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Around the menopause, changes in ovarian secretion of steroids result in changes in brain function: hot flushes and sweating later followed by changes in mood, libido and cognition. The relationship between sex steroids and brain functions are reviewed, with focus on hormonal treatments, in particular tibolone, on the postmenopausal brain and on associations between tissue levels and brain functions. Data on steroid levels in human brain are limited. Exogenous oestrogens alone or combined with progestagens reduce hot flushes and sweating, and may favourably affect anxiety, depression and mood. Testosterone alone or combined with E(2) improves libido and mood. Tibolone reduces hot flushes and sweating, and improves mood and libido, but does not stimulate endometrium or breast, like oestrogens. Tibolone is an ideal compound for studying steroid levels and metabolism in brain in view of its structural differences from endogenous steroids and its extensive metabolism required to express its endocrine effects. Brain levels of tibolone metabolites were measured in ovariectomized cynomolgus monkeys receiving tibolone for 36 days. Compared to serum, higher levels of the oestrogenic 3alpha/beta-hydroxytibolone and the androgenic/progestagenic Delta(4)-tibolone, and lower levels of sulphated metabolites are found in various brain regions. The high levels of oestrogenic metabolites in the hypothalamus explain hot flush reduction. Combined with the presence of Delta(4)-tibolone, the tibolone-induced increase in free testosterone through SHBG reduction explains androgenic effects of tibolone on mood and libido. The levels of tibolone metabolites in the monkey brain support tibolone's effects on brain functions.
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PMID:Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone. 1711 82

Gender differences in spatial recognition, and age-related declines in cognition and mood, point towards testosterone as an important modulator of cerebral functions. Testosterone appears to activate a distributed cortical network, the ventral processing stream, during spatial cognition tasks, and addition of testosterone improves spatial cognition in younger and older hypogonadal men. In addition, reduced testosterone is associated with depressive disorders. The relationship between depression and testosterone appears to partly depend upon the androgen receptor genotype of the patient, and in appropriate patients with low testosterone levels, testosterone substitution can increase positive mood and decrease negative mood. The much publicized link between testosterone and aggression is probably only of importance in athletes who supplement their testosterone levels to excessively high levels, whereas in hypogonadal men, testosterone supplementation only enhances the positive aspects of aggression such as vigour and energy. Current data suggest that testosterone supplementation in hypogonadal men of all ages will enhance many aspects of mood and cognition.
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PMID:Testosterone and the brain. 1717 54

Endocrine disease frequently interrupts sexual function, and sexual dysfunction may signal serious endocrine disease. Diabetic autonomic neuropathy and endothelial dysfunction impair erectile function, and phosphodiesterase inhibition produces only moderate benefit. The effect of diabetes on women's sexual function is complex: the most consistent finding is a correlation between sexual dysfunction and depression. Reductions in testosterone level in men are associated with low sexual desire and reduced nocturnal erections and ejaculate volume, all of which improve with testosterone supplementation. The age-dependent decline in testosterone production in men is not associated with precise sexual symptoms, and supplementation has not been shown to produce sexual benefit. In women, sexual dysfunction has not been associated with serum testosterone, but this may be confounded by limitations of assays at low concentrations and by the greater importance of intracellular production of testosterone in women than in men. Testosterone supplementation after menopause does improve some aspects of sexual function in women, but long-term outcome data are needed. More research on the sexual effects of abnormal adrenal and thyroid function, hyperprolactinaemia, and metabolic syndrome should also be prioritised. We have good data on local management of the genital consequences of oestrogen lack, but need to better understand the potential role of systemic oestrogen supplementation from menopause onwards in sexually symptomatic women.
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PMID:Sexual dysfunction in men and women with endocrine disorders. 1744 19

The number of men for whom testosterone is prescribed is rapidly increasing. The aging man normally demonstrates a gradual decline in testosterone. Symptoms of hypogonadism include erectile dysfunction, diminished libido, sarcopenia, increased adiposity, osteopenia and osteoporosis, impaired cognition, and depression. There is a paucity of data regarding both efficacy and safety of testosterone replacement therapy. Testosterone levels have been shown to modulate prostate cancer risk and progression. A prospective evaluation of prostate cancer risk with testosterone replacement therapy has not been conducted. We outline concerns and recommendations for the use of testosterone replacement therapy in the aging man.
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PMID:Testosterone replacement therapy and prostate cancer: a word of caution. 1745 66

Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.
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PMID:Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression? 1856

Testosterone deficiency syndrome (TDS) refers to the clinical signs and symptoms that result from an abnormally low testosterone level. Men with 'classic' hypogonadism can have unequivocally low testosterone levels and typical symptoms and signs. By contrast, the age-related decline of testosterone levels can be responsible for ambiguous clinical pictures, which can potentially be misinterpreted as part of the aging process or depression. Nevertheless, this decline can have detrimental effects on quality of life and on the function of multiple organ systems. TDS is underdiagnosed-its overall prevalence varies from 6% to 9.5% in community-dwelling men aged 40-70 years, and rises to 15-30% in diabetic or obese men-and undertreated; less than 10% of men with TDS receive treatment. This Review highlights potential pitfalls in the diagnosis of both clinical and biochemical components of TDS.
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PMID:Testosterone deficiency: a common, unrecognized syndrome. 1860 25

The purpose of the research was to evaluate the age-related androgenic state in men with CHD and its relations with some risk factors. In this research 118 patients were included (average age 51.1 +/- 4.2 years). Testosterone and cholesterol serum levels were estimated. The presence and type of adiposity, depression level were determined. It has been established that the average testosterone level in patients (272 +/- 23.4 ng/dl) corresponded to androgen deficiency condition. Direct correlation of serum testosterone level with abdominal type of adiposity and inverse one with atherogenic lipoprotein level and depressions has been revealed.
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PMID:[Age-related androgen deficiency in men with ischemic heart disease]. 1894 79

This study provides a critical review of the literature on depressive symptoms of partial androgen deficiency (PADAM) and their treatment with Testosterone (T). PADAM in aging males is responsible for a variety of behavioral symptoms, such as weakness, decreased libido and erectile dysfunction, lower psychological vitality, depressive mood, anxiety, insomnia, difficulty in concentrating, and memory impairment. The psychological and behavioural aspects of PADAM may overlap with signs and symptoms of major depression. Evidence of the relationship between androgen deficiency and male depression comes from studies that have assessed depression in hypogonadal subjects, the association between low T level and male depressive illness, and the antidepressant action of androgen replacement. The etiology of depressive symptoms of PADAM is multifactorial, and results from the interaction of the biological and psychosocial changes that take place during the mid-life transition. Although data derived from androgen treatment trials and androgen replacement do not support T treatment or replacement as more efficacious than placebo for major depressive disorder (MDD), the clinical impression is that, in some sub-threshold depressive syndromes, T may lead to antidepressant benefits.
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PMID:Partial androgen deficiency, depression and testosterone treatment in aging men. 1922 62

Testosterone is an important hormone involved in sexual arousal, and, indeed, a profound reduction of testosterone levels may be helpful in controlling sexual impulses in sex offenders. Earlier thought of as a sex hormone only, testosterone has been increasingly shown to have manifold actions in the adult male. Normal adult levels of androgens are required for the health of bones, a large number of metabolic functions, mood, erythropoiesis, sebaceous gland activity of the skin, and several other functions. Severe androgen deficiency is associated with pathologies of these biological systems. Androgen deprivation therapy may result in osteoporosis, weight gain with an increased visceral adiposity, impaired glucose tolerance, dyslipidemia, and emotional disturbances. Some of these features combine in the metabolic syndrome that is also frequently associated with the use of psychotropic medication in general. It leads to a moderately increased risk of fractures and diabetes mellitus (by 40%-50%), and a small increased risk of cardiovascular morbidity and depression (by 10%-20%). It should be noted that small proportionate increases in risk may be of modest clinical significance when background risks are very low. Effective and safe management of sex offenders treated with testosterone-deprivation therapy should include careful monitoring of side effects and their prevention and treatment.
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PMID:Potential side effects of androgen deprivation treatment in sex offenders. 1929 35

The role of androgens on cognitive function and mood is not well documented yet. We therefore evaluated all male participants (n=247, mean age 75.7 years) of a population-based study regarding testosterone, dehydroepiandrosterone sulfate (DHEAS), depression and Alzheimer Dementia (AD) for 5 years using the DSM-IV and NINCDS-ADRDA criteria. At study entry, low serum testosterone levels (<350 ng per 100 ml) were present in 45 (30.8%), low DHEAS (<50 microg per 100 ml) in 44 (30.1%), depression in 11 (7.5%) and AD in 7 (4.7%) men. After 5 years, the number of men with low testosterone levels increased to 52 (+15.5%), for low DHEAS to 57 (+29.5%) for depression to 34 (+219%) and for AD to 43 (+515%). Testosterone levels were not associated to prevalence or incidence of depression or dementia. Mean testosterone was 398.1 ng per 100 ml in depressive men and 431.7 ng per 100 ml in those without depression (P=0.57) and 406.3 ng per 100 ml in those with AD versus 429.5 ng per 100 ml without AD (P=0.66).
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PMID:Serum androgen levels and their association to depression and Alzheimer dementia in a cohort of 75-year-old men over 5 years: results of the VITA study. 1940 73


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