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Anabolic Running Review

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Endogenous testosterone levels

In a relatively large sample of 43 men between 20 and 40 years Shute etal. (1983) detected a distribution of visual-spatial test scores as a function of androgen levels with the best-fitting third-order polynomial function describing the curve. Shute et al. reported that normal males selected for low plasma androgens were superior on certain spatial tests, while in their sample of 48 females the reverse was true, that is, highest-androgen females were superior to low-androgen women. However, due to the high cross-reactivity of the antibody used in their radioimmunoassays the authors speak of general androgen level instead of free, non SHBG-bound testosterone, which they originally intended to measure. Gouchie and Kimura (1991) found an effect similar to that of Shute and co-workers, using not only the extremes of the group, but a simple median split to divide all subjects on the basis of saliva testosterone levels in normal men andwomen. For one of the two spatial tests (paper folding...

Effects of testosterone replacement in older men with low testosterone levels

Several studies (Blackman etal. 2002 Ferrando etal. 1998 Kenny etal. 2001 2002 Morley etal. 1993 Sih etal. 1997 Snyder etal. 1999a 1999b Steidle etal. 2003 Tenover 1992 2000 Urban etal. 1995) have established that increasing testosterone levels of older men with low testosterone levels to levels that are mid-normal for healthy, young men is associated with a significant increase in lean body mass and a reduction in fat mass (Table 8.1). Although testosterone supplementation is associated with greater gains in grip strength compared to placebo treatment, it remains unclear whether physiologic testosterone replacement can produce meaningful changes in muscle performance and physical function. In a study by Snyder et al. (1999) testosterone treatment of older men did not increase muscle strength or improve physical function, but these men were not uniformly hypogonadal and were unusually fit for their age. In addition, their muscle strength was measured by a method (Biodex dynamometer)...

Classification and symptoms of hypogonadism

The time of onset of testosterone deficiency is of greater importance for the clinical symptoms than localization of the cause. Lack of testosterone or testosterone action during weeks 8 to 14 of fetal life, the period of sexual differentiation, leads to the development of intersexual genitalia (see Chapter 3). Lack of testosterone at the end of fetal life results in maldescended testes and small penis size. In later life the onset of testosterone deficiency before or after completion of puberty determines clinical appearance (Table 13.2).

Androgen treatment in hypogonadism and effects on erythropoiesis

Anemia can be used as a diagnostic tool to evaluate whether a patient with borderline hypogonadism should receive androgen substitution therapy (e.g. Behre etal. 2000). Various forms of androgen substitution can be used for treatment of male hypogonadism (see Chapter 10), ranging from oral testosterone undecanoate, to transdermal preparations, to long acting injected esters and testosterone implants. A parameter that assures the quality of androgen substitution is restoration of normal hemoglobin and erythrocyte concentrations. In addition, frequent assessment of red blood cell mass, hemoglobin content and also hematocrit is crucial in androgen therapy surveillance in order to detect overstimulation of the erythropoietic system resulting in polycythemia, which might cause adverse side effects (see below). Therapy of hypogonadism with oral testosterone undecanoate (TU) (see Chapter 14) is effective in terms of restoring the red blood cell pool. This has been demonstrated in a mixed...

Adult testosterone levels

In the beginning, several pertinent studies were carried out in prison where usually some ofthe inmates are highly aggressive. Here, the researchers expected a significant relationship between current testosterone levels and aggression, a hypothesis that was confirmed. There is consistent data from eight studies carried out on different types of violent male offenders who showed substantially higher testosterone levels than those found in selected samples of less violent prison inmates. Kreuz and Rose (1972) were the first to find that prisoners with a history of violent crime during adolescence showed higher testosterone levels than prisoners lacking such a history. Similar positive findings were reported by Aromaki et al. (1999) Banks and Dabbs (1996) Brooks and Reddon (1996) Dabbs et al. (1987 1991 1995), Ehrenkranz et al. (1974) as well as by Mattsson et al. (1980) who also found in their study of adolescent offenders that verbal aggression and impulsive behaviour in prison...

H6 Prevalence of testosterone deficiency in patients with erectile dysfunction

Various studies have estimated the prevalence of testosterone deficiency in patients with erectile dysfunction. A systematic multidisciplinary assessment of 256 men with erectile dysfunction showed a prevalence of hypothalamic-pituitary-gonadal axis abnormalities of 17.5 . In only 12.1 did the testosterone deficiency clearly contribute to erectile dysfunction (Nickel et al. 1984). Another routine hormonal screening in 300 men presenting with a primary complaint of erectile dysfunction showed a prevalence of only 1.7 (Maatman and Montague 1986). A similar low prevalence of 2.1 was detected in 330 consecutive patients with erectile dysfunction screened for testosterone deficiency (Johnson and Jarow 1992). More recently, endocrine screening of 1022 men with erectile dysfunction detected serum concentrations of testosterone 3 ng ml in 8.0 of men. However, 40 of these patients had normal serum levels at repeated determination (Buvat and Lemaire 1997). Pituitary tumors were discovered in...

Factors affecting serum testosterone levels in elderly men

The physiological basis underlying the large inter-individual variation in serum testosterone levels seen at any age is not yet fully elucidated, but several physiological variables and factors related to lifestyle have been identified accounting for part of the wide range of normal values observed in healthy men (Kaufman and Vermeulen 1999). The apparent inter-individual variability of testosterone levels is not merely artefactual as a result of the cross-sectional design of the clinical studies, as single-point plasma testosterone estimates reflect longer-term androgen status in healthy men fairly well (Vermeulen and Verdonck 1992). The circadian variation of serum testosterone, with highest levels in the early morning and lowest levels in the late afternoon, should not play an important role in the wide range of normal testosterone levels if they are regularly evaluated in the morning (preferably before 10 a.m.). The ultradian pattern of episodic testosterone secretion undoubtedly...

Use of testosterone in male hypogonadism

The primary clinical use of testosterone is substitution therapy of male hypogo-nadism. Hypogonadism may be caused by hypothalamic, pituitary, testicular or Table 13.1 Overview of disorders with male hypogonadism classified according to localisation of cause Hypothalamic-pituitary origin (hypogonadotropic syndromes secondary hypogonadism) Idiopathic hypogonadotropic hypogonadism (IHH) Testicular origin (hypergonadotropic syndromes primary hypogonadism) Congenital anorchia Acquired anorchia Maldescended testes Klinefelter syndrome XYY syndrome XX male Mixed primary and secondary hypogonadism Late-onset hypogonadism The clinical symptoms of all syndromes and disease entities are predominantly due to a lack of testosterone or its action. The most frequent disorders requiring testosterone substitution are Klinefelter syndrome, Kallman syndrome, idiopathic hypogonadotropic hypogonadism (IHH), anorchia and pituitary insufficiency. Some disorders such as varicocele, orchitis, maldescended...

Male Hypogonadism

Male hypogonadism is defined as inadequate gonadal function manifested by deficiency in gametogenesis or secretion of gonadal hormones. Primary hypogonadism is caused by dysfunction in the testes from either chromosomal or acquired disorders (Box 35-8). Secondary hypogonadism is caused by an abnormality of the hypothalamic-pituitary axis. Males may present with infertility, decreased testicular size, changes in libido, impotency, gynecomastia, delayed puberty, or a combination of these (Swerdloff and Wang, 2004). Clinical diagnosis again begins with history, including information about sexual developmental milestones, current symptoms, ambiguous genitalia at birth, cryptorchidism, behavioral abnormalities, anosmia, surgeries, sexually transmitted diseases (STDs), and medications. History should include the presence of acute and chronic medical conditions and neurologic symptoms. Physical examination is directed toward sexual characteristics, body habitus, gyne-comastia, and signs of...

A hypothetical model of androgen action

Testosterone levels within the normal range will more or less saturate present androgen receptors and it has been demonstrated that androgenic effects will reach a plateau at certain levels, which are probably tissue-specific (Zitzmann etal. 2002a 2002b). In agreement, a study applying exponentially increasing doses of testosterone to hypogonadal men shows corresponding results (Bhasin et al. 2001) androgen effects on various parameters increased linearly with the logarithm of testosterone levels and linearly with the logarithm of the testosterone dose. In practice, this means more or less a plateau effect. Significant increments of androgenic effects caused by rising testosterone levels within the eugonadal range are only seen beyond the normal range and when clearly supraphysiological levels are reached. Therefore, it can be assumed that within the range of such a plateau of saturation, genetically determined functional differences in androgen receptor activity can be best observed,...

Influence of testosterone on sexual behaviour in men

The physiological range of testosterone levels (3-12 ng ml) is considerably higher than that necessary to maintain normal sexual functions. Testosterone levels found to be critical for sexual functions in males lie around 3ng ml (Nieschlag 1979), and they show a clear intersubject variation. On the other hand, levels at which a decline of androgen-related sexual behaviour in individual subjects occurs appears to be reproducible (Gooren 1987). Besides evidence from nonhuman primates and clinical case reports on effects of castration in human males (Nelson 1995), studies ofhypogonadal men on androgen replacement therapy provide convincing evidence of the essential role of androgens in some aspects of male sexual behaviour (Table 4.1). In patients with induced or spontaneous hypogonadism, pathological withdrawal as well as reintroduction of exogenous androgens affected the frequency of sexual phantasies, sexual arousal and desire, spontanenous erections during sleep and in the morning,...

Influence of testosterone on sexual behaviour in women

A variety of models have been used to test the relationship between testosterone and sexuality in women. Because plasma testosterone levels peak around the time of ovulation (Ferin 1996), one investigational strategy involved monitoring changes in several aspects of sexual behaviour at differerent points during the menstrual cycle. As plasma levels of estradiol also reach their highest point at the ovula-tory phase, this research design makes it difficult to prove that testosterone alone induces the increase in sexual behaviour during the midcycle portion of the menstrual cycle observed in some studies (Adams etal. 1978 Harvey 1987 Dennerstein et al. 1994 Matteo and Rissman 1984). But several well-controlled correlational studies measuring circulating testosterone in women found evidence of an androgenic enhancement of sexual behaviour. Higher testosterone levels (midcycle peaks or average levels of plasma testosterone throughout the cycle) were associated with less sexual avoidance...

Testosterone administration

Correlational data reviewed in the previous chapters suggest that aggressive behaviour and presumably also aggressiveness in men and women are related to current endogenous testosterone levels - but they do not prove a cause-effect relationship. In addition to studies on prenatal hormone treatment, research on the effects of testosterone intake in the adult female and male could possibly clarify the question whether aggression is actually testosterone-dependent. In order to understand the complexity of the relation between sex hormones and aggression one further aspect has to be considered testosterone and aggression seem to be mutually dependent. In addition to sex hormone influences on human aggression, several studies have shown that assertive or aggressive behaviour (e.g., in sport competitions or game contests) followed by a rise in status leads to an increase in testosterone levels (Booth etal. 1989 Elias 1981 Gladue etal. 1989 Gonzalez-Bono etal. 2000 Mazur and Lamb 1980 Mazur...

Clinical studies and testosterone substitution

Studies on men with idiopathic or aquired hypogonadotrophic hypogonadism appear to confirm the importance of testosterone for spatial abilities (Alexander etal. 1998 Buchsbaum and Henkin 1980 Hier and Crowley 1982 O'Connor etal. 2001). A group of men with idiopathic hypogonadotrophic hypogonadism, and presumably a lifelong testosterone deficiency, performed significantly poorer than a group of men with late onset of pathologically reduced testosterone levels or normal controls on a number of spatial tests, but not on verbal tests. As short-term androgen therapy did not restore spatial function, these findings suggest that pre-and perinatal hormonal environments have lifelong effects on intellectual function in humans. adolescents. Intramuscular injections of testosterone enhanced their concentration and performance in a verbal fluency task. However, testosterone replacement therapy in hypogonadal men does not necessarily enhance cognitive speed and memory functions. While Alexander...

Androgens and their relation to calcium regulatory hormones and IGF1

Several older reports concerned direct androgen effects on calcium regulatory hormones. It has been claimed that calcitonin concentrations are lowered in hypogo-nadal men and levels can be increased by testosterone administration (Foresta etal. 1983 1985). In rats, androgens seem to enhance hypocalcemia induced by calcitonin (Ogata etal. 1970). Concerning parathyroid hormone (PTH) concentrations, an increment under testosterone substitution therapy of hypogonadal men has been reported (Katznelson et al. 1996 Wang etal. 1996 2001). The skeletal responsiveness to PTH seems to be increased in hypogonadism, as an experimental setting Some effects of testosterone on bone tissue maybe facilitated indirectly by growth hormone (GH) and, consequently, insulin-like growth factor type 1 (IGF-1) levels. These hormones have an intrinsic effect on bone tissue, increasing bone mass and density (Baum et al. 1996 Grinspoon et al. 1995 Monson 2003). Administration of androgens to hypogonadal men...

Androgens and bone turnover in men

Small uncontrolled studies in hypogonadal men suggest an elevation of bone turnover both markers of osteoblastic activity (osteocalcin and BSAP) and osteoclastic action (urinary hydroxyproline excretion) were found to be elevated in such patients (Goldray etal. 1993 Jackson etal. 1987 Stepan etal. 1989). Correspondingly, in healthy younger men, testosterone levels are negatively associated both with serum BSAP and urinary DPD concentrations. As the CAG repeat polymorphism of the androgen receptor gene is involved in this association (longer repeats mitigating androgen effects are positively related to BSAP and DPD levels), effects are most likely directly linked to androgens and their receptor (Zitzmann et al. 2001) (see 3.4.5). It can be speculated that the lower androgen levels allow for higher bone resorption activity. In counter-regulation, bone formation would be upregulated. In case of hypogonadism, this still would result in an dysequilibrium pointing towards bone resorption....

Relation of androgens to bone tissue in healthy men

Bone density is determined both by peak bone mass achieved during skeletal development and the subsequent amount of maintenance and resorption of bone tissue. Androgens affect both processes and thus are a pivotal determinant of bone mass in men. Trabecular and cortical bone density increase dramatically during puberty, both in girls and boys (Krabbe et al. 1984), but peak cortical bone density is about 25 higher in healthy men compared to women, an observation which has been linked to higher testosterone levels present in males (Riggs et al. 2002). Bone density is maintained at a relatively stable level in younger men, then starts to decline slowly at the age of 30 to 35 years in healthy men (Fig. 7.2, Scopacasa etal. 2002 Zitzmann etal. 2002). The age-related bone loss is putatively associated with declining testosterone levels, a process partly leading to late-onset hypogonadism, but is not uniformly present. Thus, reports on sex steroid levels within the normal Fig. 7.2 Model of...

Bone density in men with disorders of androgen action

The majority of men with defective androgen action, however, present with other diagnoses with primary hypogonadism due to Klinefelter syndrome or a condition after testicular tumors and men with secondary hypogonadism due to Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, pituitary disorders of various kinds or late-onset hypogonadism (Behre etal. 2000). A marked decrease in bone density in comparison to controls is seen all these patient groups, but especially in those men with secondary hypogonadism as demonstrated by a large study involving 156 newly diagnosed untreated hypogonadal men (62 men with primary and 94 men with secondary hypogonadism) and 224 healthy controls aged 18 to 91 years. This is due to those men within a group of secondary hypogonadal patients with a congenital disorder ofgonadotropin secretion causing impaired bone maturation during puberty (Zitzmann etal. 2002). An earlier report in a smaller cohort showed similar results (Behre et al. 1997)....

Effects of androgen substitution on bone tissue

The effects of androgen replacement on bone mass have been addressed by several studies. An early report on results in a mixed group of 36 hypogonadal men demonstrated a significant increase of spinal bone density assessed by radiological methods dual-energy X-ray absorptiometry (DXA) and quantitative computer tomography (QCT) during 12 to 18 months of therapy. Corresponding results were seen in 37 men with primary and in 35 men with secondary hypogonadism. Bone density of the spine as determined by QCT increased particularly in those patients who had lower bone density at the start of the study and those who had not received gonadal steroid therapy. A more detailed approach in 32 of these patients demonstrated that this increase was due to gain of both trabecular and cortical bone tissue, while the vertebral bodyarea did not increase (Leifke etal. 1998). In a prospective multicenter trial using different transdermal testosterone preparations in 227 men with hypogonadism of...

Historical aspects of the anabolic steroid controversy

Shortly after the initial animal studies, Kenyon etal. (1940) studied the effects of testosterone propionate in eunuchoidal men, and eugonadal men andwomen. During androgen treatment, urinary nitrogen excretion diminished, with the greatest magnitude of effects observed in eunuchoidal men. Kenyon concluded presciently that The protein estimated as retained by these subjects is not accounted for by increases in the bulk of genital tissues and represents deposit of new material elsewhere in the body (Kenyon 1940). These observations, combined with the results of the animal studies, allowed the early recognition of the anabolic effects of andro-gens. It is notable that Kenyon and others were not able to demonstrate sustained increases in nitrogen retention with testosterone supplementation in eugonadal men, an observation that sparked considerable skepticism for the next fifty years about the anabolic effects of supraphysiological doses of androgens in eugonadal men. was not controlled...

Testosterone effects on fat metabolism

Percent body fat is higher in hypogonadal men in comparison to eugonadal controls (Katznelson etal. 1998). Induction of androgen deficiency in healthy men by administration of a GnRH agonist leads to an increase in fat mass (Mauras et al. 1998). Some studies of young, hypogonadal men have reported a decrease in fat mass with testosterone replacement therapy (Brodsky etal. 1996 Katznelson etal. 1996 Snyder etal. 2000) while others (Bhasin etal. 1997 Wang etal. 1996) found no change. In contrast, long-term studies of testosterone supplementation of older men have consistently demonstrated a decrease in fat mass (Kenny etal. 2001 Snyder etal. 1999 Tenover 2000). Epidemiologic studies (Khaw and Barrett-Connor 1992 Seidell etal. 1990) have shown that serum testosterone levels are lower in middle-aged men with visceral obesity. Serum testosterone levels correlate inversely with visceral fat area and directly with plasma HDL levels. Testosterone replacement of middle-aged men with visceral...

The Modulatory Effect Of Combined Epidural And General Anesthesia

Several studies have been published on the effects of epidural and intrathecal opioid administration on the surgical stress response. The main conclusion has been that, despite acceptable postoperative pain relief, these techniques have no major effect on the overall postoperative stress response.13 13 Thus, the modifying effect is not comparable with that observed during epidural local anesthesia. However, long-term intrathecal opioids may lead to hypogonadism, hypocorticism, and growth hormone deficiency.113

Effects of testosterone therapy on erection in hypogonadal men

Early studies on the relationship between androgens and erectile response in men have postulated a difference between spontaneous, sleep-related erections (nocturnal penile tumescence, NPT), which are impaired in terms of duration and degree in hypogonadism and enhanced by testosterone replacement therapy, and erections in response to visual erotic stimuli (VES), which have not been influenced by testosterone withdrawal or replacement (Bancroft and Wu 1983 Kwan et al. 1983). In a later study, nine hypogonadal men showed not only significant increases of penile circumference and rigidity of sleep-related erections after three months of androgen replacement, but also a minor, but significant improvement of both duration of erection and maximum level of rigidity following visual erotic stimuli (Carani etal. 1995).

Combined therapy with testosterone and phosphodiesterase type 5 inhibitors in patients with erectile dysfunction

Oral therapy with inhibitors of the phosphodiesterase type 5, e.g. sildenafil, varde-nafil, and tadalafil, is highly effective for therapy of erectile dysfunction (Shabsigh and Anastasiadis 2003). However, in placebo-controlled phase III clinical trials and post-marketing evaluation approximately 15 to 40 of patients do not respond to this medication. There is some evidence that patients with erectile dysfunction and testosterone deficiency respond poorly to therapy with phosphodiesterase type 5 inhibitors (Guay etal. 2001 Shabsigh 2003). One further, however not properly controlled study in patients with diabetes mellitus and erectile dysfunction not responding to sildenafil therapy showed similar results (Kalinchenko et al. 2003). 120 diabetic patients, aged 43 to 73 years, with low testosterone levels and erectile dysfunction who had failed to respond to 100 mg sildenafil at least three times were given 80-120 mg d of oral testosterone undecanoate and sildenafil for four to six...

Effects of treatment of erectile dysfunction on testosterone

A controlled, non-randomized study demonstrated that effective psychological, medical (prostaglandin E1, yohimbine) or mechanical (vascular surgery, penile prostheses, vacuum devices) therapy of erectile dysfunction leads to a sustained increase of serum testosterone levels (Jannini et al. 1999). This increase could be caused by increased LH bioavailability (Carosa etal. 2002). However, randomized controlled studies are awaited to prove this interesting hypothesis.

Role of testosterone in the development and maintenance of the prostate

After birth, serum testosterone levels decrease to a low baseline value until puberty, when they rise to the adult range (Frasier et al. 1969) (Fig. 12.2). Until puberty, the prostate remains small (approximately 1-2 g) (Isaacs 1984a). During puberty, the prostate grows to its adult size of approximately 20 g (Isaacs 1984a). Between the age of 10 and 20 years, the rate of prostatic growth is exponential with a prostatic weight-doubling time of 2.78 years (Isaacs 1984a) (Fig. 12.3). This period of exponential growth corresponds to the time period when the serum testosterone levels are rising from initially low levels seen before the age of 10 to the high levels seen in an adult male (Frasier etal. 1969) (Fig.12.2). If a boy is castrated before the age of ten, the serum testosterone levels do not rise to their normal adult level and the proliferative growth of the human prostate between 10 and 20 years of life is completely blocked (Moore 1944 Huggins and Johnson 1947). These results...

Androgen in benign prostatic hyperplasia

In BPH, there is an increase in the cellular content of the transition zone of the prostate. This neoplastic growth could involve 1) enhanced number of epithelial stem cell units, 2) enhanced number of proliferations by transit amplifying cells before these mature into non-proliferating luminal secretory cells, and or 3) decreased ability of AR to limit the proliferation of luminal secretory cells. BPH characteristically is also associated with an enhanced number of stromal cells. Since at least a subset of these stromal cells express AR and thus andromedins, androgen regulation within these stromal cells may be abnormal, leading to enhanced andromedin production. Theoretically, in order to inhibit such enhanced andromedin production, androgen ablation could be utilized to treat BPH. Unfortunately, such systemic androgen ablation has other unacceptable side effects on bone density, muscle mass, and libido. For these reasons, BPH is often treated medically with 5a-reductase inhibitors...

Surveillance of testosterone substitution therapy

The physiological effects of testosterone (Mooradian et al. 1987) can be used for monitoring the efficacy of testosterone substitution therapy. Since therapy aims at replacing the testosterone endogeneously lacking and since physiological serum concentrations are well known, serum testosterone levels also provide a good parameter for therapy surveillance. Guidelines for monitoring testosterone therapy in general have been issued by WHO (1992) and, with special focus on the ageing male, by others (Bhasin and Buckwalter 2001 Bhasin etal. 2003 Morales and Lunenfeld 2002 National Institute on Ageing 2001) and should be referred to for more details. The patient's general well-being is a good parameter to monitor the effectiveness of replacement therapy. Under sufficient testosterone replacement the patient feels physically and mentally active, vigorous, alert and in good spirits too low testosterone levels will be accompanied by lethargy, inactivity anddepressed mood (Burris etal. 1992...

General considerations

Patients and hypogonadism is not a life-threatening disease. Since development of new preparations is mainly a task of the pharmaceutical industry and hypogonadal patients did not promise to contribute a substantial economic profit, development of testosterone preparations was slow. Only recently has the question of testosterone treatment of senescent men (see Chapter 16) and, to a certain extent also the search for a hormonal male contraceptive (see Chapter 23) spurred interest in the pharmacology and application of testosterone. To day oral, buccal, injectable, implantable and transdermal testosterone preparations are available for clinical use. There are only a few studies available comparing the various preparations with the goal of identifying the optimal preparation for substitution purposes (Conway et al. 1988). While the older injectable preparations, which are still the predominant form for substitution, produce sup-raphysiological serum testosterone levels, newer...

Is ED a normal process of aging Is ED preventableIs it curable

Age-related changes in sexual function do occur and include a decrease in the amount of smooth muscle in the penis, which may affect erectile function. The sensitivity of the penis can also decrease with age, so that more stimulation is required for an erection. In men older than 60 years, levels of free testosterone in the bloodstream (the active form of testosterone) often decline. Chronic illnesses, which are more common in the elderly, also may decrease testosterone levels, which could affect the vascular response to sexual arousal and libido. Other factors that aren't necessarily restricted to older men can compound age-related changes for example, morbid obesity and excessive alcohol consumption over a long period of time decrease testosterone levels.

What is sexual dysfunction

And hearing) as well as hormonal factors. Low libido, or hypoactive sexual desire, occurs in about 15 of men and in about 20 of the general population, both men and women. Depression and anxiety may adversely affect one's libido, and depression is the leading cause of hypoactive sexual desire. Other causes of hypoactive desire include relationship factors lack of trust, intimacy conflicts, and lack of physical attraction to one's partner. The hormone testosterone is the main hormone responsible for libido in men. Testosterone levels have an effect on libido and on sexual thoughts and fantasies.

Autosomal Recessive Disease

Patients with AT also demonstrate progeric changes of the hair and skin, including early graying of the hair and atrophic, hidebound facial skin. Pigmentary changes are also frequent and consist of hyperpigmentation and hypopigmentation with cutaneous atrophy. A few patients may demonstrate partial albinism, vitiligo, and cafe au lait spots. Seborrheic dermatitis occurs in nearly all patients, and senile keratoses, atopic dermatitis, and eczema are also reported. Another prominent feature of AT is frequent sinopulmonary infections. These may range from infection of the ears, nose, and sinuses to chronic bronchitis and recurrent pneumonia. The latter two may result in bronchiectasis and pulmonary fibrosis. Chronic infections are typically due to common bacteria however, they are sometimes poorly responsive to antibiotic therapy. The predisposition to infection is associated with the presence of an abnormal thymus and a marked deficiency of IgA, which is the predominant immunoglobulin...

Hypothalamic Pituitary Axis

Hormone (GH), and to a lesser extent, thyrotropin (TSH). Other factors have an important regulatory effect on anterior pituitary function. The kisspeptin hormones are a family of peptides encoded by the KiSS-1 gene and are thought to play a critical role in reproduction. Kisspeptin receptors stimulate GnRH release and activation of the mammalian reproductive axis. Mutations in kisspeptin receptor GPR-54 cause idiopathic hypogonadotropic hypogonadism, characterized by delayed or absent puberty (Jayasena and Dhillo, 2009).

Increase of serum SHBG

The progressive increase of plasma SHBG binding capacity with age should be regarded as a third important aspect of the physiopathological mechanisms that are responsible for the age-related changes in circulating testosterone levels. Indeed, against the background of a relative inability of elderly men to respond to hypoan-drogenism by increased testosterone secretion, an independent progressive increase of SHBG binding capacity will result in an even steeper decline of free and not specifically bound (i.e. free and albumin-bound), bioavailable testosterone levels. The increase of SHBG concentrations in elderly men is remarkable as it occurs in the face of increased fat mass and insulin levels, factors known to be inversely correlated to SHBG levels, but the cause of this increase of SHBG levels remains unclear. It is unlikely that the decreased testosterone levels per se are responsible, as the increase in SHBG levels is observed at an earlier age than the decrease of testosterone...

Body composition and sarcopenia

Fat mass, and in particular abdominal fat mass is negatively associated with serum (free) testosterone levels (Van Den Beld etal. 2000 Vermeulen et al. 1999a see also section However, the direction of this association remains unclear, as low testosterone may be a positive determinant of adiposity, whereas conversely adiposity appears to be a negative determinant of serum testosterone. Moreover, altered activity of the somatotropic axis may also play an important role in the age-related changes in body composition. In any case, a negative association of free testosterone with fat mass in elderly men persists after correction for serum IGF-I levels, which are positively correlated to serum (free) testosterone and negatively to fat mass (Vermeulen etal. 1999a). The age-associated loss of muscle mass is accompanied by decreased muscle strength, which occurs regardless of the level of physical activity (Rogers and Evans 1993). Muscle weakness is an important component of frailty...

Additional clinical variables

Endogenous bio-available testosterone levels were reported to be inversely associated with depressive mood assessed with the Beck Depression Inventory in older men in the Rancho Bernardo Study (Barrett-Connor et al. 1999). In a study of selected men aged 50 to 70 years, who participated in a screening program on prostate cancer and 'andropause', there was an inverse correlation between free testosterone and depressive symptoms assessed on the Carroll Rating Scale, but serum free testosterone was not related to the prevalence of a significant score for depression (Delhez et al. 2003). In contrast others reported that declining bio-available testosterone levels were associated with lower levels of depressive symptoms on the Hamilton Depression Scale in men 55 to 76 years old (Perry et al. 2001).

Who should be considered for treatment

The age-associated decrease in serum testosterone levels raises the issue of androgen substitution in elderly males who should be treated, how and for how long This brings up the key problem of how to diagnose androgen deficiency in elderly men andwhat their testosterone requirements are (Vermeulen 2001 Vermeulen and Kaufman 2002). If distribution of serum testosterone levels in healthy young men is taken as reference, the question is whether elderly men are equally, less or more sensitive to testosterone action. Any answer to this question is complicated by the fact that, on the one hand, signs and symptoms of androgen deficiency lack specificity, while on the other hand, a useful direct biochemical measure of androgen activity is lacking. Indeed, the more we learn about testosterone action, the more it becomes clear that measures of (total or non-specifically bound) testosterone in the circulation can at best imperfectly reflect the action of testosterone and its bioactive...

Modalities of androgen substitution

Taken that the hypothalamo-pituitary-testicular axis is very sensitive to negative feedback, and even more so in elderly males (Deslypere et al. 1987 Winters et al. 1984 1997), it is important to ascertain that the dose administered increases the testosterone levels up to the physiological range and does not merely suppress LH secretion with only replacement of the deficient testosterone production by an inadequate dose of exogenous testosterone. In practical terms, full replacement doses are usually required. There is great inter-individual variability of prevailing androgen levels in the elderly, ranging from perfectly preserved to frankly hypogonadal. Part of the inter-individual variability in serum testosterone levels is explained by heredity, physiological factors and lifestyle-related factors. Many of the clinical features of aging in men are reminiscent of the clinical changes seen in hypogonadism in younger men relative hypoandrogenism may be involved in some, but certainly...

Do androgens have physiologic relevance in women

A speculative line of reasoning that androgens are physiologically important hormones in women is that there might be parallels between female and male androgen deficiency. Testosterone deficiency in men, from either surgical or natural hypogonadism, is a well defined state, and the sequelae are outlined extensively in chapter 13. These men are obese, insulin resistant, at risk for heart disease, have decreased muscle mass and strength, are certainly at risk for osteoporosis, and clearly have diminished sexual function. The question is automatically raised is there a similar clinical syndrome in women, albeit subtler We believe what little data does exist in this regard supports this contention.

Possible benefits of androgen replacement in women

Multiple studies demonstrate clear evidence that testosterone replacement enhances sexual function in hypogonadal men. In women, there is also strong data in this regard. The best-known study demonstrating a beneficial effect of androgen replacement on sexual function in women was published in 1987 (Sherwin and Gelfand 1987). This trial, although non-randomized and unblinded, did demonstrate increased arousal, fantasy, coitus and orgasm in postmenopausal women given monthly intra-muscular testosterone enanthate (150 mg) and 10 mg of E2 valerate. However, mean serum testosterone levels noted in this study were well over 200 ng dl, at least five times the physiological range seen in naturally post-menopausal women. Accordingly, a later study reported that prolonged use of this preparation resulted in virulizing effects in a number of women (Urman et al. 1991). More sexuality data exists with testosterone replacement via subcutaneous (SQ) testosterone pellets, with or without concomitant...

How Does Epilepsy Affect Womens Sexuality

Follows), and epilepsy-related dysfunction of limbic structures, in particular of the amygdala. In this respect, hyposexuality occurs more commonly with right-sided TLE. In that setting, it is associated with hypothalamic hypogonadism and low serum LH level.32 By contrast, it has been our experience that women with left-sided TLE are rarely hyposexual.

How Do Seizures Affect Reproductive Endocrine Function In

Hyposexuality is present in one-third to two-thirds of all men with TLE.47 Causes include hypogonadotropic hypogonadism (about 25 ), hypergonadotropic hypogonadism (about 10 ), and hyperprolactinemia (about 10 ).47 Reproductive dysfunction may be confined to the patient's sexuality with reproductive potential remaining normal. Unlike women with epilepsy, men with epilepsy have mostly normal fertility,33,45 although isolated cases of infertility have been observed.47 In most epileptic men with sexual dysfunction, the dysfunction is hyposexuality rarely is hypersexuality observed.47,48 Both impotence with normal libido and global hyposexuality with decline in both libido and potency are seen.46,47 Hormonally, sexual behavior is promoted by LH and androgens in men and women and by estradiol in women it is inhibited by prolactin. Men with TLE who have reproductive and sexual dysfunction tend to have right-sided lateralization of seizures,49 reduced LH pulse frequency compared with men...

Subcortical structures

The hypothalamus has been described as the major effector organ of the limbic system (Mesulam, 1985, 2000a, 2000b). Lesions of the hypothalamus often result in disturbances of sexual behaviour (Horn & Zasler, 1990). The anterior hypothalamus appears to be involved in endocrine activity and associated copulatory behaviours. Lesions here commonly produce hypogonadism and hyposexuality (Horn &

Hyperprolactinemia Prolactinomas

Patients with prolactin-secreting adenomas mostly have growth arrest, in the form of short stature, and pubertal arrest.6,9 Specifically, females are at risk for menstrual dysfunction and galac-torrea, whereas males have hypogonadism. All patients harboring prolactinomas in a Mayo Clinic study had a raised level of serum prolactin.6 Hyperprolactinemia may also occur as a result of the stalk section effect. If the pituitary stalk is compressed, so that the delivery of the prolactin inhibitor (dopamine) to the adenohypophysis is interfered with, then hyperprolactinemia may occur. Thus hyperprolactinemia occurring as a result of a prolactinoma versus the stalk section effect must be distinguished. The most common hormone deficiency associated with prolactinomas is GH.15

Endocrine Abnormalities

Monal abnormalities occur in 43 to 90 of patients at diagnosis.48 All of the adenohypophyseal hormones can be affected, including growth hormone luteinizing hormone (LH) or follicle-stimulating hormone (FSH) adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone. Deficiencies in LH and FSH lead to delayed or arrested puberty in adolescents, loss of libido, or secondary amenorrhea in adults. Low growth-hormone levels will result in growth retardation and delayed bone age. Hypothyroidism leads to poor growth, weight gain, cold intolerance, and fatigability. Forty percent of children demonstrate decreased height velocity or short stature at diagnosis, either from growth-hormone deficiency, central hypothy-roidism, delayed puberty, or a combination of these three. Impingement on the pituitary stalk leads to decreased amounts of prolactin inhibitory factors such as dopamine. This stalk effect results in hyperprolactinemia. In Fahlbusch's reported data, pre-operative endocrine...

What Are The Laboratory Findings In Hyposexual Patients Who Are Given Aeds

Total serum testosterone levels may be normal or occasionally even elevated.69 However, levels of FT or biologically active testosterone (BAT)77 are reduced. Serum estradiol is frequently elevated. In summary, the laboratory findings show (1) Usually normal serum total testosterone (2) reduced serum-free or biologically active testosterone (3) elevated SHBG (4) often elevated serum estradiol. In practical terms, the following endocrine tests should be administered to hyposexual men who are receiving AEDs total testosterone, FT, and estradiol levels in all patients and bioactive testosterone level in those patients in whom results of the former two tests are normal.77 In addition, serum LH and FSH should be checked to evaluate the possibility of hypothalamic hypogonadism.

Neurohormonal influences

During the first three days following the head injury apparently due to dysfunction of the hypothalamus. The effect on testosterone, which correlated negatively with severity of the injury on admission, persisted at the 3- to 6-month follow-up in 5 out of the 21 patients who were re-tested. The stress of the injury itself can also alter sexual responses by increasing prolactin levels, thus leading to an automatic decrease in testosterone levels (Zasler, 1998).

Complications of Surgery

The surgical resection of craniopharyngiomas is associated with significant risks to endocrine function and vision. The most common postoperative complication is diabetes insipidus, which occurs in 59 to 93 following surgery.17,27,28,58,62,68,76 All patients undergoing open resection should be warned of the very high likelihood of requiring lifelong therapy to treat partial or complete diabetes insipidus. Fahlbusch et al noted that normal preoperative anterior pituitary function was maintained in approximately 50 of patients after surgery, and the incidence of hypogonadism increased only from 77 to 80 .17 However, other series note that panhypopituitarism occurs in

The ideal tissueselective androgen

The definition of ideal depends strongly on the clinical situation. The treatment of male hypogonadism has to reveal agonistic activities in muscle, bone and brain and no activity in e.g. the prostate. As indicated the dissociation of an androgen In male hypogonadism the internal testosterone secretion is already declined. A further decrease in testosterone production is not desired. Testosterone synthesis is positively controlled by gonadotrophins, especially LH. For that reason an ideal tissue-selective androgen for treatment of hypogonadism should not decrease LH secretion.

LUSTSexuality Systems

Perhaps in this Age of Viagra new sexuality-facilitating agents are no longer needed. However, one could argue that beside the mechanical aid offered by such nitric oxide facilitating, erection-sustaining substances, there is still a substantial need for agents that facilitate the psychological side of eroticism. Based on preclinical work in animals, it is to be anticipated that certain neuropeptides and steroids may be harnessed to facilitate such ends. An abundance of neuropeptides and steroids have been identified within the fundamental sexual circuits concentrated in subcortical regions of the mammalian brain (Pfaff, 1999). For some time, it has been evident that testosterone supplementation can strengthen sexual urges in both males and females (Crenshaw and Goldberg, 1996).

Side effects and acceptability

Possible side effects of hormonal male contraception might be caused by too high or too low testosterone levels or by additional substances. Decreased testicular volumes reflecting suppression of spermatogenesis is inherent to all hormonal methods, but is not considered a serious effect by the volunteers as long as sexual function remains unaltered. Weight gain is most likely an anabolic effect of testosterone. Due to the high peak serum testosterone levels caused by testosterone enanthate in the earlier studies, acne and mild gynecomastia could be observed in individual cases. Except for local skin reactions, side effects of GnRH analogues are mainly attributable to decreased testosterone levels, not sufficiently compensated for by testosterone supplementation. Sweating and in particular, nocturnal sweating is a feature of some added progestins (see Table 23.2).

Treatment of Special Populations

Compared to postmenopausal osteoporosis, few clinical trials have been conducted evaluating therapies in men. Although alendronate and calcitonin have both been studied, only alendronate reduces fracture rates in men. Teriparatide has also been studied, but no data are yet available on fracture rates. At this time, alendronate and teriparatide are FDA-approved for the treatment of osteoporosis in men. Dae to proven benefit in reducing fractures and relative safety, alendronate should be considered first-line treatment for primary osteoporosis in men. Teriparatide should be reserved as alternate therapy in this population. Because secondary osteoporosis causes play a significant role in men, any secondary cause (e.g., hypogonadism) should be excluded or treated before considering other drug therapy.

Growth Hormone Hypersecretion Museuloskeletal Increas

Other Arthralgias, slight kyphosis, visceromegaly, reproductive problems (women amenorrhea, galactorrhea, anovulatory problems men decreased libido, hypogonadism), hyperprolactinemia, adenomatous polyps and colon cancer, esophageal and gastric cancer, parathyroid and pancreatic islet cell adenomas (MEN-I syndrome)

Testosterone buciclate

The disadvantage of all esters described so far is that they produce initially supra-physiological testosterone levels which may exceed normal levels severalfold and then slowly decline, so that before the next injection pathologically low levels may be reached. Some patients recognize these ups and downs of testosterone levels in parallel variations of general well-being, sexual activity and emotional stability. Despite these disadvantages testosterone enanthate and cypionate are still the standard therapy for male hypogonadism. A first study on the pharmacokinetics of the new WHO NIH androgen ester testosterone buciclate was performed in two groups of orchiectomized cynomol-gus monkeys (Weinbauer et al. 1986). Intramuscular injections of testosterone enanthate resulted in supraphysiological serum levels of testosterone for eight days, followed by a rapid decline with levels lower than the physiological limit after three weeks. In contrast, testosterone buciclate produced a moderate...

Abnormal HPG Regulation

White adipose tissue exhibits elevated aromatase activity and secretion of adipose-derived hormones in abdominal and visceral fat. Aromatase is an important cyto-chrome P450 enzyme involved in sexual development and is vital in the biosynthesis of estrogens from its precursor androgens, such as testosterone and dehydropi-androsterone. Ironically, obese men show signs of elevated estrogen levels as well as low levels of testosterone and follicle-stimulating hormone (FSH) 10 . Depleted levels of free and total testosterone are interrelated to aromatase overactivity in both intra-abdominal and subcutaneous fat. This condition of hypotestosteronemia low Since inhibin B levels are directly related to sperm formation, low levels observed in obese males will result in abnormal spermatogenesis. As previously mentioned, the increased estrogen levels contribute to a negative feedback effect on the hypothalamus decreasing gonodoliberin and gonadotropin release, and subsequent lowered...

Transdermal application

Testosteron Patch

The skin easily absorbs steroids and other drugs and transdermal drug delivery has become a widely used therapeutic modality. The scrotum shows the highest rate of steroid absorption, about 40-fold higher than the forearm (Feldmann and Maibach 1967). This difference in absorption rates has been exploited for the development of a transdermal therapeutic system (TTS) to deliver testosterone. 40 and 60 cm2 large polymeric membranes loaded with 10 or 15 mg testosterone when attached to the scrotal skin deliver sufficient amounts of the steroid to provide hypogonadal men with serum levels in the physiological range (Bals-Pratsch et al. 1986 1988 Findlay et al. 1987 Korenmann et al. 1987). The application of the patch to scro-tal skin requires hair clipping or shaving to optimize adherence. The membranes need to be renewed every day. When applied in the morning and worn until the next morning the resulting serum testosterone levels resemble the normal diurnal variations of serum...

Pathophysiology of Varicocele

Varicocele is associated with bilateral spermatogenic abnormalities and Leydig cell dysfunction 26-29 . The testicular histology in infertile men with varicocele is variable, but most studies report reduced spermatogenesis (hypospermatogenesis) 30, 31 , Recently, Santoro and Romeo 32 described abnormalities in the ultrastructure of testicular tissue of men with varicocele. They noted that histologic changes were less pronounced in adolescents than in adults, supporting the concept that an uncorrected varicocele is associated with a progressive decline in testicular function. The observed increase in germ cell apoptosis associated with varicocele is thought to occur as a result of hyperthermia and low testosterone levels in the testis 33 . Serum testosterone levels are lower in older ( 30 years) compared to younger men with varicocele, a trend not seen in men without varicocele, suggesting a progressive, adverse effect of varicocele on Leydig cell function 21 .

Mecanism Of Centripetal Lipid Accumulation Supraclavicular Fat And Face

Seborrhea and hirsutism may be present. In men the most common clinical manifestation of hyperprolactinemia is the progressive loss of libido and impo-tency. Oligospermia and other physical signs of hypogonadism (i.e., muscular hypotrophy, increased abdominal fat) are commonly reported. Galactorrhea or gynecomastia is present in 15 to 30 of male patients.2 Prolactinomas among men and postmenopausal women are often macroadenomas ( 1 cm), because changes in libido are not detected early. Hyperpro-lactinemia in both sexes can also be associated with anxiety, depression, fatigue, emotional instability, and hostility.10,11 Hypogonadism is separated into primary (dysfunction of the testis or ovary) or central (pituitary or hypothalamic). Clinical manifestations of hypogonadism in prepubertal children cause no symptoms, whereas in adolescents hypogonadism leads to delayed or absent pubertal development. In adult women, hypogonadism causes amenorrhea,...

Androgen dynamics in women

In women, androgens have been both celebrated and cursed as the hormones of aggression and anger and as fuel for passion . In reality, while the effects of testosterone in men have been widely studied and a clear testosterone deficiency state identified, investigation into the role of testosterone in women is a far more recent venture that is only now yielding fruit. Until recently, circulating androgens in women have simply been considered either by-products of adrenal cortical or ovarian estrogen production, with little inherent clinical relevance. As a result androgen dynamics in women, both in their reproductive and post-reproductive years, are poorly understood. Surprisingly, if one considers the contribution of the adrenal cortex, androgens circulate in levels far exceeding any other steroid hormone in women, as seen in Table 17.1 testosterone itself circulates in levels usually circulating DHEAS of that of a woman in early reproductive age (Orentreich et al. 1984). Because the...

Sarcopenia associated with chronic illnesses

Of the five placebo-controlled studies of testosterone replacement in HIV-infected men with weight loss, three (Bhasin et al. 1998 2000 Grinspoon et al. 1998) demonstrated an increase in fat-free mass and two (Coodley and Coodley 1997 Dobs et al. 1999) did not. The three studies (Bhasin et al. 1998 2000 Grinspoon et al. 1998) that showed gains in fat-free mass selected patients with low testosterone levels. Coodley and Coodley (1997) examined the effects of 200 mg testosterone cypionate given every two weeks for three months to 40 HIV seropositive patients with weight loss of greater than 5 of usual body weight and CD4 cell counts of

Hyperprolactinemia and Prolactinomas

Treatment of prolactinomas includes dopamine agonists as first-line treatment. In select subgroups, surgical excision is recommended, usually through the transsphenoidal approach. Rare patients with large, residual tumor mass after surgery not responsive to medical therapy may be offered radiation therapy. Associated hormone deficiency should also be targeted. Often, as the prolactin levels are normalized, symptoms of hypogonadism can be reversed.

LIIRII agonist medical castrations or surgical aie equivalent

To castrate levels (i.e., serum testosterone levels less than 50 ng dL 1.74 nmol L ). of degralix over LHRH agonists is the speed at which it can achieve the drop in testosterone levels castrate levels are achieved in 7 days or less with degralix, compared to 28 days with leuprolide, eliminating the tumor flare seen and need for anti-androgens, with LHRH agonists. In a trial of 610 men with advanced prostate cancer, degralix was shown to be equivalent to leuprolide in lowering testosterone levels for up to 1 year and is approved by the FDA for the treatment of advanced prostate cancer. Degralix is available as a 40 mg mL and a 20 mg mL vial for SC injection and the starting dose is 240 mg followed by 80 mg every 28 days. The starting dose should be split into two injections of 120 mg. For patients who initially received an LHRH agonist alone, castration testosterone levels should be documented. Patients with inadequate testosterone suppression (greater than 20 ng dL, 0.7 nmol L) can...

Direct effects of testosterone on erection

In a different species, the New Zealand white rabbit, castration similarly reduces intracavernosal blood pressure during stimulation of the cavernosal nerve for induced erection (Traish et al. 1999). Testosterone, but not estradiol treatment prevented the effects of castration and restored intracavernosal pressure to values comparable to those obtained in intact animals. Interestingly, no change of the neuronal nitric oxide synthase protein expression and total activity were observed after castration or testosterone replacement (Traish et al. 1999 2003). However, testosterone deficiency induced by castration or administration of GnRH agonists reduced trabecular smooth muscle content, and this reduction was restored by testosterone, and not by estradiol (Traish et al. 2003). The imbalance between smooth muscle and extracellular matrix in testosterone deficiency can lead to veno-occlusive dysfunction of the penis, and thereby cause erectile dysfunction (Mills et al. 1998). Comparable...

Relationship between infertility and testicular cancer

The subfertility documented in patients who have malignancy can also be attributed to disruption of the hypothalamic-pituitary-gonadal axis. FSH and luteinizing hormone (LH) are often abnormal in men who have malignancy. Men who have untreated Hodgkin's disease were found to have significant hypogonadism with low FSH and serum testosterone when compared with normal controls. Despite abnormally low serum testosterone, these patients had normal levels of LH suggestive of pituitary or hypothalamic dysfunction 31 . Men who had testicular cancer and an elevated FSH before initiation of therapy are noted to have lower posttreatment fertility than men who had normal FSH before initiation of treatment irrespective of treatment modality 32 . Klingmuller and colleagues 33 confirmed this correlation in patients who had seminoma and suggest using pretreatment FSH as a prognostic indicator for predicting posttreatment spermatogenesis.

Are there different types of hormone therapy Do I need to have my testicles removed

This superstimulation tells the brain to stop producing LHRH and, subsequently, the testicles stop producing testosterone. It takes about 5 to 8 days for the LHRH analogues to drop the testosterone levels significantly. The increase in testosterone that sometimes occurs initially with LHRH analogues may affect patients with bone metastases, and there may be a worsening of their bone pain, which is called the flare reaction. Such men with metastatic disease will be given an antiandrogen before starting the LHRH analogue to prevent the flare phenomenon. Degarelix is an LHRH antagonist which has been demonstrated in clinical trials to rapidly decrease serum testosterone (within 3 days) and is not associated with the initial surge of testosterone and risk of flare that is seen with LHRH agonists. It has been recently approved by the FDA. The starting dose is 240 mg given as two subcutaneous injections of 120 mg, then maintenance doses of 80 mg as one subcutaneous injection...

What are some of the side effects of hormonal therapy and how are they treated

Significant impact on bone mineral density. Low testosterone levels affect bone mineral density in men almost the same as low estrogen levels in women. The use of androgen deprivation therapy, whether it is via orchiec-tomy or LHRH analogue or LHRH antagonist with or without antiandrogen, causes decreased bone mineral density. There is an average loss of 4 per year for the first 2 years on hormone therapy and 2 per year after year 4, which is similar to the loss in women after removal of the ovaries or natural menopause. This loss of bone mineral density in men taking hormone therapy occurs for at least ten years and probably accounts for the increased incidence of fractures 5 to 13.5 of men taking hormone therapy have fractures compared to 1 in men with prostate cancer who are not receiving hormone therapy.

Androgen action on spermatogenesis

Testosterone is produced by the interstitial Leydig cells. The details and mechanisms of testosterone synthesis and secretion are presented in chapter 1. Testicular concentrations of testosterone can exceed those found in circulating blood up to 100-fold or beyond. It was thought initially that spermatogenesis requires high local amounts of testosterone. This view could not be corroborated and spermatogenesis in the rat can proceed in the presence of 5-10 of normal intratesticular androgen levels as described in the hallmark paper by Cunningham and Huckins (1979). Interestingly, it has also been observed that testosterone can inhibit certain populations of A-type spermatogonia in the rat model (Huang and Nieschlag 1986) and these observations have been corroborated in rat gonadal protection models (Meistrich and Shetty 2003). A rather obvious need for high local androgen concentrations results from the fact that sufficient peripheral testosterone levels and pulses must be provided by...

Effects of exogenous testosterone on cardiovascular risk factors

In agreement with an important role of thrombus formation in the pathogenesis of acute coronary events and stroke, prospective studies have identified various hemostatic variables as cardiovascular risk factors, among them fibrinogen and the fibrinolysis inhibitor PAI-1 or tissue plasminogen activator antigen. Administration of supraphysiological dosages testosterone to 32 healthy men participating in a trial of male contraception, led to a sustained decrease of fibrinogen by 15 to 20 over 52 weeks of treatment (Anderson etal. 1995). In this study the doubling of testosterone levels initially also led to significant decreases of PAI-1, protein S, and protein C as well as to increases of antithrombin and (p-thromboglobulin. Likewise PAI-1 was decreased in men who received the anabolic androgen stanozolol. Suppression of testosterone in patients with prostate cancer or benign prostate hypertrophy, however, by treatment with the nonsteroidal anti-androgen casodex or the GnRH agonist...

Initiation of substitution therapy and choice of preparation

Androgen Related Organs

Testosterone substitution is started when the diagnosis is established and serum testosterone levels below the normal range are found, taking into account the various influences on serum testosterone levels including diurnal variations. In order to establish a diagnosis by documenting low serum testosterone levels, usually determination of testosterone in a serum sample taken between 08.00 and 10.00 in the morning is sufficient (Vermeulen and Verdonck 1992). Pooled sera will not improve diagnostic accuracy (see Chapter 21). The symptoms of androgen deficiency can be prevented or reversed by testosterone treatment. It is important that a preparation with natural testosterone is selected for treatment so that all functions of testosterone and its active metabolites DHT and estradiol can be exerted (Fig. 13.1). Of all testosterone preparations and routes of application described in Chapter 14, intramuscular injection or oral ingestion of testosterone esters were formerly the most widely...

Subdermal application

The estimated half-life of absorption of testosterone from subdermal implants is 2.5 months. On average, approximately 1.3 mg of testosterone are released per day from the 200 mg pellet. Testosterone implants demonstrate a minor and transient accelerated initial burst release, which lasts for 1-2 days (Jockenhovel etal. 1996). The most comprehensive pharmacokinetic evaluation of testosterone implants was done in a random-sequence, cross-over clinical study of 43 androgen-deficient men with primary or secondary hypogonadism (Handelsman etal. 1990). Patients were treated sequentially with 3 regimens - six 100 mg, three 200 mg or six 200 mg implants - at intervals of at least six months. Implantation of testosterone pellets resulted in a highly reproducible and dose-dependent time-course for circulation of total and free testosterone. Testosterone concentrations reached baseline by six months after either of the 600 mg dose regimens but remained significantly elevated Fig. 14.15 Blood...

Exogenous testosterone treatment in men with cardiovascular disease

Even less information is available on the effects of testosterone on other outcomes of cardiovascular disease. In a small placebo-controlled pilot study, treatment of 20 chronic heart failure patients with weekly injections of 100 mg testosterone enan-thate led to improvements of left ventricular ejection fraction and exercise capacity (Unpublished, quoted after Liu et al. 2003). In agreement with this, treatment of 12 stable heart failure patients with 60 mg testosterone or placebo via the buccal route resulted in significant increases in serum levels of bioavailable testosterone and cardiac output and in a significant decrease of peripheral artery resistance with a maximal effect seen after three hours (Pugh et al. 2003). No study has been performed on the effects of testosterone on stroke and no study showed any positive effect of testosterone on subjective measures such as pain or walking distance or time and objective measures such as muscle blood flow, plethysmographic...

What if my testosterone level is low What are the risks and benefits of testosterone therapy

Hypogonadism is a condition in which low levels of testosterone are found in association with specific signs and symptoms, including decreased desire (libido) and sense of vitality, erectile dysfunction, decreased muscle mass and bone density, depression, and anemia. When hypogonadism occurs in an older male, it is referred to as andropause, or androgen deficiency of the aging male. Hypogonadism is estimated to affect 2 to 4 million men in the United States, and its incidence increases with age. Only about 5 of affected males are being treated. Controversy exists regarding the impact of testosterone replacement therapy on prostate cancer risk. Androgen ablation therapy remains one of the primary forms of therapy for metastatic prostate cancer. Despite the hormone responsiveness of prostate cancer there is no compelling data to associate the risk of developing prostate cancer with testosterone replacement therapy. There is also no compelling data to suggest that men with higher...

Contraindications to testosterone treatment

Testosterone suppresses spermatogenesis, a phenomenon exploited for hormonal male contraception (see Chapter 23). In hypogonadal patients with reduced sper-matogenetic function testosterone administration will also decrease sperm production. Such patients who wish to father children e.g. by techniques of artificial fertilization, should not receive full testosterone substitution therapy, at least not for the time their sperm are necessary for fertilization of eggs. This is of increasing importance as not only residual sperm in patients with secondary hypogonadism but also with Klinefelter syndrome may be able to fertilize eggs via intracyto-plasmatic sperm injection (ICSI) and induce pregnancies (e.g. Friedler et al. 2001).

Principle of hormonal male contraception

Until such results become available, the concept of azoospermia remains valid as a prerequisite for effective hormonal male contraception. However, as it is very difficult to achieve azoospermia uniformly in all volunteers participating in clinical trials for hormonal contraception and the pregnancy rates appear to be acceptably low if sperm counts drop below 1 mill ml, investigators active in the field reached a consensus that azoospermia or at least oligozoospermia

Locally produced factors

Tuner of LH and the binding proteins as fine-tuners of IGF-1 action. Many in vitro data support this model, but van Haren et al. 1992 could not show any effect of IGF-1 on the induction of cholesterol side chain cleavage P450 enzyme activity by LH in cultured Leydig cells. On the other hand, actions of IGF-II are obligatory for the FSH induction of aromatase in human follicles (Yan and Giudice 1999). The completely different effects of IGFs (no effect versus obligatory role) illustrate that in vitro investigations cannot answer the question on the physiological importance of the IGF system for induction of steroidogenic enzymes in gonadal cells. Transgenic animals with specific genes knocked out could shed new light on this problem. In this connection Baker etal. 1996 showed that mutant male mice with an inactive IGF-1 gene were reduced in size and were infertile. However, a close inspection showed that although the size of the testis was approx 40 of the normal and the total (not the...

Posterior Fossa Anomalies

In contrast to these cerebellar syndromes, the brain stem can also be the primary area affected. In its broadest definition, Mobius' syndrome refers to a combination of bilateral symmetrical and asymmetrical facial weakness associated with abnormalities of horizontal gaze, most often deficiencies of abduction. Other cranial nerve functions can be impaired as well, especially those of cranial nerves IX, XII, V, and occasionally, III. The impairment of lower cranial nerves can lead to early feeding difficulties, problems with swallowing, and atrophy of the tongue that is frequently unilateral. Neurosensory deafness may also be associated. A variety of somatic anomalies may be present in patients with Mobius' syndrome.y At least 50 percent of patients have limb anomalies. Thirty percent have talipes, and 20 percent exhibit hypoplasia of digits, transverse terminal defects, or syndactyly. The Poland anomaly and the Klippel-Feil anomaly can also be associated with the condition. Concurrent...

Autosomal Recessive Inheritance

Erythematous skin lesions in early life followed by telangiectasias, atrophy, hypo- and or hyperpigmentation, ectodermal dysplasia body hair is sparse or absent cataracts, short stature, hypogonadism, and skeletal abnormalities are common intelligence is normal lcthyosis and hypogonadism are major features microcephaly, sensorineural deafness, polyneuropathy, and hypoplastic teeth and nails are less frequent

Obesity and Male Infertility

Infertility Obesity Mechanism

Fig. 26.2 Obesity can lead to male infertility via various mechanisms. These mechanisms manifest act directly through or via interplay between reactive oxygen species (ROS) production, the hypothalamus-pituitary-gonadal (HPG) axis, as well as other physical factors (HH hypogonadotro-pic hypogonadism ED erectile dysfunction SA sleep apnea) Fig. 26.2 Obesity can lead to male infertility via various mechanisms. These mechanisms manifest act directly through or via interplay between reactive oxygen species (ROS) production, the hypothalamus-pituitary-gonadal (HPG) axis, as well as other physical factors (HH hypogonadotro-pic hypogonadism ED erectile dysfunction SA sleep apnea)

Androgen dependence of spermatogenesis

Pathophysiological situation (hypogonadotroplc hypogonadism) Although these data clearly demonstrate the ability of testosterone to initiate the spermatogenic process (Fig. 5.3), they do not prove that testosterone is indispensable for the commencement of this process. Fertile eunuchs have atrophied Leydig cells but complete spermatogenesis (Behre et al. 2000). A patient with normal to slightly elevated gonadotropin levels along with a markedly reduced testosterone concentration but complete spermatogenesis has been described (de Roux et al. 1997). Hence it appears quite possible that spermatogenic induction can occur at least in the presence of substantially lowered testosterone levels. Thus, maintenance and reinitiation of spermatogenesis by testosterone hCG in patients are possible (Nieschlag etal. 1999 Fig. 5.3). The certain diversity of results may result from the fact that hypogonadotropic hypogonadism is not a monocausal diseasebut may stem from various deficiencies (idiopathic...

Testosterone enanthate

Testosterone Enanthate Pharmacokinetics

Single-dose pharmacokinetics oftestosterone enanthate after intramuscular administration of 250 mg testosterone enanthate to seven hypogonadal patients and the best-fitted pharmacokinetic profile are shown in Fig. 14.6 (Nieschlag etal. 1976). Maximal testosterone levels in the supraphysiological range were seen shortly after injection (39.4 nmol l, tmax 10 h). Testosterone levels below the normal range were observed following day 12 after injection. The calculated values were 9911 nmol * h l for AUC, 8.5 d for MRT and 4.5 d for terminal half-life (Table 14.2). The calculated testosterone serum concentrations at steady state obtained by computer simulation correspond well to the results of published studies describing multiple-dose testosterone enanthate pharmacokinetics. In a clinical trial for male contraception 20 healthy men were injected with 200 mg wk of testosterone enanthate for 12 weeks (Cunningham et al. 1978). Minimal serum concentrations of testosterone at steady state,...

Regulation of pregnenolone metabolism

Auckland Council Structure

This enzyme system is not capable of converting all pregnenolone into testosterone. Therefore it acts as the rate-limiting step for the ultimate production of androgens. Since the enzyme activities are differentially regulated, they play an important role in determining the output of testosterone, especially during development. Thus the normal testis produces many intermediates in addition to testosterone. Although these steroids are not androgens, they represent secretion products and they may have alternative functions. This must be kept in mind when only testosterone substitution therapy is applied for treatment of hypogonadism.

Hypoandrogenism of senescence and sexual activity

Whereas normal libido requires adequate testosterone levels, as shown by the effect of testosterone withdrawal (Bagatell etal. 1994 Basaria etal. 2002) the testosterone concentration required to sustain sexual activity and maintain libido appears to be rather low (Gooren 1987 Schiavi 1996), and there is good evidence that healthy adults have substantially higher androgen levels than required for normal sexual behavior (Buena etal. 1993 Udry etal. 1985). Several authors reported differences in parameters of sexual desire or activity according to endogenous serum testosterone levels (Davidson et al. 1983 Schiavi etal. 1988 1990 Tsitouras etal. 1982 Udry etal. 1985), but there is a broad overlap of serum testosterone levels in sexually less or more active elderly men in these studies. Moreover, other studies failed to find an association between androgen levels and the perception of sexual functioning (Perry etal. 2001 T'Sjoen etal. 2003) (see also Chapters 4 and 11). Although potency...

Testosterone and erection in normal men

One controlled study involving 11 normal men tested the effects of varying serum testosterone concentrations within the normal range (Buena et al. 1993). All men received the depot GnRH agonist leuprolide acetate for suppression of endogenous testosterone to the hypogonadal range. Six volunteers received 4 mg d of a testosterone microcapsule formulation to restore testosterone levels to the low normal range (mean values 10.5 1.7 nmol l), whereas five volunteers received a dose of 8 mg d resulting in testosterone levels in the middle to high normal range (mean values 26.5 3.4 nmol l). Despite significantly different testosterone levels, albeit in the normal range, there was no difference in the number of spontaneous nocturnal erections during rapid eye movement (REM) periods as well as no difference in the magnitude and duration of tumescence as measured by NPT recordings at the base and the tip of the penis. These experimental studies in normal men indicate that variations of...

Sex hormone binding globulin and free testosterone serum levels

Sex Hormone Binding Globulin Molecule

Whereas some authors may still argue that total testosterone concentrations are not reduced in perfectly healthy elderly men, all authors agree that the free and non-specifically bound serum testosterone, generally considered to represent the serum testosterone fractions readily available for biological activity, do indeed decrease with age (for review Vermeulen 1991). In healthy ambulatory men, mean serum levels of free testosterone (FT) and of non SHBG-bound or so called bioavailable testosterone (i.e. the sum of the free fraction and the fraction loosely bound to albumin) decrease by as much as 50 between age 25 and 75 years (Ferrini et al. 1998 Vermeulen etal. 1996). The sharper decline of these fractions in comparison with total testosterone is explained by an age-associated increase of sex hormone binding globulin (SHBG) concentrations and has been confirmed in longitudinal studies (Feldman et al. 2002 Harman et al. 2001 Morley et al. 1997). In 300 healthy men aged 25-100 years...

Androgen deficiency states in women

Estrogen And Androgen Over Time Women

A core precept of endocrinology is that of an endocrinopathy, defined as a hormonal deficiency state with clearly defined adverse sequelae. This paradigm is best illustrated by hypothyroidism and subsequent replacement, or by male hypogonadism with testosterone replacement. In the previous section, we have hypothesized that a clear androgen deficiency state does not exist in women undergoing natural menopause, but there are several conditions that are associated with decreased levels of androgens in women. These include the use of postmenopausal hormone replacement therapy (HRT), (particularly orally administered), oral contraceptive use, pre-or postmenopausal oophorectomy, and adrenal suppression. Combined, these iatrogenic causes are prevalent enough to makeandrogen deficiency in women an extremely common condition. Fig. 17.3 Circulating testosterone levels through the menopausal transition Melbourne Women's Midlife Health Project (Burger 2000). Fig. 17.4 also illustrates several...

Testosterone ester combinations

Leuprorelin Testosterone Kinetics

Testosterone ester mixtures have been widely used for substitution therapy of male hypogonadism (e.g. TestovironRDepot 50 20 mg testosterone propionate and 55 mg testosterone enanthate TestovironRDepot 100 25 mg testosterone propionate and 100 mg testosterone enanthate SustanonR 250 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate and 100 mg testosterone decanoate). These combinations are used following the postulate that the so-called short-acting testosterone ester (e.g testosterone propionate) is the effective testosterone for substitution during the first days of treatment and the so-called long-acting testosterone (e.g. testosterone enanthate) warrants effective substitution for the end of injection interval. However, this assumption is not supported by the pharmacokinetic parameters of the individual testosterone esters. Both testosterone propionate and testosterone enanthate cause highest testosterone serum concentrations...

Sex Chromosomal Abnormalities

Affected children have small, firm testes, and adult patients have azoospermia. y This disorder is a common cause of primary hypogonadism and male infertility. Although a male phenotype is typical, delayed or poorly developed secondary sex characteristics are present, and about half the patients have varying degrees of gynecomastia, androgen deficiency, and eunuchoid features. These patients tend to be tall and have long legs, and adults have an increased incidence of pulmonary disease, varicose veins, diabetes mellitus, and breast cancer. y Serum levels of follicle-stimulating hormone and luteinizing hormone are increased early in the second decade, whereas testosterone concentrations are normal to low. Plasma levels of estradiol are normal or high. Affected individuals have cognitive abnormalities including impaired auditory sequential memory with delayed language development and associated learning disorders. y There is a slight lowering of the mean IQ and an increased incidence of...

What happens if my sex drive libido is low What causes it can it be treated

Your interest in sex is governed by sex hormones, primarily testosterone, and by psychosocial factors. Low testosterone levels are associated with decreased libido. Stress, depression, or anxiety may also affect your libido. In men with erectile dysfunction, interest in sex may be diminished as a result of their inability to achieve an adequate erection. Abnormalities of the testicles themselves that lead to impaired function of the testes may cause the testosterone levels to be low. Such abnormalities may include a history of testicular torsion, a history of unde-scended testes, prior testicular infections, and other congenital anomalies that affect the testes. Removal of both testes (bilateral orchiectomy) for prostate cancer or (rarely) bilateral testicular cancers causes a significant drop in testosterone level and decreases libido. Men with a single testis usually have adequate testosterone production, provided that the remaining testis is normal. Testosterone levels do decrease...

Testosterone propionate

Injections Propionate

Single-dose pharmacokinetics of 50 mg testosterone propionate after intramuscular injection to seven hypogonadal patients and the best-fitted pharmacokinetic profile are shown in Fig. 14.4 (Nieschlag et al. 1976). Maximal testosterone levels in the supraphysiological range were seen shortly after injection (40.2 nmol l, tmax 14 h). Testosterone levels below the normal range were observed following day 2 (57 h) after injection. The calculated values for AUC were 1843 nmol * h l, forMRT 1.5 d and 0.8 d for terminal half-life (Table 14.2). Judged by the data from pharmacokinetic analysis and simulation, administration of testosterone propionate is not suitable for substitution therapy of male hypogonadism because of its short-term kinetics resulting in wide fluctuations of testosterone serum concentrations and maximal injection intervals of three days for the 50 mg dose.

Chromosomal Anomalies

Mothers of infants with the Prader-Willi syndrome note decreased in utero fetal activity, and often these neonates are born in breech presentation. The affected individuals are of short stature and have small hands and feet and a narrowed cranial bifrontal diameter. y Their eyes are almond-shaped, and they often have strabismus. The face is long, and nearly 50 percent of patients have hypopigmentation of the skin. Other common features include a small phallus, cryptorchidism, and hypogonadism with a small flat scrotum. Affected infants have a feeble suck and severe hypotonia, which commonly requires the use of a feeding tube. Near the end of the first year of life, however, the hypotonia may become less severe. The degree of mental retardation may seem more prominent in early life and may be correlated with the severity of the hypotonia. At 1 to 3 years of age the patients gain considerable weight and become obese because of hyperphagia. As the hypotonia becomes less severe, they also...

Summary and future directions

Androgens circulate in appreciable amounts in women. Female serum testosterone levels rely on a complex interplay of hormonal secretion and bioconversion of peripheral prehormones. Testosterone levels are proportional to ovarian and adrenal secretion and peripheral bioconversion of the adrenal androgens DHEAS and DHEA, the predominant circulating androgens. Adrenal androgen secretion attenuates with age in a cortisol-independent fashion due to involution of the reticularis zone of the adrenal cortex. As a result, as women age, less testosterone is produced from peripheral bioconversion of DHEAS and DHEA. With the onset of menopause, while ovarian folliculogenesis ceases, the remaining theca and stroma respond to the elevated, menopausal levels of LH by greatly increasing ovarian testosterone secretion. This compensatory mechanism attenuates the age decline in serum testosterone levels from declining adrenal androgens. The combined effects create a subtle decline in serum testosterone...

Altered neuroendocrine regulation

Although the combined observations of a diminished testicular reserve for testosterone secretion and increased basal gonadotropin levels may seem in line with the view that the age-related decline of Leydig cell function results from primary testicular dysfunction, closer examination of the data suggests that other mechanisms must also be involved. Indeed, the observed responses to hCG challenges in elderly men indicate that the secretory reserve of the Leydig cells, albeit diminished, should still be sufficient to allow normalization of plasma testosterone levels, provided the endogenous drive by pituitary LH is adequate. In the face of a persistent status of relative hypoandrogenism, the only modestly increased basal levels of pituitary luteinizing hormone (LH) should be regarded as inappropriately low. Furthermore, in contrast to previous reports of a delayed or diminished LH response upon stimulation with pharmacological doses of GnRH (Nieschlag etal. 1982 Rubens etal. 1974...

Genetics vs Lifestyle

There are a number of congenital syndromes in which obesity is part of the phenotype. The best known, Prader-Willi syndrome, results from a defect in the long arm of chromosome 15 and causes poor muscle tone in the newborn period, with hyperphagia, hypogonadism, behavioral problems, and developmental delay noted later. As with other medical causes of childhood obesity, linear growth is poor while growth in weight is excessive. Although the exact mechanisms by which the genetic abnormalities lead to obesity are unclear, patients with Prader-Willi syndrome have elevated levels of ghrelin, a peptide produced in the stomach and duodenum that stimulates eating.

Clinical implications

Efforts to exploit the therapeutic benefits of testosterone in the treatment of hypogonadism, osteoporosis, wasting, and chronic consumptive disease or for contraception in a wider male population should not be deterred or hampered by concerns regarding increased cardiovascular risks. However, the possibility that spontaneous or induced hyperandrogenaemia may increase the risks for coronary artery disease in women needs to be seriously considered. Significant and independent associations between endogenous testosterone levels and cardiovascular events in men and women have not been confirmed in large prospective studies, even though cross-sectional data suggested cardiovascular diseases can be associated with low testosterone in men. However, hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity, insulin resistance, low HDL cholesterol, elevated triglycerides, LDL cholesterol and PAI-1. These gender differences and confounders render the precise...

Classification And Clinical Presentation

Serum prolactin levels at diagnosis are usually markedly elevated and correlate with tumor size. As mentioned previously, prolactin elevation from pituitary stalk compression alone is rarely greater than 150 ng mL. In addition, most patients show evidence of secondary hypogonadism in addition to elevated prolactin values.

Treatment of delayed puberty in boys

mild treatment appears to be suited for an early phase when virilization is not yet requested. Transdermal testosterone should also be a useful method to induce puberty. However, experience in a larger series of patients has not yet been reported. At the beginning of therapy it is often difficult to distinguish between boys with constitutional delay of growth and puberty, who require only temporary androgen replacement, and boys with idiopathic hypogonadotropic hypogonadism, who require lifelong androgen therapy to stimulate puberty and to maintain adult sexual function. However, boys with permanent hypogonadotropic hypogonadism will not have testicular growth induced by androgen therapy. Because pubertal growth is a product of the interaction of growth hormone (GH) and insulin-like growth factor I (IGF-I) and the hypothalamic-pituitary-gonadal axis, boys with concomitant GH deficiency will require the simultaneous administration of GH and androgens for the treatment of delayed...

Testosterone microspheres

Drugs can be incorporated into biodegradable microspheres. When injected intramuscularly, such drug-loaded microspheres provide controlled release of the substance for several weeks or even months. As an example, microencapsulated GnRH agonists have become a valuable modality in the treatment of prostatic carcinoma. Testosterone has been incorporated into poly(DL-lactide-co-glycolide) micro-spheres. When first tested in castrated monkeys single injections resulted in an elevation of serum levels above the lower limit of normal for several months (Asch etal. 1986). When similar microsphere injections containing 315 mg of testosterone were given to eight hypogonadal men, serum testosterone levels slowly increased to peak levels at about eight weeks and fell thereafter to reach pathological levels again by 11 weeks (Burris etal. 1988). In a later study the size-range and the testosterone loading of the microspheres were adjusted so that in hypogonadal men single intramuscular injections...

Testosterone microcapsules

Concentrations were already seen at the first follow-up examination on day 1. In the higher-dose group, mean serum concentrations were at the upper limit of normal at this time-point. Thereafter, testosterone levels declined rapidly in both groups with mean serum levels below 10 nmol l after 5 and 7 weeks, respectively. In the higherdose group, serum levels of free testosterone, bioavailable testosterone, estradiol and DHT exceeded the normal range for at least the first week after injection. Two subjects complained of transient tenderness and fullness at the injection sites. Multiple-dose studies are still outstanding, and therefore the appropriate injection interval for long-term therapy has not yet been determined. One disadvantage of the testosterone microcapsule formulation seems to be the early burst release of testosterone, which limits the clinically acceptable dose and shortens the maximal injection interval.

Testosterone effects on muscle performance

The data presented above have established that testosterone supplementation in men increases fat free mass, but it remains unclear whether measures of muscle performance such as maximal voluntary strength, power, fatigability, or specific tension are improved by androgen administration (Storer etal. 2003). Further, the extent to which these measures of muscle performance are related to testosterone dose or circulating concentration is unknown. To determine the dose-dependence of measures of muscle performance on testosterone dose and concentrations, we measured maximal voluntary strength, leg power, and muscle fatigability in our dose response study. Specific tension was estimated by the ratio of 1RM muscle strength to thigh muscle volume determined by MRI. Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly...

Testosterone cypionate and testosterone cyclohexanecarboxylate

In a subsequent clinical study the pharmacokinetics of testosterone cyclohexanecarboxylate were compared to the pharmacokinetics of testosterone enanthate in a single-blind cross-over study in seven healthy young men (Schurmeyer and Nieschlag 1984). After injection of either testosterone enanthate or testosterone cyclohexanecarboxylate, testosterone concentrations in serum increased sharply and reached maximum levels, 4-5 times above basal, 8-24 h after injection. During following days a parallel decay of testosterone levels occurred after injection of either ester preparations, with testosterone serum concentrations slightly, but significantly lower after testosterone cyclohexanecarboxylate injection compared to testosterone enanthate injection two, three and seven days after administration. Basal serum levels were reached seven days after testosterone cyclo-hexanecarboxylate administration and nine days after injection of testosterone enanthate.

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