Dopamine as a potential diagnostic biomarker in women’s sexual dysfunction
La dopamina como potencial biomarcador diagnóstico en la disfunción sexual de la mujer

2.1 Patients

This study involved 168 Egyptian females. They were enrolled in outpatient clinics of Gynecology, Andrology and Sexually Transmitted Diseases (STDs), Menoufia University. Women having normal sexual function were selected from employees and medical professionals working in that hospital, in addition to friends, relatives and colleges. The included women were divided into two groups; group 1; include 84 women having sexual dysfunction (FSD group) and group 2; include 84 women having normal sexual function (control group).

The study included sexually active married females ranged from 27 to 43 years [14] (age of legal marriage at 18 years [15], according to “Egypt National Child Protection Legislation”) with normal regular menstrual cycle. Any female had one or more of the following was excluded from the study: (1) irregular or any abnormality of menstrual cycles; (2) women less than 18 years [15] or post-menopausal women; (3) evident psychological disorders (e.g., depression, anxiety and schizophrenia) and neurological disorders (e.g., epilepsy, Alzheimer’s disease and ataxia); (4) the hypertensive, diabetes, pregnant, lactating females and those receiving contraceptives or hormonal therapy.

The studied females were subjected to some questionnaires to assess their demographic (age, residence, education, occupation and socioeconomic level); gynecological (level of sexual knowledge, circumcision, having children, number of children, previous marriage and years of marriage) and husband data (marital relation, husband desire and erection) as well as sexual function using female sexual function index (FSFI). The FSFI was utilized to assess FSD which has validated by Arabic language to evaluate six domains throughout the previous 4 weeks: (a) desire, (b) arousal, (c) lubrication, (d) orgasm, (e) satisfaction and (f) pain. The scale for each domain was range between 0 to 6. The total score was calculated by summation of all domain scores. It had range from 2 to 36. Total score ≤23 means sexual dysfunction (patient group), and >23 means normal sexual function (control group) [15, 16, 17].

2.2 Laboratory analysis

At 21 days after the first day of the last menstrual cycle of each participant (the mid-luteal phase), under complete aseptic conditions, morning 5 mL of venous blood was withdrawn after 10–12 hours fasting. The samples were transferred into a plain tube left to clot for 30 minutes, then centrifuged at 3000 rpm for 10 minutes. The obtained sera were kept frozen at −20 °C till time of analysis.

Estrogen [18], progesterone [19] and DHEA [20] were assayed by the IMMULITE 2500 (Diagnostic Products Corp., Los Angeles, CA, USA), which is an automated, random-access immunoassay analyzer with a solid phase washing process and a chemiluminescence detection system [14]. Prolactin was measured by electro-chemiluminescence immunoassay analyzer (ECLIA) from Roche Diagnostics (Elecsys® Prolactin II, cobas e402/801, Indianapolis, IN, USA) [13, 21]. Dopamine assay was investigated by the competitive Dopamine Enzyme Linked Immunosorbent Assay (ELISA) Kit from Abcam (ab285238) (Boston, MA, USA) according to the manufacturer instruction [22].

2.3 Statistical analysis

Statistical analysis of the present study was conducted with SPSS Version 23 (IBM Corp., Armonk, NY, USA). Quantitative data were appeared as mean ± standard deviation (SD) [14], where student t-test was used for comparison of two groups with normally distributed data, while Mann Whitney (U test) was used for not normally distributed data. Number and percentages (%) were used to express qualitative data where Chi-square (χ²) and fisher exact test were used. Correlation test (r-test) was used to test association between quantitative data. Receiver operator characteristic (ROC) curve with respective points of maximal accuracy for sensitivity and specificity were generated. Area under the ROC curve measures the accuracy of the test. An area of 1 represents a perfect result; an area of 0.5 represents a worthless result. Differences were considered significant at two-sided p-value < 0.05.

3.1 Socio-demographic, gynaecological and husband data of all subjects

The age of the studied women sexually active married with normal regular menstrual cycle (n = 168) ranged from 27 to 43 years (FSD, 36.76 ± 6.79 and normal sexual function, 36.71 ± 6.36 years; Table 1). More than half were from urban (102/168, 60.7%). Most of our participants were low educated (148/168, 88%) and had moderate socioeconomic level (113/168, 67.3%) and 109 of them had a professional occupation (47.4%). Regarding gynaecological data most of studied women had children (153/168, 91%) with a mean number of two children. About half of them were with low sexual knowledge (79/168, 47%). Most of them were circumcised (123/168, 73.2%) and 4 of them were previously married. More than half of the studied women (93/168, 55%) had excellent marital relationship. Most of the studied women reported no abnormality regarding their husband desire (141/168, 84%) and erection (150/168, 89%).

Women with longer marriages, parity, more children, circumcision, greater husband desire and erection difficulties were all found to be potential risk factors for FSD when compared to controls (p < 0.05) (Table 1).

3.2 FSFI domains of all women

Sexual desire, sexual arousal, lubrication, sexual orgasm and satisfaction scores were significantly lower in female having FSD than controls (p < 0.001 for all). However, pain score was significantly higher in those having FSD than controls (p = 0.004). The FSFI total score was significantly lower in women having FSD than those with normal sexual function (p < 0.001) (Fig. 1I).

3.3 Serum dopamine and sex hormones levels of all women

Serum estradiol levels were significantly lower in women having sexual dysfunction (33.92 ± 5.45 pg/mL vs. 57.97 ± 2.87 pg/mL, p < 0.001) than those with normal sexual function. However, serum progesterone (1.62 ± 0.52 ng/mL vs. 1.38 ± 0.05 ng/mL, p < 0.001), DHEA (3.47 ± 0.06 ng/mL vs. 1.16 ± 0.07 ng/mL, p < 0.001) and prolactin (13.45 ± 1.89 ng/mL vs. 5.00 ± 0.34 ng/mL, p < 0.001) levels were significantly higher in women having sexual dysfunction than those with normal sexual function. Serum dopamine levels were significantly lower in women having sexual dysfunction (6.68 ± 0.45 ng/mL vs. 11.48 ± 0.27 ng/mL, p < 0.001) than those with normal sexual function (Fig. 1IIA–E).

3.4 Diagnostic validity of estradiol, progesterone, DHEA, prolactin and dopamine levels in women’s with sexual dysfunction

In FSD group, a predictor of FSD was diagnosed when women had a cut-off point value of estradiol (31.7 pg/mL) with sensitivity (99%) and specificity (87%); progesterone (0.125 ng/mL) with sensitivity (74%) and specificity (1%); DHEA (4.025 ng/mL) with sensitivity (99%) and specificity (94%), prolactin (4.025 ng/mL) with sensitivity (77%) and specificity (55%); and dopamine (8.8 ng/mL) with sensitivity of (75%) and specificity of (92%) (p < 0.001 for all) (Fig. 1IIIA–C). Also, other parameters such as the accuracy with area under the curve (AUC) and 95% confidence interval (CI) for all hormones as shown in Fig. 1IIIC.

Fig. 1.Female sexual function index (FSFI) and sex hormones and dopamine levels in women’s with sexual dysfunction. (I) FSFI domains in all women. (II) Comparison of serum sex-steroid hormones, prolactin and dopamine hormone levels in all women. This figure showed serum estradiol (IIA), progesterone (IIB), dehydroepiandrosterone (DHEA, IIC), prolactin (IID) and dopamine (IIE) levels in female sexual dysfunction (FSD) and normal sexual function (control group). (III) The area under the receiver operating characteristics (ROC) curve for prolactin (IIIA) and dopamine (IIIB) levels in all participant women. Diagnostic validity, cut-off points, sensitivity and specificity of estradiol, progesterone, dehydroepiandrosterone (DHEA), prolactin and dopamine levels were assessed in all participant women (IIIC). Data were presented as mean ± SD. *p value is significant < 0.001. **p value is significant < 0.05; AUC: area under the curve; CI: confidence interval.

In the entire studied participants, all women were classified according to serum prolactin and dopamine levels into four quartiles depending on statistically cut-off points the level of prolactin and dopamine (Fig. 2A). The analysed data showed that the highest quartile levels of prolactin (quartile-3 and quartile-4 groups) (Fig. 2B) and lowest quartile levels of dopamine (quartile-1 and quartile-2 groups) (Fig. 2C) were associated with women’s with sexual dysfunction versus controls.

3.5 Serum level of dopamine and risk of women’s sexual dysfunction

In the entire studied participants, all women were classified according to serum dopamine levels (cutoff point, 8.8 ng/mL) into low and high groups (Fig. 2A,D). Therefore, 70 women had low levels of dopamine, while 98 women had high levels of dopamine. The age of women based on low dopamine group (36.4 ± 6.56) versus high dopamine group (35.91 ± 7.21) were not show any significant difference (p = 0.65). The other laboratory hormonal levels based on low dopamine levels (<8.8 ng/mL, p < 0.001) showed a significantly higher prevalence in patients with low level of estradiol (p < 0.001) and high levels of serum progesterone (p < 0.001), DEHA (p < 0.001) and prolactin (p = 0.004) (Fig. 2D).

Fig. 2.The incidence of female sexual dysfunction (FSD) among all subjects. All women were classified according to quartiles levels of prolactin and dopamine (A). Distribution of percentage % of female sexual dysfunction (FSD) among the different quartiles of prolactin (B) and dopamine (C) in FSD and normal sexual function (control group). Laboratory hormonal data of all participants according to cutoff value of dopamine levels (D). DHEA: dehydroepiandrosterone. Data were presented as a percentage %, mean ± SD. *p value is significant < 0.05.

3.6 Correlation of serum dopamine to age, FSFI domains and other hormones

In all participant women, serum dopamine levels were significant negative correlations with age (r = −0.31, p < 0.001) (Fig. 3I). There was a significant positive correlation between serum DHEA level and arousal domain (r = 0.16, p = 0.04), but negatively with pain domain (r = −0.19, p = 0.01) (Fig. 3I). There was a significant positive correlation between serum prolactin level and orgasm domain (r = 0.37, p < 0.001) but negatively with arousal (r = −0.49, p < 0.001), lubrication (r = −0.49, p < 0.001), satisfaction (r = −0.46, p < 0.001), pain domain (r = −0.40, p < 0.001) and total scores (r = −0.05, p < 0.001) (Fig. 3I). On the other hand, there was a significant positive correlation between serum dopamine level and arousal domain (r = 0.16, p = 0.04), and significant negative correlation regarding pain domain (r = −0.19, p = 0.01) (Fig. 3I).

In all participant women, there was a non-significant positive correlation between serum dopamine regarding estradiol and progesterone levels (r = 0.03, p = 0.69; r = 0.045, p = 0.56) respectively (Fig. 3IIA,B). On other hand, a significant negative correlation between serum dopamine with DHEA (r = −0.45, p < 0.001) and prolactin (r = −0.28, p < 0.001) levels was observed (Fig. 3IIC,D).

Fig. 3.Correlation of serum dopamine to age, FSFI domains and sex hormones. (I) Correlations between studied hormones and different domains among all participant women. (II) Correlation of dopamine and other sex hormonal levels in all participant women: Correlation between dopamine and estradiol level (IIA); correlation between dopamine and progesterone level (IIB); correlation between dopamine and dehydroepiandrosterone (DHEA) level (IIC); and correlation between dopamine and prolactin level (IID). DHEA: dehydroepiandrosterone; r: Spearman correlation; *p value is significant < 0.05.