Late-onset Hypogonadism In Males Research Articles

Prevention of Male Late-Onset Hypogonadism by Natural Polyphenolic Antioxidants.

Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein (Star) gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males.

NURSING IN MEN'S HEALTH CARE IN ANDROPAUSE: literature review

Andropause, also known as late-onset male hypogonadism, is a condition related to male aging that involves a gradual decrease in testosterone levels in the body. Among the main experimental symptoms, we can list: the reduction in testosterone levels, a main characteristic of andropause. This symptom unfolds into others, such as fatigue, loss of energy, reduced libido and erectile dysfunction. The general objective of this research is to describe andropause, presenting its general and clinical aspects, in addition to demonstrating the importance of nurses in relation to treatment and health promotion. To this end, it was necessary to outline the following specific objectives: prepare a description of the general characteristics of andropause; expose considerations about male aging and the need to break taboos; demonstrate the importance of the nurse's role in the guidance and treatment of andropause. This is basic, qualitative research. As for the objectives, it is classified as descriptive and exploratory. Regarding procedures, bibliographical research was used. It was concluded that it is essential for the primary care team to plan effective nursing actions to meet the needs of men in andropause, seeking to diagnose and prevent diseases related to this phase of male life.

Quercetin promotes the secretion of musk by regulating the hormone level and microbial structure of forest musk deer.

Musk is a scarce and precious medical resource secreted by male forest musk deer (FMD). Current research to promote musk secretion in FMD has used almost exclusively hormone injections, but this approach can be detrimental to the health of FMD. In order to conserve this endangered species as much as possible while increasing the production of musk, this study first used bioinformatics methods to predict the function of quercetin, a flavonoid that promotes testosterone (T) production and prevents late-onset male hypogonadism. On the basis of good prediction effect, different concentrations of quercetin were added to the diet of FMD. The results showed that quercetin could change the levels of T, luteinizing hormone releasing hormone, luteinizing hormone, and estradiol, and regulate the structure of intestinal microorganisms and musk microorganisms of FMD. Moreover, there is a correlation among musk components, hormones, intestinal microorganisms, and musk microorganisms, which indicates that the production of musk may be regulated by these three at the same time, and the addition of quercetin with 800 mg per kg diet could significantly increase the yield of muscone (P < 0.05), the most effective ingredient in musk. In addition, quercetin decreased the high level of cortisol during musk secretion, which may relieve the stress on FMD in this process. This may help to protect the health of FMD. Combined with the results of software prediction, we finally proposed a possible mechanism for the complex process of musk secretion in FMD with a view to providing ideas for further studies.

Comparison of short and long-acting testosterone replacement therapy for better sperm production and testosterone levels in male late-onset hypogonadism

Introduction: Testosterone Replacement Therapy (TRT) is the standard treatment for male late-onset hypogonadism. Short-acting and long-acting testosterone are currently available treatments and have been approved by the Food and Drug Administration (FDA). The administration of exogenous testosterone is known to increase sperm production and T levels in men suffering from late-onset hypogonadism. However, limited research compares the efficacy of these two types of TRT. Objective: This study aims to compare the efficacy of short-acting and long-acting testosterone replacement therapy on sperm production and T levels in men suffering from late-onset hypogonadism. Methods: We searched for electronic databases including PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, Allied and Complementary Medicine Database (AMED), and Google using keywords. All studies were evaluated by three independent reviewers who resolved differences by consensus. Results: We identified 21 studies that met our inclusion criteria. After applying the inclusion criteria, only 21 database sources remain for further analysis. Conclusion: Long-acting formulas affect blood more. RCTs show TU boosts libido and testosterone. Male infertility may result from long-acting TU blocking LH and FSH. TRP improves erections by increasing motile sperm and libido. Peanut allergy-related short-acting TRT causes nausea, itching, and injection-site pain.

Adult- and late-onset male hypogonadism: the clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE).

PurposeTo provide the evidence-based recommendations on the role of testosterone (T) on age-related symptoms and signs remains.MethodsThe Italian Society of Andrology and Sexual Medicine (SIAMS) and the and the Italian Society of Endocrinology (SIE) commissioned an expert task force to provide an updated guideline on adult-onset male hypogonadism. Derived recommendations were based on Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.ResultsClinical diagnosis of adult-onset hypogonadism should be based on a combination of clinical and biochemical parameters. Testosterone replacement therapy (TRT) should be offered to all symptomatic subjects with hypogonadism after the exclusion of possible contraindications. T gels and the long-acting injectable T are currently available preparations showing the best efficacy/safety profile. TRT can improve all aspects of sexual function, although its effect is limited in more complicated patients. Body composition (reducing fat mass and increasing lean mass) is improved after TRT, either in subjects with or without metabolic syndrome or type 2 diabetes. Conversely, the role of TRT in improving glycometabolic control is more conflicting. TRT can result in increasing bone mineral density, particularly at lumbar site, but no information on fracture risk is available. Limited data support the use of TRT for improving other outcomes, including mood frailty and mobility.ConclusionsTRT can improve sexual function and body composition particularly in less complicated adult and in aging subjects with hypogonadism. When hypogonadism is adequately diagnosed, T appropriately prescribed and subjects correctly followed up, no short-term increased risk of adverse events is observed. Longer and larger studies are advisable to better clarify TRT long-term efficacy/safety profile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40618-022-01859-7.

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism.

Androgen production, being important for male fertility, is mainly accomplished by the Leydig cells from the interstitial compartment of the testis. Testosterone plays a critical role in testis development, normal masculinization, and the maintenance of spermatogenesis. Within seminiferous tubules, appropriate Sertoli cell function is highly dependent on testicular androgen levels and is essential to initiate and maintain spermatogenesis. During aging, testosterone production by the testicular Leydig cells declines from the 30s in humans at a rate of 1% per year. This review outlines the recent findings regarding the use of flavonoids and isoflavonoids to improve testosterone production, contributing to normal spermatogenesis and preventing age-related degenerative diseases associated with testosterone deficiency. With the cumulation of information on the actions of different flavonoids and isoflavonoids on steroidogenesis in Leydig cells, we can now draw conclusions regarding the structure-activity relationship on androgen production. Indeed, flavonoids having a 5,7-dihydroxychromen-4-one backbone tend to increase the expression of the steroidogenic acute regulatory protein (StAR), being critical for the entry of cholesterol into the mitochondria, leading to increased testosterone production from testis Leydig cells. Therefore, flavonoids and isoflavonoids such as chrysin, apigenin, luteolin, quercetin, and daidzein may be effective in delaying the initiation of late-onset hypogonadism associated with aging in males.

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Male late-onset hypogonadism is an age-related disease, the core mechanism of which is dysfunction of senescent Leydig cells. Recent studies have shown that elimination of senescent cells can restore proper homeostasis to aging tissue. In the present study, we found that the fork head box O (FOXO) transcription factor FOXO4 was specially expressed in human Leydig cells and that its translocation to the nucleus in the elderly was related to decreased testosterone synthesis. Using hydrogen peroxide-induced senescent TM3 Leydig cells as an in vitro model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis. By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells. In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. These findings reveal the therapeutic potential of FOXO4-DRI for the treatment of male late-onset hypogonadism.

Synthesis and biological evaluation of methylpyrimidine-fused tricyclic diterpene analogs as novel oral anti-late-onset hypogonadism agents

Male late-onset hypogonadism (LOH) is reported as one of the most common age-related diseases occurred in middle-aging men. Testosterone replacement therapy (TRT) is currently the main clinical treatment for LOH, however it has obvious side effects. A 2-methylpyrimidine-fused tricyclic diterpene analog 7 was afforded as anti-LOH hit, which was screened out from our small synthetic library. Then a series of derivates were designed and synthesized based on the hit and their effects in promoting testosterone production and cytotoxicities were evaluated in mouse TM3 Leydig cells. The most potent and safe compound 29 (SH379) was obtained, which significantly promoted the expression of the key testosterone synthesis-related enzymes StAR and 3β-HSD. Further studies discovered that 29 could stimulate autophagy through regulating AMPK/mTOR signaling pathway. More importantly, 29 increased the testosterone levels and the sperm viability and motility in PADAM (partial androgen deficiency in aging males) rats obviously and displayed almost no side effects. Furthermore, Preliminary pharmacokinetics evaluation also indicated an excellent oral bioavailability of 29. Therefore, these methylpyrimidine-fused tricyclic diterpene analogs could be used as leads for the development of a new type of potential anti-LOH agent.

302 One Case of Male Late-Onset Hypogonadism Syndrome That was Benefited by Middle-Reinforcing and Qi-Benefiting Decoction (Hochu-Ekki-To)

302 One Case of Male Late-Onset Hypogonadism Syndrome That was Benefited by Middle-Reinforcing and Qi-Benefiting Decoction (Hochu-Ekki-To)

Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Late-onset Male Hypogonadism and Fertility Potential in Thalassemia Major Patients: Two Emerging Issues.

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Update on Testosterone Replacement Therapy in Hypogonadal Men.

Late-onset male hypogonadism has long been recognized as a treatable medical condition; however, misconceptions about the use of testosterone replacement therapy (TRT) have often led urologists away from its more mainstream use. This paper aims to bring the reader up-to-date on the current understanding of TRT, starting with when and who to treat. Various formulations of TRT, each with its own risks and benefits, are also detailed. Finally, a comprehensive analysis of the current literature's views into the various controversies of TRT including its impact on prostate health, sexual health, cardiovascular health, frailty, and mood is discussed.

Screening of late onset male hypogonadism with ADAM and AMS scores and impact of cognitive functions

Objective: To screen men presenting late onset hypogonadism with the conjunction of ADAM (Androgen deficiency of the Aging Male) score and AMS (Aging Male's Symptoms) score and measure its impact on cognitive function.

Peptide Targeting of Mitochondria Elicits Testosterone Formation

Testosterone (T) is the principal sex hormone responsible for growth and development of the reproductive system in male vertebrates.1 It has historically received much attention not only from the medical and scientific communities2 but also from the general public, owing to its psychological and behavioral effects.3 T drives the asymmetry of several biological processes spanning virilization to anabolism, disease prevention,1 and aging.4 In this issue of Molecular Therapy, Aghazadeh et al.5 describe a novel fusion peptide, TVS167, that can induce T formation in rat testes and increase its serum level as well as rescue its synthesis in adult male rats exposed to antagonists of the gonadotropin-releasing hormone, which constitutes the initial step in the hypothalamic–pituitary–gonadal axis governing T production. This peptide acts by exploiting the interaction between the voltage-dependent anion channel 1 (VDAC1) and the 18-kDa translocator protein (TSPO) within the mitochondrial transduceosome, a multicomponent molecular machine that controls lipid import and steroidogenesis. This peptide reveals a regulatory mechanism in the mitochondrial pathway of steroid anabolism that could provide a new target for therapeutic intervention (see model in Figure 1).

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Late onset hypogonadism in males - think of it - act on it

Late onset hypogonadism in males - think of it - act on it

Topical Testosterone Gel for the Treatment of Male Hypogonadism

ObjectiveThis review describes the current knowledge of biological external testosterone (T) application using dermal products for the treatment of late-onset male hypogonadism (LOH).MethodsAn English language search of medical literature using Pubmed was conducted between January of 1984 and March of 2012 using the search term ‘testosterone gel’. Special emphasis was given to clinical controlled trials and large case studies.ResultsWe describe the current knowledge on testosterone replacement therapy using gel applications. A reference search revealed 1567 publications; 44 were clinical studies in human patients with male hypogonadism, 80 were reviews, 27 were case reports, and 9 were retrospective studies. Data from the literature and from 20 clinical studies involving human patients were analyzed since they met the inclusion criteria of testosterone gel administration in hypogonadal males. For the purpose of this review, a total number of 2,378 human patients were studied. Overall, biological T administration resulted in improvement of sexual dysfunction and symptoms of metabolic syndrome and represented an effective and safe treatment option for hypogonadal men.ConclusionsAdministration of biological T gel appears to represent a valid alternative treatment option for male hypogonadism with a favorite efficacy and safety profile.

Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism

Studies that analyze the levels of osteoprotegerin (OPG) or receptor activator of nuclear factor kappa B ligand (RANKL) in hypogonadal men, the majority of whom have prostate cancer or are undergoing androgen-deprivation therapy, are few and inconclusive. 81 men aged 69.3 ± 0.8 years (39 men with late-onset hypogonadism and 42 age-matched controls) were recruited. Serum levels of OPG, total soluble RANKL (sRANKL), total and free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone (LH), prolactin, bone-specific alkaline phosphatase (BAP) and β-Cross Laps were assessed. Compared with controls, both OPG (p = 0.023) and sRANKL (p = 0.010) serum levels were increased in men with late-onset hypogonadism; however, when expressed as a ratio, sRANKL/OPG, the two groups were not significantly different. Simple and age-adjusted analyses showed that OPG was inversely related to FT and positively related to SHBG, E2 and BAP. In the patient population, LH demonstrated statistically significant correlations with both OPG (r = 0.274, p = 0.013) and sRANKL (r = 0.276, p = 0.018). Multiple regression analysis retained age, SHBG, E2 and BAP as independent predictors of OPG, explaining 27.71% of serum OPG variability. Late-onset hypogonadism is associated with enhanced RANKL activity. Increased bone turnover-related OPG levels may act as a coupling factor between bone resorption and formation. The results suggest anti-RANKL-agents as therapeutic tools in osteoporotic men with late-onset hypogonadism.

Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory

We measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men. Data were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prostate cancer and received 5 to 10 gm Testim 1% (testosterone gel) daily. A total of 451 patients with prostate specific antigen and total testosterone values were divided into group A (197 with total testosterone less than 250 ng/dl) and group B (254 with total testosterone 250 ng/dl or greater). The groups differed significantly in free testosterone and sex hormone-binding globulin, but not in age or prostate specific antigen. In group A but not group B prostate specific antigen correlated significantly with total testosterone (r=0.20, p=0.005), free testosterone (r=0.22, p=0.03) and sex hormone-binding globulin (r=0.59, p=0.002) at baseline. After 12 months of testosterone replacement therapy, increase in total testosterone (mean±SD) was statistically significant in group A (+326±295 ng/dl, p<0.001; final total testosterone 516±28 ng/dl) and group B (+154±217 ng/dl, p<0.001; final total testosterone 513±20 ng/dl). After 12 months of testosterone replacement therapy, increase in prostate specific antigen was statistically significant in group A (+0.19±0.61 ng/ml, p=0.02; final prostate specific antigen 1.26±0.96 ng/ml) but not in group B (+0.28±1.18 ng/ml, p=0.06; final prostate specific antigen 1.55±1.72 ng/ml). The average percent prostate specific antigen increase from baseline was higher in group A (21.9%) than in group B (14.1%). Overall the greatest prostate specific antigen was observed after 1 month of treatment and decreased thereafter. Patients with baseline total testosterone less than 250 ng/dl were more likely to have an increased prostate specific antigen after testosterone replacement therapy than those with baseline total testosterone 250 ng/dl or greater, supporting the prostate saturation hypothesis. Clinicians should be aware that severely hypogonadal patients may experience increased prostate specific antigen after testosterone replacement therapy.

Male late-onset hypogonadism: pathogenesis, diagnosis and treatment

Some aging men develop a condition of suppressed serum testosterone levels, which is associated with diffuse sexual, physical and psychological symptoms. Several terms are used for this syndrome, but late-onset hypogonadism (LOH) is preferred. The diagnosis of LOH is often uncertain because symptoms (occurring in 20-40% of men) and low circulating testosterone (found in 20% of men >70 years of age) seldom occur together. The strict diagnostic criteria for LOH include reproducibly low serum testosterone levels and sexual symptoms, including erectile dysfunction and reduced frequency of sexual thoughts and morning erections. Using these diagnostic criteria, only 2% of 40-80-year-old men have LOH. Obesity and impaired general health (including diabetes mellitus, cardiovascular and chronic obstructive pulmonary disease, and frailty) are more common reasons for low testosterone than advanced age per se. It seems logical, therefore, to begin by treating these conditions before testosterone replacement therapy is initiated. Even then, testosterone should only be used if there are no contraindications, such as unstable cardiac disease, serious prostate symptoms and high hemoglobin level. The long-term benefit of testosterone replacement therapy is uncertain, and the experimental nature of the treatment, and its associated risks, must be fully explained to the patient before treatment begins.