Sex-differences in adverse symptoms reported as side-effects by Parkinson´s disease patients receiving Deep brain stimulation (DBS) in the subthalamic nucleus

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder affecting several aspects of motor and non-motor function. Currently, no cure exists for PD. Instead, existing treatments aim to alleviate symptoms. In advanced-stage PD, Deep Brain Stimulation (DBS) is applied to relieve motor symptoms. The subthalamic nucleus (STN) is a common target area for implantation of DBS leads. While STN-DBS efficiently relieves PD motor symptoms, there have been reports of adverse side-effects. Sex-differences have been reported in a range of factors correlated with PD. However, sex-differences in patients’ experience of side-effects upon STN-DBS remain to fully uncover. This study collated reports on adverse symptoms reported as side-effects upon STN-DBS and examined their sex distribution; biological male vs biological female. Overall, most studies had a disproportion of males to females, or did not report sex at all. 17 original articles detailing side-effects reported by PD patients upon STN-DBS, while also providing information of reporting patients´ sex, were identified and analysed. Adverse side-effects were separated into three main categories ( physiological , affective , cognitive ). Articles included single case reports and larger clinical cohorts to cover the range STN-DBS related symptoms. Both males and females experienced physiological side-effects, both motor and autonomic. Males reported more gait and balance side-effects while dyskinesia was reported by both males and females. Most prominent sex-difference was detected in the affective and cognitive categories. Depression was the main affective side-effect reported by females. Males, but not females, reported aggressive behavior and sexual dysfunction upon STN-DBS. An additional observation across studies was that side-effects experienced by females were less detailed. This review of published clinical reports revealed sex-differences in adverse side-effects of STN-DBS described by PD patients and also detected sex-differences in the descriptive details of reported side-effects. These findings advocate for sex-inclusion and streamlining of data to equalize information from both sexes when reporting beneficial and adverse effects of this treatment. With lack of equal level of description across sexes, progress in treatment is hampered. Further knowledge of sex-differences will support tailor-designed treatments for improved efficacy in PD patients of both sexes undergoing, and living with, STN-DBS treatment.