Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Drug-induced gynecomastia: A systematic review and meta-analysis of randomized clinical trials

Objective: To review the evidence concerning treatment-related gynecomastia in patients taking spironolactone, antiandrogens, 5 alpha-reductase inhibitors, lipid-lowering and psychotropic drugs. Material and methods: A search of Medline and EMBASE was performed up to 30 June 2021. We included randomized controlled trials comparing the effects of a drug belonging to these classes versus placebo or versus a drug of the same class. Results: A total of 32 randomized controlled trials were included in the final review. There was an increased odds of gynecomastia in men receiving antiandrogens (OR = 17.38, 95% CI: 11.26 to 26.82; 6 trials, 9599 participants) and 5 alpha-reductase inhibitors compared to controls (OR = 1.77, 95% CI: 1.53 to 2.06; 7 series out of 6 trials, 34860 participants). The use of spironolactone in mixed gender populations was characterized by significantly higher odds of having gynecomastia compared to controls (OR = 8.39, 95% CI: 5.03 to 13.99; 14 trials, 3745 participants). No placebo-controlled trials focusing on the risk of gynecomastia in patients taking antipsychotic drugs was available, although there was a significant difference in the odds of having gynecomastia in a comparison between risperidone and quetiapine (OR = 4.32, 95% CI: 1.31 to 14.27; 3 trials, 343 participants). Limited evidence about the effects of statins on mammary glands was found. Conclusions: Antiandrogens and to a lesser extent 5 alphareductase inhibitors and spironolactone are associated with an increased risk of developing gynecomastia. Such effect can be explained by a modification of the testosterone to estradiol ratio. Gynecomastia (and galactorrhea) associated to the use of conventional and certain atypical antipsychotics can be related to high prolactin levels.

Separation and Identification of Antioxidants and Aldose Reductase Inhibitors in Lepechinia meyenii (Walp.) Epling

We previously reported that Lepechinia meyenii (Walp.) Epling has antioxidant and aldose reductase (AR) inhibitory activities. In this study, L. meyenii was extracted in a 50% MeOH and CH2Cl2/MeOH system. The active extracts of MeOH and 50% MeOH were subjected to fractionation, followed by separation using high-speed counter-current chromatography (HSCCC) and preparative HPLC. Separation and identification revealed the presence of caffeic acid, hesperidin, rosmarinic acid, diosmin, methyl rosmarinate, diosmetin, and butyl rosmarinate. Of these, rosmarinic acid, methyl rosmarinate, and butyl rosmarinate possessed remarkable antioxidant and AR inhibitory activities. The other compounds were less active. In particular, rosmarinic acid is the key contributor to the antioxidant and AR inhibitory activities of L. meyenii; it is rich in the MeOH extract (333.84 mg/g) and 50% MeOH extract (135.41 mg/g) of L. meyenii and is especially abundant in the EtOAc and n-BuOH fractions (373.71–804.07 mg/g) of the MeOH and 50% MeOH extracts. The results clarified the basis of antioxidant and AR inhibitory activity of L. meyenii, adding scientific evidence supporting its traditional use as an anti-diabetic herbal medicine. The HSCCC separation method established in this study can be used for the preparative separation of rosmarinic acid from natural products.

Consumption of single products versus fixed-dose combination medicines for hypertension and hyperlipidemia during 2015–2019 in South Korea

Background Fixed-dose combinations can simplify prescribing, and numerous combination products exist for hypertension and dyslipidemia in South Korea. This study’s aim was to compare trends in the consumption of single products versus fixed-dose combinations for hypertension and hyperlipidemia. Methods and findings We analyzed the Korean national health insurance claims database from January 2015 through December 2019. Consumption of medicines was calculated using the defined daily dose per 1,000 inhabitants per day (DIDs) and expenditures over time. During 2015–2019, the use of antihypertensive drugs increased with an annual growth rate (AGR) of 0.9% for single products and with an AGR of 35.6% for fixed-dose combinations. A notable increase was observed for antihyperlipidemic combination drugs with an AGR of 268.1% compared to single products with 35.7%. For older adults (65+ years), the consumption of drugs for hypertension and hyperlipidemia was 3–4.5 and about 3 times higher, respectively, than in adults aged 20–64 years, and a sharp increase was found in antihyperlipidemic fixed-dose combinations among older adults. A large increase was seen for C09 (agents acting on the renin-angiotensin system) with an AGR of 36.5%, especially C09DB (angiotensin II receptor blockers + calcium channel blockers) was widely used and steeply increased with 114.2%. For antihyperlipidemic drugs, C10AA (HMG CoA reductase inhibitors) accounted for a large share and sharply increased, with 52.1 DIDs in 2019 and with an AGR of 78.4%, whereas C10BA (combinations of various lipid modifying agents) increased 9.6 times from 2.9 DIDs (96 million USD) in 2015 to 27.7 DIDs (912 million USD) in 2019. Conclusion The findings of increased consumption and drug spending among older adults underscores the need for real-world evidence about health outcomes of fixed-dose combinations in this population.

MODERN CONCEPT OF CONSERVATIVE TREATMENT OF PREMATURE EJACULATION

В данной статье представлен обзор методов консервативного лечения преждевременная эякуляция. Отмечено низкая обращаемость пациентов с данной интимной проблемой, и малая информированность об успешном лечении вышеуказанной нозологии. Эффективным методом выбора является применение селективных ингибиторов захвата серотонина, а именно дапоксетина, который обладает высоким уровнем доказательности и удобен как препарат по требованию. Учеными выявлено эффективное применение дапоксетина и ингибиторов 5 альфа-редуктазы в лечении преждевременной эякуляции. This article provides an overview of the methods of conservative treatment of premature ejaculation. Patients with this intimate problem were noted to have low circulation and low awareness of the successful treatment of the above nosology. An effective method of choice is the use of selective serotonin uptake inhibitors, namely dapoxetine, which has a high level of evidence and is convenient as a drug on demand. Scientists have identified the effective use of dapoxetine and 5 alpha-reductase inhibitors in the treatment of premature ejaculation

Ejaculations and Benign Prostatic Hyperplasia: An Impossible Compromise? A Comprehensive Review

Background: Benign prostatic hyperplasia (BPH) is commonly responsible for lower urinary tract symptoms (LUTS) in men aged 50 or over. Sexual dysfunctions, such as ejaculatory disorders (EjD), go along with LUTS but are frequently overlooked in the initial evaluation. This review aimed to detail BPH-related EjD, as well as their modifications by medical, surgical, and interventional treatments. Methods: We conducted a narrative review looking for publications between 1990 and 2020, regarding physiopathology, epidemiology, evaluation, and therapeutic management (medical, surgical, and interventional) of BPH-related EjD. Results: Sixty-five articles were included in our final analysis. Forty-six percent of men presenting with LUTS reported EjD. If the prevalence increases with age and LUTS severity, the functional impairment is not correlated with age. Several self-questionnaires evaluated the sexual function, but only four approaches are specific to EjD. Medical therapies were exposed to anejaculation, rather than retrograde ejaculation (RE) (4–30% (alpha-blockers), 4–18% (5-alpha-reductase inhibitors)). Regarding surgical therapies, trans-urethral resection of the prostate (TURP) and incision of the prostate (TUIP) are associated with 50–70% and 21–35% of RE. The RE rate is important after open simple prostatectomy but can be reduced with robotic approaches and urethral sparing techniques (19%). Anatomic endoscopic enucleation of the prostate (AEEP) with or without a laser source is associated with an 11–36% RE rate, according to supramontanal preservation. Recent surgical techniques (Rezum©, Aquablation©, or Urolift©) were developed to preserve antegrade ejaculation with promising short-term results. Regardless of the surgical approach, anatomic studies suggest that the preservation of peri-montanal tissue (7.5 mm laterally; 10 mm proximally) is primordial to avoid post-operative RE. Finally, prostate artery embolization (PAE) limits the RE rate but exposes it to a 12 months 10% re-intervention rate. Conclusion: EjD concerns almost half of the patients presenting BPH-related LUTS. Initial evaluation of EjD impairment is primordial before medical or surgical therapy. Peri-montanal tissue preservation represents a key point for antegrade ejaculation preservation, regardless of the surgical option.

Bothersome Hematospermia Following Stereotactic Body Radiation Therapy for Prostate Cancer

BackgroundHematospermia following prostate radiation therapy is a benign and often self-limiting side effect. However, it may be bothersome to some men and their partners with a negative impact on sexual quality of life (QOL). This study sought to evaluate the incidence, duration, and resolution of hematospermia in patients following stereotactic body radiation therapy (SBRT) for prostate cancer.Methods227 patients treated with SBRT from 2013 to 2019 at Georgetown University Hospital for localized prostate carcinoma with a minimum follow up of two years were included in this retrospective review of data that was prospectively collected. Patients who were greater than 70 years old and/or received hormonal therapy were excluded. Hematospermia was defined as bright red blood in the ejaculate. Time points for data collection included initial consultation, pre-treatment, 1-, 3-, 6-, 9-, 12-, 18-, 24-month. All patients were treated with the CyberKnife Radiosurgical System (Accuray). Data on hematospermia including duration, resolution and recurrence was collected. Utilization of 5-alpha reductase inhibitors was documented at each visit.Results227 patients (45 low-, 177 intermediate-, and 5 high-risk according to the D’Amico classification) at a median age of 65 years (range 47-70) received SBRT for their localized prostate cancer. The 2-year cumulative incidence of hematospermia was 5.6%(14 patients). For these patients, all but one patient (93%) saw resolution of their hematospermia by two years post-SBRT. The median time for hematospermia was 9 months post-treatment. Of the 14 patients who reported hematospermia, 70% were managed with 5-alpha reductase inhibitors. Hematospermia was transient in most patients with 70% of the men reporting resolution by the next follow-up visit.ConclusionThe incidence of bothersome hematospermia following SBRT was low. Hematospermia, as noted by other studies, often self-resolves. 5-alpha reductase inhibitors may lead to quicker resolution of bothersome hematospermia.