Andropause Research Articles

Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300μM H2O2 for 8h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

An updated systematic review and meta-analysis of the effects of testosterone replacement therapy on erectile function and prostate.

Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH. Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted. The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.65-4.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.45-0.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.64-1.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.98-4.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.87-12.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.00-0.17; P=0.06) were not significantly statistical between two groups. This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).

A narrative review on inflammaging and late-onset hypogonadism.

The increasing life expectancy observed in recent years has resulted in a higher prevalence of late-onset hypogonadism (LOH) in older men. LOH is characterized by the decline in testosterone levels and can have significant impacts on physical and mental health. While the underlying causes of LOH are not fully understood, there is a growing interest in exploring the role of inflammaging in its development. Inflammaging is a concept that describes the chronic, low-grade, systemic inflammation that occurs as a result of aging. This inflammatory state has been implicated in the development of various age-related diseases. Several cellular and molecular mechanisms have been identified as contributors to inflammaging, including immune senescence, cellular senescence, autophagy defects, and mitochondrial dysfunction. Despite the extensive research on inflammaging, its relationship with LOH has not yet been thoroughly reviewed in the literature. To address this gap, we aim to review the latest findings related to inflammaging and its impact on the development of LOH. Additionally, we will explore interventions that target inflammaging as potential treatments for LOH.

Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Treatment of Late-onset Hypogonadism with Traditional Chinese and Western Medicine

Treatment of Late-onset Hypogonadism with Traditional Chinese and Western Medicine

Novel Therapeutic Approach for Late-Onset Hypogonadism.

Novel Therapeutic Approach for Late-Onset Hypogonadism.

The Effects of Geranylgeraniol on Blood Safety and Sex Hormone Profiles in Healthy Adults: A Dose-Escalation, Randomized, Placebo-Controlled Trial

Geranylgeraniol (GG), an ingredient extracted from the South American annatto plant, has been shown to benefit bone and muscle health, is crucial in the biosynthesis of menaquinone-4 and coenzyme Q10, and has pain and inflammation reduction activities. However, no known studies to date have demonstrated the safety and impact of GG supplementation in humans. This 8-week, randomized, placebo-controlled, dose-escalated trial was conducted to determine the effect of GG on blood safety and hormone markers in healthy adults. Sixty-six males and females between 30 and 49 years of age were supplemented with either GG or a placebo (PLA) for 8 weeks, with dose escalation from 150 mg to 300 mg occurring after 4 weeks in the treatment group. Changes in complete blood count and comprehensive metabolic panels were analyzed for whole study groups (males and females) while changes in sex hormone panels were analyzed for males and females independently. There were no significant changes in complete blood count, comprehensive metabolic panel, progesterone, estradiol, sex–hormone binding globulin, or dihydrotestosterone (p &gt; 0.05). An exploratory analysis of testosterone levels in a subgroup of males with baseline (Pre) total testosterone &lt; 700 ng/dL (GG = 15; PLA = 13) demonstrated a significant increase (p &lt; 0.05) from Pre to Week 8 in total-, free-, and bioavailable testosterone (+7.5%, +15.0%, and +14.8%, respectively). This study demonstrates that GG does not significantly change the composition of blood chemistry, hematology, or sex hormone profiles in adult males or females. Given the effects observed in the exploratory analysis in a subgroup of males, GG supplementation may be beneficial for testosterone enhancement in male populations subject to low testosterone (i.e., aging males and those with late-onset hypogonadism), but further research is needed.

Impact of testosterone levels and testosterone replacement ther-apy on men’s health

Various studies have shown that testosterone levels heavily impact many areas of a man’s health. Low serum testosterone (and, by analogy, late onset hypogonadism) may be responsible for such conditions as type 2 diabetes, obesity in abdominal area, and most of all, heightened cardiovascular risk (CV). Among other outcomes researchers have pointed out metabolic syndrome and dyslipidemia, as well as increased risk of anxiety disorders and major depressive disorder. There have also been reports of testosterone’s influence on fertility, bone mineral density and the development of polycythemia. All of these effects can be linked to the increased levels of inflammatory markers caused by low testosterone and lead to higher risk of premature death. Overly high testosterone, however, has been proven to have a notable influence on men’s personality, as well as other psychological and social traits, both in endogenously elevated testosterone level, and in patients with history of anabolic- androgenic steroid use. The last decade’s research of testosterone’s impact on the organism has brought contradictory results. Therefore, examination and understanding of the influence of its abnormal levels proves important to not only guarantee the best quality of hypogonadism treatment, but also to efficiently prevent any side effects or complications associated with testosterone use.

Correlation between Higher Aging Males' Symptoms Scores and a Higher Risk of Lower Urinary Tract Symptoms.

Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone levels with aging and is associated with various symptoms, including lower urinary tract symptoms (LUTSs). Although some reports have shown that testosterone replacement treatment for LOH improves LUTSs, no large study has revealed a correlation between LUTSs and LOH. This study investigated the correlation between the severity of LOH and LUTSs in Japanese males >40 years of age using a web-based questionnaire with the Aging Males' Symptoms (AMS) scale. We asked 2000 Japanese males to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2000 individuals, 500 individuals were assigned to each age group. The IPSS total score was positively correlated with the severity of AMS (shown as median [mean ± SD]): no/little group, 2 (3.67 ± 5.36); mild group, 6 (7.98 ± 6.91); moderate group, 11 (12.49 ± 8.63); and severe group, 16 (14.83 ± 9.24) (p < 0.0001). Individuals with higher AMS values, representing cases with severe LOH symptoms, had a higher risk of experiencing nocturia and LUTSs than those with lower AMS values.

The Impact of a Web-Based Educational Initiative in Malang Regency: Enhancing Late Onset Hypogonadism (LOH) Awareness Through Community Service

Late Onset Hypogonadism (LOH), commonly known as andropause, poses significant hormonal challenges for elderly men, impacting their overall quality of life. With testosterone levels naturally declining from the age of 30 and accelerating beyond 40, this hormonal imbalance can manifest in symptoms that degrade the well-being of men. This community service initiative aimed to improve understanding and early detection of LOH among the Indonesian male population. A web-based application, "Skrining Andropause" was developed, allowing individuals to self-assess their LOH risk through the validated Androgen Deficiency in the Aging Male (ADAM) questionnaire. The application included educational videos to enhance public awareness of andropause. Pre- and post-tests were conducted as success indicators, involving 40 male participants aged 40 and above in Malang Regency. Statistical analyses were performed to assess the impact on knowledge related to andropause across different educational backgrounds and age groups. Significant improvement in public understanding of andropause was observed (p=0.000). While educational backgrounds were not significantly associated with initial knowledge (p=0.100), nor with the increase in pre-to-post-test scores (p=0.100). When associating age groups with initial knowledge (p=0.308) and the increase in pre-to-post-test scores (p=0.308), results were not statistically significant. The observed substantial improvement in andropause understanding highlights the efficacy of our educational approach. Respondents, irrespective of educational background, shared a baseline understanding, with those with basic education showing the most significant improvement. Notably, the youngest age group displayed the highest baseline awareness. However, the oldest age group exhibited the least responsiveness to our educational media.

Bibliometrics and visualization analysis of literature on male hypogonadism from 2000 to 2023: research focus and frontiers.

Male hypogonadism can seriously affect male health and fertility, yet comprehensive bibliometric and visualization analyses of research in this area have been lacking. This study aimed to examine the distribution of literature, identify research hotspots, and discern development trends in male hypogonadism by analyzing 4026 English documents published between 2000 and 2023 using bibliometric and visual analyses. The results indicated a significant increase in publications and citations related to male hypogonadism over the past two decades, with the United States, the University of Florence, Maggi M, and the Journal of Clinical Endocrinology & Metabolism recognized as the most productive and highly cited country, institution, author, and journal, respectively. The article titled "The GPR54 gene as a regulator of puberty" received the highest number of citations. The keywords were categorized into four distinct clusters, including the etiology and pathogenesis of male hypogonadism, symptoms of late-onset hypogonadism, testosterone replacement therapy and its contraindications, the correlation between male hypogonadism and metabolic syndrome (MetS), obesity, and the epidemiology of male hypogonadism. The most frequently co-occurring keywords were "hypogonadism", "testosterone", and "men", while "oxidative stress" was the most prominent burst keyword. The analysis also identified "male infertility" and "oxidative stress" as the primary burst keywords in the last five years, indicating their emerging high-interest topics. Overall, this study provides a comprehensive overview of male hypogonadism research, offering valuable insights for researchers interested in this area, including potential collaborators, current research hotspots, and future research directions.

EMAS position statement: Testosterone replacement therapy in older men.

Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. Literature review and consensus of expert opinion. TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

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.

Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men

Background Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. Materials and methods The study included 78,615 men of age 55–67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995–2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. Results Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3–0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75–1.01 and HR = 0.93; 95% CI 0.87–1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. Conclusion Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.

α-Tocotrienol in rice bran enhances steroidogenesis in mouse Leydig cell via increased gene expression of steroidogenic acute regulatory protein and induction of its mitochondrial translocation.

Rice is a staple food in the Asian region and one of the world's major energy sources. Testosterone is a steroid hormone that maintains physical, sexual, and cognitive ability, and its decline causes health problems like late-onset hypogonadism. Evaluation of various grain extracts showed rice bran to stimulate testosterone secretion from Leydig model cells. α-Tocotrienol was found as a bioactive compound in rice bran, and mechanistic analysis showed the stimulation of steroid hormone synthesis through enhanced gene expression of steroidogenic acute regulatory protein as well as inducing mitochondrial localization of the protein. Preliminary study showed an increasing trend in serum testosterone levels in mice by oral intake of α-tocotrienol. These results suggest that α-tocotrienol intake may be effective in preventing symptoms caused by low testosterone levels.

FRI437 Regenerative Treatment With Platelet-rich Plasma In Patients With Refractory Erectile Dysfunction: The Predictive Value Of Mean Platelet Volume

Abstract Disclosure: D. Francomano: None. S. Iuliano: None. R.A. Condorelli: None. R. Cannarella: None. S. La Vignera: None. A.E. Calogero: None. E.A. Greco: None. G. Antonini: None. A. Aversa: None. Objective: Refractory erectile dysfunction (ED) is a common disorder in men regardless of the presence of late-onset hypogonadism. Being rich in growth factors, chemokines, and angiogenic factors, platelet-derived biomaterials contained in platelet-rich plasma (PRP) are particularly useful as some of the major therapeutic regenerative agents. PRP plays a crucial role in nerve cell regeneration, axon myelinization, progenitor cell homing and migration, and anti-fibrosis and anti-apoptosis of damaged cavernous nerve, and vascular corporal tissues (J Endocrinol 2001;170:395). Based on these findings, this study aimed to evaluate whether the mean platelet volume (MPV) may predict the efficacy of PRP before its intracavernous injection in patients with ED poorly responsive to phosphodiesterase type 5 inhibitors (PDE5i) and normal testosterone levels. Methods: 150 ED patients [age: 51±16.7 years; mean international index of erectile function (IIEF)-5: 12±2.6; mean peak systolic velocity (PSV): 32±5.5 cm/sec; and MPV=9.3±1.1 fl) underwent a single-shot treatment of PRP for their inability to respond to oral PDE5i. All patients were evaluated at baseline for MPV, at baseline and 1 month after intracavernous PRP injection for IIEF5, and dynamic penile duplex ultrasound (d-PDU) according to our previously published procedure (Andrology, 2021; 9:1457). Results: All patients had a significant improvement in ED symptoms (IIEF5: 12±2.6 vs. 19±3.0; p&amp;lt;0.0001) and a significant improvement in d-PDU (PSV: 32±5.5 vs. 42±7.6 cm/sec; p&amp;lt;0.0001). ROC curve analysis showed a significant accuracy (72.1%, C.I. 64.0 - 80.2, p&amp;lt;0.0001) for MPV in identifying clinically PRP-responsive patients with favorable outcomes (≧ +4 points in the IIEF5 score). In particular, an MPV &amp;lt;8.95 was recognized as the best threshold with a sensitivity of 90% and a specificity of 54.1%. Conclusion: This study provides the first evidence that the efficacy of a single PRP injection correlates with baseline MPV in patients with ED and poor response to PDE5i. An MPV value of less than 8.95 fl. identifies patients with a lower response to treatment who could benefit from re-treatments with more PRP injections. Presentation: Friday, June 16, 2023

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.

Do "testosterone boosters" really increase serum total testosterone? A systematic review.

Testosterone boosters are heavily marketed on social media and marketplaces to men with claims to significantly increase testosterone. Lax industry regulation has allowed sales of supplements to thrive in the absence of verification of their purported benefits. Our primary objective was to systematically review all data published in the last two decades on testosterone boosters and determine their efficacy. Our outcome of interest was total testosterone increase versus placebo in four different populations: male athletes, men with late-onset hypogonadism infertile men and healthy men. Following search and screening, 52 studies were included in our review, relating to 27 proposed testosterone boosters: 10 studies of cholecalciferol; 5 zinc/magnesium; 4 Tribulus terrestris and creatine; 3 Eurycoma longifolia and Withania somnifera; 2 betaine, D-aspartic acid, Lepidium meyenii and isoflavones; while the remainder were single reports. Our findings indicate that most fail to increase total testosterone. The exceptions were β-hydroxy β-methylbutyrate and betaine, which can be considered effective for male athletes. Eurycoma longifolia, a blend of Punica granatum fruit rind and Theobroma cacao seed extracts (Tesnor™) and purified Shilajit extract (PrimaVie™) can be considered possibly effective for men with late-onset hypogonadism; Eurycoma longifolia and Withania somnifera possibly effective for healthy men; and a non-hormonal aromatase inhibitor (Novadex XT™) possibly effective for male athletes.

Exploring the Treatment, Symptoms and Management of Male Andropause: The Analysis of Guidance and Counselling Imperative as Sub-Normality in Men

Menopause and the man equivalent, andropause, are normal process of aging, however, the symptoms associated with either are often frustrating, confusing and often depressing. This study examine the meaning of andropause, cause , symptom, treatment, Implications, recommendation as well as other therapies associated with andropause. The implications for counselling were discussed. The focus was on the key strategies the counsellor should adopt in helping men to cope with andropause develop positive attitude towards it. Andropause is also called “ Male menopause”. Andropause is a typical problem that affect men as they approach middle age. It’s the point of your life when your reproductive system is slowing down and testosterone level drop. some men may not seem to notice the difference when their testosterone begins to decrease, it can be an extreme change for others. When this happens, our andropause treatment for men can give your body the hormones it needs in order to relieves your symptoms.

Well-known polypeptides of deer antler velvet with key actives: modern pharmacological advances.

Deer antler velvet, with kidney tonifying, promoting the production of essence and blood, strengthening tendons and bones, not only has a thousand-year medicinal history but also its modern pharmacology mainly focuses on its active polypeptides on motor, nerve, and immune systems. The purpose of this report is to fill the gap in the comprehensive, systematic, and detailed review of polypeptides during the recent 30years (1992-2023). The research method was to review 53 pharmacological articles from the Public Medicine, Web of science, ACS, and Science Direct database sources by searching the keywords "pilose antler," "deer velvet," "Pilose Antler Peptide (PAP) and Velvet Antler Polypeptide (VAP)." The results showed that deer antler polypeptides (DAPs), by regulating EGF, EGFR, MAPK, P38, ERK, NF-κB, Wnt, PI3K, Akt, MMP, AMPK, Stir1, NLRP3, HO-1, Nrf, Rho, TLR, TGF-β, Smad, Ang II, etc., revealed their effects on seven system-related diseases and their mechanisms, including osteoarthritis, intervertebral disc degeneration, osteoporosis, Alzheimer's, Parkinson's, triple-negative breast cancer, liver injury, liver fibrosis, cardiovascular disease, acute lung injury, and late-onset hypogonadism. In conclusion, DAPs have good effects on motor and other system-related diseases, but the secondary and tertiary structures of DAPs (0.5-1800 KDa) need to be further elucidated, and the structure-activity relationship study is still unavailable and needs to be covered. It is expected that this review may provide the necessary literature support for further research. The activities and mechanisms of polypeptides from the past 30years (1992-2023) are summarized covering seven systems, related diseases, and its regulatory genes and proteins.