Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

BACKGROUND AND OBJECTIVE: PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. METHODS: Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. RESULTS: Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. CONCLUSIONS: PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

Association of NE, leptin, and 5-HT with electrophysiological parameters in patients with primary premature ejaculation.

OBJECTIVE: To investigate the possible role of serum norepinephrine (NE), leptin, and 5-hydroxytryptamine (5-HT) and their correlations with sympathetic skin response located in the penis (PSSR) in primary premature ejaculation (PPE). METHODS: We compared the serum level of NE, leptin, and 5-HT, intravaginal ejaculatory latency time (IELT) and the premature ejaculation diagnostic tool (PEDT) scores between 57 PPE patients and 42 healthy control men as controls, who were recruited between September 2016 and January 2019. Additionally, the amplitude and latency of PSSR were measured and compared between the two groups. RESULTS: Compared with healthy men, both leptin and NE increased significantly in PPE patients (P = .003, P = .005), while serum 5-HT remarkably decreased (P = .002). Serum leptin, NE, and 5-HT were significantly correlated with the diagnosis of PPE, PSSR amplitude, and latency. Moreover, compared with single serum indicator, NE/5-HT and leptin/5-HT had a stronger correlation with both PSSR amplitude (r = .8377, P < .001; r = .9323, P < .001, respectively) and latency (r = -.8058, P < .001; r = -.8901, P < .001, respectively). CONCLUSION: Significant differences in leptin, NE, and 5-HT are observed between PPE patients and the controls, which supports the hypothesis of hyperactive sympathetic nerve system (SNS) in PPE. Additionally, leptin/5-HT ratio may serve as an ideal indicator for reflecting SNS activity and predicting treatment response in PPE patients in the future.

Association Between Post-Ejaculatory Refractory Time (PERT) and Premature Ejaculation (PE).

INTRODUCTION: Patients with premature ejaculation (PE) often complain of difficulty in having second erection, which is not yet investigated using scientific methodology. AIM: Evaluation of the association between post-ejaculation refractory time (PERT) with PE by comparing PERT in premature ejaculators with their age-matched control subjects. METHODS: After ethical committee approval and written informed consent from the participants were obtained, men in a monogamous stable sexual relationship and reporting PE were recruited into the study. Sexually active, matched control subjects were recruited for comparison. Exclusion criteria were erectile dysfunction, diabetes mellitus, cardiovascular diseases, hypogonadism, psychiatric conditions, instrumentation of the genitourinary tract, genitourinary anomalies, and genitourinary infections. Both the premature ejaculators and their control subjects were evaluated with the PE diagnostic tool before initiation of the study. They were asked to record their IELT and PERT over 4 weeks. The statistical analysis was done to obtain descriptive statistics, namely, mean and SD, paired t-tests, and logistic regression analysis. P < .001 was considered significant. MAIN OUTCOME MEASURE: There was a statistically significant association between prolonged PERT and PE in patients with PE compared with their age-matched control subjects. RESULTS: 102 premature ejaculators and an equal number of matched control subjects were evaluated from January 2016-December 2017. The average PERT in premature ejaculators and control subjects was 330 ± 296.63 minutes and 105.64 ± 98.59 minutes, respectively (P < .0001). Increasing age was associated with increasing PERT. PE was more common in patients when PERT exceeded a threshold of 590 minutes. CLINICAL IMPLICATIONS: Until now, the association between PE and PERT with matched-pair analysis was not reported. Our study addresses this association, which can add a new paradigm in the evaluation and management of PE. STRENGTH & LIMITATIONS: The association between PE and prolonged PERT using a statistically appropriate, adequately powered methodology is the strength of the study. The inability to address the causal association between prolonged PERT and PE because of the paucity of evidence at present is the limitation of the study. We believe that the results of this study could trigger further research into such an association, so the mystery of such an association can be unraveled. CONCLUSIONS: The association between prolonged PERT and PE, as seen in our study, is a finding, that needs further research to establish a causal association. However, reporting such an association is necessary because it is contrary to the present understanding. Bhat GS, Shastry A. Association Between Post-Ejaculatory Refractory Time (PERT) and Premature Ejaculation (PE). J Sex Med 2019;16:1364-1370.

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation

Abstract Purpose: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). Materials and Methods: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. Results: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. Conclusions: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation.

PURPOSE: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). MATERIALS AND METHODS: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. RESULTS: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. CONCLUSIONS: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Pharmacokinetics, Safety, and Tolerability of Multiple Doses of the Novel Oxytocin Receptor Antagonist Cligosiban in Development for Premature Ejaculation: Two Randomized Clinical Trials in Healthy Subjects.

BACKGROUND: Cligosiban (formerly IX-01) is a selective oxytocin receptor antagonist being developed for the treatment of premature ejaculation (PE). AIM: To investigate the plasma pharmacokinetics, safety, and tolerability of multiple oral doses of cligosiban in healthy male subjects; measure the amount of cligosiban in semen; and evaluate the potential of cligosiban to modulate CYP3A4. METHODS: Both studies were double-blind, placebo-controlled, parallel group designs involving sequential cohorts of 12 subjects each. Cligosiban dosage regimens were 100 mg, 400 mg, 800 mg, 1200 mg, 1,600 mg and 2,400 mg once daily for 10 days, administered as an aqueous dispersion. OUTCOMES: Blood samplings for cligosiban assays and safety assessments were performed throughout both studies. Semen was collected on day 9 at 2-4 hours postdose in study 1 only. Safety assessments included monitoring of adverse events, 12-lead electrocardiography, vital signs, and laboratory safety assessments. Urine samples for assessment of the 6ß-hydroxycortisol/cortisol ratio were collected before dosing on days 1 and 10. RESULTS: Cligosiban was rapidly absorbed after both single and multiple dosing, with maximum plasma concentrations typically measured at 1-3 hours postdose. The terminal half-life was approximately 12 hours, and steady state was achieved by day 3. Exposure increased approximately proportionally to dose after single dosing but less than proportionally after multiple dosing. Accumulation ratios were higher at the lower doses compared with higher doses (2.3 at 100 mg vs 1.1 at 2,400 mg). The mean amount of cligosiban in semen ranged from 0.22 to 2.01 µg over the 100-1,200 mg dose range (<0.0003% of the administered dose). There were no meaningful differences in the urinary 6ß-hydroxycortisol/cortisol ratio after multiple dosing with cligosiban. Cligosiban appeared to be well tolerated at all dose levels. CLINICAL IMPLICATIONS: Cligosiban is well tolerated following once-daily dosing over a wide dose range and does not appear to modulate CYP3A4 activity, suggesting limited potential for perpetrating drug-drug interactions via this mechanism. STRENGTHS & LIMITATIONS: The 2 controlled trials show good toleration and pharmacokinetic data, including negligible amounts of cligosiban in semen at doses expected to be therapeutic. Toleration of cligosiban will need to be confirmed in studies in patients with PE. CONCLUSION: Cligosiban showed a good safety profile at doses predicted to be therapeutic or supratherapeutic along with a pharmacokinetic profile appropriate for as-required or once-daily dosing. There was no evidence that cligosiban inhibited or induced CYP3A4 at doses up to 2,400 mg. Muirhead GJ, Osterloh IH, Whaley S, et al. Pharmacokinetics, Safety, and Tolerability of Multiple Doses of the Novel Oxytocin Receptor Antagonist Cligosiban in Development for Premature Ejaculation: Two Randomized Clinical Trials in Healthy Subjects. J Sex Med 2019;16:213-222.

Pharmacokinetics, Safety, and Tolerability of Single Oral Doses of a Novel Oxytocin Receptor Antagonist-Cligosiban-in Development for Premature Ejaculation: Three Randomized Clinical Trials in Healthy Subjects.

INTRODUCTION: Cligosiban is a selective oxytocin receptor antagonist being developed for the treatment of premature ejaculation (PE). AIM: Three clinical studies investigated the pharmacokinetics (including effect of food and formulation), central penetration, safety, and tolerability of single oral doses of cligosiban in healthy subjects. METHODS: Study 1 was a double-blind, randomized, placebo-controlled, crossover design in 3 cohorts of 10 subjects each. Single doses of 0.3-2,400 mg cligosiban were administered as aqueous solutions or dispersions under fasting and fed (800 mg only) conditions. Studies 2 and 3 were open-label, randomized, crossover designs in 12 subjects each. Study 2 investigated 800 mg cligosiban administered as capsules and aqueous dispersion under fasting conditions, and capsules under fed conditions. Study 3 investigated 1,600 mg cligosiban administered as caplets and aqueous dispersion under fasting conditions, and caplets under fed conditions. MAIN OUTCOME MEASURES: Blood sampling for cligosiban assay and safety assessments were conducted throughout all studies. Cerebrospinal fluid (CSF) samples for cligosiban assay were collected in study 2. RESULTS: Cligosiban was rapidly absorbed under fasting conditions with peak concentrations generally occurring within 1-2 hours post-dose regardless of formulation. Maximum observed plasma concentration (Cmax) and area under the concentration time curve extrapolated to infinity (AUC0-∞) increased approximately dose-proportionally from 0.3-10 mg, but sub-proportionally from 30-2,400 mg. Cligosiban exposure was similar when administered as a dispersion or capsule (800 mg) under fasted conditions, but higher (87% increase) when administered as a caplet compared to the dispersion (1,600 mg). Food decreased the rate of absorption for all 3 formulations (median time to Cmax 3-6 hours compared to 1-2 hours fasted) but increased the extent of absorption (Cmax and AUC0-∞ increased by 75-149% and 33-49%, respectively). Cligosiban was detected in CSF at concentrations approximately 40% of unbound plasma concentrations. Cligosiban was well tolerated at all doses. CLINICAL IMPLICATIONS: Cligosiban is well tolerated over a wide dose range, and has the pharmacokinetic properties to be taken as required prior to sexual intercourse in men with PE and to antagonize the oxytocin receptor in the brain and spinal cord. STRENGTHS & LIMITATIONS: Three controlled trials show similar toleration and pharmacokinetic data. Cligosiban in CSF indicates its likely presence in all central nervous system tissue. These data need to be investigated and confirmed in multiple-dose studies prior to investigation in phase-II studies in men with PE. CONCLUSION: Cligosiban had a good safety/tolerability profile at doses predicted to be therapeutic or supra-therapeutic and a pharmacokinetic profile appropriate for "as-needed" dosing for men with PE. Osterloh IH, Muirhead GJ, Sultana S, et al. Pharmacokinetics, Safety, and Tolerability of Single Oral Doses of a Novel Oxytocin Receptor Antagonist-Cligosiban-in Development for Premature Ejaculation: Three Randomized Clinical Trials in Healthy Subjects. J Sex Med 2018;15:1547-1557.

Serum vitamin D level may be a novel potential risk factor for premature ejaculation: a comparative study.

PURPOSE: To compare serum level of vitamin D [25(OH)D] in patients with life-long premature ejaculation (LPE) versus healthy controls. METHODS: Healthy married potent males were recruited from February 2017 to January 2018. Group A included 40 patients suffering from LPE who were compared versus 40 healthy controls (Group B). Participants suffering from hormonal disorders, obesity, neurological, psychological, or chronic diseases or taking medications that may affect ejaculatory function, serum level of vitamin D, or the accuracy of intra-vaginal ejaculation latency time (IELT) were excluded. LPE was self-reported by the patients with subsequent feelings of frustration and measured by premature ejaculation diagnostic tool (PEDT) and IELT using stopwatch handled by their partners. 25(OH)D was measured by obtaining 2 ml of venous blood. Statistical analysis was performed using Student t, Mann-Whitney, Chi square tests, logistic regression analysis, and Spearman correlation. RESULTS: Sixteen (20%) participants had vitamin D insufficiency/deficiency. All of them were in PE group. 25(OH)D correlated significantly with IELT (r2 = 0.349; p < 0.001) and PEDT (r2 = 0.425; p < 0.001). There was no statistically significant difference in age (p = 0.341), BMI (p = 1) or IIEF-5 (p = 0.408) in both groups. 25(OH)D was significantly lower in patients than controls (35.75 vs. 58.92 ng/ml, p < 0.001). ROC analysis revealed that the best cut-off value of 25(OH)D to detect patients suffering from LPE was 50.65 ng/ml with a sensitivity and specificity of 85% for both. 25(OH)D remained a significant risk factor for LPE in the logistic regression analysis (p < 0.001). CONCLUSIONS: The current study showed that vitamin D has significant association with LPE and correlates significantly with IELT and PEDT.

Serotonin transporter (5-HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation.

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico-limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5-HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence-based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence-based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22-25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5-HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI-II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self-estimated IELT and intercourse satisfaction (r = -0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5-HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence-based lifelong premature ejaculatory dysfunction patients.

Visceral adiposity index is associated with premature ejaculation inversely: a cross-sectional study.

OBJECTIVE: Visceral adiposity index (VAI) is a novel indicator for the assessment of visceral obesity. In this study, we aimed to evaluate the relationship between VAI and premature ejaculation (PE). MATERIALS AND METHOD: A total of 300 men were included in the study. Hundred and fifty men with PE and 150 men without PE (control). All men were evaluated for PE by premature ejaculation diagnostic tool (PEDT). VAI levels were calculated using body mass index (BMI), high density lipoprotein and triglyceride (TG) levels. RESULTS: Mean age of the study groups was 34.3 ± 5.2 (30-60) years and the mean age of the controls were 35.9 ± 5.3 (30-60) years. The men with PE had lower BMI, TG levels, waist circumference (WC) and higher high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level was 4.13 ± 0.7 in study group and 5.72 ± 1.6 in control group, respectively. VAI levels were statistically higher in men without PE (p < .001). DISCUSSION: Our cross-sectional study demonstrated a negative correlation between VAI and PE. VAI is superior index for the evaluation and calculation the relationship between obesity and PE.

Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE.

Assessment of hormonal activity in patients with premature ejaculation

ABSTRACT Purpose Premature ejaculation is considered the most common type of male sexual dysfunction. Hormonal controls of ejaculation have not been exactly elucidated. The aim of our study is to investigate the role of hormonal factors in patients with premature ejaculation. Materials and Methods Sixty-three participants who consulted our outpatient clinics with complaints of premature ejaculation and 39 healthy men as a control group selected from volunteers were included in the study. A total of 102 sexual active men aged between 21 and 76 years were included. Premature ejaculation diagnostic tool questionnaires were used to assessment of premature ejaculation. Serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, total and free testosterone, thyroid-stimulating hormone, free triiodothyronine and thyroxine were measured. Results Thyroid-stimulating hormone, luteinizing hormone, and prolactin levels were significantly lower in men with premature ejaculation according to premature ejaculation diagnostic tool (p=0.017, 0.007 and 0.007, respectively). Luteinizing hormone level (OR, 1.293; p=0.014) was found to be an independent risk factor for premature ejaculation. Conclusions Luteinizing hormone, prolactin, and thyroid-stimulating hormone levels are associated with premature ejaculation which was diagnosed by premature ejaculation diagnostic tool questionnaires. The relationship between these findings have to be determined by more extensive studies.

Relation between blood vitamin B12 levels with premature ejaculation: case-control study.

The aim of this study was to investigate whether vitamin B12 levels are associated with premature ejaculation (PE). A total of 109 subjects (56 PE and 53 controls) were included in this study. PE was defined as self-reported intravaginal ejaculatory latency time (IELT) based on the Diagnostic and Statistical Manual of Mental Disorders IV criteria and those who had had an IELT of <2 min was considered as PE. All participants were evaluated using premature ejaculation diagnostic tool (PEDT), International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). The vitamin 12 levels were measured in all subjects. The mean age between the PE and controls was comparable (p = .084). Mean IIEF and BDI scores between the two groups did not statistically differ. The mean IELT values in the PE group were significantly lower than in the control group (p < .0001). PE patients reported significantly lower vitamin B12 levels compared with the controls (213.14 vs. 265.89 ng ml-1 ; p < .001). The ROC analysis showed a significant correlation between the diagnosis of PE and lower vitamin B12 levels. This study has demonstrated that lower vitamin B12 levels are associated with the presence of PE. This work also shows a strong correlation between vitamin B12 levels and the PEDT scores as well as the IELT values.

Assessment of hormonal activity in patients with premature ejaculation.

PURPOSE: Premature ejaculation is considered the most common type of male sexual dysfunction. Hormonal controls of ejaculation have not been exactly elucidated. The aim of our study is to investigate the role of hormonal factors in patients with premature ejaculation. MATERIALS AND METHODS: Sixty-three participants who consulted our outpatient clinics with complaints of premature ejaculation and 39 healthy men as a control group selected from volunteers were included in the study. A total of 102 sexual active men aged between 21 and 76 years were included. Premature ejaculation diagnostic tool questionnaires were used to assessment of premature ejaculation. Serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, total and free testosterone, thyroid-stimulating hormone, free triiodothyronine and thyroxine were measured. RESULTS: Thyroid-stimulating hormone, luteinizing hormone, and prolactin levels were significantly lower in men with premature ejaculation according to premature ejaculation diagnostic tool (p=0.017, 0.007 and 0.007, respectively). Luteinizing hormone level (OR, 1.293; p=0.014) was found to be an independent risk factor for premature ejaculation. CONCLUSIONS: Luteinizing hormone, prolactin, and thyroid-stimulating hormone levels are associated with premature ejaculation which was diagnosed by premature ejaculation diagnostic tool questionnaires. The relationship between these findings have to be determined by more extensive studies.

Levels of estradiol and testosterone are altered in Chinese men with sexual dysfunction.

An estimated 20-30% of adult men have at least one manifestation of sexual dysfunction, the most common of which are premature ejaculation (PE) and erectile dysfunction (ED). Emerging evidence has suggested an association between the regulation of hormones with the processes of erection and ejaculation. In this study, we aim to investigate the relationship between sexual dysfunction, namely, PE and ED, and the levels and ratios of estradiol to testosterone in Chinese men. A retrospective case-control study was performed involving 878 male patients aged from 18 to 74 years (mean: 36 years). The ratio of estradiol to testosterone was significantly higher for subjects with ED (7.45 ± 3.09 × 10(-3) ; p < 0.001), and combined PE and ED (6.66 ± 3.05 × 10(-3) ; p = 0.032) compared with that of the control group (6.01 ± 2.61 × 10(-3) ). The ratio was also significantly higher for ED patients when compared with PE patients (5.26 ± 2.18 × 10(-3) ; p < 0.001). Furthermore, compared with the control group, subjects with PE had similar levels of estradiol (95.47 ± 37.86 pmol/L vs. 94.12 ± 32.32 pmol/L; p = 0.678) but significantly higher levels of testosterone (18.66 ± 6.03 nmol/L vs. 16.82 ± 4.93 nmol/L; p < 0.001). This contrasted with the ED group, which showed similar levels of testosterone (16.96 ± 5.86 nmol/L vs. 16.82 ± 4.93 nmol/L; p = 0.773) and significantly higher levels of estradiol (116.88 ± 40.81 pmol/L vs. 94.12 ± 32.32 pmol/L; p < 0.001) compared with control. Subjects with combined ED and PE also had a significantly higher level of estradiol (104.98 ± 43.99 pmol/L vs. 94.12 ± 32.32 pmol/L; p = 0.014) and similar levels of testosterone (17.30 ± 7.23 nmol/L vs. 16.82 ± 4.93 nmol/L; p = 0.503) compared with control. In conclusion, this study involving Chinese males with sexual dysfunction reports, for the first time, that there is an association between sexual dysfunction and changes in levels of estradiol and testosterone. Further studies are required to ascertain the role of sexual hormone regulation in sexual function.

Association Between Changes in Serum 5-Hydroxy-Tryptamine Concentrations and Improvement in Clinical Symptoms in Primary Premature Ejaculation with Paroxetine Treatment.

BACKGROUND: This study aimed to investigate the association between changes in serum 5-hydroxy tryptamine (5-HT) concentrations and improvement in clinical symptoms in primary premature ejaculation with paroxetine treatment. MATERIAL AND METHODS: A total of 142 men aged 18-65 years with a history of lifelong premature ejaculation and an intravaginal ejaculation latency time (IELT) <120 s were included in this study. Patients were divided into 3 groups according to IELT: IELT ≤30 s (group A), (IELT >30 s and ≤60 s (group B), and IELT >60 s and <120 s (group C). Patients in the 3 groups were administered paroxetine hydrochloride 20 mg/d for 8 weeks. Blood samples were obtained from the candidates in the screening period and after 8 weeks of treatment. Plasma 5-hydroxy-tryptamine (5-HT) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Reliable data from 125 patients were obtained. There were 41 patients in group A, 40 in group B, and 44 in Group C. IELT and serum 5-HT concentrations were significantly improved in the 3 groups after treatment (all P<0.001). The mean change and fold increase in IELT and the mean change in serum 5-HT concentrations in group A were significantly higher than those in groups B and C (all P<0.001). The mean change and fold increase in IELT and the mean change in serum 5-HT concentrations in group B were significantly higher than those in group C (all P<0.001). Significantly more patients in group A achieved clinical benefits than those in groups B and C (P<0.001). CONCLUSIONS: Improvement in serum 5-HT concentrations has obvious association with primary premature ejaculation symptom improvement with paroxetine use.