Sexual function is an important issue for PwMS. Young adults with MS particularly may see SD as the most negative feature of the illness, given the variety of disturbances of sexual function, and the indirect effects on mental health, quality of life and intimate relationships, at a time of life when sexual activity may be at a peak and seen as particularly important. Sexual function is however often not a standard part of the consultation with healthcare professionals for PwMS , despite calls for its inclusion [28–30], and is therefore frequently underdiagnosed .
Our data on a large sample of PwMS world-wide confirmed that SD is common, with over half of the sample reporting one or more problems with sexual function, and that SD is associated with lower satisfaction with sexual function. Lack of sexual interest was the most common problem in women while difficulty with erection was the most common in men. The prevalence of SD in our study was lower than in previous reports. One study found that 73.1 % of PwMS reported one or more sexual disturbances. This was nearly double compared to those with other chronic diseases (39.2 %) and many times higher than healthy controls (12.8 %) . Others suggest a higher prevalence in the general population, at about 40–45 % of women and 20–30 % of men . However, definitions are not directly comparable between studies, and our sample is not likely to be representative of the general MS population. It is probable that our sample would have lower levels of SD than other studies given that our sample was notably young, educated and had a lower level of disability .
For the sexual function scale of the MSQOL-54 score, we showed significant independent associations with age, marital status, employment status, level of disability, physical activity, clinical fatigue, screening positive for depression and antidepressant use. Age, depression, antidepressant use, fatigue, and level of physical activity were also independent predictors associated with satisfaction with sexual function. Similarly, clinical fatigue, depression and antidepressant use were independent determinants of the presence of SD, along with age, marital, and employment status, as well as the modifiable factor, diet.
This suggests that sexual function and dysfunction for PwMS have very complex determinants related to an interplay of individual, lifestyle and disease characteristics, strongly influenced by the presence of depression, the use of antidepressants, and fatigue. We have previously demonstrated modifiable lifestyle factors are important predictors in their own right of fatigue  and depression risk , and may therefore indirectly affect sexual function and satisfaction with sexual function. Here, we were able to demonstrate that diet and level of physical activity are associated with these outcomes even after adjusting for other relevant factors.
Although smoking showed significant unadjusted associations with our outcomes, in the final regression models, it did not reach a significance level of <.05. Smoking has previously been linked with erectile dysfunction , probably mediating its effects via microvascular circulatory impairment, although the mechanism in women has not been well studied. Regular exercise would likely counteract this mechanism, and our data suggest an association with sexual function score, and satisfaction with sexual function after adjusting for depression and fatigue. Similarly, better diet may have beneficial effects directly on the microvasculature, but also improve satisfaction with sexual function through indirect effects such as amelioration of metabolic syndrome, known to have adverse effects on sexual function [35, 36].
To our knowledge, only two studies have thus far discussed the effect of lifestyle modification on SD [11, 37]. These studies suggest that increasing physical activity improves symptoms of SD, however it is possible that positive effects of exercise on mood mediated the observed improvements. Our data suggest these effects are independent determinants of SD. Modifying other factors such as smoking, obesity and alcohol consumption may also improve SD if managed early in life, before middle age .
SD is very common in people with depression in the general population, who have a 50 to 70 % risk ; this relationship appears to be bi-directional, in that people with SD have a greatly heightened risk of depression . As depression occurs very commonly in PwMS [38, 39], with a lifetime prevalence of around 50 % , this contributes to the very high prevalence of SD in PwMS. A number of studies have shown that quality of life with respect to SD is lower in PwMS who have depression [21, 39]. PwMS should be screened for depression as early prevention and treatment of depression has many benefits including a potential benefit for people who experience SD . However, antidepressant use was clearly associated with the presence of sexual dysfunction, lower odds for satisfaction with sexual function and lower sexual function score, independent of the other factors including screening positive for depression.
Fatigue also has a complex relationship with depression, and so may be expected to be associated with SD for PwMS. Our study however confirmed associations with the outcomes that were independent of and additional to the associations with depression. Fatigue has been shown to be significantly associated with SD in a number of studies [16, 19, 23, 29, 41]. A significant relationship was found between SD and the presence of physical disorders impeding sexual activity, in particular fatigue , and although reported by people with a range of chronic disease, appears to be a particular problem for PwMS .
Associations between SD and various MS-related clinical and socio-demographic variables have been investigated in other studies [19, 20, 23, 42]. Meaningful correlations were found between SD and age, male gender, low education level, unemployment, length of disease, length of marriage, anxiety, age of husband, physical ability, cognitive deterioration, length of medication use, primary progressive MS, frequency of intercourse, number of pregnancies and number of children [16, 19, 20]. While age, marital status, level of education, employment status, number of children, and level of disability were associated with our sexual health outcomes, we did not find an independent association of gender or medication use in our data.
There is potential for a lifestyle risk factor modification approach to the management of SD in PwMS, given the strong associations of better lifestyle behaviours with reduced depression risk  and fatigue , both known to adversely affect sexual function . In type 2 diabetes, another chronic disease with strong lifestyle associations, intensive lifestyle intervention in obese women resulted in a significantly greater proportion remaining sexually active, improvements in sexual function, and greater likelihood of remission of SD at 1 year . Lifestyle approaches to management of SD in PwMS are however uncommon, and there is little supporting research.
Given the important role of depression in SD, our data suggest that a more holistic approach to the management of depression in PwMS is required. This is particularly important given the associations we have demonstrated of antidepressant use with SD, sexual satisfaction and overall sexual function. Others have previously called for judicious use of antidepressant medication on a background of routine use of lifestyle modification for the treatment of depression . A drug-only approach to management of depression in PwMS appears a poor therapeutic approach. Attention to lifestyle risk factors, psychosocial interventions and psychological therapy may decrease depression risk in their own right but also increase sexual satisfaction . From a practical viewpoint, PwMS often have worse fatigue and particularly low energy in the afternoon and night time, increasing the likelihood of SD and avoidance of sexual activities. On this basis, PwMS may also be advised to engage in sexual activity earlier in the day to reduce SD due to fatigue .
All data in our study were self-reported, and therefore were unable to be verified, although previously validated tools were used where possible. We did not measure the presence of depression directly, but screened for depression risk. SD was determined by categorising participants in two groups depending on their responses to items on the sexual function scale of the MSQOL-54; this method has not previously been used or validated, but does allow for future studies to directly compare data with ours. Participants were English speaking and able to complete the survey online, and most were young women. This sample may therefore not be generalizable to all PwMS, despite the variety of backgrounds of participants and size of the sample. Finally, our study examined associations and is cross-sectional, hence we cannot assert causality.