Participants

Out of 141 eligible people who were invited to participate in the study, 131 accepted. The reasons for refusing to participate in the study were lack of time to be interviewed (7) and reluctance to discuss their sexual function (3 people). Some participants agreed to be interviewed but did not attend the clinic for the blood test (125 had the blood tests taken, 84 men and 41 women). As stated before, the blood test was included in the regular follow-up of the clinics’ patients.

Descriptive data

Of the 131 people who accepted to participate, 90 (68.7%) of them were men, 28 (21.4%) had a partner, 78 (59.5%) lived with their origin family, 45 (34.2%) people had achieved high school education, and their mean age was 44.8 years. Regarding their clinical characteristics, 90 (68.7%) had a diagnosis of schizophrenia or another long-term psychotic disorder, 73 (55.7%) were treated with paliperidone, 70 (53.4%) received equivalent daily doses of antipsychotics under 6 mg of risperidone, 15 (11.5%) people were in treatment with serotonin reuptake inhibitors, 21 women were premenopausal (none under hormonal treatment), 53 (40.5%) participants had one or more somatic disorders (hypertension, diabetes, dyslipidaemia, cardiopathy, obesity, or benign prostatic hyperplasia), 92 (70.2%) people were smokers, and 22 (16.8%) occasionally consumed alcohol. The sociodemographic and clinical characteristics of the sample are described in Table 1. The precise combinations of antipsychotic drugs prescribed are detailed in Table 2.

Table 1. Sociodemographic and clinical characteristics of the sample Variable Values

Total n (%) /Mean (SD)

Median (interquartile range)

Men n (%)/ Mean (SD)

Median (interquartile range)

Women n (%)/ Mean (SD)

Median (interquartile range)

Age 44.8 (11.1) 42.9 (10.8) 49 (10.6)

Diagnosis

Schizophrenia

Schizoaffective disorder

Bipolar disorder

Other

89 (67.9%)

22 (16.8%)

12 (9.2%)

8 (6.1%)

66 (73.3%)

11 (12.2%)

7 (7,8%)

6 (6,7%)

23 (56.1%)

11 (26.8%)

5 (12.2%)

2 (4.9%)

Years since diagnosis 16.1 (10.9) 15.7 (10.8) 16.7 (11.1) Years on antipsychotic treatment 11.9 (10.9) 11.5 (10.9) 12.6 (10.9) Long-acting injectable antipsychotic

Paliperidone

Aripiprazole

Risperidone

First-generation antipsychotics

46 (35.1%)

73 (55.7%)

7 (5.3%)

5 (3.8%)

25 (27.8%)

55 (66.15)

6 (6.7%)

4 (4.4%)

21 (51.2%)

18 (43.9%)

1 (2.4%)

1 (2.4%)

Antipsychotic polypharmacy

69 (52.7%)

48 (53.3%) 21 (51.2%) Antipsychotics in combination

Only sparing

Only raising

Raising and sparing

42 (32%)

44 (33.6%)

45 (34.4%)

22 (24.4%)

35 (38.9%)

33 (36.7%)

20 (48.8%)

9 (22%)

12 (29.3%)

Antipsychotics dose in mg of Risperidone 7.4 (5.5) 7.6 (5.3) 6.9 (5.8) Categorized antipsychotic dose in mg of risperidone

Under 6 mg

6,1 to 12 mg

12,1 and more

46 (51.1%)

29 (32.2%)

15 (16.7%)

9 (42.9%)

9 (42.9%)

3 (14.3%)

15 (75%)

2 (10%)

3 (15%)

Treatment with antidepressants (SRI, MAOI and TCA)

No

Yes

116 (88.5%)

15 (11.5%)

81 (90%)

9 (10%)

35 (85.4%)

6 (14.6%)

Antipsychotics and antidepressants in combination

Only sparing

Only raising

Raising and sparing

36 (27.5%)

44 (33.6%)

51 (38.9%)

20 (22.2%)

35 (38.9%)

35 (38.9%)

16 (39%)

9 (21.9%)

16 (39%)

Somatic disorders potentially affecting sexual function

None

Hypertension

Diabetes

Dyslipidaemia

COPD

Obesity

Cardiopathy

Benign prostate hypertrophy

78 (59.5%).

12 (9.2%)

11 (8.4%)

40 (30.5%)

10 (7.6%)

4 (3.1%)

3 (2.3%)

1 (0.5%)

56 (62.2%)

7 (7.8%)

7 (7.8%)

25 (27.8%)

6 (6.7%)

3 (3.3%)

2 (2.2%)

1 (1.1%)

22 (53.7%)

5 (12.2%)

4 (9.8%)

15 (36.6%)

4 (9.8%)

1 (2.4%)

1 (2.4%)

0

Smoking

No

Yes

35 (27.6%)

92 (72.4%)

22 (25.3%)

65 (74.7%)

13 (32.5%)

27 (67.5%)

Alcohol consumption

No

Yes

109 (83.2%)

22 (16.8%)

70 (77.8%)

20 (22.2%)

39 (95.1%)

2 (4.9%)

Educational level

Incomplete

Compulsory education

Intermediate education

Higher education

19 (14.6%)

43 (33.1%)

44 (33.8%)

24 (18.3%)

15 (16.9%)

29 (32.6%)

34 (38.2%)

11 (12.4%)

4 (9.8%)

14 (34.1%)

10 (24.4%)

13 (31.7%)

Employment status

Working or studying

Unemployed

Incapacity to work

Retired by age

17 (13%)

30 (22.9%)

83 (63.4%)

1 (0.8%)

14 (15.6%)

19 (21.1%)

57 (63.3%)

0

3 (7.3%)

11 (26.8%)

26 (63.4%)

1 (2.4%)

Couple / Partner

Yes

No

28 (22.3%)

103 (77.7%)

16 (17.8%)

74 (81.2%)

12 (29.3%)

29 (70.7%)

Form of cohabitation

Alone

With the family of origin

With their own family

Shared house

With partner

In a charity shelter

18 (13.7%)

78 (59.5%)

13 (9.9%)

8 (6.1%)

9 (6.9%)

5 (3.8%)

13 (14.4%)

58 (64.4%)

4 (4.4%)

6 (6.7%)

4 (4.4%)

5 (5.6%)

5 (12.2%)

20 (48.7%)

9 (22.0%)

2 (4.9%)

5 (12.2%)

0

Satisfaction with sexual life (0 to 10)

 

0 to 1.9 Extremely low

2 to 4.9 Low

5 to 7.9 Acceptable

8 to 10 Satisfactory

6 (4-8)

22 (16.8%)

18 (13.7%)

58 (44.3%)

33 (25.2%)

6 (4-8)

10 (11.1%)

15 (16.7%)

41 (45.6%)

24 (26.7%)

5 (1-7)

12 (29.3%)

3 (7.3%)

17 (41.5%)

9 (22%)

BPRS 28 (21-38) 28.5 (21-38) 26 (20-35) SALSEX Score

0 No dysfunction

1 Mild dysfunction

2 Moderate dysfunction

3 Severe dysfunction

54 (41.2%)

30 (22.9%)

10 (7.6%)

37 (28.2%)

34 (37.8%)

23 (25.6%)

7 (7.8%)

26 (28.9%)

20 (48.8%)

7 (17.1%)

3 (7.3%)

11 (26.8)

Hyperprolactinemia*

No

Yes

Mild

Moderate

Severe

53 (42.4%)

72 (57.6%)

48 (38.4%)

11 (8.8%)

13 (10.4%)

37 (44%)

47 (56%)

40 (47.6%)

0

7 (8.3%)

16 (39%)

25 (61%)

8 (19.5%)

11 (26.8%)

6 (14.6%)

Testosterone*

Normal

Low

n.a.

39 (50%)

39 (50%)

n.a. Menopause

No

Yes

n.a. n.a.

21 (51.2%)

20 (48.8%)

SRI: Serotonin reuptake inhibitors; MAOI: Monoamine Oxidase Inhibitors; TCA: Tricyclic antidepressants; COPD: Chronic Obstructive Pulmonary Disease. Table 2. Antipsychotics in combination prescribed to the participants N (%) LAI Aripiprazole (monotherapy) 25 (19,1%) LAI Aripiprazole and oral olanzapine 1 (0,8%) LAI Aripiprazole and oral paliperidone 1 (0,8%) LAI Aripiprazole and oral quetiapine 9 (6,9%) LAI Aripiprazole, oral quetiapine and clozapine 1 (0,8%) LAI Aripiprazole, oral quetiapine and haloperidol 1 (0,8%) LAI Fluphenazine 2 (1,5%) LAI Fluphenazine and oral paliperidone 1 (0,8%) LAI Paliperidone (monotherapy) 43 (32,8%) LAI Paliperidone and oral levomepromazine 1 (0,8%) LAI Paliperidone and oral olanzapine 8 (6,1%) LAI Paliperidone, oral olanzapine, and levomepromazine 1 (0,8%) LAI Paliperidone and oral quetiapine 20 (15,3%) LAI Paliperidone, oral quetiapine, and levomepromazine 1 (0,8%) LAI Paliperidone, oral quetiapine, and olanzapine 4 (3,1%) LAI Paliperidone, oral quetiapine, and ziprasidone 2 (1,5%) LAI Paliperidone, oral risperidone, and quetiapine 2 (1,5%) LAI Risperidone (monotherapy) 2 (1,5%) LAI Risperidone and oral olanzapine 1 (0,8%) LAI Risperidone and oral paliperidone 1 (0,8%) LAI Risperidone and oral quetiapine 1 (0,8%) LAI Risperidone, oral quetiapine and levomepromazine 1 (0,8%) LAI Zuclopenthixol (monotherapy) 1 (0,8%) LAI Zuclopenthixol, oral olanzapine, and levomepromazine 1 (0,8%) Total 131 (100%) In all cases, the first antipsychotic is the long-acting injectable and the other(s) are oral. LAI: Long-acting injectable. Main results

According to the SALSEX scores, 77 (58.8%) people, 56 (62.2%) men, and 21 (51.2%) women had some extent of sexual dysfunction. The majority of men and women with sexual dysfunction had a severe dysfunction. The most frequent sexual dysfunction symptom in men (50%) and women (34.1%) was diminished sexual desire. More details are described in Table 3.

Table 3. Prevalence of sexual dysfunction symptoms Variable Total Men Women SALSEX SALSEX: Any degree of dysfunction 77 (58.8%) 56 (62.2%) 21 (51.2%) Spontaneously reports the alteration 16 (12.2%) 13 (14.4%) 3 (7.3%) Loss of libido 59 (45%) 45 (50%) 14 (34.1%) Delayed orgasm or ejaculation 54 (41.2%) 38 (42.2%) 16 (39%) Lack of orgasm or ejaculation 49 (37.4%) 34 (37.8%) 15 (36.6%) Erectile dysfunction/Vaginal lubrication 55 (42%) 41 (45.6%) 14 (34.1%) Good tolerance of the changes in their sexual relations 81 (61.8%) 53 (58.9%) 28 (68.3%)

Out of the 125 people who had a blood test, 47 (56%) men and 25 (61%) women had hyperprolactinaemia.

The prevalence of all the symptoms of sexual dysfunction was analysed to determine which factors could influence their presence or absence. For men, hyperprolactinemia was related to erectile dysfunction (P = 0.04), ejaculation difficulties (P = 0.02), and delayed ejaculation (P = 0.01). For women, vaginal lubrication difficulties could be associated with having one or more somatic disorders (P = 0.02), but no other statistically significant correlations were found.

Different qualitative variables were considered to be potential factors for differences in the prevalence of sexual dysfunction: the psychiatric diagnosis, the combination of antipsychotics and antidepressants the person received, the categorized dose of antipsychotics, the severity of the mental disorder, the somatic disorders present, the presence of hyperprolactinemia, low testosterone, menopause, alcohol consumption, smoking habit, and having a sexual partner. Chi-square tests were calculated to detect the differences between different values of each of these variables and the prevalence of sexual dysfunction. Table 4 includes the prevalence of sexual dysfunction considered as dichotomous variables (present in any severity/absent) according to these potential factors. Among the male participants, higher categorized doses of antipsychotics (P = 0.023), having hyperprolactinemia (P = 0.045), and smoking (P = 0.027) were factors for the presence of sexual dysfunction. The postmenopausal women who smoked and those with hyperprolactinemia had a higher prevalence of sexual dysfunction. However, for this group, the low frequencies in some cells may invalidate the chi-square test results (P = 0.043, both for hyperprolactinemia and smoking).

Table 4. Prevalence of any degree of sexual dysfunction considering variables potentially causing sexual dysfunction and measured through the three instruments (percentages shown by row) Variable Categories Prevalence of sexual dysfunction Men (n (%)) Premenopausal women (n (%)) Postmenopausal women (n (%)) Diagnosis Schizophrenia 40 (60.6%) 7 (53.8%) 5 (45.5%) Schizoaffective disorder 8 (72.7%) 5 (100%) 3 (50%) Bipolar disorder 5 (71.4%) 1 (33.3%) 0 Personality disorder 2 (50%) 0 0 Severe anxiety disorder 1 (50%) 0 0 Antipsychotics combination Sparing 12 (54.5%) 7 (63.6%) 1 (11.1%) Raising 22 (66.7%) 4 (50%) 2 (50%) Sparing & raising 22 (62.9%) 2 (100%) 5 (71.4%) Antipsychotic dose in mg of risperidone Under 6 mg 25 (54.3%) 5 (55.69%) 5 (33.3%) 6,1 to 12 mg 17 (58.6%) 7 (77.8%) 1 (50%) 12,1 and more 14 (93.3%) 1 (33.3%) 2 (66.7%) Somatic disorders No 36 (64.3%) 9 (60%) 1 (14.3%) Yes 20 (58.8%) 4 (66.7%) 7 (53.8%) Hyperprolactinemia No 22 (59.5%) 5 (55.6%) 1 (14.3%) Yes 31 (66%) 8 (66.7%) 7 (53.8%) Low testosterone No 26 (66.7%) n.a. n.a. Yes 24 (63.2%) n.a. n.a. Alcohol No 43 (61.4%) 12 (60%) 8 (42.1%) Yes 13 (65%) 1 (100%) 0 Smoking No 11 (44%) 4 (57.1%) 1 (14.3%) Yes 45 (69.2%) 9 (64.3%) 7 (53.8%) Sexual partner No 46 (62.2%) 9 (60%) 7 (50%) Yes 10 (62.5%) 4 (66.7%) 1 (16.7%) n.a: not applicable. The figures highlighted in bold show statistically significant differences between the different variable levels.

The prevalence of hyperprolactinemia by gender and treatment with different combinations of antipsychotics and antidepressants is detailed in Table 5. Statistically significant differences were found among antipsychotic groups (sparing, raising, and both) for the presence of hyperprolactinemia. This relation was confirmed by gender, for men (P < 0.001) and for women (P < 0.001), even when considering menopause (premenopausal women P = 0.014, postmenopausal women P < 0.001). Those drugs causing hyperprolactinemia more frequently among men and premenopausal women were the prolactin raising, while for postmenopausal women, they were the prolactin raising and the combination of prolactin sparing and raising drugs. However, for women, the frequency of some cells in the table may compromise the validity of the chi-square tests. Following the same pattern, the drug combinations (sparing, raising, and both) were also related to the severity of hyperprolactinemia, both for men and women (chi-square test P < 0.001). Higher categorized doses of antipsychotics were related to the presence of hyperprolactinemia for men but not for women. Hyperprolactinemia was more frequent among men with low testosterone (chi-square test P = 0.03).

Table 5. Prevalence of hyperprolactinemia by gender and treatment with different antipsychotic and antidepressant combinations Gender Antipsychotics and antidepressants Hyperprolactinemia (n (%)) Hyperprolactinemia severity Men* Sparing (n = 19) 0 Sparing and raising (n = 32) 23 (71.9%)

Mild 22 (73.3%)

Moderate 1 (3.3%)

Raising (n = 33) 7 (72.7%)

Mild 18 (54.5%)

Moderate 6 (18.2%)

Women Total Sparing (n = 20) 5 (25%)

Mild 3 (15%)

Moderate 2 (10%)

Sparing and raising (n = 12) 11 (91.7%)

Mild 2 (16.5%)

Moderate 6 (50%)

Severe 3 (25%)

Raising (n = 9) 9 (100%)

Mild 3 (33.3%)

Moderate 3 (33.3%)

Severe 3 (33.3%)

Premenopausal Sparing (n = 11) 3 (27.3%)

Mild 2 (18.2%)

Moderate 1 (9.1%)

Sparing and raising (n = 8) 7 (87.5%)

Moderate 5 (62.5%)

Severe 2 (25%)

Raising (n = 2) 2 (100%)

Moderate 1 (50%)

Severe 1 (50%)

Postmenopausal Sparing (n = 9) 2 (22.2%)

Mild 1 (11.1%)

Moderate 1 (11.1%)

Sparing and raising (n = 4) 4 (100%)

Mild 2 (50%)

Moderate 1 (25%)

Severe 1 (25%)

Raising (n = 7) 7 (100%)

Mild 3 (42.9%)

Moderate 2 (28.6%)

Severe 2 (28.6%)

Of the quantitative variables, only age followed the normal distribution, so non-parametrical tests were applied (Spearman’s Rho) to calculate bivariate correlations. For men, sexual satisfaction correlated negatively with the BPRS score (r=−0.30, P < 0.01) and the SALSEX (r = −0.55, P < 0.01) scores. The prolactin values showed positive correlations with the dose of antipsychotics (r = 0.54, P < 0.001), year