Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

The impact of water pollution on the health of older people.

Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature onset of age-related health problems. Water pollutants can in general be classified as chemical (both organic and inorganic), physical, and biological agents. Certain chemical pollutants have been found to disrupt hormonal balance by blocking, mimicking, or disrupting functions within the intricate homeostasis of the human body. Moreover, certain water pollutants, including specific pesticides and industrial chemicals, have been associated with neurological and psychiatric disorders, such as mood swings, depression, cognitive decline, and anxiety, impacting both women and men. Water pollution is also associated with physical ailments, such as diarrhea, skin diseases, malnutrition, and cancer. Exposure to specific pollutants may promote premature menopause and vasomotor symptoms, elevate the risk of cardiovascular disease, and reduce bone density. In men, exposure to water pollution has been shown to reduce LH, FSH, and testosterone serum levels. The oxidative stress induced by pollutants prompts apoptosis of Sertoli and germ cells, inhibiting spermatogenesis and altering the normal morphology and concentration of sperm. Environmental estrogens further contribute to reduced sperm counts, reproductive system disruptions, and the feminization of male traits. Studies affirm that men generally exhibit a lower susceptibility than women to hormonal changes and health issues attributed to water pollutants. This discrepancy may be attributed to the varied water-related activities which have traditionally been undertaken by women, as well as differences in immune responses between genders. The implementation of effective measures to control water pollution and interventions aimed at safeguarding and enhancing the well-being of the aging population is imperative. The improvement of drinking water quality has emerged as a potential public health effort with the capacity to curtail the onset of cognitive impairment and dementia in an aging population.

The severity of andropause symptoms and its relationship with social well-being among retired male nurses: a preliminary cross-sectional study.

BACKGROUND: Andropause is a syndrome that occurs due to decreased androgen levels in men. Various aspects of health, such as social well-being, can affect andropause status during men's retirement. This study aimed to determine the severity of andropause symptoms and its relationship with social well-being among retired male nurses. METHODS: This preliminary cross-sectional study was conducted on 284 retired male nurses in Ardabil (northwest of Iran). The participants were selected through the census sampling method. Data were collected using a demographic information form, the Male Andropause Symptoms Self-Assessment Questionnaire (MASSQ), and the Social Well-Being Scale (SWBS). Data were analyzed using SPSS software (version 22.0). RESULTS: The study found that the overall mean scores of the severity of andropause symptoms and social well-being among retired male nurses were 57.24 ± 12.62 (range = 35-91) and 94.54 ± 12.77 (range = 75-123), respectively. The highest and lowest mean scores between dimensions of social well-being were related to social contribution (20.26 ± 2.47) and social acceptance (15.26 ± 2.77), respectively. Multiple linear regression analysis revealed that subscales of social well-being, age, marital status, and spouse's menopause were predictors of the severity of andropause symptoms among retired male nurses. The selected predictors accounted for 53.1% of the total variance in severity of andropause symptoms (F = 36.613, p < 0.001). CONCLUSION: The results showed a moderate to severe prevalence of andropause among retired male nurses and a significant association between andropause and social well-being. The study suggests further research to examine sexual orientation and other factors that may affect andropause in retired male nurses.

Aging effects in adrenal cortex of male Mongolian gerbil: A model for endocrine studies.

The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.

Validity and Reliability of the Turkish Male Andropause Symptoms Self-Assessment Questionnaire.

Objective: This study was planned to examine the validity and reliability of the Turkish version of the Male Andropause Symptoms Self-Assessment Questionnaire (MASS-Q). Materials and Methods: One hundred and twenty-five men with a mean age of 54.24 ± 6.51 years participated in the study. First, participants' demographic data were recorded. Then, the MASS-Q was adapted to Turkish. The assess the reliability and validity of the Turkish MASS-Q, internal consistency, test-retest reliability, and criterion validity analyses were administered. For the reliability test, the scale was readministered 1 week later. Test-retest reliability was examined with the intraclass correlation coefficients (ICCs). Internal consistency was defined by Cronbach's alpha. Regarding the validity analysis, content validity was determined according to expert opinions. For criterion validity, the Aging Male Symptoms-Questionnaire (AMS-Q) was used. Results: According to the results of the analysis, the ICC values between the test-retest scores of the total and subdimensions (sexual, somatic, psychic, and behavior) of the MASS-Q were found to be 0.987, 0.939, 0.973, 0.951, and 0.887, respectively (P < 0.05). Cronbach's alpha values of the total and subdimensions (sexual, somatic, psychic, and behavior) of the MASS-Q were calculated as 0.924, 0.870, 0.747, 0.865, and 0.667, respectively. According to the ICC values obtained, it was found that the MASS-Q had a high degree of reliability. According to the internal consistency results, the sexual and psychic subdimensions were found to be quite reliable, whereas the somatic and behavioral subdimensions were found to be sufficiently reliable. According to the criterion validity results, a very high and high correlations were found between the AMS-Q scores and the MASS-Q scores (r = 0.636-0.938, P = 0.001). Conclusion: As a result, it was determined that the Turkish version of the MASS-Q is a valid and reliable scale that can be used in Turkish men.

Clinical outcome of testosterone supplementation assessed by andropausal male symptom scores in type 2 diabetes testosterone-deficient patients receiving testosterone compared to those not receiving testosterone: A nested case-control study.

BACKGROUND AND AIMS: This study aimed to explore the proportion of andropause in male patients with type 2 diabetes using an aging male symptoms scale and assess the clinical outcome of testosterone supplementation in patients with deficient testosterone levels at a tertiary care hospital. METHODS: Male patients with diabetes and total serum testosterone levels (≤12 nmol/L) were included in the study. Patients with testosterone supplementation, the standard of care among testosterone-deficient male patients, were included in the study (n = 35). Those not exposed to testosterone supplementation were considered controls (n = 35) and reassessed over 14 weeks for aging male symptom scores (AMS). RESULTS: The prevalence of andropause among the participants was 11% (117/1057). Data was analyzed as per protocol analysis. Exposure group had a frequency of 25.80%, and 19.35% in moderate and severe symptoms of AMS scores. Non-exposure group had frequency of 26.66% and 23.34% in moderate and severe symptoms of AMS scores. A significant mean difference (t = -2.93, P-value <0.05) was noted between exposure and non-exposure to testosterone supplementation. CONCLUSION: Results concluded that andropause is prevalent in patients with type 2 diabetes and low testosterone levels. Testosterone therapy affects aging andropausal symptoms such as the feeling of general well-being, joint pain and muscular ache, sleep problems, anxiety, and libido among patients with type 2 diabetes.

The Prevalence of Andropause and Its Relationship With Sexual Quality of Life Among Older Iranian Men.

Available evidence indicates insufficient knowledge about the status of andropause and sexual quality of life among Iranian older men. The study aimed to investigate the prevalence of andropause and its relationship with sexual quality among older adults. This descriptive-analytical study was conducted among 576 older people referred to urban health centers in Mashhad, Iran. The eligible samples were selected through the cluster sampling method. To collect data, the male andropause symptoms' self-assessment questionnaire and the sexual quality of life-male were used. Forty-seven of the respondents (n = 271) were diagnosed with a "moderate" level of andropause. A strong negative correlation was identified between the sexual quality of life and the severity of andropause (r = -.366, p < .001). Sexual quality of life and andropause was also affected by age, marital status, health status, and exercise. Thirty-six percent of the changes in the quality of sexual life of older men were influenced by the independent variables (adjusted R2 = .36; R2 = .40; R = .63). The findings indicated that andropause has highly prevailed among the participants. There was a meaningful association between andropause and sexual quality of life among older men. Further studies are recommended to investigate sexual orientation qualitatively and to discover other factors influencing andropause among adult men.

Vitamin D, testosterone and depression in middle-aged and elderly men: a systematic review.

Depression is one of the common psychiatric disorders during elderly. This systematic review aims to present the relationship between vitamin D deficiency, depression and testosterone serum concentration in the middle-aged and elderly men. We performed a comprehensive search in the Google Scholar, PubMed, ProQuest, Web of Science, Cochrane, Science Direct, and Scopus databases to collect any relevant published studies. The data of the articles that had been investigated the relationship between depression and 25-hydroxy vitamin D (25[OH]D) serum concentration (nine studies), or testosterone and 25[OH]D (six studies), as the primary outcomes, were included in our review. The results of the cohort and cross-sectional studies have shown that vitamin-D deficiency is associated with the incidence of depression in older men. In addition, documents have reported the positive association between vitamin D and testosterone, and previous studies have shown that testosterone can involve in the mood. We have proposed scientific mechanisms that have shown vitamin D may also play a protective role in depression through its effect on the testosterone. Therefore, it is a low risk and safe recommendation for the middle-aged and elderly men to use the vitamin D supplement or exposure to the sunlight to prevent depression.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

Effect of Tetragonia tetragonoides (Pall.) Kuntze Extract on Andropause Symptoms.

Testosterone and free testosterone levels decrease in men as they age, consequently inducing andropause symptoms, such as weight gain, fatigue, and depression. Therefore, this study aimed to evaluate the reducing effect of New Zealand spinach (NZS) on these androgenic symptoms by orally administering its extract to 26-week-old rats for four weeks. Biochemical blood testing was conducted, and the andropause symptoms-related indicators and muscular endurance levels were examined. In the NZS extract-treated rats, the decrease in muscle mass was suppressed, and immobility time was reduced in the forced swim test. In addition, the grip force and muscular endurance of the forelimbs were significantly increased compared to the control group; therefore, NZS extract exhibits a positive effect on the maintenance of muscle mass and improves muscular endurance. The representative male hormones, testosterone and progesterone, in the NZS extract-treated group were 1.84 times and 2.48 times higher than those in the control groups, respectively. Moreover, cholesterol and low-density lipoprotein, which affect lipid metabolism, were significantly reduced in the NZS extract-treated group. Overall, NZS extract shows potential for further development as a functional food material for improving muscle strength and relieving andropause symptoms.

Does Coronavirus Disease 2019 Kill More Elderly Men than Women Due to Different Hormonal Milieu.

Preliminary data depicts a much greater prevalence and high case-fatality rate in advanced age males as compared to age-matched women with severe acute respiratory syndrome-coronavirus-2 infections with high morbidity, mortality, high referral, and admission to intensive care unit with severe sequelae. However, the literature search revealed both for and against studies in this context. Thus, at present, in light of the mixed studies, it cannot be established whether low testosterone levels in aging hypogonadal males create a permissive environment for severe response to coronavirus disease 2019 (COVID-19) infection and can it increase the morbidity or mortality, or on the contrary if the virus inhibits androgen formation. Hence, it is highly warranted to establish the said hypothesis by conducting large statistically powered clinical studies in future. Further, it is highly indicated that impact of sex hormones and gender on the incidence and case fatality of the disease and hormones as a treatment according to sex and gender for COVID requires further scientific research by the research community before it is actually recommended to mitigate the COVID-19 disease course among elderly men and women at large.

Counselling for Testosterone Therapy in Mid Life Men.

Testosterone is frequently used for the optimization of mid-life health. This therapy is effective and safe if accompanied by adequate counseling, before prescription, and during administration. In this opinion piece, we discuss the style and substance of medication counseling for testosterone therapy. The role and scope of counseling are highlighted, with a focus on screening, diagnosis, medication counseling, sexual counseling, and monitoring. This article should prove useful for all health care professionals.

Current Management and Controversies Surrounding Andropause.

Andropause is a condition surrounded by controversies, whether it be through its diagnosis or management. As we learn more about the pathophysiology of hypogonadism, our perspectives on the risks and benefits of testosterone therapy have shifted. We attempt to discuss the most modern and relevant points of controversy currently affecting the field. Throughout this review, we discuss the art of diagnosing hypogonadism as well as the association or lack thereof between testosterone replacement therapy and cardiovascular disease, prostate cancer, thrombosis, antiaging effects, exogenous steroid abuse, and diabetes mellitus.

Medical Treatment of Hypogonadism in Men.

Urologists may commonly diagnose hypogonadism in adult men experiencing an age-related decline in serum testosterone. Low serum testosterone in conjunction with symptoms such as decreased libido, fatigue, memory deficit, or decreased vitality is described as testosterone deficiency syndrome. There are numerous therapeutic options, although each is unique in its formulation, administration, and side-effect profile. For this reason, treatment can prove to be challenging for each unique patient case. The clinician must carefully monitor key serum markers before and during treatment. With careful dosing and monitoring, therapeutic benefit can be achieved reliably and sustainably.

The Lost Penis Syndrome: A New Clinical Entity in Sexual Medicine.

INTRODUCTION: The "lost penis syndrome" (LPS) is a term often used in non-clinical settings to describe the subjective perception of the loss of cutaneous and proprioceptive feelings of the male organ during vaginal penetration. Although deserving clinical attention, this syndrome did not receive any consideration in the medical literature. Notwithstanding, it represents a relatively unexceptional condition among patients in sexual medicine clinics, and it is often reported together with other sexual dysfunctions, especially delayed ejaculation, anejaculation, male anorgasmia and inability to maintain a full erection. OBJECTIVES: To draft a new conceptual characterization of the LPS, defined as a lack of penile somesthetic sensations during sexual penetration due to various causes and leading to several sexual consequences in both partners. METHODS: Based on an extensive literature review and physiological assumptions, the mechanisms contributing to friction during penovaginal intercourse, and their correlation to LPS, have been explored, as well as other nonanatomical factors possibly contributing to the loss of penile sensations. RESULTS: Efficient penile erection and sensitivity, optimal vaginal lubrication and trophism contribute to penovaginal friction. Whenever one of these processes does not occur, loss of penile sensation defined as LPS can occur. Sociocultural, psychopathological and age-related (ie, couplepause) factors are also implicated in the etiology. Four types of LPS emerged from the literature review: anatomical and/or functional, behavioral, psychopathological and iatrogenic. According to the subtype, a wide variety of treatments can be employed, including PDE5i, testosterone replacement therapy and vaginal cosmetic surgery, as well as targeted therapy for concomitant sexual comorbidity. CONCLUSION: We held up the mirror on LPS as a clinically existing multifactorial entity and provided medical features and hypotheses contributing to or causing the occurrence of LPS. In the light of a sociocultural and scientific perspective, we proposed a description and categorization of this syndrome hypothesizing its usefulness in daily clinical practice. Colonnello E, Limoncin E, Ciocca G, et al. The Lost Penis Syndrome: A New Clinical Entity in Sexual Medicine. Sex Med Rev 2022;10:113-129.

Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.

CONTEXT: Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. OBJECTIVE: We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. METHODS: This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). CONCLUSION: Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause.

Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen - activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.