|Year : 2020 | Volume
| Issue : 2 | Page : 55-63
Erectile dysfunction and statins: The assorted view of preponderance
Hayder M Al-kuraishy, Ali I Al-Gareeb, Thabat J Al-Maiahy
Department of Pharmacology, Toxicology and Medicine, College of Medicine, Almustansiriya University, Baghdad, Iraq
|Date of Submission||20-May-2019|
|Date of Decision||29-Nov-2019|
|Date of Acceptance||20-Dec-2019|
|Date of Web Publication||30-Mar-2020|
Hayder M Al-kuraishy
Department of Pharmacology, Toxicology and Medicine, College of Medicine, Almustansiriya University, Baghdad
Source of Support: None, Conflict of Interest: None
Objective: To explore the association between statin therapy and the risk of erectile dysfunction by literature review.
Methods: We conducted diversities of search strategies including electronic database searches of MEDLINE, Scopus, Pubmed and Web of Science using MeSH terms, keywords and title words during the search. Reference lists of identified and public articles were reviewed. In addition, only English articles were considered and case reports were not concerned in the review. The key features of recognized applicable search studies were considered and the conclusions were summarized in a narrative review.
Results: Different studies gave a consensus that erectile dysfunction was regarded as an early sign of silent cardiovascular disorder and hidden atherosclerosis. Different studies reported that statins might induce erectile dysfunction through induction of peripheral neuropathy, cognitive deficits, and reduction of circulating testosterone. However, most of recent studies illustrated that statins led to a significant improvement in erectile function and sexual health in men with age over forty years. Atorvastatin advanced endothelial nitric oxide concentrations through activation and upregulation of endothelial nitric oxide synthase and rescued phosphodiesterase-5 inhibitors non-responders since nitric oxide and cyclic guanosine monophosphate increased penile blood flow and improved erectile function.
Conclusions: According to the assorted view of preponderance, statins improved erectile dysfunction is more dominant than statins induced erectile dysfunction. Therefore, statins regardless of its property improve erectile dysfunction through amelioration of penile endothelial dysfunction, and penile neuronal reflexes that are inter-related during sexual excitation and penile erection.
Keywords: Erectile dysfunction; Statins; Testosterone
|How to cite this article:|
Al-kuraishy HM, Al-Gareeb AI, Al-Maiahy TJ. Erectile dysfunction and statins: The assorted view of preponderance. Asian Pac J Reprod 2020;9:55-63
|How to cite this URL:|
Al-kuraishy HM, Al-Gareeb AI, Al-Maiahy TJ. Erectile dysfunction and statins: The assorted view of preponderance. Asian Pac J Reprod [serial online] 2020 [cited 2021 May 6];9:55-63. Available from: http://www.apjr.net/text.asp?2020/9/2/55/281074
| 1. Introduction|| |
Erectile dysfunction is defined as a failure or inability to maintain penile erection for suitable pleasure during sexual intercourse . It affects more than 150 million worldwide, which may be doubled by 2025. Erectile dysfunction is often linked with different cardio- metabolic disorders such as type 2 diabetes mellitus (T2DM), hypertension, ischemic heart disease and hypogonadism. It has been reported that erectile dysfunction is associated with ischemic heart disease since erectile dysfunction proceeds and heralds the onset of ischemic heart disease .
The prevalence of erectile dysfunction is surprisingly high, affecting 40% of the population. This prevalence is affected by population characteristics and methods used for the assessment of erectile dysfunction. Since single question may be used for assessment of erectile function while other trials used more sophisticated and validated questionnaires. Although erectile dysfunction affects sexual and mental health, the rates of consultation for erectile dysfunction remain low and not all patients respond to the phosphodiesterase inhibitors .
Vasculogenic erectile dysfunction is related to different risk factors including T2DM, hypertension, smoking and dyslipidemia. Moreover, the presence of erectile dysfunction indicates the underling cardiovascular disorders and complications; thus, assessment of erectile function should be part of the evaluation of hypertensive patients mainly those over 50 years . Medical literature and different epidemiological trials illustrated that age is strongly linked to erectile dysfunction. Also, modifiable risk factors such as smoking, sedentary life and dyslipidemia are regarded as second main causes of erectile dysfunction which could be reversed .
Dyslipidemia is strongly associated with erectile dysfunction since every mmol/L increase in serum cholesterol is associated with a 32% increase in erectile dysfunction. Therefore, hyperlipidemia is correlated with erectile dysfunction due to the development of endothelial dysfunction through the impairment of nitric oxide (NO) synthesis and release .
Statins that are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG- CoA) reductase inhibitor are the first-line in the treatment of hyperlipidemia and major cardiac events regardless of lipid profile due to pleiotropic properties. Statins improve endothelial function prior to the improvement of total cholesterol ,. However, there are conflicting reports regarding the impact of statins on sexual function. The negative effects of many drugs on male sexual function are well-known. However, the relationship between statins and male sexual function is not clear. A number of studies have hypothesized that statins were associated with erectile dysfunction; whereas, some others advocated that statins improve erectile dysfunction . Therefore, the objective of the present study was to elucidate the potential effect of statins therapy on the erectile dysfunction regarding the assorted view of preponderance.
| 2. Search Approach and Strategy|| |
A diversity of search strategies was taken on and assumed which included electronic database searches of MEDLINE, Scopus, Pubmed and Web of Science using MeSH terms, keywords and title words during the search. No time limits in this study, so we can know the previous and recent views, regarding the potential effects of statins on the human erectile dysfunction. The terms used for these searches were as follows: [statins or cholesterol-lowering agent] AND [erectile dysfunction or impotence or failure of erection or penile erection or premature ejaculation] AND [HMG- CoA OR HMG-CoA antagonists or HMG-CoA inhibitors] AND [male erectile dysfunction or dyslipidemia induced-impotence or diabetic induced-impotence or autonomic neuropathy or insulin resistance]. Reference lists of identified and public articles were reviewed. In addition, only English articles were considered and case reports were not concerned in the review [Figure 1]. The key features of recognized applicable search studies were considered and the conclusions were summarized in a narrative review.
| 3. Statins Induced-Erectile Dysfunction|| |
Normally, an international index of erectile function (IIEF) is used for the estimation of male erectile function. It is composed of five scores: normal IIEF (22-25), mild erectile dysfunction (17-21), moderate erectile dysfunction (12-16), severe erectile dysfunction (8-11) and very severe (less than 7). The prevalence of erectile dysfunction depends on the studied population. In some studies, the abridged 5-item version of IIEF-5 addresses the relevant domains of male sexual function (i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction). The questionnaire is self-administered in clinical settings . Moreover, erectile dysfunction is not screened on a regular basis at cardiology departments in such a high-risk population. In the younger cohort of acute myocardial infarction patients, only 2 out of 25 patients informed their cardiologists about their erectile dysfunction and nobody diagnosed the older patients with erectile dysfunction. As well, erectile dysfunction with reported data is highly prevalent in the group of young acute myocardial infarction survivors. The IIEF-5 questionnaire seems to be a very useful diagnostic tool in the cardiology practice in order to not neglect such an important symptom. There is no direct correlation between erectile dysfunction and type of coronary artery disease. Patients with a single-vessel disease are suffering from erectile dysfunction as well as those with multiple coronary diseases .
Different observational studies confirmed that statin therapy leads to significant erectile dysfunction. Solomon et al illustrated that statin therapy decreases IIEF from 21.0 to 6.5 and within six months of statin therapy; IIEF was negatively correlated with age and statins duration . Likewise, Hall et al demonstrated an association between statin therapy and erectile dysfunction only in male patients with age less than 55 years in a study involved 1 899 patients with cardiovascular complications with or without T2DM . No obvious characteristics could be identified in patients developing erectile dysfunction. Spontaneous reports are often compounded with imperfect clinical formation. The elapsed time of drug exposure to the progress of erectile dysfunction ranged from 1 day to several years, which concurs with other literature. Since the pathways for their actions and the structures of the various types of statins can decrease the cholesterol levels, testosterone synthesis may be affected. This mechanism might make the association between erectile dysfunction and types of statins clear since libido is closely related to serum testosterone levels . Besides, malfunctions of low-density lipoprotein receptor affect de novo synthesis of cholesterol, therefore, statins and/ or hyperlipidemia are found to be risk factors in the initiation of erectile dysfunction .
3.1. Statins induced-hormonal changes
Statins therapy leads to a significant reduction in total and free testosterone that is linked with the development of erectile dysfunction. This reduction is due to notable inhibition of testicular steroidogenesis by statins. As well, long-term statin therapy causes testicular atrophy and hypogonadism which ultimately lead to erectile dysfunction . Previously, Stanworth et al promulgated that statins therapy reduced total testosterone but not free or bioavailable one which is the active form and correlated with erectile and gonadal functions . Statins inhibit testosterone production only at higher doses, as well as, atorvastatin but not simvastatin reduced total testosterone due to higher potency and duration of atorvastatin. Also, atorvastatin suppresses the hepatic production of sex hormone-binding globulin causing a significant decline in the circulating total testosterone .
Amid different studies concerning the effect of statins on testosterone levels and erectile function, the study of Bolat et al disclosed a great link between statins and erectile dysfunction through the reduction of testosterone levels. It has been shown that disruption of cholesterol biosynthesis by statins directly or indirectly affects sexual function and erectile function. Shortterm uses of atorvastatin in the management of cardiovascular complications cause a significant reduction in penile intra- cavernosal pressure which is important for a full erection. As well, this short-term effect also leads to a moderate reduction in total testosterone . These effects contribute to erectile dysfunction; thus in consideration of statins therapy, patients with ischemic heart disease should regard the risk of erectile dysfunction. Moreover, long-term statin therapy leads to the accumulation of elastic and collagen fiber in the penile tissue that may affect the intra- cavernosal pressure. It has been reported that elastic fibers undergo degradation and fragmentation with increasing age and severity of the disease accelerating cardiovascular mortality parallel to collagen accumulation .
In reality, testosterone plays an essential role in the regulation of endothelial and vascular functions. Testosterone prevents vascular remodeling through inhibition of vascular inflammation and oxidative stress. Physiological testosterone leads to vasodilatation through activation of NO production and by increasing endothelial nitric oxide synthase (eNOS) expression, these effects are partly mediated by the endothelial androgen receptors . Therefore, low testosterone due to different reasons leads to endothelial dysfunction and induction of oxidative stress. So, testosterone replacement therapy inhibits oxidative stress, vascular inflammations and intima-media thickness in men patients with ischemic heart disease . Therefore, testosterone is very important for erectile function since it increases neuronal activations toward the penis, stimulates the releases of oxytocin and dopamine from the brain medial pre-optic area (which are involved in the sexual arousal), and preservation of penile blood flow through activation of NO synthase . Therefore, theoretically, a reduction of testosterone levels by statin therapy leads to penile endothelial dysfunction and decreases the responsiveness during sexual excitation which eventually causes erectile dysfunction. Although it was statistically non-significant, hypoandrogenemia may be a reasonable cause. Rearrangement of the two different types of fibers in the penis may be associated with a decrease in the intra- cavernosal pressure. However, further comprehensive experimental studies investigating the effect of cavernosal collagen and elastic fibers on erection with longer follow-up periods are needed to judge this hypothesis .
3.2. Statins induced-neuropathy
Drug induced-peripheral neuropathy is one of the leading causes after diabetes mellitus. This type is of an enormous degree in early diagnosis given that discontinuing the induced drugs leads to significant improvement . Statins cause distal axonal damage, degeneration of myelin sheath and nerve root deterioration. Nevertheless, the potential role of statins in the induction of peripheral neuropathy has not been verified since most statins induced-peripheral neuropathy was reported as a case report . The main mechanism of statins induced-peripheral neuropathy is linked to the decrease of cholesterol which is essential for myelin sheath of peripheral neurons . In addition, statin therapy leads to a significant reduction of coenzyme Q10 which causes impairment of neuronal energy. Coenzyme Q10 is an endogenous antioxidant essential for mitochondrial transport chain found in all cell membranes which participates in the regulation and prevention of lipid and protein peroxidations . Moreover, longterm therapy with statins leads to autonomic neuropathy due to ganglionopathy as statins may cause degeneration of sensory and autonomic ganglions . It is well known that erectile dysfunction is a complication of autonomic and peripheral neuropathies caused by T2DM or induced by drugs. Therefore, statins induced- peripheral neuropathy may be a causative factor for erectile dysfunction which can be attenuated by the administration of coenzyme Q10. It has been shown that one case for every 2 200 statin users developed large fibre neuropathy, which might be due to neuronal mitochondrial dysfunction caused by the inhibition of ubiquinone and/or depletion of neuronal membrane cholesterol . The association between small fibre neuropathy and statin therapy is inadequate. Until that time, Lo et al confirmed the association between statins and painful neuropathy .
In contrast, the Hernandez-Ojeda’s study reported significant ameliorative effects of statins on autonomic neuropathy . Nevertheless, the study of Wallach-Klidemoes et al reported a dose- independent effect of statins in the induction neuropathy, so there is no noticeable dose-response pattern between statins and risk of neuropathy which may give evidence for the negative association between statins and risk of neuropathy . Therefore, the risk of statins induced-neuropathy is typically developed after long-term therapy and therefore statins-induced neuropathy is cumulatively dose-dependent . Moreover, in vitro previous studies have shown that peripheral and autonomic neurons are less susceptible to the toxic effect of statins compared to the spinal neurons suggesting a different mechanism of neuronal toxicity. Hydrophilic statins, like pravastatin and rosuvastatin, demonstrated less peripheral neuronal damage compared with lipophilic statins, like simvastatin and rosuvastatin, due to the difference in the compartmental pharmacokinetics ,. For that reason, the risk of statins induced- erectile dysfunction through induction of neuropathy is unlikely as it is affected by dose, duration and type of statins which are variable among statins user patients.
3.3. Statins induced-cognitive impairment
Short-term statin therapy is associated with different central adverse effects like cognitive impairment, depression and fatigue . Evans et al illustrated a significant association between cognitive deficit and statin therapy . Regardless of cognitive deficit, it causes significant erectile dysfunction due to the overt reduction in cerebral glutaminergic neurotransmission. Therefore, phosphodiesterase-5 (PDE5) inhibitors improve cognitive and erectile functions through inhibition of central PDE5 enzyme and potentiation of cerebral glutaminergic neurotransmission^].
On the other hand, different studies illustrated that statin therapy improves or not affect cognitive functions . Alternatively, there is evidence of a link between inflammation and depression. Several studies refer to elevated levels of pro-inflammatory cytokines and C-reactive protein in the depression and cognitive deficit . Accordingly, drugs with anti-inflammatory properties, such as statins, could be useful in the treatment of depression and cognitive dysfunctions . Undoubtedly, evidence from observational studies suggests that statins are associated with improvement in depressive mood and in quality of life . Thus, the role of statins induced- cognitive impairment is minimally implicated in the pathogenesis of erectile dysfunction as it is not proofed sufficiently and controversy about it still presents.
| 4. Statins Improved-Erectile Dysfunction|| |
Different studies gave a consensus that erectile dysfunction is regarded as an early sign of silent cardiovascular disorder and hidden atherosclerosis. Therefore, amelioration of cardiovascular complications by statins leads to significant improvements of erectile function and sexual health in men with age over forty years . It has been reported that erectile dysfunction is a consequence of endothelial dysfunction since injured endothelium causes a significant reduction of NO which is necessary for corporal vasodilation during sexual excitation and erection. Erectile dysfunction leads to failure in response to PDE5 inhibitors . Statins significantly reverse endothelial dysfunction through inhibition toxic effect of low-density lipoprotein on the vascular endothelium which consequently improves erectile dysfunction. As well, high cholesterol and low high-density lipoprotein is linked with the development of erectile dysfunction .
Cavernosal endothelial cells have specific and unique characteristics: they expressed high levels of mRNA for collagen type IV which was involved in distensibility of sinusoidal spaces and rigid erection. Likewise, cavernosal endothelial cells have specific tight junctions which play a role in maintaining of intra-cavernosal pressure during erection . T2DM and cardiovascular disorders lead to first alterations in the cavernosal endothelial tight junction before any pathological changes in the coronary and other vascular endothelial beds . Therefore, the cavernosal endothelial dysfunction precedes vascular endothelial dysfunction; thus, statins ameliorates erectile dysfunction through prevention of cavernosal endothelial dysfunction before the full prone effect on the lipid profile .
Moreover, systemic review and meta-analysis studies confirmed that statins therapy in patients with dyslipidemia and cardiovascular disorders improve erectile function. This therapy increases the IIEF score by 3.27 points compared with the placebo effect; thus, it improves mild-moderate erectile dysfunction only . The potential mechanisms of statins induced-improvement of erectile function are due to the down-regulation of penile RhoA/Rho- kinase pathway. Rho-kinase inhibits the regulatory subunit of myosin phosphatase within smooth muscle cells and maintains the contractile tone under the low-cytosolic calcium concentrations. Upregulated Rho-kinase activity has been reported in erectile dysfunction, so Rho-kinase inhibitors (Y-27632 and SAR 407899) have potent erectile effects and offer another therapeutic target for the treatment of erectile dysfunction. This pathway is associated with a decline in response to PDE5 inhibitors. As well, statins inhibit geranylpyrophosphate which is essential for activation of the RhoA/Rho-kinase pathway . Moreover, atorvastatin inhibits diabetic induced-RhoA/Rho-kinase pathway activation and prevents RhoA membrane translocation in animal model studies ,. Besides, statins significantly improve erectile dysfunction through enhancement of endothelial NO. Atorvastatin advances endothelial NO concentrations through activation and upregulation of eNOS synthase. Therefore, atorvastatin rescues PDE5 inhibitor non- responders since NO and cyclic guanosine monophosphate increase penile blood flow and improve erectile function .
As initially mentioned, in spite of the reduction of total testosterone by statins therapy, free testosterone does not affect the main active androgen which is engaged with erectile function. Recently, Hsieh and Huang’s study confirmed that rosuvastatin therapy reduces free testosterone and free androgen index, but does not affect erectile function and sexual activity in patients with T2DM .
As previously mentioned, different reports and review studies showed that statins may lead to peripheral and autonomic neuropathy which per se causes erectile dysfunction. Zangiabadi et al illustrated that atorvastatin improves diabetic polyneuropathy within six months of treatment through amelioration of nerve electrophysiological variables . Atorvastatin mainly improves the distal segment of peripheral neurons. The mechanisms of atorvastatin in amelioration of peripheral neuropathy include inhibition of oxidative stress induced-neuropathy, suppression of pro-inflammatory cytokines, restoring the activity of neuroprotective matrix metalloproteinase-7, and blocking neuronal peroxynitrite accumulation . Moreover, statins prevent ischemia induced-neuronal death and preserve neuronal conductive velocity with significant protection of vasa neuronum ,. Therefore, statins improve erectile dysfunction through the preservation of peripheral neurons as the erectile function is solely depending on intact peripheral and autonomic neurons .
It has been reported that cognitive deficits, depression and impaired vigilance are associated with erectile dysfunction . Abbasi et al illustrated that both simvastatin and atorvastatin have potential antidepressant effects and improve cognitive deficits in patients with acute coronary syndrome . The mechanisms of the antidepressant effect of statins are related to increase of limbic system tryptophan, reduction of brain oxidative stress and neuro- inflammations, improvement of cerebral blood flow, and prevention of neuronal ischemia . Recent studies show that statins, regardless of its type, prevent and ameliorate erectile dysfunction in diabetes mellitus and following prostatic surgery ,.
Moreover, different recent studies illustrate that prolonged statins therapy improve erectile dysfunction-related quality of life. As well, statins augment the response to the aphrodiasic agents ,. It has been reported that chronic inflammatory status may cause endothelial dysfunction and subsequent coronary and penile endothelial dysfunctions . Prolonged statins therapy improves endothelial function through anti-inflammatory and anti- oxidant actions. Hereby, statins improve erectile dysfunction via amelioration of penile endothelial functions ,.
The 26 studies regarding statins improved/induced erectile dysfunction in the present review are summarized in [Table 1].
| 5. Conclusion|| |
In this review, there are conflicting findings regarding the potential effect of statins therapy on the erectile dysfunction. Some studies implicate statins as a causative cause of erectile dysfunction, while most of studies report the beneficial effect of statins in prevention of erectile dysfunction. Therefore, this study concludes that statins, regardless of its property, improve erectile dysfunction through amelioration of penile endothelial dysfunction, penile neuronal reflexes and antidepressant effects which are interrelated during sexual excitation and penile erection. For these reasons, the assorted view of preponderance confirms that statins improve erectile dysfunction mainly through the enhancement of erectile endothelial functions.
Conflict of interest statement
The authors declare that there is no conflict of interest.
All authors gave deep thanks to the head of Al-Mustansiriyia University for his great scientific supports.
All authors carried out the conception, wrote, read and approved the final manuscript.
| References|| |
Al-Kuraishy HM, Al-Gareeb AI. Erectile dysfunction and low sex drive in men with type 2 DM: The potential role of diabetic pharmacotherapy. J Clin Diagn Res
Dostálová G, Hlubocká Z, Bayerová K, Belohlávek J, Linhart A, Karetová D. Erectile dysfunction in young myocardial infarction survivors: Evaluation, follow up. Am J Mens Health
Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, et al.
High prevalence of erectile dysfunction in diabetes: A systematic review and meta-analysis of 145 studies. Diabet Med
Moore RA, Edwards JE, McQuay HJ. Sildenafil (Viagra) for male erectile dysfunction: Ameta-analysis of clinical trial reports. BMC Urol
Tung SY, Chang YK, Liu SP, Hsieh JT, Chang HC. PD27-01 penile Doppler ultrasound as a diagnostic tool for percutaneous transluminal angioplasty for vasculogenic erectile dysfunction. J Urol
Calogero AE, Burgio G, Condorelli RA, Cannarella R, La Vignera S. Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction. Aging Male
Hu JL, Chen HX, Chen HR, Wu Y, Sun XW, Li Z, et al.
Novel noninvasive quantification of penile corpus cavernosum lesions in hyperlipidemia-induced erectile dysfunction in rabbits by two- dimensional shear-wave elastography. Asian J Androl
Al-Kuraishy HM, Al-Gareeb AI. Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins. J Lab Physicians
Alkuraishy HM, Al-Gareeb AI, Waheed HJ. Lipoprotein-associated phospholipase A2 is linked with poor cardio-metabolic profile in patients with ischemic stroke: A study of effects of statins. J Neurosci Rural Pract
Ghalayini IF, Al-Ghazo MA, Al-Azab R, Bani-Hani I, Matani YS, Barham AE, et al.
Erectile dysfunction in a Mediterranean country: Results of an epidemiological survey of a representative sample of men. Int J Impot Res
Corona G, Rastrelli G, Morgentaler A, Sforza A, Mannucci E, Maggi M. Meta-analysis of results of testosterone therapy on sexual function based on international index of erectile function scores. Eur Urol
Rhoden EL, Telöken C, Sogari PR, Souto CV. The use of the simplified international index of erectile function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. Int J Impot Res
Byrne M, Doherty S, Fridlund BG, Martensson J, Steinke EE, Jaarsma T, et al.
Sexual counselling for sexual problems in patients with cardiovascular disease. Cochrane Db Syst Rev
2016; (2): 1-36.
Solomon H, Samarasinghe YP, Feher MD, Man J, Rivas-Toro H, Lumb PJ, et al.
Erectile dysfunction and statin treatment in high cardiovascular risk patients. Int J Clin Pract
Hall SA, Kupelian V, Rosen RC, Travison TG, Link CL, Miner MM, et al.
Is hyperlipidemia or its treatment associated with erectile dysfunction? Results from the Boston Area Community Health (BACH) survey. J Sex Med
Azad AK, Setunge S, Selim S, Chowdhury SH, Rahaman MF, Chowdhury MA, et al.
Dyslipidaemia as a risk factor for erectile dysfunction in type 2 diabetes mellitus patients. Diabet Metab Syndr Clin Res Rev
Akdoğan M, Nasır Y, Cengiz N, Bİlgİlİ A. The effects of milled Tribulusterrestris, Avena sativa
, and white ginseng powder on total cholesterol, free testosterone levels and testicular tissue in rats fed a high-cholesterol diet. Ankara Univ Vet Fak
Corona G, Boddi V, Balercia G, Rastrelli G, De Vita G, Sforza A, et al.
The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. J Sex Med
Stanworth RD, Kapoor D, Channer KS, Jones TH. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabet Care
Ishola IO, Tijani HK, Dosumu OO, Anunobi CC, Oshodi TO. Atorvastatin attenuates testosterone-induced benign prostatic hyperplasia in rats: Role of peroxisome proliferator-activated receptor-γ and cyclo-oxygenase-2. Fund Clin Pharmacol
Bolat MS, Bakırtaş M, Fırat F, Akdeniz E, Çınar Ö, Erdemir F. The effect of atorvastatin on penile intracavernosal pressure and cavernosal morphology in normocholesterolemic rats. Turk J Urol
Suzuki N, Sato Y, Hisasue SI, Kato R, Suzuki K, Tsukamoto T. Effect of testosterone on intracavernous pressure elicited with electrical stimulation of the medial preoptic area and cavernous nerve in male rats. JAndrol
Kelly DM, Jones TH. Testosterone: Avascular hormone in health and disease. J Endocrinol
Traish AM, Saad F, Feeley RJ, Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl
Rastrelli G, Corona G, Maggi M. Testosterone and sexual function in men. Maturities
Suzuki N, Sato Y, Hisasue SI, Kato R, Suzuki K, Tsukamoto T. Effect of testosterone on intracavernous pressure elicited with electrical stimulation of the medial preoptic area and cavernous nerve in male rats. J Androl
Jones MR, Urits I, Wolf J, Corrigan D, Colburn L, Peterson E, et al.
Drug-induced peripheral neuropathy, a narrative review. Curr Clin Pharmacol
Baker SK, Tarnopoisky MA. Statin-associated neuromyotoxicity. Drug Today
Al-Kuraishy HM, Al-Gareeb AI, Hussien NR, Al-Naimi MS, Rasheed HA. Statins an oft-prescribed drug is implicated in peripheral neuropathy: The time to know more. J Pak Med Assoc
Montano SJ, Grünler J, Nair D, Tekle M, Fernandes AP, Hua X, et al.
Glutaredoxin mediated redox effects of coenzyme Q10 treatment in type 1 and type 2 diabetespatients. BBA Clin
Gemignani F, Giovanelli M, Vitetta F, Santilli D, Bellanova MF, Brindani F, et al.
Non-length dependent small fiber neuropathy. A prospective case series. J Peripher Nerv Syst
Nisahan B, Kumanan T, Rajeshkannan N, Peranantharajah T, Aravinthan M. Erectile dysfunction and associated factors among men with diabetes mellitus from a tertiary diabetic center in Northern Sri Lanka. BMC Res Notes
Kiortsis DN, Filippatos TD, Mikhailidis DP, Elisaf MS, Liberopoulos EN. Statin-associated adverse effects beyond muscle and liver toxicity. Atherosclerosis
Lo YL, Leoh TH, Loh LM, Tan CE. Statin therapy and small fibre neuropathy: A serial electrophysiological study. J Neurol Sci
Hernández-Ojeda J, Román-Pintos LM, Rodríguez-Carrízalez AD, Troyo-Sanromán R, Cardona-Muñoz EG, del Pilar Alatorre- Carranza M, et al.
Effect of rosuvastatin on diabetic polyneuropathy: Arandomized, double-blind, placebo-controlled phase Ha study. Diabet Metab Synd Ob
Wallach-Kildemoes H, Stovring H, Holme Hansen E, Howse K, Pétursson H. Statin prescribing according to gender, age and indication: What about the benefit-risk balance? J Eval Clin Pract
Grover HS, Luthra S, Maroo S. Are statins really wonder drugs? J Formos Med Assoc
Murinson BB, Haughey NJ, Maragakis NJ. Selected statins produce rapid spinal motor neuron loss in vitro. BMC Musculosk Disord
Raju SB, Varghese K, Madhu K. Management of statin intolerance. Indian J Endocrinol Metab
King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacother J Hum Pharmacol Drug Ther
Evans MA, Golomb BA. Statin-associated adverse cognitive effects: Survey results from 171 patients. Pharmacother J Hum Pharmacol Drug Ther
Fernandes BS, Steiner J, Bernstein HG, Dodd S, Pasco JA, Dean OM, et al.
C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: Meta-analysis and implications. Molecul Psychiat
Stafford L, Berk M. The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: Proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiat
Parekh A, Smeeth D, Milner Y, Thuret S. The role of lipid biomarkers in major depression. Healthcare
Shim YS, Pae CU, Kim SW, Kim HW, Kim JC, Koh JS. Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: A pilot study. Int J Impot Res
Jenrow KA, Liu J, Brown SL, Kolozsvary A, Lapanowski K, Kim JH. Combined atorvastatin and ramipril mitigate radiation-induced impairment of dentate gyrus neurogenesis. J Neurooncol
Trivedi D, Wellsted DM, Collard JB, Kirby M. Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction: Additional data from the erectile dysfunction and statin trial. BMC Urol
Hutchings DC, Anderson SG, Caldwell JL, Trafford AW. Phosphodiesterase-5 inhibitors and the heart: Compound cardioprotection? Heart
Katsiki N, Reiner Ž, Tedeschi Reiner E, Al-Rasadi K, Pirro M, Mikhailidis DP, et al.
Improvement of endothelial function by pitavastatin: Ameta-analysis. Expert Opin Pharmacother
Wessells H, Sullivan CJ, Tsubota Y, Engel KL, Kim B, Olson NE, et al.
Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function. Physiol Genomics
Ryu JK, Jin HR, Yin GN, Kwon MH, Song KM, Choi MJ, et al.
Erectile dysfunction precedes other systemic vascular diseases due to incompetent cavernous endothelial cell-cell junctions. J Urol
Leenders GJ, Smeets MB, van den Boomen M, Berben M, Nabben M, van Strijp D, et al.
Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging. Arterioscler Thromb Vasc Biol
Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the international index of erectile function scale. Europ Urol
Morelli A, Chavalmane AK, Filippi S, Fibbi B, Silvestrini E, Sarchielli E, et al.
Atorvastatin ameliorates sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyperactivation. J Sex Med
Cai Z, Zhang J, Li H. Two birds with one stone: Regular use of PDE5 inhibitors for treating male patients with erectile dysfunction and cardiovascular diseases. Cardiovasc Drugs Ther
Lasker GF, Maley JH, Kadowitz PJ. A review of the pathophysiology and novel treatments for erectile dysfunction. Adv Pharmacol Sci
Zemankova L, Varejckova M, Dolezalova E, Fikrova P, Jezkova K, Rathouska J, et al.
Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin. J Physiol Pharmacol
Hsieh CJ, Huang B. Rosuvastatin decreases testosterone levels but not sexual function in men with type 2 diabetes. Diabetes Res Clin Pract
Zangiabadi N, Shafiee K, Alavi KH, Assadi AR, Damavandi M. Atorvastatin treatment improves diabetic polyneuropathy electrophysiological changes in non-insulin dependent diabetic patients: A double blind, randomized clinical trial. Minerva Endocrinol
Ali TK, Al-Gayyar MM, Matragoon S, Pillai BA, Abdelsaid MA, Nussbaum JJ, et al.
Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury. Diabetologia
Camera A, Hopps E, Caimi G. Diabetic microangiopathy: Physiopathological, clinical and therapeutic aspects. Minerva Endocrinol
Jin Z, Jung Y, Yi CO, Lee JY, Jeong E, Lee JE, et al.
Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via
regulation of lipocalin-2-associated neuroinflammation. Korean J Physiol Pharmacol
Pfaff DW, Baum MJ. Hormone-dependent medial preoptic/lumbar spinal cord/autonomic coordination supporting male sexual behaviors. Mol Cell Endocrinol
Popp R, Kleemann Y, Burger M, Pfeifer M, Arzt M, Budweiser S. Impaired vigilance is associated with erectile dysfunction in patients with sleep apnea. J Sex Med
Abbasi SH, Mohammadinejad P, Shahmansouri N, Salehiomran A, Beglar AA, et al.
atorvastatin for improving mild to moderate depression in post-coronary artery bypass graft patients: A double-blind, placebo-controlled, randomized trial. J Affect Disord
Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. Statins for the treatment of depression: A meta-analysis of randomized, double- blind, placebo-controlled trials. J Affect Disord
Ding F, Shan C, Li H, Zhang Y, Guo C, Zhou Z, et al.
Simvastatin alleviated diabetes mellitus-induced erectile dysfunction in rats by enhancing AMPK pathway-induced autophagy. Andrology
2020; doi: 10.1111/andr.12758
Koontz B, Chittester E, Niedzwiecki D, Hunt A, Ahmad A. Is statin use at time of prostate cancer radiation associated with protection of patient-reported erectile function? J Sex Med
Cassidy-Vu L, Keating M, Watson K. Does treatment with a statin improve erectile dysfunction symptoms? Evid Based Pract
Gratzke C, Andersson KE, Diemer T, Weidner W, Stief CG. Practical guidelines for the treatment of erectile dysfunction and Peyronie’s disease. In: Chapple CR, Steers WD. (eds.) Practical urology: Essential principles and practice
. London: Springer; 2011, p. 373-383.
Kadhim SS, Al-Windy SA, Al-Nami MS, Al Kuraishy HM, Al Gareeb AI. Statins improve periodontal disease-induced inflammatory changes and associated lipid peroxidation in patients with dyslipidemia: Two birds by one stone. J Int Oral Health
Joseph P, Lonn E, Bosch J, Lopez P, Zhu J, Keltai M, et al.
Long-term effects of statins, blood pressure-lowering, and both on erectile function in persons at intermediate risk for cardiovascular disease: A substudy of the heart outcomes prevention evaluation-3 (HOPE-3) randomized controlled trial. Can J Cardiol
La Vignera S, Condorelli RA, Vicari E, Calogero AE. Statins and erectile dysfunction: A critical summary of current evidence. J Androl