Testosterone Enhancement Program

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Endocrinology of ageing

In men, several hormonal systems show a gradual decline in activity during ageing, represented by a decrease in their bioactive hormone concentrations. The 'andropause' is characterized by a gradual decline in serum total and bioavailable testosterone, due to a decrease in testicular Leydig cell numbers and in their secretory capacity, as well as by an age-related decrease in episodic and stimulated gonadotropin secretion (Vermeulen 1991). Both cross-sectional (Vermeulen 1991) and longitudinal (Morley et al 1997) studies have shown that in healthy males mean serum total testosterone (T) levels decrease by about 30 between age 25 and 75, whereas mean serum free T levels decrease by as much as 50 over the same period. The steeper decline of free T levels is explained by an age-associated increase in sexhormone binding globulin (SHBG) binding capacity (Vermeulen & Verdonck 1972). Conflicting results have been reported concerning the question of whether luteinizing hormone (LH)...

Pituitary Gland Abnormalities

Pituitary gland abnormalities are a rare cause for male infertility. In such circumstances, the pituitary gland fails to release hormones necessary to promote sperm production. The pituitary gland in the man produces two important hormones for sexual reproduction luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The primary function of LH is to act on specialized cells within the testicles to manufacture the male hormone testosterone. FSH has the main purpose of stimulating the production of sperm. In most cases of pituitary gland abnormalities, either LH or FSH or both are greatly reduced. This drop in hormones results in lowered testosterone levels and also reduced sperm production.

Diabetes And Erectile Dysfunction

The ability to get an adequate erection depends upon adequate blood flow to the penis and intact nerve function. Men with diabetes whose nerves to the penis are damaged and or whose blood supply to the penis is reduced may not be able to get a strong erection. Before blaming nerve damage and blood supply problems for erectile dysfunction, however, it is important to exclude other causes such as low testosterone levels, medicines (for blood pressure and depression), alcohol, and cannabis (marijuana). Psychological issues such as depression, job stress, and other relationship problems may also contribute to erectile dysfunction.

Male reproductive ageing using the Brown Norway rat as a model for man

Cross-sectional and longitudinal studies in men showed that serum testosterone declined with ageing (Vermeulen 1991). Even though serum total testosterone may be in the normal range, the free or bioavailable testosterone levels are frequently lower in elderly men (Gray et al 1991, Korenman et al 1990, Baker et al 1976, Harman & Tsitouras 1980). Low testosterone levels in older men are associated with sexual dysfunction, loss of bone, decreased muscle mass and strength, increased body fat, frailty, and poorer quality of life (Swerdloff & Wang 1993). The low circulating serum testosterone levels are usually associated with elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in aged men. However, such increases in LH may be inappropriately low compared to those of young men with similar low serum testosterone levels. In search of an animal model to examine the process and mechanisms of reproductive ageing, we and others have defined the BN rat as...

Testicular dysfunction

Reproductive ageing in the BN rat is characterized by low serum testosterone levels (Zirkin et al 1993, Wang et al 1993, 1999). Low serum testosterone levels are also a hallmark of the ageing male demonstrated in both cross-sectional and longitudinal studies (Vermeulen 1991, Gray et al 1991). We studied serum testosterone levels and sperm concentration in 6, 9, 12, 15, 18 and 31 month-old BN rats. Beginning at 15 months, plasma testosterone and inhibin levels both showed a progressive decline with age (Fig. 1). Intratesticular testosterone and inhibin concentrations were not lower, and in fact appeared to be higher in testes that showed marked regression, because of the loss of seminiferous tubule content in the testis (Wang et al 1993,1999). The decrease in serum testosterone was due to decreased Leydig cell secretory capacity as demonstrated by Zirkin et al (1993), Zirkin & Chen (2000) and Chen et al (1994, 1996). The Leydig cell dysfunction resulted from reductions in the levels...

Polycystic Ovarian Syndrome

Treatment of PCOS, especially if fertility is desired, should probably consist of metformin (113-117) and possibly lifestyle changes in diet and exercise (118). Drugs that improve insulin sensitivity, such as metformin and the glitizones (rosiglitizone and pioglitazone), are thought to reverse not only the metabolic features of PCOS but also the excess ovarian steroidogenesis and gonadotropin stimulation (119). Treatment with metformin or a thiazolidinedione can often normalize menses and can result in conception in a previously infertile woman. Metformin inhibits glycogenolysis, decreasing hepatic glucose output and also improving peripheral insulin sensitivity. Metformin was first used for PCOS in 1994 by Velazquez et al. (120). Their study in 26 women with PCOS used metformin at 1500 mg d for 8 wk. Not only did the women have significant improvement in hyperglycemia, but there was a 52 drop in testosterone levels and several spontaneous pregnancies. Subsequently, at least eight...

Overview of the ensemble GHIGF1 axis

GHRH is an established primary agonist driving the biosynthesis and pulsatile secretion of GH in all mammalian species (Giustina & Veldhuis 1998). Conversely, somatostatin (SS) is a dominant inhibitory signal, which antagonizes the exocytotic secretion of GH, but not its biosynthesis or storage (Hofland & Lamberts 1996). GHRPs are potent and selective oligopeptidyl GH secretagogues (Bowers et al 1984), mimicked by certain non-peptidyl agonists and exemplified endogenously by a 3Ser-octanoylated 28-amino acid GHRP-like ligand (Smith et al 1997, Howard et al 1996, Kojima et al 1999, Mueller et al 1999). The foregoing trilogy of neuropeptidyl regulators controls GH secretion via topographically and biochemically distinct receptors and secondary signalling molecules (Barinaga et al 1985, Giustina & Veldhuis 1998, Mayo 1992, Mueller et al 1999). These diverse, but uniquely interactive, features create (a) cooperative mechanisms of biological control, and (b) multiple vulnerable...

Etiologic Classification

Roidism, hypogonadism, polycystic ovarian syndrome hypothalamic lesions secondary to trauma, surgery, or primary or metastatic tumor genetic syndromes like leptin deficiency, leptin receptor melanocortin receptor defects, Prader-Willi, Bardet-Biedl, and Down's and drugs such as insulin, sulfonylureas, glucocorticoids, antiepileptics, antipsychotics, and depoprovera.

Hypothesis 2 testosterone depletion reduces the potency andor efficacy of GHRHs actions

Based on the foregoing physiology, and testosterone's ability to rescue hypo-somatotropism in older men (Gentili et al 2000), we postulate that testosterone can (a) enhance endogenous GHRH secretion and or (b) facilitate somatotrope responsiveness to GHRH. To this end, we are carrying out clinical experiments to drive the GHRHergic signalling pathway in older men while simultaneously fixing inputs by SS and GHRP before and after testosterone supplementation.

The hypothalamic release andor actions of SS in ageing men

Fourfold stimulation by short-term (3 week) parenteral testosterone supplementation of (i) GH secretory burst mass (ii) 24 h rhythmic GH release (iii) GH ApEn (irregularity measure) and (iv) serum IGF1 concentrations in older men FIG. 6. Fourfold stimulation by short-term (3 week) parenteral testosterone supplementation of (i) GH secretory burst mass (ii) 24 h rhythmic GH release (iii) GH ApEn (irregularity measure) and (iv) serum IGF1 concentrations in older men aromatizable and non-aromatizable androgens in the rodent (Giustina & Veldhuis 1998, Mueller et al 1999, Chihara et al 1981, Frohman 1996). Indeed, diethylstilbestrol administration to young men and the normal preovulatory milieu in young women enhance GH release stimulated by secretagogues that putatively withdraw SSergic restraint (Frantz & Rabkin 1965). Given such divergent clinical data, it will be crucial to clarify how testosterone deficiency modulates SSergic signalling in the human.

Early Diagnosis Of Hemochromatosis Phenotyping Vs Genotyping

Early diagnosis of hemochromatosis permits treatment of iron overload and thereby prevents premature death due to hepatic cirrhosis (and primary liver cancer) and diabetes mellitus complications.1-1,2-1 Preventing iron overload may also reduce the frequency or severity of arthropathy, hypogonadotrophic hypogonadism and other endocrinopathic disorders, and cardiac abnormalities. 1,2

Effects of Estrogen on Risk Factors for Diabetes

Another characteristic of postmenopausal women is androgenicity associated with low SHBG levels, which is also considered an important risk factor for insulin resistance and type 2 diabetes (120). In the Rancho Bernardo Study, SHBG was found to be inversely correlated with type 2 diabetes and impaired glucose tolerance (IGT) in postmenopausal women (130). In this regard, Andersson and associates (131) also reported that low SHBG levels were associated with type 2 diabetes in both men and women. Furthermore, they also reported that serum testosterone levels were positively correlated with the degree of insulin resistance in women. Estrogen, in contrast to androgens may increase SHBG levels. These increases in SHBG were associated with improved glucose homeostasis (132). In this context, it is also interesting that the incidence of diabetes is higher in men than in women until women reach menopause (133).

Changes in circulating androgens

The significance of changes in androgen secretion is a neglected area of female reproductive ageing. One important study has documented a 50 fall in circulating total and free testosterone concentrations in normal regularly cycling women between the ages of 20 and 40 (Zumoff et al 1995). This has been postulated to reflect declining levels of adrenal androgen precursor secretion. Across the menopausal transition itself, studies from the authors' laboratory indicate that there is no significant change in the circulating concentrations of total testosterone, whilst there is a fall in sex hormone binding globulin and an increase in free androgen index (Burger et al 2000b). Studies from other investigators suggest that there may be a further increase in circulating androgen levels in the late 50s and 60s (Laughlin 2000). The precise consequences of these changes in androgen for womens' health in general are unknown. On the other hand, loss of androgen as may occur following ovariectomy...

Hypothalamic causes of secondary amenorrhoea

Secondary hypogonadotrophic hypogonadism may result from systemic conditions including sarcoidosis, tuberculosis as well as following head injury or cranial irradiation. Sheehan's syndrome, the result of profound and prolonged hypotension on the sensitive pituitary gland, enlarged by pregnancy, may also be a cause of hypogonadotrophic hypogonadism in someone with a history of a major obstetric haemorrhage 40 . It is essential to assess the pituitary function fully in all these patients and then instigate the appropriate replacement therapy. Ovulation may be induced with pulsatile subcutaneous GnRH or human menopausal gonadotropins (hMG). The administration of pulsatile GnRH provides the most 'physiological' correction of infertility caused by hypogonadotrophic hypogonadism and will result in unifollicular ovulation, while hMG therapy requires close monitoring to prevent multiple pregnancy. Purified or recombinant FSH preparations are not suitable for women with hypogonadotrophic...

Luteinizing hormonetestosterone axis

As critical illness becomes prolonged, hypogonadotropic hypogonadism ensues (Vogel et al 1985, Woolf et al 1985). Circulating levels of testosterone become extremely low, often undetectable in men whereas oestradiol concentrations are reduced to a lesser degree, thereby increasing the oestradiol testosterone molar ratio. The progressive decline in serum gonadotropin levels, however, appears to lag behind the rapid decline in serum testosterone. In men with PCI, a high LH pulse frequency with an abnormally low LH pulse amplitude is seen and this has been interpreted as an impaired LH response to very low circulating testosterone levels (Van den Berghe et al 1994b). Endogenous dopamine, opiates IL1, and the 'relatively spared' oestradiol level may be involved in the pathogenesis of the gonadotropin deficiency. Androgen treatment in men affected by prolonged critical illness failed to induce conclusive clinical benefit (Tweedle et al 1972). An alternative approach with exogenous...

Clinical Features

Normal fetal position, and difficult delivery. The hypotonia is evident in the newborn period, accompanied by poor sucking and failure to thrive. Hypogonadism resulting in cryptorchidism and scrotal hypoplasia in males and labial hypoplasia in females are also seen in the newborn period.

Genitourinary Complications

Damage the lower sacral nerves, can result in sexual dysfunction, and should be discussed with the patient early if suspected. Recent work using the Brief Male Sexual Function Inventory (BMSFI) found that pelvic fractures of all types had a significantly profound negative effect on the sexual function of male patients, persisting for at least two years and possibly longer (101). Erectile dysfunction after blunt trauma and pelvic fracture has been documented to be between 20 and 80 (102).

Further investigations of male infertility

Where surgical sperm retrieval may be considered while elevated levels are suggestive of failure of spermatogenesis (Table 45.13). In rare cases undetectable levels of FSH can be suggestive of hypogonadotrophic hypogonadism where treatment with exogenous FSH may be effective. Testosterone and LH measurements are helpful in the assessment of men where androgen deficiency is suspected or where there is a need to exclude sex steroid abuse or steroid secreting tumours of the testes or adrenals. As men with hyperprolactinaemia have sexual dysfunction, it is necessary to exclude elevated prolactin levels in men with loss of libido and impotence. Persistently elevated prolactin levels warrant further investigations such as imaging of the pituitary gland.

Conventional treatment for male infertility

Hypogonadotrophic hypogonadism responds to gonado-trophin treatment although this has yet to be evaluated in the context of RCTs. Data from uncontrolled observational studies report that administration of FSH and hCG is well tolerated and effective in achieving an acceptable sperm count in 80 of men. Pulsatile GnRH may be as effective as hCG and hMG in improving sperm production in these situations.

Endocrine abnormalities and bone loss in ageing men

Except after orchiectomy, men do not have an equivalent of the rapid phase of bone loss that women experience following menopause. After accounting for the absence of this phase, the patterns of late bone loss and of the increases in serum PTH and bone resorption markers in ageing men are virtually superimposable upon those occurring in women (Riggs et al 1998). In the past, it has been difficult to attribute male bone loss to sex steroid deficiency because men do not have an equivalent of menopause, and because serum total testosterone levels decrease only marginally with age except for a small subset of elderly men who develop clinical hypogonadism. However, in the last 5 years, thinking on this issue has undergone a sea change. First, in population studies, we (Khosla et al 1998) and others have shown that although levels of serum total testosterone and oestrogen decrease only slightly in men with ageing, there are major decreases in biologically available levels of both sex...

Basic Gonadal Physiology and Terminology

The gonads in both sexes serve the same dual functions, namely, the production of gametes and sex steroids. These functions are clinically quiescent in children but subsequently are induced at puberty and then maintained through much of adulthood by the glycoprotein pituitary gonadotropins leutinizing hormone (LH) and follicle-stimulating hormone (FSH). By historical convention these names refer to events and structures within the ovary, but their structures are identical in both men and women and their functions in each gender are largely similar. The secretions of these gonadotropins are largely regulated by classic feedback inhibition from circulating gonadal products, with LH being excreted by the sex steroid levels in blood and FSH by proteins (inhibins) produced by developing gametes (Fig. 1). When inadequate gonadal function results from a defect within the gonad itself, the condition is referred to as primary gonadal failure. Hypogonadism resulting from pituitary or...

Hormones and Aging Hope Springs Eternal

Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with changes in cognition. Cher-rier and coinvestigators (2001) examined the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. The investigators raised the circulating total testosterone in the treatment group an average of 130 from baseline at week 3 and 116 at week 6. Because of aromatization of testosterone, estradiol increased an average of 77 at week 3 and 73 at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with their baseline evaluation and the performance of the placebo group. Although no one has investigated if hormonal treatment with testosterone can restore the age-related decrease of...

Androgen Replacement in Hypogonadal Women

Premenopausal circulating testosterone levels in women are approximately 10-fold lower than those seen in healthy men (22). They are maintained by the Who to Screen for Testosterone Deficiency indirect production of testosterone from adrenal dehydroepiandrosterone (DHEA) and androstenedione and by the direct secretion of testosterone from the ovary. Adrenal DHEA secretion begins to decline in most women after the age of 30. This has been referred to as adrenopause and occurs at differing rates between individuals. Ovarian testosterone secretion declines by approximately 30 at menopause and then disappears almost entirely within the next decade. Although few studies have investigated the biologic effects of testosterone in women, several reports indicate that testosterone supplementation in ovariecto-mized women and some late menopausal patients results in a significant improvement in libido and sexual fantasy. More recent reports suggest, in addition, that testosterone supplementation...

Levels of testosterone estrogen and progesterone

In males testosterone levels reach 250 ng L by the second trimester of gestation. 2-3 months after birth, the levels fall to 50ng L and remain low until puberty (age 12-17), when they rise to adult levels of 500-750ng L. Levels of testosterone decline slowly after middle age, but inadequate testosterone levels can be augmented by hormone replacement therapy (Wilson et al. 1998). In females, testosterone levels are normally low 30-50 ng L throughout life (Forest 1975). Serum testosterone is converted into inactive metabolites by the liver.

Hormone receptors in the retina

Salyer et al. using Long-Evans rats found that prenatally and early postnatally in normal rats males had thicker retinas than females. This increased thickness was reduced using flutamide, an androgen inhibitor, but not significantly so compared to normal males or testosterone-treated males, indicating that the process was not entirely mediated through AR. Females at this life-stage had undetectable testosterone levels, but when these females were treated with testosterone their retinal thickness did not differ significantly from normal or testosterone-treated males. To help rule out the conversion of testosterone to estrogen Salyer et al. using immunocytochemistry found no aromatase present in the neuroretina at this stage of development, but they did find quantities of it in the retinal pigment epithelium (RPE) (Salyer et al. 2001). Interestingly, Kobayashi et al. found evidence of 17 3-hydroxysteroid dehydrogenase type IV in the RPE of chick...

Classification of Epimutations

Characterized by neonatal muscular hypotonia, hypogonadism, hyperphagia and obesity, short stature, small hands and feet, sleep apnoea, behavioural problems and mild to moderate mental retardation (estimated prevalence, 1 25,000 newborns). PWS is caused by the loss of function of imprinted genes which are active on the paternal chromosome only. Although all of the genes in the critical region are known, it is unclear which are the PWS genes. In patients with an imprinting defect, which is found in approximately 1 of cases, all paternally expressed genes are silent. Of these patients, 10 have a PWS-SRO deletion, whereas 90 have a primary epimutation (see Sect. 2.2). Almost all of the other PWS patients have a large paternally derived chromosomal deletion, or maternal uniparental disomy.

Examination and investigation of patients with PCOS and secondary amenorrhoea

A total testosterone is adequate for general screening (Table 39.1). It is unnecessary to measure other androgens unless total testosterone is > 5 nmol l. Insulin suppresses SHBG, resulting in a high free androgen index (FAI) in the presence of a normal total T. The measurement of SHBG is not required in routine practice and will not affect management.

Male factor infertility

HYPOGONADOTROPHIC HYPOGONADISM Hypogonadotrophic hypogonadism is a rare condition caused by congenital or acquired hypothalamic and pituitary failure. Where the condition is congenital, evidence of androgen deficiency usually leads to a diagnosis at puberty. A complete absence of GnRH results in absence of secondary sexual characteristics and total testicular failure. Many affected men have anosmia (Kallman's syndrome). Manifestations are less profound in men with partial deficiency. A diagnosis of hypogonadotrophic hypog-onadism is confirmed by low or undetectable levels of gonadotrophins (LH and FSH) and testosterone. Trauma, tumours or chronic inflammation can cause adult onset hypothalamic hypogonadism presenting with infertility.

Secondary sexual characteristics absent normal height

The aetiology of the association between this and hypog-onadotrophic hypogonadism is still to be clarified but these patients have galactose-1-phosphate uridyltrans-ferase and this acute toxic syndrome causes ovarian cellular destruction which is thought to be due to the accumulation of galactose metabolites which may induce programmed cell death (apoptosis).

Absence of secondary sexual characteristics

In this particular situation, it is extremely important to make an assessment of the patient's height. If the patient is of normal height for age, measurement of gonadotrophin will reveal levels that are either low or high. Low levels of gonadotrophins confirm the diagnosis of hypogo-nadotrophin hypogonadism, and elevated levels should provoke the clinician to perform a karyotype. The 46XX patient will have premature ovarian failure, the resistant ovary syndrome or gonadal agenesis while the XY female will have 46XY gonadal agenesis or testicular enzymatic failure. If stature is short gonadotrophin levels will either be low, as associated with an intracranial lesion or high which, following a karyotype, will almost certainly indicate Turner syndrome or a Turner mosaic. In patients with hypogonadotrophic hypogonadism treat-mentshould be towards managing any avoidable problem or in the isolated GnRH deficiency hormone replacement therapy will need to be instituted to induce secondary...

Spironolactone Induced Gynecomastia

Subsequently, in patients who develop gynecomastia, blood testosterone levels decrease and blood estradiol levels increase. These changes come about by increases in metabolic clearance rate of testosterone as well as an increase in peripheral conversion to estradiol. Consequently, excessive stimulation of breast tissue as a result of an imbalance between estrogen and testosterone in the body leads to increased ductal proliferation and tender breast enlargement in males. Discontinuation of the drug results in slow reversal of this process sometimes requiring several months for complete normalization of breast size.

Aetiology of primary amenorrhoea

Hypogonadotrophic hypogonadism Congenital Acquired Weight loss anorexia Excessive exercise Hyperprolactinaemia Hypergonadotrophic hypogonadism Gonadal agenesis XX agenesis XX or XY agenesis Gonadal dysgenesis Turner mosaic Hypogonadotrophic hypogonadism Hypergonadotrophic hypogonadism

Women Interested in Fertility

Weight loss counseling is also important. It has been reported that weight loss of 5-7 of body weight will improve menstrual function (64-66). In a randomized trial, weight loss was associated with decrease in total testosterone and insulin levels, and four of six women had documented ovulation (67). In contrast, none of the five women in the control group ovulated. In another study, women with PCOS were placed on a low-calorie diet and randomized to placebo versus metformin (65). After 6 mo, the women in the metformin arm of the study had greater reduction of body weight (mean 9.7 kg) and abdominal fat and a decrease in serum fasting insulin (40 ), testosterone (35 ), and leptin levels. In addition, they had a significant improvement in menstrual irregularity.

Endocrine investigations Table 391

Failure at the level of the hypothalamus or pituitary is reflected by abnormally low levels of serum gonadotropin concentrations, and gives rise to hypogo-nadotrophic hypogonadism. Kallman's syndrome is the clinical finding of hyposmia and or colour blindness associated with hypogonadotrophic hypogonadism - usually a cause of primary amenorrhoea. It is difficult to distinguish between hypothalamic and pituitary aetiology as both respond to stimulation with gonadotropin releasing hormone (GnRH). A skull X-ray should be performed and CT or MRI if indicated.

Tertiary prevention of hypothyroidism Avoiding Complications

Autoimmune thyroiditis (see next paragraph) and in patients with hypopituitarism. Therefore, in patients with clinical features suggesting primary adrenal insufficiency (e.g., weight loss, hyperpigmentation, nausea, or vomiting) or pituitary disease (e.g., visual field deficits, diplopia, or hypogonadism), the possibility of hypoadrenalism should be excluded by adrenocorticotropic hormone stimulation testing.

Effect of Insulin Resistance Treatment on Polycystic Ovary Syndrome Weight Loss

Weight reduction also decreases androgen levels and restores ovulation in women with PCOS (202). Most of the studies suggest a significant reduction in total testosterone and a significant increase in SHBG, positively affecting the free testosterone levels. This effect is probably as a result of the improvement in hyperinsulinemia that directly affects ovarian androgen production. Metformin (1500 mg), when administered daily for 4-8 weeks in obese women with PCOS, resulted in a decrease in insulin and free testosterone levels (210). Metformin at the above dose improved insulin sensitivity, decreased serum LH and increased serum follicle-stimulating hormone and SHBG (211). Higher plasma insulin, lower serum androstenedione and less severe menstrual abnormalities are baseline predictors of

Women Not Interested in Fertility

A newer alternative is metformin, which is a dimethyl biguanide and an antihyperglycemic agent. It has been in clinical use since 1957 but was only recently approved by the Food and Drug Administration for the treatment of type 2 DM. Metformin decreases hepatic gluconeogenesis, increases peripheral glucose uptake, and decreases free fatty acid oxidation (50,51). The first study describing its use in women with PCOS showed a 29 decrease in total testosterone, 39 decrease in free testosterone, 50 increase in SHBG, and menstrual regulation with evidence of ovulation (52). There are few randomized studies comparing the long-term outcomes in women treated with OCPs versus metformin. In one study, women randomized to metformin showed a decrease in BMI, fasting glucose, and testosterone levels compared with the ethinyl estradiol-cyproterone acetate group (53). Although an improvement in menstrual cyclicity was noted in six of eight subjects on metformin, the efficacy of this treatment in...

Alcohol

Consuming alcohol of more than one or two drinks per day can affect the quality and quantity of sperm, lower testosterone levels, and contribute to impotence. A 1996 research study from Finland showed that moderate alcohol consumption can kill off some sperm-producing cells within the testicles and also may cause abnormal sperm shapes. A normally shaped sperm should resemble a streamlined tadpole with an oval head and long tail. Abnormally shaped sperm vary in appearance and may have two tails, a tapered head, a crooked kinky shape, or an unusually large or small head. Any of these abnormalities make it so that the sperm is unable to penetrate the surface of the egg and therefore unable to successfully fertilize the egg. Men who partake in heavy alcohol consumption that is, more than six drinks per day are more likely to suffer from low sperm count, poor sperm motility, and abnormal sperm shape.

Androgen effects

Like most steroids and drugs, testosterone binds with varying affinity to circulating proteins notably SHBG and albumin. It is often stated or assumed that various measures of 'free' testosterone are superior markers of androgen supply to, and or net effects upon, androgen sensitive tissues than measurement of total testosterone, the gold standard for biochemical confirmation of androgen deficiency. The so-called 'free hormone' hypothesis has a long and tortuous history (Edwards & Ekins 1988, Pardridge 1988, Mendel 1989). Regarding testosterone, claims of superiority for derived testosterone assays are based exclusively on theoretical arguments without clinical validation yet even in theory, freer movement of unbound testosterone into tissues would be just as likely a priori to result in faster metabolic inactivation as enhanced biological effects on target tissues. Derived testosterone assays include direct measurement of free (non-protein-bound) testosterone by equilibrium...

Discussion

Studies together with the other published data, you can conclude that testosterone most probably has beneficial effects, but it is in people who are hypogonadal. This does not mean that every single man should get testosterone supplementation. The other unanswered question which I think is the big one is whether high, almost pharmacological doses are needed to produce effects, or whether lower doses, such as those delivered by patch techniques, are sufficient. We have a long way to go we clearly need long, well-controlled trials. We also need to know who we are entering into these trials. I know some of these are in development, but so far I'm not aware of any funding agency that has been prepared to study the 3000 4000 men needed, equivalent to the women's health studies, to really answer these questions. Until we have these, we should treat men who are clearly hypogonadal, no matter what their age, and there will be a good outcome. There are three controlled trials that David didn't...

Chromosome Disorders

Klinefelter's syndrome is a sex chromosome abnormality that occurs in 1 of 600 males, with a karyotype of 47. Individuals with Klinefelter's syndrome possess an extra X chromosome XXY. Clinical characteristics are variable and include some learning and developmental disabilities, hypogonadism, small testes, and gynecomastia occuring in puberty. The condition can be managed by administering testosterone supplements beginning in adolescence. As with some other sex chromosome abnormalities, adults with Klinefelter's syndrome are usually infertile. hypogonadism underdeveloped testes or ovaries

Sex Hormones

Although the biological basis of sex differences in the brain's structure and function has not been entirely elucidated, there are at least two reasons that the brains of men and women might be different, size and laterality of cognitive processes. These two reasons, however, are not entirely independent. As I mentioned earlier, men's brains are larger than women's brains and there are more neurons. Although these differences are at least in part developmental, it is unknown whether these differences between men's and women's brains are induced by differences in hormonal exposure during development, are related to genetic differences independent of the hormonal influence, or are a combination of both. Men's and women's brains from the fetus to old age are exposed to different sex hormones, and hormones might influence thought patterns, moods, and behavior, both during development and after maturation. As mentioned previously, one of the major differences between the brains of men and...

Dnmt2 Dnmt3a

Adult testes had severe hypogonadism. Females showed a maternal-effect lethal in that heterozygous progeny of homozygous females died before midgestation. Maternal methylation imprints were markedly disrupted, while genome-wide methylation patterns were normal.

The thalassaemias

This condition is due to a defect in beta chain synthesis caused by heterogeneous point mutations within the beta-globin gene, with nearly 180 different mutations associated with its phenotype. It interferes with red cell maturation and increases red cell destruction within the marrow and spleen. Major forms have lifelong chronic dyserythropoietic anaemia with splenomegaly and skeletal deformity. With inadequate transfusion profound anaemia, marked skeletal deformity of the long bones and skull, recurrent infections and death occurs. With adequate transfusion anaemia is controlled but transfusion-related iron overload will result in endocrine abnormalities, pancreatic, hepatic and cardiac failure. This results in failure of pubertal growth, delayed sexual development and hypogonadotrophic hypogonadism affecting fertility. Thus only a small number of successful pregnancies are reported 15-17 . With significant left ventricular dysfunction or arrhythmias pregnancy may be best avoided....

Praderwilli Syndrome

Hormones (e.g., hypogonadism), disruption in appetite control, and altered regulation of the autonomic nervous system (the nervous system associated with involuntary reactions). In infancy, PWS is associated with a poor sucking reflex and weak muscle tone. In later childhood, it is associated with

Responses to ART

Symptoms of reduced libido and sexual dysfunction that result in hypogo-nadism should improve within a few weeks of instituting adequate T replacement. Strength and energy complaints may take somewhat longer to improve. Although there are several excellent studies showing beneficial affects of ART upon muscle mass, strength, sexual function, libido, and skeletal mass in men with severe hypogonadism (34,35), fewer data are available regarding patients with more subtle T deficiency. Since ART is designed primarily to improve quality of life, it is my practice to discontinue such therapy after 3 mo in patients who find no symptomatic benefit.

Lipids

Although there has been some variation in study conclusions, epidemiological and observational studies have generally concluded that low endogenous testosterone levels in men are associated with lipid profiles consisting of decreased high-density lipoprotein (HDL) cholesterol levels and increased total cholesterol, triglycerides and LDL levels compared to normal or higher levels. This is referred to as Hypoandrogen Metabolic Syndrome (HAM) and often accompanies the metabolic syndrome of central obesity and insulin resistance (Kaushik et al. 2010). Multiple studies have reached a similar conclusion and found that men with higher levels of testosterone generally have better lipid profiles including high HDLs and lower triglycerides (Kaushik et al. 2010). Supplementation of testosterone in hypoandrogenesis is generally considered to decrease HDLs and only modestly affect LDLs (Mendelsohn and Karas 2005). Lower testosterone levels in men have also been linked to central adiposity, insulin...

Sexual Functioning

While most studies of ED have used physiological evaluations, such as electro-myography (EMG), pharmacologic testing, and penile angiography, a notable exception is a study that evaluated male sexual function after bilateral internal iliac artery emboli-zation (BIIAE) for pelvic fracture (26). Ramirez et al. (26) conducted a telephone survey using a questionnaire consisting of 24 items that assessed medical history, urinary function, and male sexual function. Three groups were surveyed those who had a pelvic fracture and received BIIAE (group 1), those who had a pelvic fracture and did not receive BIIAE (group 2), and a healthy control group (group 3). There were 16 subjects in each group. Items assessing male sexual function included subjective rankings of sexual drive, erection firmness, ejaculatory function, and overall sex life. Additionally, subjects were queried regarding how personally problematic they found their sex life.

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