Zinc improves sexual performance and erectile function by preventing penile oxidative injury and upregulating circulating testosterone in lead-exposed rats.

AIM: The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function. METHODS: Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days. RESULTS: Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities. CONCLUSION: This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.

Fadogia agrestis (Schweinf. Ex Hiern) Stem Extract Restores Selected Biomolecules of Erectile Dysfunction in the Testicular and Penile Tissues of Paroxetine-Treated Wistar Rats.

Inadequate release of nitric oxide (NO) by the penile tissue impacts negatively on penile erection causing erectile dysfunction (ED). Fadogia agrestis has been implicated in the management of ED without information on key biomolecules associated with ED in male rats. Therefore, this study evaluated the influence of aqueous extract of Fadogia agrestis stem (AEFAS) on key biomolecules associated with ED in the penile and testicular tissues of male Wistar rats induced with ED by paroxetine. Thirty male rats were assigned into 6 groups (I, II, III, IV, V and VI) of 5. Group I (sham control, without ED) was administered distilled water orally. Paroxetine-induced ED rats in groups II (negative control), III (positive control), IV, V and VI received distilled water, sildenafil citrate (SC, 50 mg/kg body weight) and AEFAS at 18, 50 and 100 mg/kg body weight respectively. Paroxetine lowered/reduced (p < 0.05) the MF, IF, EF, NO, cGMP, catalase, SOD, T-SH, GSH and GST whilst it prolonged/increased ML, IL, EL, PEI, AChE, PDE5, arginase, ACE, TBARS and H2O2. Contrastingly, AEFAS like sildenafil citrate increased (p < 0.05) the penile and testicular NO, cGMP, catalase, SOD, T-SH, GSH and GST and reduced AChE, PDE5, arginase, ACE, TBARS and H2O2 to levels that compared favourably (p > 0.05) with those of sham control. The study concluded that AEFAS restored the NO/cGMP pathway and ED-associated key enzymes in the penile and testicular tissues of male rats via antioxidant means. The study recommended the use of aqueous extract of Fadogia agrestis stem in managing ED after clinical trials.

Aqueous extract of Massularia acuminata exerts erectogenic effect by modulating critical enzymes and hormones in streptozotocin-induced erectile dysfunction in rats.

Massularia acuminata stem is often used in folkloric medicine in the management of erectile dysfunction (ED), without full scientific basis for its action. Thus, the effects of aqueous extract of M. acuminata stem (MAS) on sexual activity, hormonal action, enzymatic activity and levels of molecules associated with erectile function were assessed. ED was induced by single intraperitoneal injection of 50 mg/kg body weight of streptozotocin in rats and treated with sildenafil citrate or MAS (50 or 100 mg/kg) orally for 2 weeks. The results revealed that there was significant (p < 0.05) reduction in mounting and intromission frequencies, testosterone, luteinizing hormone, and nitric oxide levels, as well as elevation in mounting and intromission latencies, phosphodiesterase 5, arginase, acetylcholinesterase, adenosine triphosphatidase, and adenosine deaminase activities, nitric oxide, thiobarbituric acid reactive species, and glycated haemoglobin levels were observed in ED rats in comparison with the control rats. Treatment with MAS or sildenafil citrate significantly (p < 0.05) modulated the sexual behaviour, biochemical parameters and histological architecture, with 100 mg/kg of MAS having the best erectogenic effects. Furthermore, phenolic characterization revealed that catechin and kaempferol as the main phenolic compounds present in MAS, that can act in synergistically or additively with other phytochemicals to confer erectogenic effect.

Grapefruit peel extract mitigates paroxetine-induced erectile dysfunction in rats through stimulation of erectile response, antioxidant status, and inhibition of key enzymes related with impaired penile erection.

Despite the antidepressant potency of paroxetine, its side effect of erectile dysfunction is burdensome. Grapefruit peels (GFPs) are underutilized cultivar wastes with wide range of therapeutic potentials which have been attributed to their antioxidant behavior and phenolic contents' abilities to effectively inhibit enzymatic activities and manage endothelial dysfunction in cardiovascular disorders. This study aims to investigate the erectogenic potentials of GFP extract in a rat model of paroxetine-induced ED. Experimental rats were sectioned into five groups: [1: control; 2: paroxetine (10 mg/kg); 3: paroxetine + sildenafil (5 mg/kg); 4: paroxetine + GFP (50 mg/kg); 5: paroxetine + GFP (100 mg/kg)] and treated for 28 days. Sexual behavior of rats was assessed and effect of GFP on ecto-5' nucleotidases, phosphodiesterase-5, and adenosine deaminase (ADA) activities was determined in rats' penile tissues. The levels of malondialdehyde, nitric oxide (NO) as well as superoxide dismutase (SOD) and catalase activities were also determined. HPLC-DAD analysis showed the presence of naringin, rutin, caffeic acid, quercitrin, quercetin, and kaempferol glycoside. Oral administration of paroxetine reduced erectile response as revealed by their low intromission and mounting numbers as well as high intromission and mounting latencies. Paroxetine caused a significant elevation of ADA and phosphodiesterase-5 activities and malondialdehyde levels with drastic reduction in levels of NO, SOD, and catalase activities in rats' penile tissues. However, GFP extract reversed PDE-5, ADA, and antioxidant activities to normal levels, raised the concentration of NO. These results suggest the erectogenic effects and protective potentials of GFP extract against paroxetine-induced erectile dysfunction. PRACTICAL APPLICATION: Grapefruit peels are an environmental menace in many countries and this study showed that the peels can be used in the prevention / management of erectile dysfunction. The therapeutic potentials of the peels are due to the presence of bioactive compounds such as flavonoids and phenolic acids. Therefore, exploring the erectogenic potentials of the peels will translate to conversion of the wastes to therapeutic products.

Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Abrupt-onset, profound erectile dysfunction in a healthy young man after initiating over-the-counter omeprazole: a case report.

BACKGROUND: Proton pump inhibitors are frequently used (and often overused) medications with adverse effects including vitamin B12 deficiency, Clostridium difficile colitis, and increased risk of chronic kidney disease. Erectile dysfunction is largely unrecognized as an adverse effect of proton pump inhibitors despite increasing evidence that proton pump inhibitors may contribute to impaired nitric oxide generation and endothelial dysfunction. CASE PRESENTATION: A 38-year-old Caucasian man with mild hypertension and no other significant medical history developed profound erectile dysfunction within 2 days of initiating over-the-counter omeprazole therapy, with erectile function rapidly normalizing following discontinuation of the drug. At the time of the episode, the patient was on a stable dose of lisinopril and was taking no other medications or supplements. In the 2 years following the episode, the patient has had no further erectile difficulties. CONCLUSION: Further study of erectile dysfunction as an adverse effect of proton pump inhibitors is needed. In the meantime, proton pump inhibitors should be considered as a potential cause of erectile dysfunction in healthy young patients and as a cause or contributor to erectile dysfunction in older patients in whom erectile dysfunction is often attributed to age or comorbidities.

Phytochemical Screening by LC-ESI-MS/MS and Effect of the Ethyl Acetate Fraction from Leaves and Stems of Jatropha macrantha Müll Arg. on Ketamine-Induced Erectile Dysfunction in Rats.

Jatropha macrantha Müll Arg. L is also known as "huanarpo macho" and used in the Peruvian traditional medicine as an aphrodisiac and erectile dysfunction (ED). The aim of this study was to determine the phytochemical constituents in leaves and stems ethyl acetate fraction (LEAF and SEAF) of J. macrantha and to compare the antioxidant activity and the ameliorative effect on ketamine-induced erectile dysfunction in rats. The phytochemical constituents were determined by LC-ESI-MS/MS, the total phenolic compounds and total flavonoids (TPC and TF) by Folin-Ciocalteu and aluminum chloride, respectively. The antioxidant activity was determined by DPPH, ABTS, and FRAP assays. Experimental groups were divided as follows: I: negative control; II: positive control (ketamine at 50 mg/ kg/d); III: sildenafil 5 mg/kg; IV, V, VI: LEAF at 25, 50 and 100 mg/kg, respectively, and VII, VIII, IX: SEAF at 25, 50, and 100 mg/kg, respectively. The phytochemical analysis revealed the presence mainly of coumarins, flavonoids, phenolic acids, and terpenes. TPC of LEAF and SEAF were 359 ± 5.21 mg GAE/g and 306 ± 1.93 mg GAE/g, respectively; TF in LEAF and SEAF were 23.7 ± 0.80 mg EQ/g, and 101 ± 1.42 mg EQ/g, respectively. The DPPH, ABTS, FRAP in SEAF were 647 ± 3.27; 668 ± 2.30; and 575 ± 2.86 µmol TE/g, respectively, whilst LEAF showed 796 ± 3.15; 679 ± 0.85; and 806 ± 3.42 µmol TE/g, respectively. Regarding sexual behavior, LEAF showed a better effect in mount frequency, intromission frequency, ejaculation frequency, mount latency, intromission latency, ejaculatory latency, and post ejaculatory latency than SEAF. As conclusion, LEAF of J. macrantha at 50 mg/kg showed a better effect on sexual behavior in male rats with erectile dysfunction than SEAF but not higher than sildenafil.

Tangeretin ameliorates erectile and testicular dysfunction in a rat model of hypertension.

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT1R) and gp91phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT1R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT1R/gp91phox expressions and testicular eNOS and StAR expression.

Simultaneous analysis of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

In this paper, an ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF HRMS) method was developed and validated for screening, confirmation and quantitation of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements. The analytes were well separated by the mobile phase consisted of 0.1% formic acid solution and acetonitrile with gradient elution at a flow rate of 0.3 mL/min. The MS analysis was operated in positive mode and the mass error of the 31 compounds were below 2.9 ppm. The method validation showed good linearity with coefficients of determination (r2) higher than 0.9973 for all analytes. LODs and LLOQs ranged from 0.005 to 0.50 µg/g or µg /mL and from 0.02 to 1.24 µg /g or µg/mL, respectively. The accuracy was in the range of 86.6% to 113.7%, while the intra-and inter-day precision were in the ranges of 0.9-7.6% and 0.9-11.4%, respectively. The absolute and relative matrix effect were in the range of 65.8-115.6% and 0.6-13.3%. The mean recoveries were in the range of 80.5-116.9%. The stability ranged from 0.4% to 8.5%. Among 200 batches of herbal-based dietary supplements, sildenafil and/or tadalafil were found to be added illegally in two samples, while not very high concentration of icariin was detected in one sample. The Q-TOF mass spectrometry has been proved to be a very powerful and efficient tool for rapid screening of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements, ensuring food safety and public health.

Orange peels modulate antioxidant markers and key enzymes relevant to erection in the penile tissue of paroxetine-treated rats.

In comparison to other antidepressant drugs, erectile dysfunction (ED) is more pronounced in paroxetine use. On the other hand, orange (Citrus sinensis) peels commonly consumed in various forms are used in folkloric medicine for ED management. Thus, this study evaluated the effect of orange peels infusion on sexual behaviour, nitric oxide (NO) level and some enzymes (arginase, phosphodiesterase-5 [PDE-5], acetylcholinesterase [AChE] and adenosine deaminase [ADA]) in paroxetine-treated rats. Erectile dysfunction was induced with paroxetine (10 mg/kg body weight). The animals were grouped into five (n = 6): normal rats; paroxetine-induced rats; paroxetine-induced rats treated with sildenafil citrate (5 mg/kg); paroxetine-induced rats treated with orange peels infusion (50 mg/kg); Paroxetine induced rats treated with orange peel infusions (100 mg/kg). The results revealed a significant decrease in sexual behaviour, NO level and the activities of antioxidant enzymes, while there was a significant increase in arginase, PDE-5, AChE and ADA activities in paroxetine-induced rats. However, orange peel infusions ameliorated erectile dysfunction in paroxetine-treated rats. This study showed some possible biochemical basis underlying the use of orange peels infusion in erectile dysfunction management.

Towards Improving Post-SSRI Sexual Dysfunction by Using Nutriceuticals: Lessons from a Case Study.

Post-selective serotonin reuptake inhibitors (SSRIs) sexual dysfunction (PSSD) is a new clinical entity occurring after the antidepressant intake, and it is characterized by the fact that patients continue to present sexual side effects after the discontinuation of the drugs. PSSD mainly consists of hypo-anesthesia of the genital area, loss of libido, and erectile dysfunction. Although different management options have been proposed, there is no consensus on the treatment for this syndrome. Herein we report on a young man affected by PSSD who regained sexual functioning after 3-month treatment with EDOVIS, a dietary supplement containing L-citrulline and other commonly used aphrodisiacs. Clinicians should be aware about the possibility of persistent sexual side effects induced by serotoninergic antidepressants and take into considerations the use of nutraceuticals to overcome PSSD.

Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing.

A case of erectile dysfunction induced by red yeast rice in lipid-lowering therapy.

This paper studies a 39-year-old male patient who takes red yeast rice (RYR) for self-therapy in lipid-lowering for 3 weeks. Results show that RYR can decrease most of the blood lipid components but without selectivity. During the treatment, the patient developed erectile dysfunction (ED) and accompanied by a dramatic decrease in sexual desire. The ED symptom gradually disappeared within 5 weeks after stopping RYR intake.

Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity.

To investigate the effect of hyperhomocysteinaemia (HHCy) on penile erectile function in a rat model, a methionine-rich diet was used in which erectile function, the reproductive system, and nitric oxide synthase were characterized. The intracavernous pressure, apomorphine experiments, measurement of oxidative stress, hematoxylin and eosin staining, immunohistochemistry analysis, reverse transcription-polymerase chain reactions and measurement of endothelial nitric oxide synthase activity were utilized. Our results showed that erections in the middle-dose, high-dose, and interference (INF) groups were significantly lower than the control (P < 0.05). INF group, being fed with vitamins B and folic acid, demonstrated markedly improved penile erections compared with the middle-dose group (P < 0.05). HHCy-induced eNOS and phospho-eNOS protein expression was reduced and the antioxidant effect was markedly impaired. The data of the present data provide evidence that HHCy is a vascular risk factor for erectile dysfunction by impairing cavernosa endothelial nitric oxide synthase activity. Intake of vitamins B can alleviate this abnormality.

Antihypertensive therapy causes erectile dysfunction.

PURPOSE OF REVIEW: Erectile dysfunction is a common sexual disorder affecting 40% of men in the United States. However, the pathophysiologic mechanism involved in the causation of erectile dysfunction is multifactorial and not well delineated. RECENT FINDINGS: Several recent studies disclose that erectile dysfunction is the result of multiple interrelated comorbid conditions that include hypertension, coronary artery disease (CAD), heart failure, and diabetes mellitus among them. In addition to comorbid conditions, certain cardiovascular and antihypertensive drugs are also involved in the development of erectile dysfunction, with the most prominent being the thiazide type diuretics, the aldosterone receptor blockers, and the ß-adrenergic receptor blockers. Also, knowledge by the patient of the drug and its action on erectile dysfunction may increase the incidence of erectile dysfunction (Hawthorn effect). Before treatment is initiated, patients should be screened for the presence of erectile dysfunction, because this condition is associated with hypertension, CAD, heart failure, diabetes mellitus, and their treatment and an appropriate treatment regimen should be selected. If that fails, the addition of phosphodiesterase 5 inhibitors to the treatment regimen is recommended. The only exception is a patient with CAD treated with organic nitrates, in which the coadministration of phosphodiesterase 5 inhibitors is strictly prohibited. SUMMARY: Knowledge of the various comorbid conditions and their treatment associated with the development of erectile dysfunction will help the caring physician to treat his patients appropriately and safely. All these aspects will be discussed in this review.

5α-Reductase inhibitors in androgenetic alopecia.

PURPOSE OF REVIEW: The authors will review the current literature on efficacy and safety of 5-alpha reductase inhibitors (5αRIs) for androgenetic alopecia (AGA). RECENT FINDINGS: The 5αRI finasteride and dutasteride are effective in treating AGA and promoting hair regrowth. 5αRI can be given orally, topically and more recently through mesotherapy. However, there has been an increasing concern about permanent sexual adverse events such as impotence and infertility. Most of these reports are published as case reports, and two studies reporting persistent sexual side-effects after discontinuation of finasteride had serious method limitations, as patients were recruited from a website. To our knowledge, permanent sexual adverse events have yet to be published in higher quality studies, such as randomized controlled trials. Although patients treated with 5αRIs have an increased incidence of sexual adverse events, these events decrease if discontinued or over time with continued therapy. SUMMARY: Sexual side-effects are uncommon and resolve spontaneously in most patients even without discontinuing therapy. Significant effort is underway to find delivery systems that optimize delivery and reduce systemic absorption of topical 5αRs including hydroxypropyl chitosan and liposomal and nanoparticulate systems.

[Therapeutic efficacy of Bushengzhuyang Fang (Yangjing Capsule) on phytoestrogen-induced erectile dysfunction: an experimental study].

OBJECTIVE: To investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats. METHODS: Fifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH). RESULTS: At 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group. CONCLUSION: High-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial.

RATIONALE: Saffron (Crocus sativus L.) has shown aphrodisiac effects in some animal and human studies. OBJECTIVES: To assess the efficacy and tolerability of saffron in fluoxetine-related sexual dysfunction. METHODS: This was a 4-week randomized double-blind placebo-controlled study. Thirty-six married male patients with major depressive disorder whose depressive symptoms had been stabilized on fluoxetine and had subjective complaints of sexual impairment entered the study. The patients were randomly assigned to saffron (15 mg twice per day) or placebo for 4 weeks. International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4. RESULTS: Thirty patients finished the study. Baseline characteristics as well as baseline and final depressive symptoms scores were similar between the two groups. Effect of time × treatment interaction on the total score was significant [Greenhouse-Geisser-corrected, F (1.444, 40.434) = 6.154, P = 0.009]. By week 4, saffron resulted in significantly greater improvement in erectile function (P < 0.001) and intercourse satisfaction domains (P = 0.001), and total scores (P < 0.001) than the placebo group. Effect of saffron did not differ significantly from that of placebo in orgasmic function (P = 0.095), overall satisfaction (P = 0.334), and sexual desire (P = 0.517) domains scores. Nine patients (60%) in the saffron group and one patient (7%) in the placebo group achieved normal erectile function (score > 25 on erectile function domain) at the end of the study (P value of Fisher's exact test = 0.005). Frequency of side effects were similar between the two groups. CONCLUSIONS: Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction.

Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

INTRODUCTION: 5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. AIM: The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. METHODS: We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in the literature were reviewed and discussed. Results. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. CONCLUSIONS: We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.

Targeting vascular structure for the treatment of sexual dysfunction.

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular disease often coexist and have many common risk factors. In hypertension, the structure of blood vessels is modified such that there is an increase in medial wall thickness relative to lumen size. Certain antihypertensive agents have been found to induce a regression of vascular structure such that a "hypertensive" vessel appears phenotypically more like that from a normotensive. AIM: To provide an update on the findings to date on the impact of vascular remodeling on erectile function. MAIN OUTCOME MEASURES: Review of peer reviewed literature related to vascular remodeling induced by antihypertensive agents and the potential impact on sexual function. METHODS: A literature review was performed on clinical and experimental evidence regarding the association between cardiovascular disease and ED, the impact of vascular remodeling on these conditions, the impact of antihypertensive therapy on ED, and the mechanisms of antihypertensive drug-induced remodeling. RESULTS: There is increasing evidence that ED may be an early marker for progressing cardiovascular disease. Certain antihypertensive agents have beneficial effects on both vascular structure and erectile function. The major site of resistance in the penile vasculature occurs at the level of the pudendal artery. Although structural remodeling has not yet been investigated in this vessel specifically, antihypertensive drugs have been shown to induce remodeling of the pudendal-penile vasculature and cavernosal arteries. Antihypertensive drug-induced vascular remodeling can be characterized by a decrease in the ratio of wall thickness to lumen diameter, and may result from vascular smooth muscle cell apoptosis, rearrangement of cells around a smaller lumen, and/or changes in the extracellular matrix composition depending on the vessel type. CONCLUSION: Determining the mechanisms involved in antihypertensive drug-induced vascular remodeling in the pudendal vasculature may provide novel targets for the treatment of ED.