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PubMed2006

HIV-associated hypogonadism.

Hypogonadism in men with HIV disease is an ongoing concern, even among patients whose viral replication is under control and who have normalized CD4+ cell counts. Men with HIV disease may be more prone to a syndrome of "early andropause," marked by dysregulation of the hypothalamic-pituitary axis and the associated signs and symptoms. Testosterone is primarily bound to plasma proteins, mainly albumin and sex hormone-binding globulin; testing for levels of free testosterone may be necessary when total testosterone levels are equivocal. In managing patients with hypogonadism, forms of testosterone replacement that provide stable physiologic levels of testosterone may be preferable to those that result in supraphysiologic levels.

Adult↗
PubMed2003

Advanced age at diagnosis is an independent predictor of time to death from prostate carcinoma for patients undergoing external beam radiation therapy for clinically localized prostate carcinoma.

BACKGROUND: Whether age at diagnosis is predictive of time to prostate carcinoma specific death after external beam radiation therapy (RT) for patients who are diagnosed with clinically localized prostate carcinoma during the prostate specific antigen (PSA) era has not been investigated previously. METHODS: A multivariate Cox regression analysis was used to evaluate the ability of pretreatment risk group and age at diagnosis to predict time to all causes of death and time to death from prostate carcinoma for 381 patients who underwent RT for clinically localized prostate carcinoma. RESULTS: Age at diagnosis, as a continuous variable (P(continuous) = 0.04), and risk group (P(categorical) = 0.02) were independent predictors of time to death from prostate carcinoma, whereas only age at diagnosis (P(continuous) = 0.01) was a predictor of time to all causes of death. When analyzed as a categorical variable, beginning at age 73 years, age at diagnosis was an independent predictor (P(categorical) < 0.04) of time to death from prostate carcinoma. Upon further analysis, this finding was limited to high-risk patients. For example, age > or = 75 years at diagnosis predicted for a shorter median time to death from prostate carcinoma (6.3 years vs. 9.7 years; P = 0.002) in high-risk patients. CONCLUSIONS: Patients with clinically localized, high-risk prostate carcinoma who were diagnosed at age > or = 73 years and were treated with RT had a worse prognosis compared with patients who were diagnosed age < 73 years, raising the possibility that a more aggressive prostate carcinoma biology may develop during andropause.

Age Factors↗
PubMed2003

New achievements and pharmacotherapeutic approaches to impotence in the elderly.

Erectile dysfunction (ED) has a negative impact on the quality of life of elderly men, but impotence is not an absolute concomitant of aging. Aging changes influencing sexual function in men consist of a decreased capacity to reach arousal by imagination or view, fragility of erection, and an increase in the refractory period. These events may be part of the andropause syndrome, which includes a decrease in intellectual activity, fatigue, depression, decreases in body hair, lean body mass and bone mineral density, accompanied by an increase in weight. As a consequence, the overlap of aging processes, concurrent diseases and social situations to which elderly men are subject, results in the great variability reported in epidemiological studies. In the same way, the complex physiology of erection depends on the social, environmental, or physical context in which it occurs. New achievements in research on intracellular mechanisms of erection and on the neuroendocrinology of aging contribute to better understanding the pathophysiology of ED in the elderly. For example, testosterone declines with age with great interindividual variability, since other hormonal changes are also involved. What currently can be easily identified is the alteration of LH-testosterone feedback alterations, although hormone levels fall in the normal range. Nevertheless, the extent to which age-dependent decline in hormones leads to health problems that may affect the quality of life remains to be clarified. Several concepts on aging-related processes have been challenged, and conditions that were once accepted as physiologically age-related are now thought to lead to medical problems, but until now erectile dysfunction remains underreported, underdiagnosed, and undertreated, especially in the elderly. Nowadays, we are witnessing a rapid growth in available pharmacotherapies, from intracavernous injections of vasoactive drugs, to powerful new oral agents, with differing pharmacological dynamic and kinetic properties. New options for treatment are therefore possible, taking into account both the possibility of changing ineffective drugs and augmenting efficacy by means of synergistic associations. This rich generation of progress is certainly contributing to a better medical approach to sexuality in aging people.

Age Distribution↗
PubMed2006

The male biological clock.

Do men have biological clocks that affect their hormone levels, fertility, and the genetic quality of their sperm? Women can no longer be viewed as solely responsible for age-related fertility and genetic problems. The effects of andropause and advanced paternal age on fertility and offspring are still under investigation. Further research is needed to fully characterize the associated risks and to treat the underlying abnormalities. A better understanding of the cellular and biochemical mechanisms of "gonadal" aging is important in order to determine safe, effective ways to delay this process and "rewind" the male biological clock. The benefits may include decreasing the potential for adverse genetic consequences in offspring, improvement in the sexual and reproductive health of aging males, and increase a woman's chance of having healthy children by correcting defects in the male reproductive system.

Aging↗
PubMed1999

Sarcopenia, hypermetabolism, and aging.

Sarcopenia is a constant in aging. Observed over long periods, it can reach 1% per year. But it is such a tenuous phenomenon that it cannot be observed over short periods at steady state. The aging phenomenon mainly hits fibers, Type II but on aged muscle thin, normal, and hypertrophic fibers cohabit with sclerosis and fat increases. Sarcopenia is difficult to study, due to the lack of simple clinical, biochemical, or imaging measures. Anthropometric data are largely dependent on water content. DEXA gives better information on appendicular muscle loss. Measures of strength analyze functional outcomes of sarcopenia. Sarcopenia appears largely multifactorial. Hormonal changes, e.g., drop in growth hormone, menopause, and andropause, explain impaired protein synthesis. Disuse (sedentary, bed rest) may explain chronical protein lysis. But the main factors for muscle lysis imply life events and occurring diseases. Cytokines (IL6, TNF alpha) and stress hormones (cortisol) induce quick protein lysis in muscle. Rapid and intensive successive aggressions during life cannot be compensated by slowed synthesis. Harmful consequences of sarcopenia explain many disabilities of old age: loss of strength, inducing itself loss of mobility, falls, equilibrium disorders, poor ADL: loss of nutritional reserves (protein and glycogen) impairing capacities of immune response. Muscle loss spoils vital functions as respiration. Treatment remains rather limited to resistance exercise. Although, these results are thin, they are the only ones to be validated in all the elderly even the frail or the old. However it is not efficient during the evolution of an inflammatory process. The powerful action of cytokine and cortisol on muscular hypermetabolism must be incited for early treatment of any infectious or inflammatory event. Nutritional supplementation has no efficiency in the absence of malnutrition and without exercise. Although mobility impairments mainly due to sarcopenia are the first cause of disablement in the elderly, we lack information on etiology, evolution, and measurement of sarcopenia. We also lack controlled therapeutical studies.

Aged↗
PubMed2001

Sexual dysfunction and depression: etiology, prevalence, and treatment.

Sexual dysfunction and depression are very common conditions that are age-related and chronic. In men, epidemiologic studies have confirmed a strong correlation between erectile dysfunction and symptoms of depression. Both conditions have a significant negative impact on the quality of life of patients and their partners. Several studies showed that restoration of normal sexual function improves the quality of life of patients and their partners, regardless of treatment method. The literature review and recent observations emphasize the multifactorial nature of sexual dysfunction and, more specifically, erectile dysfunction and underline the importance of the comorbidity and bidirectional relationship between erectile dysfunction and depression. Research is progressing on the possible link between andropause, sexual dysfunction, and depression, thus opening potential new opportunities to address issues of aging-related morbidities.

Depressive Disorder↗
PubMed1989

The questionable physiologic and epidemiologic basis for a male climacteric syndrome: preliminary results from the Massachusetts Male Aging Study.

This paper examines the physiologic and epidemiologic evidence for a widely discussed syndrome termed either 'mid-life crisis', 'male menopause', 'male climacteric', or increasingly, 'andropause'. The paper is divided into 2 parts: (1) a review of evidence from physiologic studies conducted over the last decade that examine endocrine function in aging males; (2) a description of the salient features of an ongoing multidisciplinary epidemiologic study (the Massachusetts Male Aging Study) of a sample of approximately 1700 men aged 40-69 yr, randomly sampled from the general population. This study is markedly different in size and content from studies conducted to date. Preliminary findings suggest that age per se may be a relatively unimportant contributor to endocrine variability and that anthropometrics and life style phenomena may be at least as important.

Adult↗
PubMed1990

Changes in hepatic androgen sensitivity and gene expression during aging.

The hepatic tissue of the male rat exhibits a gradual decline and ultimate loss in androgen responsiveness during in vivo aging. Appearance of the age-associated androgen insensitivity can be delayed by dietary calorie restriction, an effective means for life-span extension. The androgen receptor mRNA is detectable in the liver only in its androgen-responsive state. Pubertal appearance of hepatic androgen sensitivity is remarkably correlated with the concomitant appearance of a cytoplasmic androgen binding (CAB) protein. Androgen resistance during senescence is associated with the loss of hepatic CAB activity as well. We are investigating the molecular basis for the temporal modulation of this hormone sensitivity through studies on the differential expression of two androgen-responsive marker genes. These are the androgen-repressible SMP-2, and the androgen-inducible alpha 2u-globulin. Androgen resistance of hepatocytes during aging results in repression of the alpha 2u-globulin gene, and derepression of the SMP-2 gene. The structural organizations for both of these genes have been characterized. The role of nuclear transcription factors (androgen receptor and any other transacting factor(s) which may be involved) in the coordinate regulation of alpha 2u-globulin and SMP-2 during aging and nutritional manipulation is being explored to establish the molecular mechanism of andropause in the liver.

Aging↗
PubMed2004

Soy isoflavone phyto-pharmaceuticals in interleukin-6 affections. Multi-purpose nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-inflammatory therapy.

Interleukin-6 is a pleiotropic cytokine which plays a crucial role in immune physiology and is tightly controlled by hormonal feedback mechanisms. After menopause or andropause, loss of the normally inhibiting sex steroids (estrogen, testosterone) results in elevated IL6 levels that are further progressively increasing with age. Interestingly, excessive IL6 production promotes tumorigenesis (breast, prostate, lung, colon, ovarian), and accounts for several disease-associated pathologies and phenotypical changes of advanced age, such as osteoporosis, rheumatoid arthritis, multiple myeloma, neurodegenerative diseases and frailty. In this respect, pharmacological modulation of IL6 gene expression levels may have therapeutical benefit in preventing cancer progression, ageing discomforts and restoring immune homeostasis. Although "plant extracts" are used in folk medicine within living memory, it is only since the 20th century that numerous scientific investigations have been performed to discover potential health-protective food compounds or "nutraceuticals" which might prevent cancer and ageing diseases. About 2000 years ago, Hippocrates already highlighted "Let food be your medicine and medicine be your food". Various nutrients in the diet play a crucial role in maintaining an "optimal" immune response, such that deficient or excessive intakes can have negative consequences on the organism's immune status and susceptibility to a variety of pathologies. Over the last few decades, various immune-modulating nutrients have been identified, which interfere with IL6 gene expression. Currently, a broad range of phyto-pharmaceuticals with a claimed hormonal activity, called "phyto-estrogens", is recommended for prevention of various diseases related to a disturbed hormonal balance (i.e. menopausal ailments and/or prostate/breast cancer). In this respect, there is a renewed interest in soy isoflavones (genistein, daidzein, biochanin) as potential superior alternatives to the synthetic selective estrogen receptor modulators (SERMs), which are currently applied in hormone replacement therapy (HRT). As phyto-chemicals integrate hormonal ligand activities and interference with signaling cascades, therapeutic use may not be restricted to hormonal ailments only, but may have applications in cancer chemoprevention and/or NF-kappaB-related inflammatory disorders as well.

Animals↗
PubMed2004

Current controversies in testosterone testing: aging and obesity.

The interpretation of the total serum testosterone concentration is problematic because it is related directly to the serum SHBG concentration.Frequently, an estimate of the serum free testosterone concentration is obtained to better assess the clinical status of the patient. We reviewed five methods for the determination of free testosterone or a surrogate test/index and the problems with these methods. The calculated free testosterone or BAT (highly positively correlated) are recommended as the preferred tests to assess biologically-active testosterone, although interlaboratory values may differ because standards are not available. The controversies in evaluating gonadal function are illustrated by the andropause (elevated SHBG) and obese men (decreased SHBG).

Aging↗
PubMedDate not supplied

Sex hormone receptors in the human eye.

Dissimilarities in ocular physiopathology exist between human males and females. These differences can be observed in the lacrimal and other eye-associated glands, the ocular surface, the crystalline lens, and the retinochoroid complexes. Literature on the subject revealed that because of sex steroid hormone (estrogen, progesterone, and androgen) actions, various physiological conditions, such as age, menstrual cycles, pregnancy, and menopause or andropause, where the hormone milieu changes, affect vision. Well-designed scientific studies are lacking on the subject, although such studies hold much potential value. This review analyzes the relatively new area of hormones and vision.

Aging↗
PubMed2003

Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth.

Little is known about the roles of androgens in the regulation of redox state in the prostate, a cellular process believed to profoundly influence normal and aberrant prostate functions. We demonstrate that castration induced discrete oxidative stress (OS) in the acinar epithelium of rat ventral prostate (VP), as evident from marked increases in 8-hydroxy-2'-deoxy-guanosine and 4-hydroxynonenal protein adducts in the regressing epithelium. Testosterone replacement partially reduced OS in VP epithelia of castrates, but the level remained higher than in intact rats. Quantification of steady-state mRNA levels of 14 genes involved in the anabolism and catabolism of reactive oxygen species (ROS) showed that castration resulted in dramatic increases of three ROS-generating NAD(P)H oxidases (Noxs) including Nox1, gp91(phox), and Nox4, significant reductions of key ROS-detoxifying enzymes (superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5), and unchanged levels of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase. Testosterone replacement in castrated rats partially reduced expression of Noxs but restored expression of superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5 to complete normalcy and induced a compensatory increase in expression of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase in the regenerating VP. Expression of superoxide dismutase 1, glutathione S-transferase-pi, and glucose-6-phosphate dehydrogenase was unaffected by castration and testosterone replacement. These findings indicate androgen-deprivation induces OS in the rat VP through elevation of ROS anabolism and diminution of antioxidant detoxification. Androgen replacement partially reduces OS in rat VP to precastration levels. Expression of Noxs remained high amid a broad-based recovery of antioxidant defense mechanism(s). These data might have implications on the use of androgen blockade for prostate cancer prevention and androgen therapy for andropause treatment in elderly men.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Androgen deficiency in the aging male: when, who, and how to investigate and treat.

Androgen deficiency in the aging male (ADAM), also known as andropause, affects an estimated 1 in 200 men. The abnormally low levels of testosterone in these men can usually be managed with androgen supplementation therapy. Because a large proportion of urologic patients are men at or beyond middle age, urologists should be familiar with ADAM, its clinical manifestations, the rational approach to its diagnosis and treatment, and the consequences of treatment. Equally important is responsibility for the patient's monitoring, because prolonged androgen replacement therapy can be associated with significant complications, particularly in the prostrate.

Age Factors↗
PubMed2000

Diseases of aging.

By definition, diseases of aging become clinically manifested in elderly patients. However, their pathogenetic basis has to be sought earlier in life. The general thread of this presentation relies on the concept of an evolutionary-Darwinian view of the development of age-related diseases. In essence, this concept states that we may have to "pay" for genetic traits that play a beneficial role earlier in life by the later development of diseases since there is no post-reproductive selective pressure that may have eliminated the potential late onset detrimental effects of such genes. Examples for this kind of trade-off are taken from diseases involving the immune system (infections), the endocrine system (andropause), the nervous system (Alzheimer's disease), the locomoter system (osteoporosis), the cardio-vascular system (atherosclerosis) and cancer.

Adult↗
PubMed2002

Androgens and aging men.

This article underlines the hormonal and clinical events characterizing the so-called andropause, as they may be described from an extensive review of the literature and some data obtained with the French colleagues of the author. Evidence-based hormonal intervention has to be positioned against anti-aging entrepreneurs who peddle hormones at random. The desequilibrium in aging men between the unchanged level of plasma cortisol and the profound decrease of androgens deserves cautious studies to eventually oppose this unbalanced hormonal situation effectively and safely.

Aging↗
PubMed2004

Perception of males' aging symptoms, health and well-being in elderly community-dwelling men is not related to circulating androgen levels.

Aging in men is associated with a progressive but variable decline in androgen production. In aging men there is also an increased occurrence of symptoms such as lack of concentration, nervousness, impaired memory, depressive mood, insomnia, lack of energy and general sense of well-being, decreased libido and erectile dysfunction, periodic sweating, bone and joint complaints, reduction of strength and increased adiposity. This ill-defined male climacterium syndrome is often referred to as "andropause", with the underlying implication that it is at least in part related to (relative) androgen deficiency. Recently an "aging males" symptoms' (AMS) rating scale was developed aimed at a more systematic description of severity of symptoms related to a clinically defined "male climacteric". We studied the relationship of male climacteric symptoms as assessed by the AMS with androgen levels and other questionnaires assessing the perception of health and well-being. Serum levels of sex steroids, sex hormone binding globulin and gonadotropins were measured in blood samples of 161 healthy, ambulatory, elderly men, aged 74-89 years who also completed the AMS scale. Mean value of total, free and bioavailable testosterone in this group was 401.6, 6.8 and 151.4 ng/dl, respectively, with 24.7, 32.4 and 52.2% of the values under the normal range for young men. The results of the AMS scores mostly suggested mild psychological and mild to moderate somatovegetative symptoms. However, clear sexual symptoms were reported in 88% of cases. None of the three AMS domain scale scores significantly correlated with testosterone, free testosterone or bioavailable testosterone. Significant correlations were observed between results for the AMS scores and those for other health questionnaires, but none of the subscores for the latter questionnaires correlated with androgen serum levels. In conclusion, the results of this study have shown that, as assessed by the AMS, healthy ambulatory elderly males over 70 had a high perception of sexual symptoms with mild psychological and mild to moderate somatovegetative symptoms. These data failed to support the view that in healthy elderly men, "climacteric symptoms" can predict androgen levels.

Aged↗
PubMed2003

Testosterone and behavior.

In older men and women testosterone clearly improves libido and perhaps sexual activity. A number of authors have tried to describe a set of behavioral symptoms associated with the andropause. In older women testosterone seems to decrease dysphoria. In men the effects of testosterone on mood are less clear. In older men testosterone enhances spatial memory and possibly verbal and working memory. Table 2 summarizes the putative behavioral effects of testosterone. [Table: see text] There is a clear need for better designed large-scale behavioral studies to determine the effects of testosterone in older men and women.

Aged↗
PubMedDate not supplied

Vitamin D and prostate cancer.

Our recent epidemiological study (Ahonen et al., Cancer Causes Control 11(2000) (847-852)) suggests that vitamin D deficiency may increase the risk of initiation and progression of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19000 middle-aged men free of clinically verified prostate cancer. More than one-half of the serum samples had 25OH-vitamin D (25-VD) levels below 50 nmol/l, suggesting VD deficiency. Prostate cancer risk was highest among the group of younger men (40-51 years) with low serum 25-VD, whereas low serum 25-VD appeared not to increase the risk of prostate cancer in older men (>51 years). This suggests that VD has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25-VD concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25-VD levels delayed the appearance of clinically verified prostate cancer by 1.8 years. Since these results suggest that vitamin D has a protective role against prostate cancer, we tried to determine whether full spectrum lighting (FSL) during working hours could increase serum 25-VD concentrations. After 1-month exposure, there was no significant increase in the serum 25-VD level, although there was a bias towards slightly increasing values in the test group as opposed to decreasing values in controls. There was no significant change in the skin urocanic acid production. The possibility to use FSL in cancer prevention is discussed. In order to clarify the mechanism of VD action on cell proliferation and differentiation, we performed studies with the rat and human prostates as well prostate cancer cell lines. It is possible that 25-VD may have a direct role in the host anticancer defence activity, but the metabolism of vitamin D in the prostate may also play an important role in its action. We raised antibodies against human 1alpha-hydroxylase and 24-hydroxylase. Our preliminary results suggest that vitamin D is actively metabolised in the prostate. Vitamin D appears to upregulate androgen receptor expression, whereas androgens seem to upregulate vitamin D receptor (VDR). This may at least partially explain the androgen dependence of VD action. VD alone or administered with androgen causes a suppression of epithelial cell proliferation. VD can activate mitogen-activated kinases, erk-1 and erk-2, within minutes and p38 within hours. Also, auto/paracrine regulation might be involved, since keratinocyte growth factor (mRNA and protein) was clearly induced by VD. Based on these studies, a putative model for VD action on cell proliferation and differentiation is presented.

Adult↗