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.

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.

El climaterio como etapa fisiológica crucial en la prevención de la enfermedad cardiovascular / The climacteric as a crucial physiological stage in the prevention of cardiovascular disease

El climaterio es una etapa fisiológica que permite al médico reconocer tempranamente los riesgos de patologías y la gran oportunidad de revertirlas. Este trabajo examinará la evidencia actual de la terapia hormonal en la prevención primaria de la enfermedad cardiovascular en mujeres, así como la importancia que igualmente tienen la indemnidad de los ovarios, el peso normal, el uso correcto de antibióticos, la preservación de la microbiota intestinal, las dietas antioxidantes, los estilos de vida saludables y el obligatorio abandono del hábito de fumar.

The andro-accelerator hypothesis.

Testosterone levels are known to decline with advancing age. However, there are frequent reports of inappropriate social behaviour involving middle-aged men, suggestive of hyperandrogenic state. The andro-accelerator hypothesis seeks to explain this phenomenon. This states that external stimuli, both asexual and sexual in nature, can increase or accelerate testosterone production, by stimulating the hypothalamo-pituitary-testicular axis, and resetting this axis at a higher level. This article discusses the concepts of andro-conditioning due to endocrine disruptor stimuli or endocrine disruptor social content, explores the clinical and public health relevance of the andro-accelerator hypothesis, and calls for a focus on addressing androgen imbalance, achieving "androequanimity", rather than treating andropause as a disease.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis.

Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569 847, corpus uteri 382 069, ovary 295 414, vulva 44 235, and va​gina 17 600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy, and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45 years, early menopause. The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. Our methods comprised a literature review and consensus of expert opinion. The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal, or vulvar cancer, as these tumors are not considered to be hormone dependent.

Concurrent training protocol for men with androgen deficiency in the aging male: a randomized clinical trial.

BACKGROUND: The androgen deficiency in the aging male (ADAM) affects physical, sexual, and psychological aspects with characteristics symptoms of middle-aged men. The practice of regular physical activity and physical exercise can attenuate these symptoms. The aim of this randomized clinical trial is to propose a physical exercise protocol based on concurrent training for middle-aged men with ADAM. METHOD: Randomized clinical trial with a 6-month intervention will randomly divided into two groups: experimental group (EG) and control group (CG). Four evaluations will be carried out, (1) pre-intervention; (2) in the first month of intervention; (3) in the third month of intervention; (4) post-intervention, evaluating: physical, psychological, sexual, and hormonal aspects. The intervention protocol with concurrent training will have duration of 6 months; frequency of 3 times weekly, with 60 min per session. The two-way ANOVA test will be used for the inter-group and intra-group comparisons with repeated measurements, and also Sydak's comparison test. CONCLUSION: This protocol was developed with the intent of easing the symptoms of ADAM. In addition, it is believed that the concurrent training protocol could be capable to recover hormonal, physical, psychological, and sexual aspect of middle-aged men with ADAM.

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway.

The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-ß) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

Awareness and experience of andropause symptoms in men referring to health centers: a cross-sectional study in Iran.

INTRODUCTION: Andropause is a gradual process and more similar to menopause in women. Knowledge and experience of symptoms of andropause is an important discussion is in their lives. OBJECTIVES: This study aimed to determine Awareness and Experience of Andropause Symptoms in Men referring to Health Centers in Rasht, Iran. MATERIALS AND METHODS: This cross-sectional and analytical study included 140 men over 40 years referring to one of health centers. Collection tool of this study was a questionnaire consisting of three parts. The first part was about demographic characteristics, The second part was a researcher-made questionnaire, The third part was Aging Male Scales (AMS) questionnaire. Data were analyzed by descriptive and analytical statistics. RESULTS: This study showed 73.6% had experience symptoms of andropause. The mean knowledge score (of 20 score) for the 3/3 ± 4/9, with the level of education, occupation and income was statistically significant (p < 0.05). There was significant relationship the andropause symptoms with BMI and occupation (p < 0.05). CONCLUSION: Based on the results of this study, despite the fact that the majority of men over age 40 had experienced symptoms of andropause, but their awareness about andropause was very low.

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

BACKGROUND: Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. METHODS: One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). RESULTS: Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (<55 years) men had significantly higher values of NEP serum activity than younger women. Significantly lower ACE serum activity was detected in older men compared to younger men. In women, significantly higher ACE2 serum activity was observed in older women compared to younger women. CONCLUSIONS: These results suggest a differential effect of aging on the activity of RAS enzymes in men and women, especially with respect to the breakpoint of andropausia/menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

[Gender Features of Radical Oxidation of Lipids in Menopausal Women and Men in Andropause].

Aims: Our aim was to assess lipid peroxidation ­ antioxidant protection in menopausal women and men in andropause and to compare these processes in different gender and age groups. Materials and Methods: 74 women and 37 men were examined. This study was a prospective, randomized cohort study. Women were divided into perimenopausal group (n=22, mean age 49.03±3.13), postmenopausal group (n=15, mean age 54.43±4.54) and control (n=37, mean age 34±1.2). Men were divided into a group of andropause (n=20, mean age 50.38±2.63) and control (n=17, mean age 35.21±4.75). Body mass index in the main and control groups was comparable. Questionnaires, clinical examination, assessment of the lipid peroxidation-antioxidant defense system, and the calculation of oxidative stress ratio were conducted to all participants of the study. Results: In women from the reproductive phase transition to its extinction increases content of compounds with conjugated double bonds by 22% (p<0.05) in perimenopause and by 27% (p<0.05) in postmenopause, increases content of the ketodienes and coupled trienes by 21% (p<0.05) in perimenopause relative to the control group and reduced by 27% (p<0.05) in postmenopausal women relative to the group of perimenopause. The antioxidant system in women observed the following changes: decrease in the α-tocopherol levels in postmenopausal women by 37% relative to control and by 22% (p<0.05) to compare perimenopause; reduction of retinol level by 29% (p<0.05) in the perimenopause and by 39% (p<0.05) in postmenopause relative to control, increasing of the content of GSSG by 18% (p<0.05) in postmenopause to compare control. When comparing groups of men statistically significant differences were not found. When comparing the groups according to gender, we revealed in men the increased content of compounds with conjugated double bonds by 38% (p<0.05), the GSSG by 13% (p<0.05), reduced content of the ketodienes and coupled trienes by 43% (p<0,05), α-tocopherol by 24% (p<0.05), SOD activity by 9% (p<0.05).Coefficient oxidative stress in perimenopausal women was 2,5, in postmenopausal ­ 3,48, in andropause ­ 0,97. Conclusions: Expressed lipid peroxidation activity is more physiological in andropause than in menopause. Men in andropause have large functional reserves and adaptive capacity than menopausal women.

Modification Effects of Changes in Job Demands on Associations Between Changes in Testosterone Levels and Andropause Symptoms: 2-Year Follow-up Study in Male Middle-Aged Japanese Workers.

PURPOSE: The purpose of this longitudinal study was to ascertain if changes in job demands modify associations between changes in testosterone levels and andropause symptoms in male Japanese workers. METHOD: A baseline survey including job demands and the Aging Males' Symptoms scale, lifestyle factors, and blood levels of testosterone was conducted in 2007. Among 192 men (mean age ± SD 52.2 ± 7.6 years) who completed all relevant questionnaires and provided blood at baseline, 104 men (50.9 ± 7.2 years) were followed up in 2009. Changes of variables in 2 years were calculated (data of follow-up minus those of baseline). RESULTS: Testosterone levels were increased significantly, whereas job demands and somatic symptoms were reduced significantly, at follow-up. Changes in testosterone levels were negatively associated with changes in total andropause symptoms, psychological symptoms, and sexual symptoms (standardized ß = -0.27, -0.24, and, -0.29, p < 0.05, respectively), after adjustment for confounders. Changes in job demands were positively associated with changes in somatic symptoms (standardized ß = 0.21, p < 0.05). Significant interactions of changes in testosterone levels and job demands were noted for changes in psychological symptoms (standardized ß = 0.26, p < 0.05). For men with a 1-SD reduction in job demands, negative associations between changes in testosterone levels and psychological symptoms were intensified, but not for men with a 1-SD increase in job demands. CONCLUSION: Andropause symptoms may be affected by changes in testosterone levels and job demands. Change in job demands may modify associations between changes in testosterone levels and andropause symptoms.

Hormonal determinants of the severity of andropausal and depressive symptoms in middle-aged and elderly men with prediabetes.

Andropausal and depressive symptoms are common in aging males and may be associated with hormone deficiency. We investigated the severity of andropausal and depressive symptoms, as well as their hormonal determinants, in 196 middle-aged and elderly men (age range: 40-80 years) with prediabetes (PD) and in 184 healthy peers. PD was diagnosed according to the definition of the American Diabetes Association. The severity of andropausal and depressive symptoms was assessed using the Aging Males' Symptoms Rating Scale and the Self-Rating Depression Scale. Total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) were measured. The prevalence of andropausal syndrome in men with PD was significantly higher than that in healthy men (35% vs 11%, respectively). In men with PD aged 40-59 years, the severity of sexual, psychological, and all andropausal symptoms was greater than in healthy peers, while in elderly men (60-80 years), only the severity of psychological symptoms was greater than in healthy peers. The severity of depressive symptoms in the middle-aged men with PD was greater than in healthy peers, while the severity of depressive symptoms in elderly men with PD and healthy peers was similar. The higher prevalence of andropausal symptoms was independently associated with cFT and IGF-1 in middle-aged men and with TT and DHEAS in elderly men with PD. The more severe depression symptoms were associated with low TT and DHEAS in middle-aged men and with low cFT and DHEAS in elderly men with PD. In conclusion, the prevalence of andropausal symptoms, especially psychological, was higher in prediabetic patients as compared to healthy men, while the severity of depressive symptoms was higher only in middle-aged men with PD. Hormonal determinants of andropausal and depressive symptoms are different in middle-aged and elderly patients, but endocrine tests are necessary in all men with PD.

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.

This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-ß precursor protein processing towards the production of mitogenic Aß; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease.

Testosterone application decreases the capacity for ACTH and corticosterone secretion in a rat model of the andropause.

The culminating phase of ageing in males-andropause is characterized by enhanced activity of the hypothalamic-pituitary-adrenal axis and frequent glucocorticoid excess. In parallel, free testosterone deficiency provides the baseline hormonal milieu for the ageing male. The aim of this study was to illustrate (using diverse microscopic and biochemical methodologies) the effects of testosterone application on the capacity for adrenocorticotropic hormone (ACTH) and corticosterone secretion in a rat model of the andropause. Middle-aged Wistar rats were divided into sham-operated (SO; n=8), orchidectomized (Orx; n=8) and testosterone treated orchidectomized (Orx+T; n=8) groups. Testosterone propionate (5 mg/kg b.w./day) was administered for three weeks, while SO and Orx groups received the vehicle alone. ACTH cells and the adrenal cortex were stained using immuno-histochemical, immuno-fluorescent and histochemical procedures. Circulating concentrations of testosterone, estradiol, ACTH and corticosterone, as well as the adrenal tissue corticosterone levels were measured by immunoassays. Testosterone application led to increased (p<0.05) serum concentrations of sex steroids. Consequently, in Orx+T rats the ACTH cell nuclei volume increased (p<0.05) by 34%, while the volume density of ACTH cells and their relative intensity of fluorescence decreased (p<0.05) by 46% and 21%, respectively, in comparison with the corresponding parameters in the Orx group. Testosterone also induced vasodilatation in the adrenocortical zona fasciculata, and decreased (p<0.05) the ACTH concentrations and adrenal tissue corticosterone levels by 38% and 31%, respectively, compared to the Orx group. In conclusion, testosterone administration caused a decrease in the capacity for ACTH and corticosterone secretion in a rat model of the andropause.

Are andropause symptoms related to depression?

BACKGROUND: Andropause is a middle-age condition in which men experience changes in their physical, spiritual and emotional health. The association between andropause and psychological symptoms such as depression are not very clear yet. AIMS: The objective of this study was therefore to determine the association between the 'Aging Males Symptoms Scale' (AMS) and depression. METHODS: A cross sectional study was conducted among 521 old men. To collect data, the AMS and the Patient Health Questionnaires 2 and 9 were used to screen depression, in addition to questions on background and fertility. Multiple linear regression analysis was used to assess the association between andropause symptoms and depression. RESULTS: Based on our results and the AMS score, 51.5% of the study population had clinical symptoms of androgen disorder, 3.7% of which had severe symptoms. There was a strong correlation between the AMS score and depression. Depression, diabetes, cigarette smoking and spousal age retained their significant associations even after entering the relevant demographic, anthropometric, smoking and disease variables in the multivariable model. As a positive predictive factor, depression had the strongest association with AMS. CONCLUSIONS: Based on our results, there is a direct association between andropause symptoms and depression, where the increasing AMS score corresponds with the severity of depression. DISCUSSION: Our results show the need of screening for depression when evaluating andropause symptoms.

Late onset hypogonadism of men is not equivalent to the menopause.

Some men between the ages 45 and 60 years develop complaints and symptoms reminiscent of menopausal complaints in women. So, parallels were sought between the changes in female and male endocrinology during that period of life. Indeed, men do show a decline of serum testosterone from age 40 to 50 years onwards but it is a slow decline of 1-2% per year and over time it may amount to hypogonadism. The mechanism of a decline in serum testosterone in men does not resemble the menopause; it is partially an aging neuroendocrine system with a less efficient testosterone production but equally or more important, the result of inhibition of testosterone production by metabolic factors in relation to visceral obesity. These effects are in part reversible with weight loss. A hypogonadal state in aging men has deleterious effects. Mortality of all causes is highest in men with low testosterone impacting on their metabolic state leading to diabetes mellitus, cardiovascular disease, osteoporosis, and sexual dysfunction. Normalization of testosterone in aging hypogonadal men has a beneficial effect on the above pathologies. The fear that testosterone treatment of elderly men would lead to prostate disease has not been substantiated in studies. So, while men do not have a 'menopause', testosterone deficiency in old age deserves serious attention.

Andropause--lessons from the European Male Ageing Study.

Andropause or late-onset hypogondism (LOH) is a situation where a middle-aged or older man has low serum testosterone (T) in conjunction with diffuse symptoms reminiscent of those of genuine male hypogonadism (e.g. reduced sexual function, loss of vigor, muscle weakness, depression). Opinions about the diagnostic criteria, prevalence and treatment options of andropause vary considerably amongst experts. We review here some salient findings on the prevalence, diagnostic criteria and impact on health of andropause, obtained from the European Male Ageing Study (EMAS), a multicenter study of ageing among community-dwelling middle-aged and older men.