Two studies showed that male gender was an independent predictive factor for treatment with DBS in PD patients in the United States of America (14, 15). This was later replicated in another study (16). Similarly, the proportion of women in the presurgical evaluation for DBS was lower, but the likelihood of positive approval was higher for women than for men (16). Nevertheless, the proportion of women undergoing DBS was lower in women than in men (16). Another study reported that men were overrepresented in DBS treatment compared to the total number of hospitalizations of patients with PD (17). Dalrymple et al. examined differences based on the primary indication for DBS. They demonstrated that men were more likely to be treated with DBS for medication refractory tremor than women (18). Interestingly, Vinke et al. reported that more women underwent STN-DBS surgery after moving from awake to asleep surgery (19).

A study that examined gender disparity from diagnosis to DBS found no gender differences in the interval between diagnosis and surgery or DBS outcomes (20). Interestingly, women had a greater reduction in motor scores before surgery ON medication than men (20). On the other hand, women were more likely to be rejected for DBS because of depression at presurgical evaluation (16) and they were more likely to decide against DBS because of personal preference (21). Men, on the other hand, were more likely not to receive DBS because they had been lost to follow-up in the outpatient clinic before the decision whether to operate has been made (21). One study examined the gender-specific patterns in the decision-making process before DBS (22) and found that while the male decision-making process was mostly characterized by “taking own initiative” and “agreeing when offered”, the female decision-making process was also characterized by “hesitation and waiting”. Women were also more afraid of complications and needed more support from their social environment during the presurgical evaluation (22). In contrast, two other studies found no difference between the arguments for and against DBS (16, 23).

Regarding motor symptoms, a total of 14 studies were analysed, five of which reported better improvement in overall motor scores or subscores in male STN-DBS PD patients and two reported better motor improvement in female STN-DBS PD patients. Most studies reported equal improvement in overall motor function in male and female patients after STN-DBS (16, 24–31). However, three studies reported unequal improvement within bradykinesia subscores (16, 30, 32). Accolla et al. reported equal improvement in total motor scores, but men improved significantly more than women in Unified Parkinson’s Disease Rating Scale (UPDRS) percentage scores for bradykinesia and in absolute hand tapping test scores (30). This is consistent with the findings of Jost et al. who found that total motor scores improved equally in men and women, but bradykinesia improved significantly more in men than in women (16). Interestingly, Yuan et al. demonstrated that both genders improved significantly in “OFF medication-ON stimulation” conditions, but only men improved in the “ON medication-ON stimulation” conditions. This was reported for total scores and most subscores, including the bradykinesia subscore (32).

In a long-term longitudinal study, it was found that the overall motor scores of men improved more than those of women at 1 year follow-up (33). This was related to worse limb akinesia and gait in women than men. However, at 3- and 5 years follow-up, both genders improved equally. Interestingly, only women significantly improved in postural stability. This could be due to women having better overall motor scores, lower score for limb akinesia and lower axial subscore before surgery (33). Another long-term study found equal improvement for total motor scores and subdomains (bradykinesia, axial, rigidity, and tremor) in men and women at 1 year follow-up (25). However, at 5 years follow-up, total motor scores improved equally, but tremor improved significantly only in women (25). In the longest reported follow-up study, they looked at post-surgical motor outcomes in “ON medication-ON stimulation” conditions (34). They found that motor scores and bradykinesia subscores deteriorated in women from 5 years after surgery, but in men from 10 years after surgery. Furthermore, at 1 year follow-up, only men had improvement in rigidity. Women had lower tremor subscores at all times after surgery, but the tremor subscore did not change significantly in neither men nor in women. It is worth mentioning that at baseline women had better total motor scores ON medication, less tremor and less dyskinesias compared to men (34).

In a retrospective study, specifically looking into postural abnormalities, the authors reported that male gender was a predictive factor for upper camptocormia after STN-DBS (35). Two other studies, looking into possible predictive factors for motor improvement, did not find gender as a significant predictive factor for postural abnormalities (31, 36). One of these studies reported that in women with PD preoperative levodopa responsiveness was a better predictor for motor improvement than for male patients (31). Chiou et al. also examined gender-specific predictive factors: men had better motor improvement if they had lower levodopa equivalent daily dose (LEDD) preoperatively, worse motor scores including tremor, or better response to medication of tremor and rigidity (29). On the other hand, women had better motor improvement after surgery if they had worse motor scores preoperatively, better Activities of Daily Living (ADL), or better medication response of akinesia (29).

Regarding LEDD, a total of eight studies were reviewed, with two reporting a greater LEDD reduction in male patients (24, 37). One 10 years follow-up study reported a significant LEDD reduction only in men but not in women LEDD in whom LEDD returned to values before surgery at 5 years after the surgery (34). However, other studies did not report differences in LEDD reduction between genders (20, 21, 25, 30, 33).

Regarding cognition, a total of seven studies were reviewed, with three reporting improvement or better prognosis of cognition in female patients. Although it is known that STN-DBS does not lead to a decline in general cognitive abilities (38, 39), one study found that male gender was a predictive factor for the development of dementia after STN-DBS (40). In addition, another study found that only women showed significant improvement on cognitive tests after STN-DBS (26). While one study reported improvement in the cognitive domain of the quality of life scale PDQ-39 after STN-DBS (28), another study found no difference in the cognitive domain of the PDQ-39 between genders (16). Other studies report no significant differences in cognition in both men and women after STN-DBS (24, 25, 32).

Regarding depression, a total of seven studies were reviewed (24–27, 32, 41, 42), with one study reporting greater improvement in depression in female patients (41) and one study reporting greater improvement in depression in male patients after STN-DBS (26). Furthermore, a longitudinal study reported that women had more depressive symptoms in all phases of STN-DBS surgery and LEDD was positively correlated with depressive symptoms only in women (27). Although depressive symptoms appeared to decrease more in women than in men, further analysis showed significant modulation by gender, but not for STN-DBS time or the interaction between STN-DBS time and gender (27). Importantly, this and other studies consistently reported that women had more severe depressive symptoms than men before surgery (24, 27, 32, 41). In general, most other studies showed equal improvement in depression in both genders (24, 25, 32, 42).

With regard to impulsivity and impulsive disorders, a total of three studies were analysed, one of which found an improvement in impulsivity only in men with PD after STN-DBS (26), and two reporting an increase in impulsivity behaviour in women. Namely, a study examining impulse control behaviours (ICB) after STN-DBS, reported that more women developed new-onset ICB than men, resulting in a higher prevalence of ICB in women (43). In addition, one study examined loss-chasing behaviour as part of gambling behaviour, which is a form of impulse control disorders (ICD) (44), and found that the value of chasing losses increased more in women than men with STN-DBS.

Anxiety was measured in two studies, with one study reporting higher anxiety symptoms in women before surgery (32), but neither study found significant improvement in anxiety in men or women after surgery (32, 42).

One study examined the possible personality changes after STN-DBS, in which no significant differences in personality were found before and after STN-DBS in neither men nor women with STN-DBS (27).

With regard to the voice, a total of four studies were analysed, two of which reported changes in voice characteristics in men and one of which reported changes in voice characteristics in women with PD after STN-DBS. Namely, Lee et al. demonstrated that only men showed improvement in correlation dimension as a measure for voice quality after STN-DBS compared to patients with PD patients without STN-DBS (46). In addition, two other studies reported that women showed worsening on more voice characteristics (e.g., jitter and shimmer) than men (47, 48) and also improvement on less voice characteristics compared to men OFF stimulation (47), but the results were statistically significant in only one study (47). Interestingly, another study found that only women showed several significant changes in voice characteristics with different medication and stimulation conditions (49).

Regarding weight change after STN-DBS, a total of four studies were analysed, three of which reported gender-specific differences in certain characteristics of weight change after STN-DBS. In general, studies show that men and women endure weight gain after STN-DBS (50–52). Regarding possible gender differences in weight gain, a study showed that after STN-DBS body mass index (BMI) increased more in women than in men (53). Furthermore, in two of these studies both fat-free mass and fat mass increased in men, while only fat mass increased in women (51, 52).

Regarding sexual outcomes, a total of four studies were analysed, one of which reported worse scores in men and one reported improvement of sexual functions in men with PD after STN-DBS. Two studies did not find overall improvement or any gender differences after STN-DBS (42, 54) in sexual functions, with Castelli et al. reporting that only men improved on the dissatisfaction subscore of the reduced version of the Gollombok Rust inventory of sexual satisfaction (GRISS) (42, 55). When considering male patients under 60 years, total improvement of sexual functions was observed on the reduced version of the GRISS (42). On contrary, one study reported that men had worse scores in sexual functions measured by NMSS after STN-DBS (16), Interestingly, Pedro et al. found that age was a predictor of sexual dysfunction in both sexes, but quality of life (QoL) was better in men with erectile dysfunction than in women with sexual dysfunction (54).

Two studies have investigated urinary symptoms and observed improvements in urinary outcomes (urinary incontinence and frequency) for both men and women (56, 57). However, one of these studies, which also included urodynamic tests, specifically reported that women demonstrated improvements in more urinary outcomes, such as residual urine and American Urological Association Symptom Index, than men (57).

One study investigated pain scores showed that only men with PD improved significantly in total pain scores after STN-DBS. Nevertheless, men had more improvement in the subdomains of musculoskeletal and chronic pain (37).

A study investigated restless legs syndrome (RLS) and showed better improvement in men than in women with PD after STN-DBS (32).

With regards to QoL and its subdomains, a total of six studies were analysed, three of which reported a better improvement of QoL in men and two in women. Men improve more in QoL (32) and on more subdomains than women (16, 25, 32) as measured by the PDQ-39 (58), PDQ-8 (59), and SF-36 (60). In contrast, Dietrich et al. demonstrated that women showed more improvement in QoL than men (27) and Hariz et al. reported that only women showed improvement in QoL and on more subdomains as measured by the PDQ-39 (28).

Regarding ADL, a total of nine studies were analysed, with one reporting gender-related differences of ADL after STN-DBS. Namely, after STN-DBS female gender could be a predictive factor for functional dependence (defined as an ADL score below 80%) as measured by the Schwab and England Activities of Daily Living Scale (61, 62). However, most studies report equal significant improvement in ADL in both men and women after STN-DBS (24–26, 28–30, 32, 33).