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Anabolic Running Review

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Osteopenia Osteoporosis

In addition to HIV infection, other factors such as malnutrition, diminished fat tissues, steroid treatment, hypogonadism, immobilization and treatment with PIs and NRTIs, seem to play a role in the pathogenesis of this disorder. Osteopenia and osteoporosis are often asymptomatic. Osteoporosis occurs mainly in the vertebrae, lower arms and hips. The following tests should be performed on all patients with AIDS a lumbar spine X-ray in the standard anteroposterior and lateral views, bone density measurement (DEXA scan) of the lumbar spine and hip and laboratory blood tests, including calcium, phosphate and alkaline phosphatase. Osteopenia should be treated with 1000 I.E. vitamin D daily and a calcium-rich diet or calcium tablets with a dose of 1200 mg day. Patients should be advised to exercise and give up alcohol and nicotine. In cases with osteoporosis, aminobiphosphonates should be added. Because testosterone suppresses osteoclasts, hypogonadism should be treated (Cheonis 2002,...

The Endocrinology Of Birds Vocalization

In relation with these testosterone-dependent vocalizations, seasonal changes in song structure correlate with periods of dramatically increased testis size and testosterone production (Leitner et al., 2001). Although the overall relationship between testosterone and singing is well established, there are only a few studies of how variation in steroid levels relate to individual variation in song. Experimental manipulations show that testosterone levels in the dark-eyed junco (Junco hyemalis) (Ketterson et al., 1992) influence song rates. However, two correlative studies provide negative evidence for such a relationship in other species testosterone levels are not related to song output in the barn swallow (Hirunda rustica) (Saino and Moller, 1995) or to repertoire size in the red-winged blackbird (Agelaius phoenicus) (Weatherhead et al., 1993). This lack of correlation is to be expected if there are individual differences in the responsiveness of the brain vocal systems to...

The choice between Thl and Th2 responses in humans nature versus nurture

Nature Nurture Human Development

Neuroendocrine factors have a powerful effect on immune responses. Populations stressed by war or natural disasters have an increased incidence of infections such as tuberculosis and typhus, but under these circumstances it is difficult to estimate the relative contributions of defective public health and of increased host susceptibility to infection. Bernton et al (1995) studied the immunological and endocrine changes in military recruits under conditions of 'mental and physical stress approaching that found in combat', and found raised cortisol levels and reduced DHEA cortisol ratios in these recruits. Testosterone levels, delayed-type hypersensitive responses and T cell mitogenic responses decreased, while IgE levels increased. The authors suggested that stress induced a Th1 to Th2 shift.

Optic Pathway Hypothalamic Gliomas

The distinction between optic pathway and hypothalamic gliomas is difficult, as anterior hypotha-lamic tumors often blend imperceptibly into the area of the optic chiasm or tracts. Children with hypotha-lamic tumors may present with the diencephalic syndrome, characterized by failure to thrive, emaciation, and loss of subcutaneous fat in the presence of accelerated long bone growth 16 . Other presenting symptoms associated with hypothalamic tumors include precocious puberty, obesity, diabetes insipidus, hypogonadism, and lethargy. If the tumor extends into the region of the foramen of Monro, obstructive hydrocephalus with signs and symptoms of increased intracranial pressure will ensue.

Prohormone convertase 1 deficiency

Further evidence for the role of the melanocortin system in the regulation of body weight in humans comes from the description of a 47-year-old woman with severe childhood obesity, abnormal glucose homeostasis, very low plasma insulin but elevated levels of proinsulin, hypogonadotropic hypogonadism and hypocortisolemia associated with elevated levels of POMC (O'Rahilly et al., 1995). This subject was found to be a compound heterozygote for mutations in prohormone conver-tase 1, which cleaves prohormones at pairs of basic amino acids, leaving C-terminal basic residues which are then excised by carboxypeptidase E (CPE) (Jackson et al., 1997). We have also recently identified a child with severe, early-onset obesity who was a compound heterozygote for complete loss of function mutations in PC1 (Jackson et al., 2003). Although failure to cleave POMC is a likely mechanism for the obesity in these patients, PC1 cleaves a number of other neuropeptides in the

Selected Photomicrographs

Syndrome Cat Cry

Microdeletion abnormalities. (A) Prader-Willi syndrome. The microdeletion at 15ql 1-13 is shown on chromosome 15, which was inherited from the father (paternal). The photograph of a 10-year-old boy with Prader-Willi syndrome shows hypogonadism, hypotonia, obesity, short stature, and small hands and feet. (B) Angel man's syndrome (happy puppet syndrome). The microdeletion at 15ql1-13 is shown on chromosome 15, which was inherited from the mother (maternal). The photograph of a 5-year-old boy with Angelman's syndrome shows the boy's happy disposition the syndrome is characterized by inappropriate laughter and severe mental retardation (with only a 5-10 word vocabulary). (C) DiGeorge syndrome. The microdeletion at 21 q 11 is shown on chromosome 21. The photomicrograph of a lymph node from a patient with DiGeorge syndrome shows the absence of T lymphocytes within the inner cortex (iC, paracortex, or thymic-dependent zone). The outer cortex (OC) shows abundant B lymphocytes...

Pharmacological Treatment of the Paraphilias

In paraphilias where elevated sexual drive does not remit to other treatments, the use of antiandrogens is indicated. In contrast to the SSRIs and other antidepress-ants, where the effects on libido are indirect, the antiandrogens have a direct suppressing effect on testosterone levels. Most of the current knowledge regarding the use of antiandrogens stems from research with sex offending populations, although the use of testosterone reducing agents has also been reported in transvestic individuals who cannot control cross-dressing behaviors (153). Use of antiandrogenic medications in the treatment of paraphilias usually must be Some researchers argue that long-acting gonadotropin-releasing hormone (GnRH) agonist analoges are the most potent antiandrogens, have the fewest side-effects, and therefore are the most promising pharmacological treatment for the future (159). Either leuprolide or triptorelin is given intramuscularly in doses of 3.75 or 7.5 monthly. These agents suppress...

The Effects Of Drugs On Womens Orgasmic Ability

Antipsychotic medications have also been reported to inhibit orgasm in women (41). This is likely attributable to the blockade of dopamine receptors in areas critical for sexual function (e.g., medial preoptic area, paraventricular nuclei), or indirectly from increased prolactin levels, extrapyramidal side effects, or sedation. A retrospective clinical study of women taking antiepilepsy drugs (primarily benzodiazepines) reported they found orgasm less satisfying than did the healthy, unmedicated controls (42). These effects were not attributable to alterations in free testosterone levels with antiepilepsy medication use. In a 3 month, prospective, open-label study of 44 women who had undergone hysterectomy and oophorectomy, monthly injections of estrogen and testosterone increased the rates of orgasm during the first 3 weeks following treatment, compared with the woman's own baseline and compared to estrogen alone or no treatment (57). Similar results were noted in a well-controlled...

Reproductive biology

The basic crocodilian breeding system is polygynous (one male, multiple females), although short-term monogamous pair bonding has been described in Nile crocodiles and possibly other species. Multiple paternity (several males, same female) has also been recorded in some social situations. Once sexual maturity is reached, dictated by size rather than age, reproductive activity follows an annual cycle. Environmental triggers such as changing temperature, rainfall, humidity, and day length trigger hormonal changes in each sex. In males, testosterone levels rise, testes increase in weight, and sperm production increases. In females, estradiol levels rise, triggering the liver to produce vitellogenin for yolk production in the ovaries, and follicle size increases prior to ovulation. Double clutches have been reported in mugger crocodiles (C. palustris) and Nile crocodiles, influenced by extended environmental conditions favorable to breeding.

Biological Theories of the Paraphilias

Regarding understanding paraphilic dysregulation from a biological perspective, the most compelling data is found in studies with androgens. It is known that testosterone levels strongly correlate with sexual drive in women, and aggressive sexual offenders often are found to have higher androgen levels than controls (117,118). Among the most robust data supporting biological factors underlying sexually deviant behavior is the elevation of androgen levels found in convicted rapists (119). However, the implications of these findings for the paraphilias are unclear at this time.

Congenital leptin deficiency

Mice Leptin Deficiency

In 1997, we reported two severely obese cousins from a highly consanguineous family of Pakistani origin who had undetectable levels of serum leptin and were found to be homozygous for a frameshift mutation in the ob gene (AG133), which resulted in a truncated protein that was not secreted (Montague et al., 1997). We have since identified four further affected individuals from three other families who are also homozygous for the same mutation in the leptin gene. All the families are of Pakistani origin but not known to be related over five generations. A large Turkish family who carry a homozygous missense mutation have also been described (C105T) (Strobel et al., 1998). All subjects in these families are characterised by severe early onset obesity and intense hyperphagia. Some of the Turkish subjects who are adults failed to undergo pubertal development with biochemical evidence of hypogonadotropic hypogonadism (Ozata et al., 1999).

Terminology and Definitions

Hypogonadism refers to the consequences of diminished function of the gonads occurs at any age and for a variety of reasons and is classified into two forms on the basis of the source of the problem, that is, either of testicular origin, or as a result of disorder in the hypothalamic-pituitary axis (Fig. 4.3). Sex-related phenomena associated with hypogonadism are described in the Hormones section of this chapter. The term andropause indicates a particular type of hypogonadism that is related to aging in men and is said to consist of the following diminished sexual desire and erectile function, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density resulting in osteoporosis, and increase in visceral fat and obesity (24). The word andropause is an attempt to draw a parallel in men to

Nondietary Prostate Cancer Risk Factors

Of an androgenic profile associated with prostate cancer development.27 Smokers have higher circulating testosterone levels than nonsmokers.28 While there is no direct link between androgen levels and sexually transmitted diseases, androgen levels may be modestly correlated with indices of sexual activity.29

The Myotonic Dystrophies an Overview

Myotonic dystrophy (dystrophia myotonica, DM) is a dominantly inherited neuromuscular disease that is characterized by a distinctive combination of clinical features, including skeletal muscle myotonia and weakness wasting, cardiac muscle arrhythmias and conduction defects, unusual ocular cataracts, insulin insensitivity, male hypogonadism, balding and hypogammaglobulinemia (Harper 2001). Moreover, the genetic basis of DM is novel because this disease is caused by the expansion of different, but structurally similar, microsatellite repeats in two unrelated genes. Type 1 DM (DM1) is associated with the expansion of a d(CTG) repeat poly r(CUG) positioned in the 3'-untranslated region (UTR) of the DMPK gene, while type 2 disease (DM2) results from a d(CCTG) expansion poly r(CCUG) in the first intron of ZNF9 (Brook et al. 1992 Liquori et al. 2001). Congenital DM (CDM), which is the most severe form of this disease, is exclusively associated with very large d(CTG) expansions in the DMPK...

Clinical Progression Of Ws

The progression of clinical changes in WS can usefully be thought of as having three distinct phases. The first of these comprises the absence of an adolescent growth spurt followed over the subsequent decade by the appearance of graying and loss of hair, the development of skin changes, and of cataracts. A second wave of changes, often first seen late in the third or in the fourth decades of life, include skin ulceration, hypogonadism, and reproductive failure, together with a progressive worsening of the primary changes. A third phase may follow with the development of clinically important disease processes such as atherosclerosis, osteoporosis, diabetes mellitus, and cancer. These diseases occur proportionately earlier in WS patients than in otherwise normal individuals of comparable age, and are an important cause of premature morbidity and mortality. The three leading causes of death in WS patients are atherosclerotic cardiovascular disease, neoplasia, and, in a minority of...

Adult Onset GHD and Osteoporosis

One study of 95 adults, ranging in age from 21-74 yr and identified as GH deficient on the basis of provocative tests, showed low bone density of the lumbar spine compared to normal controls. This significant deficit in bone density persisted when patients with untreated hypogonadism were excluded (20). Two smaller studies showed reduced bone density of the total body (21), femoral neck, Ward's triangle, and greater trochanter (22) in patients with adult-onset GHD compared to normals. In both of these studies, a significant correlation was found between bone density and serum levels of IGF-1, an integrated marker of GH secretion. Because patients with adult-onset GH deficiency were by definition endocrinologically intact through adolescence, they presumably had normal skeletal development and reached a normal peak bone mass. Therefore, osteopenia in such patients, can only be explained on the basis of accelerated loss of bone during adulthood.

Diseases of genomic imprinting

Neurobehavioral disorders with distinct clinical manifestations (Ferguson-Smith et al., 2004 Nicholls and Knepper, 200l). Patients with PWS present with hypotonia at birth, obesity, short stature, mental retardation, hypogonadism and a characteristic facial appearance. AS is characterized by microbrachycephaly, large mouth with tongue protrusion and prognathism mental retardation is severe with absence of speech. Both diseases are associated with deficiencies in the same region of human chromosome 15q11-q13 due to an unequal crossing over between low copy repeats. These deletions are of paternal origin in PWS

The Prader Willi Syndrome

An excellent clinical summary of Prader-Willi syndrome (PWS) is provided in the literature (Holm et al., 1993 Cassidy, 1997). PWS is a multisystemic disorder with numerous manifestations of hypothalamic insufficiency. The neonatal and infantile period is marked by hypotonia, poor suck, feeding problems, and poor weight gain with a failure to thrive. In contrast, between 1 and 6 years of age, excessive weight gain with central obesity occurs, resulting from a voracious appetite. There is global developmental delay, mild to moderate mental retardation, and various learning problems. Characteristic cranio-facial features include dolichocephaly, narrow face or narrow forehead, almond-shaped eyes, small mouth with thin upper lip and downturned corners. Hypogonadism is marked, with hypoplasia of the genitals in both sexes and hypomaturity later on.

Clinical Description Of The

The condition was first described some 40 years ago (Prader et al., 1956). The clinical phenotype of PWS is characterized by neonatal hypotonia and developmental delay, followed by hyperphagia and major obesity, short stature, secondary hypogonadism, mild dysmorphism, small hands and feet, and mild to moderate mental retardation with learning disability. Consensus diagnostic criteria have been established and proven to be satisfactory for the clinicians (Holm et al., 1993). The frequency of the syndrome is on the order of 1 in 10,000 to 1 in 15,000 (Cassidy, 1984). Aside from a ravenous appetite, several behavior problems are noted, such as frequent temper tantrums, obsessive-compulsive behavior, stubbornness. There is a variable degree of mental retardation, usually not severe the average IQ is around 60, with a range of 20-80. Obesity is the main clinical and psychosocial problem. As a result, a tendency to develop type II diabetes mellitus is seen in adolescence, and cardiovascular...

Does He have an Endocrinological Cause to His ED

Androgen and prolactin levels are of particular concern. Hyperprolactinaemia occurs secondary to stress, drugs (such as neuroleptics and infertility treatments), cirrhosis, breast manipulation, or pituitary adenoma tumour. A high level of circulating prolactin causes inhibition of gonadotrophin releasing hormone which lowers levels of testosterone. Men with low testosterone levels may exhibit a decrease in sexual interest. Causes of low testosterone include renal failure, hypogonadism, bilateral cryptorchidism, other hypothalamic-pituitary-gonadal axis dysfunctions, Addison's disease, adrenalectomy, Kleinfelter's syndrome, cytotoxic therapies, mumps orchitis, and age related testicular degeneration as well as antiandrogen medications (e.g., cyproterone acetate, spironolactone, etc.). Androgens have also been shown to influence the activity of NOS in the corporal smooth muscle, which suggests a more direct effect of low levels of testosterone on erectile function. Approximately 52 of...

Activation And Regulation Of Sexual Response Processing of Sexual Information

A surprising finding from our studies was the ease with which healthy women become genitally aroused in response to erotic film stimuli. When watching an erotic film depicting explicit sexual activity, most women respond with increased vaginal vasocongestion. This increase occurs within seconds after the onset of the stimulus, which suggests a relatively automatized response mechanism for which conscious cognitive processes are not necessary. Even when these explicit sexual stimuli are negatively evaluated, or induce little or no feelings of sexual arousal, genital responses are elicited. Genital arousal intensity was found to covary consistently with stimulus explicitness, defined as the extent to which sexual organs and sexual behaviors are exposed (66). This automatized response occurs not only in young women without sexual problems, but also in women with a testosterone deficiency (67), in postmenopausal women (68,69), and in women with sexual arousal disorder (42). Such responses...

Acquired Delayed Ejaculation

The onset of ejaculation delay may be sudden or gradual and deteriorates progressively to global unremitting ejaculatory inhibition. A rather normal delay of ejaculation occurs during aging. Androgen deficiency or hypogonadism may be accompanied by loss of sexual desire and delay of ejaculation. Any neurological disease, injury, or surgical procedure that traumatizes the lumbar sympathetic ganglia and the connecting nerves (multiple sclerosis, diabetic neuropathy, abdo-minoperineal resection, lumbar sympathectomy) may lead to a delay or failure of ejaculation. A wide range of drugs (SSRIs, tricyclic antidepressants, antipsychotics, alpha-sympathicolytics) can impair the ejaculatory process through central and peripheral mechanisms. Alcohol can delay or abolish ejaculation by a direct effect after acute abuse and indirectly by neurological or hormonal disturbances during chronic abuse.

Dietary Prostate Cancer Risk Factors

There are at least seven major dietary macro- or micronutrients that are under intense scrutiny currently as dietary risk or protective factors (Table 15.1). Prominent among these is dietary fat or some component of fat (e.g., saturated fat), which first received attention as a mechanism to possibly explain the low risk in native Asian populations and the apparent rapid shift in risk upon migration of Asian populations to the United States. There are suggestive data that increased fat consumption is associated with higher circulating testosterone levels, providing a possible mechanism for a fat-prostate cancer relation

Organ Systems Affected By Low T Levels

Cognitive function decreases with aging. Most of the age-related changes in cognition are associated with vascular and or degenerative diseases that cause anatomic changes in the central nervous system. The possibility that an age-related fall in T causes functional changes in cognition is of great interest. In a study involving 407 men aged 50 to 91 years at baseline and followed for an average of 10 years, Moffat and colleagues showed that higher free T indices were associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning, and a reduced rate of decline in visual memory (Moffat et al., 2002). On the other hand, men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster decline in visual memory. Of course, changes in the CNS could cause hypogonadism rather than be caused by hypogonadism. In another study by Barrett-Conner and associates, low...

Congenital General Anosmia

The most well studied group of syndromic CGA is related to the Kallmann syndrome. Such patients exhibit hypogonadotropic hypogonadism and anosmia, secondary to failure of gona-dotropin-releasing hormone (GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. The prevalence of the disease has been estimated at 1 in 10,000 in males and five to seven times lower in females. Three different modes of inheritance have been reported in familial cases of Kallmann Syndrome, X chromosome-linked, autosomal dominant, and autosomal recessive (39). The X-linked form of the Kallmann Syndrome has been well characterized, being caused by mutations in the gene KALI (chromosome Xp22.3) (40-42). The KALI protein, anosmin-1, is a locally restricted component of basement membranes and or extracellular matrices during the organogenesis period (39). It has been found to enhance axonal branching from olfactory bulb output neurons (43) and to affect...

Biological Correlates of Gender

Although the effects of testosterone on aggression in humans are not as clear as they are in other animals, a weak correlation between the two variables has been found. However, this finding does not necessarily mean that high testosterone levels cause aggressive behavior the result can also be interpreted as indicating that repeated aggression increases the level of testosterone in the blood (Archer, 1991). With respect to the female hormone estrogen, Hampson (1990) and Kimura and Hampson (1993) reported that women perform better on tests of motor coordination and verbal facility but poorer on tests of spatial reasoning during times of the month when estrogen levels in the blood are highest.

Contraindications And Precautions

As licorice may questionably reduce testosterone levels in men, it should be used with caution in men with a history of impotence, infertility or decreased libido (Armanini et al 1999, Zava et al 1998). It exhibits mineralocorticoid, anti-inflammatory, antioxidant, mucoprotective and ulcer-healing activity in humans. Antiviral, antibacterial, antitumour, expectorant and hepatoprotective effects have also been demonstrated in animal or test tube studies. Significant effects on oestrogen and testosterone levels remain to be established in controlled trials as evidence is inconsistent.

Special Situations Requiring Interventions for Men with ED

Testosterone Deficiency Androgen replacement can improve libido, erection rigidity, and sexual satisfaction in men with demonstrable low serum levels of testosterone (106). In a large cohort of 1461 men presenting with ED, just over one-sixth (17.7 ) at initial screening had biochemical evidence to suggest the possibility of hypogonadism. More rigorous estimation of serum testosterone, associated parameters, and the presence of clinical symptoms resulted in 3 of the population having a diagnosis of hypergonadotropic hypogonadism. Of these, one-fifth agreed to a trial of testosterone therapy but two-thirds of this eligible group also required another erectogenic agent to resolve the ED (107).

Evolution Of Current Treatment Approaches

Urologists have made important contributions to the treatment of erectile dysfunction. Both the Small-Carrion and inflatable penile prostheses were introduced in the 1970s. Although patents for vacuum erection devices were obtained as early as 1917, the introduction of the vacuum erection pump by Osborn in 1974 resulted in this being a common solution for many men before the introduction of other treatment options. Alprostadil intracorporal injections were introduced in the 1980s. However, the popularity of treatment approaches decreased dramatically with the introduction of sildenafil in 1998 and the subsequent introduction of tadalafil and vardenafil. Now a man could take an effective oral agent that allowed sexual behavior to occur in a more natural way. Understandably, as the primary etiology of erectile dysfunction for majority of aging men is vascular (13,14), the main focus of therapeutic oriented research of erectile dysfunction has been the vascular dysfunction insufficiency...

Detection and Assessment

A physical examination and laboratory screening (e.g., complete blood count, liver function, serum testosterone level, serum vitamin B12, thyroid function) may be performed to exclude potential systemic causes of depressive symptomatology. Testosterone deficiency associated with depressive symptomatology (e.g., anhedo-nia, fatigue, and sexual dysfunction) has been described in males with PD and may possibly be managed with testosterone replacement therapy (120). Likewise, symptoms of hypothyroidism (e.g., anxiety, difficulty with concentration, dysphoria, fatigue, irritability, and motor retardation) resemble depressive symptomatology and are treatable with thyroid replacement. It is also important to ensure that patients are on optimal doses of antiparkinson drugs to minimize motor fluctuations that may contribute to mood fluctuations.

Molecular Mechanisms And Defects Hypothalamus

Two animal models of GHRH deficiency have been described. In one, administration of monosodium glutamate (MSG) to mice causes a selective loss of arcuate nuclei neurons (14,15). MSG-exposed rodents have impaired growth, obesity, hypogonadism, and hypothyroidism (16). The other animal model of GHRH deficiency is the Gsh-1 homeobox gene knockout mouse (17). Homeobox genes encode a family of DNA binding proteins, and the Gsh-1 gene encodes a product necessary for GHRH gene transcription and translation. Gsh-1 knockout mice have extreme postnatal dwarfism, sexual infantilism, leukopenia, significant perinatal mortality, a shortened life span, and biochemical evidence of GHRH deficiency. Their anterior pituitary glands are one-third normal size and possess decreased numbers of somatotrophs and lactotrophs.

Fertility and Aging Men An Introduction to the Male Biological Clock

The levels of sex hormones in men decline with age. The roughly 1 per year decline in testosterone levels after age 30 has been termed andropause, or ''symptomatic hypogonadism in the aging male.'' Rhoden and Morgentaler estimate that between 2 and 4 million men in the United States alone suffer from hypogonadism, but only 5 of men are getting treatment for their symptoms. or as sudden as that associated with menopause, but it can be equally significant for fertility and overall well-being. Recently, there has been a lot of interest in declining testosterone levels in men. The roughly 1 per year decline in testosterone levels after age 30 has been termed andropause and is associated with a plethora of congenital and acquired disease-syndromes (McLachlan, 2000). Previous longitudinal studies have demonstrated that abnormally low testosterone levels are present in elderly men (Sparrow et al., 1980 Harman et al., 2001 Feldman et al., 2002). Several large-scale studies in healthy, fertile...

Diagnosis

Patients should routinely be questioned and examined for cardiovascular risk factors, such as smoking, hypertension, adiposity, type 2 diabetes, and family history. For an accurate assessment of blood lipid levels, it is recommended to obtain blood after a fasting of at least 8 hours. Total cholesterol and triglycerides together with LDL and HDL cholesterol should be obtained prior to the initiation of, or switch to, a new potent antiretroviral therapy and repeated 3 to 6 months later. Fasting glucose should be assessed with at least a similar frequency. The oral glucose tolerance test (OGTT) is a reliable and accurate instrument for evaluating insulin resistance and glucose intolerance. An OGTT may be indicated in patients with suspected insulin resistance such as those with adipositas (BMI > 27 kg m2), a history of gestational diabetes and a fasting glucose level of 110 to 126 mg dl (impaired fasting glucose). An intravenous glucose tolerance test or hyperinsulinemic-euglycemic...

Case 11

In another abstract, a 12-year-old boy of normal intelligence, with an early history of hypotonia, failure to thrive, developmental delay, and hypogonadism, followed by precocious puberty and obesity was reported to carry a familial balanced, t(13 14) Robertsonian translocation (Linck et al., 1996). He had inherited his single ''free'' chromosome 14 from his mother and preliminary results from the analysis of DNA polymorphisms demonstrated maternal UPD14 (heterodisomy). The phenotype in this case included short stature, small hands and feet, mild developmental delay, hypotonia, premature puberty, hypogonadism, scoliosis, and mild dysmorphic features.

Sexual Dysfunction

Changes in both women and men decline on a steady slope with age. For women, a further incremental decline is related to falling estradiol levels probably more so than declines in testosterone levels (Dennerstein, Randolph, Taffe, Dudley, and Burger, 2002). The factors that affect a woman's sexuality include first and foremost aging, the length of her sexual relationship with her partner, her own or her partner's health problems, loss of a partner, and psychosocial stressors (Dennerstein, 2005). Moreover, sexual function or dysfunction in women is multidimensional. The problem may rest with desire, arousal, and inorgasmia. It is also nonlinear a woman can have responsive desire vs. innate desire (arousal before desire). Her sexual functioning at menopause or at any time along the lifespan is highly related to her previous behavior or level of interest, her feelings toward her partner, and her partner's status. Not surprisingly, a new partner puts a new set of variables in play for a...

Duplication 17q2

Skeletal, cardiac, and renal anomalies, hypogonadism, and macroorchidism. Ophthalmic manifestations include epican-thus, hypertelorism, up- or downward slanting of the palpebral fissures, strabismus, anterior segment abnormalities of the Rieger syndrome, colobomata, and enophthalmia.18,31,100

Magea4

Most of the etiologic and epidemiologic associations appear to point to an origin in atypical germ cells. The association of testicular maldescent and the formation of testicular tumors has been known for more than 200 years,84,85 and atypical germ cells have been identified in cryptorchid testicles.22 Similarly, testicular cancer is found more commonly in patients with testicular dysgenesis, infertility, and Kleinfelter's syndrome (with expression of an XXY chromosome). Additional epidemiologic associations include reduced body muscle mass and a lower prevalence of male pattern baldness, which may imply lower circulating testosterone levels, as either a cause or an effect of testicular cancer.86 Although testicular trauma and mumps orchitis have largely been discounted as antecedents of GCTs,87 88 earlier studies suggested that both could have mechanisms of oncogenesis predicated on testicular atrophy and the consequent evolution of atypical germ cells. Similar mechanisms have been...

Adrenal Androgens

Sperm counts and concentrations are usually attained by that time and testosterone levels and muscle mass peak soon after. Whether the later phase of female reproductive maturation is properly understood as a part of pubertal development or as a different trajectory of adult reproductive function deserves fuller consideration.

Mercury

In workers exposed to mercury vapor (urinary mercury levels 71.2 g g creatinine), sex-hormone binding globulin level in serum inversely correlated with duration of exposure, whereas no correlation was observed with serum levels of FSH, LH, and testosterone neither with respect to duration of exposure nor mercury levels in blood and urine (McGregor and Mason, 1991). A significant positive correlation between serum total testosterone, but not free testosterone, and cumulative mercury exposure was found in workers exposed to mercury vapor for an average of 10 years (mean urinary mercury 27 ig g creatinine and mean blood mercury 9.5 g L (Barregard et al., 1994). In rats, mice, guinea pigs, and hamsters exposed to inorganic mercury (mercuric chloride, intraperitoneally, 1, 2, or 5 mg kg day for 1 month), the highest dosage caused testicular degeneration and cellular deformation of the seminiferous tubules and the Leydig cells in all species, whereas the lowest dosage caused testicu-lar...

Sex Steroids

In contrast to estrogen, well-designed and adequately powered interventional trials examining the effects of testosterone replacement on bone metabolism in elderly men are lacking. Therefore, the effects of androgen supplementation on BMD are largely unknown. Testosterone has been shown to retard atherosclerosis in rodent models however, prospective or cross-sectional studies have failed to reveal any consistent association of testosterone levels and coronary artery disease (Alexandersen et al., 1999). Similarly, there is no convincing evidence supporting an association of DHEA(S) with atherosclerosis. These studies suggest that estrogen, but not testosterone or DHEA(S), plays a key role in osteoporosis and atherosclerosis.

Clinical Biology

A critical role in prostate development or car-cinogenesis. Despite the presence of elevated serum concentrations of adrenal androgens, patients with hypogonadotrophic hypogonadism have abnormal prostate development but do not develop prostate neoplasia. Males castrated at or prior to puberty seemingly never develop prostate cancer.

Down Syndrome

Adults with DS show a variety of age-related changes in physical and functional capacities suggestive of premature or accelerated aging (Martin, 1978), including changes in skin tone, hypogonadism, increased frequency of cataracts, increased frequency of hearing loss, hypothyroidism, seizures,

Biological Factors

Biological and biosocial risks are also involved in persistently delinquent and particularly aggressive adolescents (Raine, 1997 Rowe, 1994). Genetic factors play a significant role in differences in temperament and cognitive functions (Plomin, 1994). Biological dispositions for criminal behaviour can also emerge prenatally through alcohol abuse and smoking during pregnancy, perinatally through birth complications or post-natally through deprivations in emotional care, stimulation, and nutrition during infancy (Hodgins, Kratzer and McNeil, 2002 Moffitt, 1993 Raine, 1993). However, biological risks should not be viewed in too isolated a manner. For example, prenatal and perinatal complications seem to become only significant for specific forms of delinquency when they are accompanied by social risks such as lower-class milieu, parental rejection, or family instability (Brennan, Mednick and Raine, 1997 Hodgins et al., 2002). A deprived relationship with the primary caregiver can impair...

Etiology

Possible associations with androgen levels have been explored, using proxies. Two presumed proxies for testosterone levels are a history of severe acne during puberty and male pattern baldness as both are associated with somewhat higher testosterone levels. A history of both conditions may be less frequent among men who develop testicular cancer.84 In addition, testicular germ cell tumors and CIS are observed in patients who are in a low-androgen state.89 While animal experiments show that androgen is required for testicular descent,90 a limited number of epidemiologic studies suggest that a high proportion of boys with cryptorchidism have normal androgen action and response.91,92 Some cases of hypospadias have been attributed to defects of androgen action or response, but this mechanism appears to account for only a small proportion of

Testosterone

Treatment with T is approved for the care of clearly established male hypogonadism at any age. However, there have been few studies (especially randomized, double-blind, and placebo-controlled) on the use of T in healthy middle-aged or older men who may have a T level in the low range of a young adult but may also have one or more symptoms that are common both to hypogonadism and aging. The IOM report summarized their review of studies on the use of T in older men by cautioning that although finding 31 placebo-controlled trials, the largest sample size involved 108 subjects, the duration of treatment in 25 of the trials was 6 months or less, and only one lasted more than 1 year. In what might be interpreted as understatement, the report concluded that assessments of risks and benefits have been limited, and uncertainties remain about the value of this therapy for older men (21 pp. 1-2).

Demographics

Male orgasmic disorder is found in all races and ethnic groups. In the case of the lifelong type of the disorder, manifestations will occur around the age of puberty. In certain genetic hypogonadism disorders, such as Klinefelter's syndrome, certain bodily signs and symptoms may alert the physician. Similarly, in associated thyroid, testicular and pituitary abnormalities, there may be other manifestations of the underlying disorder. In the acquired type of male orgasmic disorder, the patient will have had the previous experience of normal sexual function. In these cases, it is usually a situational factor that precipitates the disorder.

Therapy

Megestrol acetate, a synthetic gestagenic hormone, shows some benefit as an appetite stimulant in wasting syndrome, as demonstrated in a double-blind, randomized study (Von Roenn 1994). Its main problems are typical steroidal side effects, including hypogonadism (which should really be avoided in cases of wasting syndrome). We therefore do not currently recommend the use of this drug. Hypogonadism is a frequent problem in patients with wasting syndrome. It is therefore useful to determine testosterone levels (age-dependent ). If levels are low, testosterone substitution has proven useful, both for weight gain and quality of life (Grinspoon 1998). This effect is sustained, even with long-term use (Grinspoon 1999). If testosterone levels are normal, substitution in cases of wasting syndrome is not indicated. In women, one should generally be very cautious with administration of androgenic hormones. There are other anabolic steroids available in addition to testosterone, such as...

Treatment

In terms of available evidence, the best treatment for elderly obese patients is exercise. Cardio-respiratory fitness is an important determinant of health status in the elderly and can be improved by exercise. The majority of elderly women actually achieve the currently recommended levels of exercise during activities of daily living, including housework. However, this level of activity does not appear to be protective against obesity and its consequences. There is now evidence from a large number of studies that exercise in the elderly is beneficial in terms of glucose tolerance, cardiac and respiratory function, improved function and quality of life. Patients have traditionally been instructed that aerobic exercise is most beneficial. Meaningful amounts of aerobic exercise may not be achievable in many with functional limitation and severe obesity. Furthermore, there is often a worsening of symptoms and well-being in the short term, and this may decrease adherence to programs of...

Myotonic Dystrophy

CTG trinucleotide repeat expansion in the DM1 locus on chromosome 19q13.32 affects the expression of two adjacent genes DMPK and SIX5 and leads to myotonic dystrophy, an autosomal dominant disorder characterized by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and electrocardiogram changes. Filippova et al. (55) demonstrated that CTCF binding sites flank the CTG repeat and act as insulator element between DMPK and SIX5. Similar to the H19 and Igf2 genes, methylation of these sites eliminates binding of CTCF. Thus, methylation of the DM1 locus in myotonic dystrophy disrupts the insulator function. The role of CTCF in the insulator function has been proposed also in establishing a regulatable epigenetic switch for X chromosome inactivation (56,57) and in cancer (58).

Gonadal Toxicity

In addition to impairment of spermatogenesis, injury to Leydig's cell function is a potential toxic effect of chemotherapy. Elevations of FSH levels were observed in 24 of a cohort of 32 patients who received platinum-based chemotherapy.54 Of these 24 patients, 15 had elevated LH levels. Two patients, each with a remaining testicle, had low testosterone levels. This underscores the problem of compensated (and sometimes uncompensated) Leydig's cell function. Testosterone replacement can be implemented if clinically indicated.

Bardet Biedl syndrome

Bardet-Biedl syndrome (BBS) is a rare (prevalence < 1 100000), autosomal recessive disease characterized by obesity, mental retardation, dysmorphic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism and structural abnormalities of the kidney or functional renal impairment (Katsanis et al., 2001b). Bardet-Biedl syndrome is a genetically heterogeneous disorder that is now known to map to at least eight loci 11q13 (BBS1) (Mykytyn etal., 2002) 16q21 (BBS2) (Nishimura etal., 2001) 3p13-p12 (BBS3) (Sheffield et al., 1994) 15q22.3-q23 (BBS4) (Mykytyn et al., 2001) 2q31 (BBS5) (Young et al., 1999) 20p12 (BBS6) (Katsanis etal., 2000 Slavotinek etal., 2000) 4q27 (BBS7) (Badano et al., 2003) and 14q32.11 (BBS8) (Ansley et al., 2003). Although BBS had been originally thought to be a recessive disorder, Katsanis and colleagues proposed that clinical manifestation of some forms of Bardet-Biedl syndrome requires recessive mutations in...

Major Risk Factors

In the late 1980s and early 1990s, we initiated a series of studies to determine whether there was any evidence ofunderlying differences in the androgen milieu among populations at widely varying risk of PCA, i.e., African-Americans, USA whites, and rural Japanese, that might suggest an androgen role in this variability. We found that African-American men have substantially higher testosterone levels at a young age than young men in the other two groups (12), and that Japanese men, while not having lower testosterone than whites as anticipated, have substantially lower circulating levels ofandrostanediol glucuronide (13). This hormone is a whole body index of the enzyme required to bioactivate

Sex Hormones

Testosterone Whether licorice consumption affects testosterone levels is still unknown, as conflicting results have been obtained from clinical studies. Armanini et al have conducted a series of trials investigating the effects of licorice on testosterone levels in males with mixed results (Armanini et al 1999, 2003a). One study showed that licorice (7 g day equivalent to 0.5 g GA) was able to reversibly reduce testosterone levels within 7 days, by inhibiting 17,20-lyase (involved in the conversion of 17-hydroxyprogesterone to androstenedione) and 17-beta-hydroxysteroid dehydrogenase (involved in the conversion of androstenedione to testosterone) (Armanini et al 1999). Another study twice attempted to replicate these results, but was unable to detect an effect on testosterone levels in either study the authors suggest that inappropriate use of statistical tests in the first study may explain the varying results (Josephs et al 2001).

Prader Willi syndrome

Hypotonia, mental retardation, short stature, hypo-gonadotropic hypogonadism and hyperphagia (increased food intake) and obesity. Children with PWS display diminished growth, reduced lean body mass and increased fat mass - body composition abnormalities resembling those seen in growth hormone (GH) deficiency. GH treatment in these children decreases body fat, and increases linear growth, muscle mass, fat oxidation and energy expenditure (Carrel et al., 1999). One suggested mediator of the obesity phenotype in PWS patients is the enteric hormone ghrelin, which is implicated in the regulation of mealtime hunger in rodents and humans and is also a potent stimulator of growth hormone secretion. Several groups have shown that children and adults with PWS have fasting plasma ghrelin levels which are 4.5-fold higher in PWS subjects than in equally obese controls and thus may be implicated in the pathogenesis of hyperphagia in these patients (Cummings et al., 2002 Haqq etal., 2003).

Prognosis

The prognosis of the patient with male orgasmic syndrome is dependent on whether the condition is lifelong or acquired and the condition's causes. Prognosis is best when it can be demonstrated that the condition is related to some extrinsic or environmental factor that can be corrected or ameliorated. The prognosis is also favorable in those cases that are due to a remedial organic condition such as a thyroid disorder or hypogonadism. The prognosis is guarded when the disorder is found to be secondary to a deep-seated and chronic psychological or actual psychiatric problem that, in itself, carries an unfavorable prognosis.

Hormonal Treatment

Contextual, and societal) and or physical factors negatively affecting sexual interest and arousability. On the basis of available data, no specific testosterone regimen or dose can yet be recommended. The chosen formulation of testosterone must have pharmacokinetic data indicating that it produces blood levels within the normal premenopausal range. Achieving physiological free testosterone levels by transdermal delivery appears to be the best approach.

T Levels And Aging

The decline in T levels with aging when associated with symptoms and signs of androgen deficiency has been called andropause. This association also has been referred to as androgen deficiency in the aging male (ADAM), partial androgen deficiency in the aging male (PADAM), aging-associated androgen deficiency (AAAD) or late-onset hypogonadism. The term andropause is inaccurate because men do not have menses and because androgen secretion gradually decreases, and usually is

Impotence

In men, zinc deficiency may lead to impaired testosterone synthesis, resulting in hypogonadism and impotency. One placebo-controlled study has investigated whether oral zinc supplementation improves erectile dysfunction. The study involved 20 uraemic haemodialysis patients and showed that 6 months treatment with oral zinc acetate (25 mg elemental zinc) taken twice daily 1-2 hours before meals resulted in greater libido, improved potency and more frequent intercourse compared to placebo (Mahajan et al 1982). Active treatment also resulted in significant increases in plasma zinc, serum testosterone, and sperm count and decreases in serum levels of

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