Discussion

This study provides relevant information about the impact of the sexual function on the HR-QoL of PD patients. In addition, it also highlights a possible profile of patients that may not feel comfortable talking about their sexuality during the medical appointment hiding a possible problem.

For the present work it was analysed data from 861 patients (from 6 European countries: United Kingdom, Portugal, Spain, France, Italy and Germany) collected in the PRISM study: A European survey of the burden of Parkinson’s Disease in patients and their caregivers.

For the primary aim of this work, all the patients that answered the PDQ-39 questionnaire (a patient-reported measure of health status and quality of life) were included (a total of 859 patients). The median PDQ-39 summary score was 29.1 (P25-75: 18.0 to 43.9), with the highest median domain scores occurring in Bodily discomfort (41.7; P25-75: 25.0 to 58.3), Mobility (35.0; P25-75: 15.0 to 62.5) and Emotional well-being (33.3; P25-75: 16.7-54.2), although these were subject to wide variation between respondents. These PDQ-39 scores are in line with the findings reported in other studies, being associated with a worse HR-QoL than the general population.⁷

The results for the association between sexual function and HR-QoL were presented using 3 different scales to evaluate sexual function: MOS-SFS, the question about sexuality (compulsive urges) of the QUIP and questions 18 and 19 of the NMSQuest.

An association between an increase in the MOS-SFS total score and an increase in the PDQ-39 total score was observed. In our model we also considered other

Discussion 34 variables that could be associated with the HR-QoL (gender, age, time since the diagnosis and number of comorbidities). So, holding all other variables constant we could observe a positive significant association between the MOS-SFS total score and the PDQ-39 total score, suggesting that a worsening of the sexual function seems to be associated with a worsening on the HR-QoL of these patients. In addition, patients with more comorbidities, women and people with more time with the disease also was associated to a worse HR-QoL.

With regards to the PDQ-39 domains, it was observed an association between an increase in the MOS-SFS total score and the total score of all the 8 domains.

This association was significant for all the domains except for “Mobility”.

Despite this work does not allowed us to stablish a causal relation, this suggests that a worsening in sexual function may be associated with difficulties in performing the activities of daily living, problems related to emotional well-being, a feeling of stigma, need for social support, worsening of cognition, difficulties in communication and feeling of bodily discomfort.

In the survey developed within the PRISM study, the scale used to the assessment of sexual function was the MOS-SFS. However, looking at all the questions asked to these patients, we identified three additional questions present in other scales that also gathered relevant information for the present topic. Once we had this information, we considered that it would be relevant to also explore if the association between the answers given to these questions and HR-QoL was in line with the results obtained in the association’s analysis between the MOS-SFS and the PDQ-39 scores. Thus, the analysis of the association between PDQ-39 score and the answer to the question about the presence of compulsive sexual behaviour (evaluated in the QUIP) was made, as well as the association between PDQ-39 score and answer to the questions 18 and 19 of NMSQuest (question 18: Feeling less interested in sex or more interested in sex; question 19: Finding it difficult to have sex when you try).

Concerning to the results obtained in the QUIP’s question about compulsive sexual behaviour, it was observed that patients reporting sexual compulsive urges had a higher score on the PDQ-39 scale. In the analysis of the association of this answer and the individual domains of the PDQ-39 we can see that the domains for which we found a significant result were Emotional well-being, Social support and Cognition. Despite in the other domains we haven’t achieved a statistically significant result a trend can be observed showing that patients reporting compulsive sexual behaviour tend to have higher scores in all the domains of the PDQ-39 (meaning a worse HR-QoL). In the evaluation of these patients, it is also fundamental to consider that some medicines tend to contribute to the development of this sexual behaviour (namely a class of medicines named dopamine agonists). A further analysis of the impact of using this class of medicines and the general HR-QoL in the patients included in this cohort would be interesting.

The NMSQuest addresses several topics related to non motor symptoms in PD patients including sexual functioning. Regarding the answers to question 18, it was observed a significant difference in the PDQ-39 total score between patients that answered “Yes” and patients that answered “No” (p<0.001). Patients that answered “Yes” are associated with a higher PDQ-39 total score, meaning that patients reporting “Feeling less interested in sex or more interested in sex” seems to be associated with a worsening in the HR-QoL. Additionally, it was also observed a difference in the PDQ-39 total score between patients that answered

“Yes” to question 19 of the NMSQuest and patients that answered “No”

(p=0.003). As seen for the question 18, also in the question 19 patients answering

“Yes” are associated with a higher PDQ-39 total score, meaning that patients reporting “Finding it difficult to have sex when you try” also seems to be associated with a worsening in the HR-QoL.

Discussion 36 In the analysis of the association of the answers to question 18 and the individual domains of the PDQ-39, we can observe a significant result for all the domains:

patients reporting problems with their sexuality in this question also reported a worse HR-QoL. With regards to question 19, the PDQ-39 domains' total score that showed a significant association were: Activities of daily living, Emotional well-being, Stigma, Social support, and Cognition. Despite in the other domains we haven’t achieved a statistically significant result a trend can be observed for all of them showing that patients reporting problems with their sexual function tend to have higher scores in all the domains of the PDQ-39 (meaning a worse HR-QoL).

Considering all this information about the association between sexual function and HR-QoL it was observed that independently of the questionnaires used and independently of talking about hyposexuality or hypersexuality, in this cohort, the results obtained were very aligned and all pointed in the same direction:

patients reporting sexual issues tend to have a worse HR-QoL. These results can be relevant for the clinical practice highlighting the importance of addressing this subject during the consultation once sexual function may have an important impact on the life of PD patients.

In the models developed for this study, we also considered other variables for their potential to impact the HR-QoL: age, number of comorbidities, gender, and time since diagnosis. It was observed that on some of the analyses done these variables were significantly associated to the HR-QoL of these patients. Of these variables, a highlight should be done for gender. Overall, in this work, we can observe a trend for a worse HR-QoL in the female population. Despite it is known that symptoms in PD may be delayed in women²⁷ in this study it is suggested that this population may need additional consideration. With regards to sexual function, in another study that analysed this cohort of patients,

significantly more male than female subjects reported sexual dysfunction.²⁸ Despite this, 50% of the women reported orgasm dysfunction and 48% reported a decreased sexual desire. These numbers are considerably higher than the prevalence in the general population²⁸ and in our work we also found that women tend to be less open to answer questions about their sexuality, which highlights again the importance of actively addressing these symptoms in women.

Previous studies have shown that psychiatric diseases, namely depression and anxiety, may have a relevant impact on the HR-QoL.^25,26 Despite their importance, we did not include these two variables in the presented model because information about them is also present in the PDQ-39 (the dependent variable). For another side, studies have also shown that depression and anxiety may have an important impact on the sexual function of people in general and specifically people with PD.^19,20 Despite these specific association were not tested in this work, the domain Emotional well-being of the PDQ-39 has two questions focused on the presence of anxiety and depressive feelings. The results found in this work seems to be aligned with the previous publications: a significative association between sexual function and Emotional well-being was found independently of the scale used.

Despite our efforts to include in the models relevant variables that could impact HR-QoL, looking into the R² obtained in all the analysis it is possible to understand that the amount of variation of the PDQ-39 total score and their individual domains that is explained by our model is not very extensive and other variables would also contribute to explaining the HR-QoL of these patients.

Since this is an exploratory analysis additional dedicated studies are important in this field.

As referred previously, in this study, the sexual function was addressed mainly using the MOS-SFS. However, during the data collection process, the fulfilment

Discussion 38 of this scale was not mandatory and a very high frequency of missings was observed. Out of the 861 patients included in the study, just 374 (43,4% of the included patients) filled this scale. Having into account the high rate of missings we decided to look at the demographic characteristics of the “non-responders”

trying to find a possible profile of patients that tend to not feel so comfortable talking about their sexuality.

In our cohort we could observe that male population answered significantly more than female population to this questionnaire, suggesting that women may not feel so comfortable talking proactively about their sexuality. The same trend was observed in older patients. Additionally, considering the countries, we also found significative differences regarding the number of responders: while in the United Kingdom and Germany the percentage of patients that filled the MOS-SFS (“responders”) was almost equal to the number of patients that did not answer it (“non-responders”), in France, Italy, Spain and Portugal we can observe a higher percentage of “non-responders”. This may be due to cultural specificities and more research on this area would be desirable. The number of responses to this questionnaire was also significantly different for different educational levels:

people with higher educational levels tended to answer MOS-SFS more often.

Significative differences in the number of “responders” and “non-responders”

were not found considering the number of comorbidities or the time since diagnosis. This is an exploratory analysis and more research would be important to validate these findings. In this study, we observed that women, older patients, from France, Portugal, Spain and Italy and with a lower level of educational degree may need additional attention from the clinician regarding the evaluation of their sexual function. This is even more important considering that, in this cohort, we could observe that “non-responders” reported a significantly worse HR-QoL than the patients that answered the MOS-SFS.

This work presents some limitations. On one side, as this is an exploratory analysis and target sample recruitment is not based on achieving a given level of statistical power, limited sample size means that there is a probability that our analysis may result in ‘Type II errors’ (failing to reject a null hypothesis when it is false). The sample size may limit the ability to perform some meaningful analyses, however, in our analyses a number of significative associations were found.

With regards to the data collection, it is also important to highlight that this was a voluntary survey (with data being collected via an online survey) and so we may have some bias. Where available, validated instruments are used to collect data.

However, there is potential for inaccurate recollection and, for some questions, subjective differences, for example in perceptions of symptoms. It may also exist a limitation regarding the validity of responses (respondents are anonymous, and it was not possible to screen and confirm that all responses come from PD patients). The methodology aimed to address this limitation by reaching out broadly to people with PD in each of the included countries to participate, through patient groups and clinics. However, because of this, it is also acknowledged that the sample may include more patients who are engaged in patient groups than those who are not (and this population may be not representative of the global population of patients with PD).

Conclusions 40