mean age: 67.51±8.27) were recruited between December 2007 and February 2011. Unified Parkinson’s Disease Rating Scale and Hoehn–Yahr stages, Hamilton depression and anxiety scales, Mini-Mental State Examination and Arizona Sexual Experiences scale were the measures.
Results: Determinants of SD in the whole group were age and anxiety. Age at disease onset and anxiety designated SD in female group, while age and severity of motor symptoms designated SD in male group.
Conclusion: Both in males and females, gonadal steroids decline with advancing age. Dopamine has role in desire, erection, reward-seeking behavior phases of sexuality. Dopamine depletion may cause SD with its dual effects, including erectile dysfunction as well as motor disturbances in PD in male patients. Anxiety effect females more than males due to affected body image and perception of the self.
Neurodegenerative process of Parkinson’s Disease (PD) spreads to affect the mesocortical, mesolimbic, and autonomic central nervous system regions with progression of the disease, and patients frequently develop non-motor disabling symptoms, including sexual dysfunction (SD), which has been only limitedly studied (1). Neurological diseases including PD may deteriorate sexual functions in elderly population (2-8). Sexuality is coordinated by neurologic, vascular and endocrine systems (9), thus neurological disorders can change the processing of sexual stimuli to preclude arousal and to increase desire. Advance in age, severity of the disease and depression were the major determinants in previous studies (5-8).
Sexual physiology differs between genders and advance in age affects genders in different ways. The difference between men and women in ageing and sex is that women experience a quick transition with menopause in which hormonal changes will occur in a short period; and in men hormone changes occur gradually during a longer period. Distinct hormonal physiologies may also influence pathophysiology of PD. In females there is general agreement that gonadal steroids and exogenous estradiol promote striatal adaptation in the partially injured nigrostriatal dopaminergic pathway to protect against striatal dopaminergic neuron loss. In contrast, the body of evidence suggests that in males gonadal factors have negligible or even harmful effects (10-14). These protective effects of gonadal hormones may be the reason of the lower incidence of PD in women (15).
Moreover, male and female patients show different patterns of SD in PD (5,16-19). In females, SD manifests mainly as decreased arousal, difficulty in reaching orgasm and low orgasm satisfaction (5,16); whereas in males predominant signs are erectile dysfunction, premature ejaculation or loss of capacity to ejaculate (18,20). Welsh and colleagues (5) compared 27 female patients with PD with a healthy control group (age and marital status matched) and found that patients were less satisfied with their sexual activities. In a study designed to assess SD in Turkish patients with PD, Çelikel and colleagues (16) found reduced sexual drive and satisfaction with orgasm in women, but no difference in men. On the contrary, some studies reported a higher frequency of sexual problems in male patients (19,21). For instance, according to Brown and his colleagues (19), prevalence of SD in male patients was 65%, while 36% of female patients had SD.
Due to the complex nature of the disease, there are still ambiguities regarding SD in PD. It is aimed to investigate determinants of SD in male and female patients with PD in this study.
Seventy-nine outpatients (46 male, 33 female; mean age: 67.51±8.27, range: 46-85) with idiopathic PD were enrolled between December 2007 and February 2011. The local ethical committee approved the study and each participant has given a written informed consent. After initially obtaining socio-demographic data, Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn–Yahr (H&Y) stage during the on phase (22,23) were the tools to assess clinical characteristics of the disease. Hamilton Depression Scale (HAM-D) (24), Hamilton Anxiety Scale (HAM-A) (25) and standard Mini-Mental State Examination (MMSE) (26,27) were also used to assess depression, anxiety and cognitive impairments which may affect sexual functions. Due to insufficient motor ability to perform sexual activity and to obtain homogeneous groups, patients with H&Y stage 4 and 5 were excluded. Patients scoring less than 23 points on the MMSE were also excluded. Patients reporting urological or gynecological problems and patients ever used exogenous estrogen replacement therapy were excluded too.
Sexual functions were assessed with Turkish version of the Arizona Sexual Experiences Scale (ASEX), which has two parallel forms for both genders (28,29). ASEX is a 5-item, Likert-type self rating scale. Each item could be rated from 1 to 6 and total scores range between 5-30. Higher scores mean worse sexual functions. Two parallel forms differ in the third item: penile erection/vaginal lubrication (drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm and satisfaction with orgasm).
For statistical analysis, SPSS for windows (version 13.0) was used. p<0.05 was accepted as significant. For categorical variables t test for continuous and Chi-square test for categorical variables were applied. Correlations between clinical and demographic characteristics and ASEX scores were evaluated with Pearson’s correlation test. Three sets of linear regression analyses were run to obtain determinants of SD measured by ASEX total scores in the whole group, in female and male groups.
Sociodemographic and clinical characteristics are presented in Table 1 and 2. Age (p=0.259), education (p=0.342, χ2=2.15), duration of the disease (p=0.319) and age at disease onset (p=0.099) did not differ between groups. Great majority of the participants had sexually active spouse, only four participants were single.
Sixty five patients were receiving levodopa medication and groups did not differ in terms of levodopa use rates (m/f: 36/29, p=0.27, χ2=1.21). Mean daily dose of levodopa was 416.7 milligrams (sd: ±335.4). 49 patients were receiving agonists and no difference was detected between groups (m/f: 30/19; p=0.49, χ2=0.48). Six male patients were receiving neuroleptic medications. 14 patients had benign prostate hypertrophy, 3 had malignancies, 1 had osteoporosis and 1 had hyperthyroidism. All of the female participants were postmenopausal and all disease onsets were after menopause. Nine patients reported family history of PD and 6 reported family history of essential tremor. Patients with prostate hypertrophy (n=14) were compared to patients without prostate hypertrophy (n=32) in terms of ASEX scores. No difference was detected between groups (for the total ASEX score, p=0.82, z=-0.23).
Arizona sexual experiences scale total score correlated with age (r=0.31, p=0.005), age at disease onset (r=0.25, p=0.027) and HAM-A score (r=0.36, p<0.001) in the whole group (Table 3). HAM-A score significantly correlated with HAM-D in the whole group (r=0.62, p<0.01). Cognition subscore UPDRS significantly correlated to HAM-A (r=0.36, p<0.01) and HAM-D (r=0.6, p<0.01) scores. Treatment complication subscore of UPDRS correlated with HAM-D score (r=0.28, p=0.014). No other significant correlation was detected between HAM-A and HAM-D scores to any subscore of UPDRS.
In the female group, ASEX total score correlated with age (r=0.41, p=0.018), age at disease onset (r=0.48, p=0.004) and anxiety score (r=0.49, p=0.004); whereas in the male group, ASEX total score correlated with age (r=0.46, p=0.001), age at disease onset (r=0.35, p=0.017), UPDRS total (r=0.5, p<0.001), motor (r=0.45, p=0.002), daily life (r=0.41, p=0.004) scores and mean daily levodopa dose (r=0.37, p=0.011) (Table 4). HAM-A score significantly correlated with HAM-D score in the male group (r=0.84, p<0.001), however in the female group HAM-A and HAM-D scores did not show any correlation (r=0.26, p=0.122). Only cognition subscore of UPDRS showed significant correlation with HAM-A (r=0.58, p<0.001) and HAM-D (r=0.69, p<0.001) scores in the male group. No other subscores of UPDRS showed any correlation in the male group. In the female group, HAM-D score correlated to UPDRS cognition (r=0.43, p=0.014) and treatment complication (r=0.49, p=0.004), but HAM-A score did not show any correlation with UPDRS scores. Duration of the disease correlated to HAM-D scores (r= -0.24, p=0.035) but not HAM-A scores. No significant correlation was detected between HAM-A and HAM-D scores and age and age at disease onset.
Determinants of SD (ASEX total score) in the whole group were age (p=0.003) and anxiety (p=0.001) in linear regression analysis (F=10.702; df: 2.76; Adjusted R2: 0.199) (Table 4). In the female group, determinants of SD were age at disease onset (p=0.012) and anxiety (p=0.011) (F=9.424; df: 2.30; Adjusted R2: 0.345). In the male group, determinants of SD were age (p=0.004) and severity of motor symptoms (p<0.001) (F=13.338; df: 2.43; Adjusted R2: 0.354).
Both in males and females, gonadal steroids decline with advancing age may cause SD. In a study with a large healthy sample (n=1455) most common reported problems in males were: lack of interest (65%), erectile dysfunction (90%), anxiety about performance (75%) and inability to climax (73%) (30). Levels of sex hormones and decrease with age of sex hormones may vary among different ethnic groups. SD may also be due to dopamine loss in PD. Dopamine has roles in desire, erection, reward-seeking behavior and sexuality. Dopamine replacement may improve these symptoms and this treatment may also cause the hypersexuality seen in some patients with PD (31).
Clinical and pathological differences between males and females in PD have been shown in many studies. Estrogen has several effects on dopamine neurotransmission (32). The amount of synaptic contacts is changed by the estrous cycle according to the estrogen levels. In addition, estrogen increases dopamine synthesis and release with many complex mechanisms, and inhibits dopamine reuptake. Also, estrogen has an effect on the expression of dopamine receptors in the basal ganglia. In addition, estrogen has been found to protect nigrostriatal neurons from toxins.
Patients with PD present anxiety symptoms with a frequency rate of 67% (33). Anxiety is shown to deteriorate quality of life in PD (34). Autonomic symptoms of anxiety, fatigue, tension in muscles, insomnia, vigilance and attention deficiency and agitation are some features of anxiety that may resemble some symptoms of PD such as akathisia or dyskinesia. Hamilton Anxiety Scale is an instrument to assess anxiety, however somatic symptoms are weighted heavily and that makes it difficult to distinguish symptoms of anxiety and symptoms of PD. Nevertheless, Krummer and colleagues (35) showed that HAM-A is a valid and reliable measure of anxiety in PD.
In contrast to previous studies reporting no correlation between SD and depression or anxiety in PD (3,5-7,19,36), anxiety levels (in the whole group and in the female group) predicted SD in this study. Cultural diversities may be influential on perception of sexuality. Women are reported to be more preoccupied with and influenced by the body image in PD (5). Furthermore with similar levels of disease severity, women perceive greater disability than men with PD (32). Higher disability perception and impaired body image may be the reason of higher rate of anxiety in female patients with PD in comparison to male patients, consistent with some previous studies (37,38).
Contradictory results have been reported whether anxiety is associated to motor symptoms in PD or not. It has been suggested in two studies that anxiety may cause worsening in motor symptoms in PD (33,39), while three studies found no relation between severity of motor symptoms and anxiety in PD (40-42). High levels of anxiety have also been reported to be associated to treatment complications such as dyskinesia or on/off fluctuations (39,43). In this study, we found a correlation between depression and treatment complications in the whole group and in female group; however, no significant correlation was detected between severity of motor symptoms and anxiety or depression.
Consistent with previous studies (4-6), motor functions predicted SD in male patients. Studies comparing subjects with physical disability and patients with PD in terms of SDs reported that there were no difference between groups (7,8), that may mean physical disability of the patients with PD is the reason of SD. Dopamine depletion may cause SD with its dual effects, including erectile dysfunction as well as motor disturbances in PD (1). Besides, with increasing severity of disabling physical illness, autonomic, limbic and neocortical association areas, such as frontal and temporal cortex may be compounded with functional deficits (30). Sexual functions correlated with severity of the illness and mean daily levodopa dose in male patients indicating a dopaminergic involvement in this study. However, SD may not necessarily arise solely from the neurodegenerative processes of PD. Several other disease-related factors, such as the psychosocial stress, burden of chronic illness, changed appearance, fatigue, relative immobility in bed, difficulty in fine finger movements, and lowered self-esteem associated with increasing loss of independence, may contribute substantially to SD (4).
Relatively small sample size is a limitation of this study. Cross-sectional design did not let to establish medication effects evidently. More detailed urologic/gynecologic anamnesis and examination would let to control other causes of SD. Longitudinal studies may provide more detailed data in different phases of the disease.
Central and peripheral physiology of sexual response has been clarified to some extent, but information about neuronal circuits implicated in sexual functions remains fragmentary. PD is a complex disease and has physical, psychological, neurobiological and pharmacological features. Multidisciplinary future researches including neurology, psychiatry, gynecology and endocrinology are required for SD in female patients with PD. Dopaminergic medication effects are needed to be further investigated with follow up researches particularly in male patients. In evaluation of SD, functional roles of dopamine on sexual physiology are of particular importance in PD. External dopaminergic agents may be imperfect sources of dopamine to supply the deficits in certain circuits employed for sexual functions in PD.
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2Nörolog, Haseki Eğitim ve Araştırma Hastanesi, Nöroloji Kliniği, İstanbul - Türkiye
3Doç. Dr., Haseki Eğitim ve Araştırma Hastanesi, Bölüm ve Hareket Bozuklukları Polikliniği, İstanbul - Türkiye
Amaç: Parkinson hastalığının (PH) karmaşık doğası ve farklı cinsel fizyolojileri nedeni ile kadın ve erkek hastalar, farklı biçimlerde cinsel işlev bozukluğu yaşıyor olabilirler. Bu çalışmada amaç, Parkinson hastası kadın ve erkeklerde cinsel işlev bozukluklarının belirleyicilerinin araştırılmasıdır.
Yöntem: İdiyopatik PH olan ve ayakta tedavi gören 79 hasta (yaş ortalaması 67.51±8.27 olan 46 erkek, 33 kadın) Aralık 2007 ile Şubat 2011 tarihleri arasında çalışmaya alındı. Bileşik Parkinson Hastalığı Derecelendirme Ölçeği, Hoehn-Yahr Evrelemesi, Hamilton Depresyon ve Anksiyete Derecelendirme Ölçekleri, Kısa Akıl Muayenesi ve Arizona Cinsel Yaşantılar Ölçekleri ölçüm aygıtlarıydı.
Bulgular: Yaş ve anksiyete çalışmaya dahil edilen tüm hastalarda, hastalık başlangıç yaşı ve anksiyete kadın hastalarda, yaş ve motor semptomların şiddeti erkek hastalarda cinsel işlev bozukluklarının belirleyicileriydi.
Sonuç: Gonadal steroidler yaşın ilerlemesiyle birlikte, hem erkeklerde hem kadınlarda azalır. Dopamin cinselliğin; istek, sertleşme ve ödül arama davranışı gibi birimlerinde görev alır. Dopamin azalması, erkek hastalarda sertleşme bozukluğuna neden olur ve motor işlevleri etkileyerek, cinsel işlev bozukluğuna yol açar. Anksiyete, kendini algılama ve etkilenmiş beden imajına bağlı olarak gelişir ve erkeklere göre kadınları daha fazla etkiler.