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Anabolic Running Review

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Anabolic Running Review Summary


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Leptin and Congenital Leptin Deficiency

Total leptin deficiency or insensitivity is associated with hypothalamic hypogonadism in humans and rodents. Leptin treatment restored luteinising hormone secretion and pubertal development in leptin-deficient patients, confirming its critical role in reproduction. It was proposed that high levels of leptin observed in children might reflect leptin resistance, as seen in obesity, serving to maintain sufficient food intake and growth and prevent the onset of premature puberty. Central leptin administration decreases the expression of

Interventions To Reduce Cytokines

Testosterone levels decline with aging in both men 87 and women 88 . Testosterone replacement in men increases muscle mass 89-91 and strength 92, 93 , and decreases fat mass 90, 94, 95 . Adipocytes are a potent source of cytokines, including TNF-a and leptin. The effect of testosterone on functional status may be mediated by reducing cytokine excess through an effect on adipocytes 96-98 .

Biological Aspects Of Pubertal Development

Estrogen and testosterone levels also differ between the two sexes at puberty. Estradiol levels at puberty increase in females then remain elevated during periods of each menstrual cycle. In males, estradiol levels increase until their growth spurt (at midpuberty) then decrease again. On the other hand, while males experience substantial increases in testosterone and androstenedione (a weaker androgen than testosterone) at puberty, there is only a slight rise in females. The sexes also differ in their levels of dehydroepiandrosterone (DHEA) and DHEAS (sulfated form of DHEA), hormones which mark the beginning of adrenarche, the period of initial increases in adrenal androgen hormones, at 6 to 7 years of age in both sexes. Levels of DHEA and DHEAS are similar between the sexes until late puberty, when males begin to have higher levels than females. This difference persists into adulthood (Fechner, 2002).

Sexual function and cardiovascular drugs

All drugs that interfere with sympathetic autonomic activity, including diuretics, can potentially interfere with male sexual function, expressed as a failure of ejaculation or difficulty in sustaining an erection. Nevertheless, placebo-controlled trials have emphasised how common a symptom this is in the untreated male population (approaching sometimes 20-30 ). It is also likely that hypertension itself is associated with an increased risk of sexual dysfunction since loss of NO production by the vascular endothelium is an early feature of the pathophysiology of this disease. Laying the blame on antihypertensive medication is probably

Biochemical Features Of The Recq4 Helicase

To determine if each helicase can be expressed in specified tissues or organs, we analyzed the expression of all five RecQ helicase genes in various human organs and tissues by Northern blotting (Fig. 6). The data show that RECQL4, WRN, and BLM are expressed in a tissue specific-fashion, and support the idea that a close correlation exists between the site of gene expression and the site (tissue or organ) of disease phenotypes. For example, WRN is expressed highly in pancreas, testis, and ovary, and WS patients often show clinical symptoms of diabetes and hypogonadism. Also, BLM is highly expressed in the thymus

Pubertal Status Effects

Since hormonal changes are the cause of the changes in physical growth and development, it is often difficult to disentangle hormonal and status effects on adjustment. For example, as described in the previous section, a study by Angold and colleagues (1998) found that only after reaching Tanner stage III were girls more likely than boys to experience higher rates of depressive disorder. However, subsequent analyses showed that effects of elevated estradiol and testosterone levels eliminated effects due to secondary sexual characteristics (Angold et al., 1999). This study suggests that when pubertal status effects on adjustment are found, they are likely be driven by hormonal changes.

Molecular characteristics of cannabinoid receptors Cnrs

In order to determine whether there are introns in the coding sequences of human, rat and mouse CB1 and CB2 Cnr genes, primer pairs spanning the cDNA sequences of these genes were generated to test whether the DNA fragments amplified by these primer pairs were identical with both genomic DNA and cDNA templates. The hypothesis we tested was that if the DNA fragment sizes were identical with both templates, then the gene was intronless, if not, the intron location, size and structure can be determined. To determine whether the structure of the testis CB1 receptor gene or its transcripts is different from those in the brain, we isolated DNA and RNA from rat testes and brain and used them as templates for PCR with primer pairs. There was no difference in sizes of the PCR amplified DNA bands between brain DNA and RNA, between testes DNA and RNA or between the brain and testis DNA or RNA. Specified amplified DNA bands were identified by Southern hybridization with human CB1 cDNA as probe,...

Sertolileydig Cell Tumors Treatment Issues

This classification of tumors includes tumors comprised of Sertoli cells only, as well as tumors containing both Sertoli and Leydig cells. Tumors composed of Sertoli cells only are uniformly stage I, and only one death has been reported 64 . Sertoli-Leydig cell tumors, also called arrhenoblastomas, are rare, accounting for less than 0.2 of all ovarian tumors, and usually present in adolescents and young adults. Since stage is the most important predictor of outcome, these patients should be accurately staged (Table 13.5). Over 95 of these tumors are confined to one ovary at the time of diagnosis therefore, a normal-appearing uterus and contralateral ovary can usually be preserved. Patients with disease greater than IB, with poorly differentiated tumors, or with heterolo-gous elements present should be treated with BEP 65 or paclitaxel and carboplatin. Patients can be followed with physical examinations and with serum aFP, inhibin, and testosterone levels. Of the 18 of patients who...

Anabolic Agents and Testosterone

Muscle mass, but with unknown clinically meaningful changes in muscle function and disease outcome in HIV-infected men 98-102 . Morley et al. safely administered testosterone to older men with hypogonadism and noted an increase in the upper-arm strength of this population 52,103 . Dolan et al. found that testosterone administration increased muscle strength in low-weight HIV-infected women and suggested that it may be a useful adjunctive therapy to maintain muscle function in this group of patients 104,105 .

Testosterone Replacement

Data from the Baltimore Longitudinal Study on Aging (890 men), suggested that 20 of the men over 60 years of age, 30 over 70 years, and 50 over 80 years were hypogonadal, as defined by a total testosterone level < 325 ng dl (11.3 nmol l), 46 . It is widely believed that total testosterone declines 1 per year after the age of 50 years 4 . Thus, the decline in testosterone follows a time course similar to the decline in muscle strength and muscle mass. Many individuals believe that it is the decline in testosterone over time that results Morley et al. 47 studied 37 men aged 69-89 years old. Twenty-six of the men had a mean total testosterone level of < 272 ng dl. They were administered 200 mg of testosterone enanthate every 2 weeks for 3 months. Alternating cases was the method used to assign subjects to treatment or placebo groups. The authors reported a nine-fold increase in bioavailable testosterone and a significant increase in right-hand muscle strength. Sih et al. 48 reported...

Indications For Oestrogen Therapy

Replacement therapy in hypoestrogenaemia. This term refers to decreased oestrogen production due to ovarian disease, or to hypothalamic pituitary disease (hypogonadotropic hypogonadism). Treatment is by cyclic oestrogen (conjugated oestrogens 0.625 1.25 mg daily or ethinylestradiol 20-30 micrograms daily for 21 days) plus a progestogen, medroxyprogesterone 2.5 to 10 mg daily for the last 10 to 14 days of oestrogen treatment. An alternative treatment is the oral contraceptive (see p. 721).

Gonadal Toxicity Following Malignancy Treatment

The loss of germ cells exerts secondary effects on the hypothalamic-pituitary-gonadal axis. Germinal apla-sia reduces the size of the testes. Consequently, testic-ular blood flow decreases, thus reducing the testosterone levels in the circulation.14 Because testosterone is a negative regulator of luteinizing hormone (LH), which is secreted by the pituitary, and LH is the primary stimulator of testosterone synthesis by the Leydig cells, LH increases to maintain constant serum testosterone levels. In addition, inhibin secretion by the Sertoli cells declines and, as inhibin limits follicle-stimulating hormone (FSH) secretion by the pituitary, serum FSH levels tend to rise.

Benefit 1 Greater Experimental Control

Wild-type mice, despite having average testosterone levels. Shows an environmental influence on testosterone levels, which in turn may influence dominance and aggression. Testosterone levels and aggression were higher in dominant individuals. Muehlenbein Adult male Testosterone levels were correlated with Holekamp & Adult male Testosterone levels were higher in testosterone levels correlated with social rank among immigrant males. Shows a relationship between testosterone levels and aggression, as well as between testosterone levels and social rank. Shows a relationship between testosterone levels and social rank. Shows a relationship between testosterone levels and social rank. In another study, researchers were interested in examining the effects of the estrogen receptor alpha gene on aggression (Ogawa, Lubah, Korach, & Pfaff, 1997). Previous research in mice had discovered that one pathway by which testosterone leads to aggression is through conversion into the hormone...

Benefit 3 Greater Opportunities for Naturalistic Observations

Research by Wingfield, Hegner, Dufty, and Ball (1990) in a variety of bird species illustrates the benefits of naturalistic observations of animals. These investigators recorded data on testosterone levels as well as aggressive and paternal behaviors in a wide variety of monogamous and polygynous bird species. Wingfield and colleagues proposed the challenge hypothesis to account for the relationship between testosterone levels and aggressive behavior in birds. The challenge hypothesis posits that fluctuations in testosterone levels during the breeding season are more closely related to aggressive behavior than to sexual behavior. Specifically, testosterone levels seem to rise as the mating season commences but peak during periods of intermale competition, suggesting that the increases in testosterone levels facilitate aggression. In addition, this theory suggests that testosterone only relates to aggression when there is competition over mates or territory. Thanks to Wingfield and...

Appetite Stimulants Progestational Agents

Originally used as a therapy in hormone-sensitive tumours, the observation that in a substantial number of patients appetite and weight increased led to it being studied in cancer cachexia 81 . It has been widely promoted as a therapy for cachexia and anorexia, although whether patient function or quality of life is improved is less clear. Appetite can be increased after only a short period of treatment 82 . Improvements in well-being may also occur in some patients without obvious changes in nutritional status 83 . Although it has not been assessed in all studies, there appears to be little impact on lean body mass, which is currently thought to be the most important body compartment in modulating function. In fact, a detrimental effect on muscle has been demonstrated in elderly males 84 and the weight gain seems largely secondary to increased fat and some fluid 85 . This is consistent with observations in AIDS patients 86, 87 . Megestrol acetate has...

Pituitary Disorders and Weight Loss Hypopituitarism

Total or partial hypopituitarism may occur in patients with pituitary adenomas, following pituitary surgery or radiation, or after head injury. Deficiency of any or all of the six major hormones (lutheinising hormone LH , follicle stimulating hormone FSH , thyroid, GH, thyroid stimulating hormone TSH , ACTN, and prolactin) can occur. The most common symptom in both men and women is secondary hypogonadism, because of LH and FSH deficiencies or secondary to hyper-prolactinaemia. In children, cessation of growth and delayed puberty are common.

Natomy And Physiol

Inguinal Hernia Physical Exam

Male sexual function depends on normal levels of testosterone, adequate arterial blood flow to the inferior epigastric artery and its cremasteric and pubic branches, and intact neural innervation from a-adrenergic and cholinergic pathways. Erection from venous engorgement of the corpora cavernosa results from two types of stimuli. Visual, auditory, or erotic cues trigger sympathetic outflow from higher brain centers to the T11 through L2 levels of the spinal cord. Tactile stimulation initiates sensory impulses from the genitalia to S2 S4 reflex arcs and parasympathetic pathways via the pudendal nerve. Both sets of stimuli appear to increase levels of nitric oxide and cyclic GMP, resulting in local vasodilation.

Intrauterine Adhesions Ashermans Syndrome

Intrauterine scarring leading to an unresponsive endometrium is most commonly due to injury to the pregnant or recently pregnant uterus. However, any mechanical, infectious, or radiation factor can produce endometrial sclerosis and adhesion formation. The sine qua non for development of IUA is endometrial trauma, especially to the basalis layer. The adhesions usually are strands of avascular fibrous tissue, but they also may consist of inactive endometrium or myometrium. Myometrial adhesions usually are dense and vascular, carrying a poor prognosis. Women with atrophic and sclerotic endometrium without adhesions carry the worst prognosis. This condition usually is found after radiation or tuberculous endometritis and is not amenable to any therapy. Postpartum curettage performed between the second and fourth weeks after delivery, along with hypoestrogenic states such as breast-feeding or hypogo-nadotropic hypogonadism, is associated with extensive intrauterine scar formation. Uterine...

Screening for Osteoporosis

Osteoporosis may also occur in men, although with a lower incidence than it does in women. Along with the risk factors noted above, the prolonged use of corticosteroids, presence of diseases that alter hormone levels (such as chronic kidney or lung disease) and undiagnosed low testosterone levels increase the risk of osteoporosis in men.


Many female AT patients have congenital hypoplasia of the ovaries and menarche may be delayed or absent (4,18). Male patients have been shown to have histological abnormalities of their testes, and incomplete spermatogenesis has been reported (19,20), although hypogonadism is less frequent and milder than in affected females.


Gonadal hormones were the first biochemicals studied in relationship to sensation seeking. The reasons for this selection were based on the gender differences (males higher than females) and age changes (a peak in late adolescence and a drop at subsequent ages) on the SSS. Testosterone has similar gender and age differences. Another finding suggestive of gonadal differences is that high sensation seekers tend to have more sexual experience with more partners than low sensation seekers (Zuckerman, Tushup, & Finner, 1976). Indeed, in males testosterone and estradiol were correlated with both SSS scores (particularly Disinhibition) and sexual experience (Daitzman & Zuckerman, 1980). Estradiol in males is produced by conversion of androgens to estradiol. The aromatization hypothesis suggests that androgens in males have their major motivational effects after conversion to estrogenic metabolites (Brain, 1983). SSS scores of hypogonadal men with low testosterone levels were compared...


Two proteins identified in the survey, termed ALMS1 and OFD1, have previously been identified genetically as being linked to human diseases. In particular, the C-terminal half of ALMS1 was localized to the centrosome by tagging 21 and, independently, antibodies to OFD1 have been shown to decorate the centrosome 31 . Both proteins need further investigation to confirm their association with the cen-trosome but their identification as candidate centrosome components is intriguing. The diseases caused by defects in these genes are relatively rare and poorly understood. Patients with Alstrom syndrome (ALMS1) display a complex set of symptoms. Childhood obesity starts at the early age of 6 months and many patients develop type 2 diabetes. The disease is also associated with neurosensory defects and subsets of patients show dilated cardiomyopathy, hepatic dysfunction, hypothyroidism, male hypogonadism, short stature and mild developmental delay 32, 33 . The symptoms of oral-facial-digital...


With aging, testosterone levels decrease because of failure of the hypothalamic-pituitary-gonadal axis 33 . The decline in testosterone occurs at the rate of about 1 per year, beginning at 30 years of age. Loss of testosterone leads to an increase in adipocyte precursors and a decrease in satellite precursors. In addition, it is associated with a decline in muscle-protein synthesis. Testosterone replacement in older persons increases muscle mass and, to a lesser degree, muscle strength 34 . Decreased creatine intake Peripheral vascular disease Hypogonadism Cytokine excess Myostatin excess


The subjects ranged in age from 21 to 77 years with a median age of 43 years. Twenty-five individuals were Caucasian and 20 were Black. Twenty percent of the individuals had age-matched z-scores in the spine of -1 or poorer, whereas only 8.8 had similar age-matched z-scores in the proximal femur. Osteopenia in the spine was correlated with duration of disease and hypogonadism. Total body calcium was increased even in osteopenic patients suggesting that excess growth hormone insulinlike growth factor-1 (GH IGF-1) caused a positive bone balance except in the spine. Thirteen percent of subjects in this study had BMD values in the spine that were two or more SDs above the age-matched mean BMD value.

Hormone Effects

Angold and colleagues have conducted a number of studies on links between pubertal factors and depression. The first study assessed age, pubertal timing, and Tanner stage on the probability of depression in both boys and girls over four waves of data collection from the Great Smoky Mountains Study (Angold, Costello, & Worthman, 1998). Depression included three diagnoses DSM-IV major depressive episode, dysthymia, and minor depressive disorder. Findings revealed that only after the transition to mid-puberty (Tanner Stage III and above) were girls more likely than boys to be depressed. Timing of the pubertal transition did not affect depression, whether measured by onset of menarche or Tanner stage development. These findings imply that some aspect of puberty itself was related to depression, rather than the age at which the pubertal level was achieved. Further analyses considered HPG axis hormonal effects on depression in girls, in order to disentangle the effects of the...

Case Scenario 122

The special chemistry section received laboratory requests for the following hormones total testosterone, free testosterone, FSH, midfollicular LH, mid-follicular prolactin, androstenedione, DHEAS, dihydrotestosterone, andro-standiol glucuronide, and sex hormone-binding globulin. Many of these laboratory tests were to be sent to a reference laboratory. The referral database was consulted so that the correct type of specimen was collected and proper storage and handling conditions were met prior to performing the tests at the reference laboratory. The patient was a 23-year-old African-American female with a preliminary diagnosis of hirsutism and infertility. Previous laboratory results showed a slightly elevated 8 00 a.m. plasma cortisol level but a low-dose dexamethasone test showed normal cortisol suppression. The following laboratory results were obtained initially from the special chemistry section

Thalassemia Major

2 were hormone deficient and not receiving sex-steroid replacement. A control group consisting of 20 healthy subjects was matched for age, sex, height, and weight. Bone density was measured by DXA (SOPHOS L-XR-A) at the PA lumbar spine and proximal femur. In this cross-sectional study, bone density at the PA lumbar spine was reduced in groups 1 and 2 compared to the control group. The reduction was greater in group 2 than in group 1. Proximal femoral bone density was reduced in group 2 only in comparison to the control group. The authors suggested that the treatment of hypogonadism with sex hormone replacement therapy was beneficial in the prevention and treatment of osteoporosis in thalassemics.

Laboratory Features

Endocrine abnormalities were found in two-thirds of our patients at presentation. Hypogonadism was the most common abnormality, and 71 of males had erectile dysfunction. Twenty-four of 28 patients who had serum testosterone levels measured had a reduction. Gynecomastia was found in 17 men. Prolactin levels were not increased. Hypothyroidism was found in 14 of patients. An additional 12 had a mild increase in the thyroid-stimulating hormone level but had normal thyroxin levels. Abnormalities of the adrenal-pituitary axis were present in 16 . In five additional patients, adrenal insufficiency developed during follow-up.

False Transmitter

Gynaecomastia and lactation occur due to interference with dopaminergic suppression of prolactin secretion. Any failure of male sexual function is probably secondary to sedation. Because of its adverse effects methyldopa is no longer a drug of first choice in routine long-term management of hypertension, but remains popular with obstertricians for the hypertension of pregnancy.

Endocrine Effects

Other researchers have failed to verify the findings of Kolodny's group. Seven separate studies involving over one hundred chronic cannabis smokers have individually demonstrated an absence of significant effect upon human testosterone levels (Block et al., 1991 Cushman, 1975 Erdolu et al., 1985 Hembree et al., 1976 Mendelson et al., 1974, 1978 Schaefer et al., 1975). In 1976, Kolodny and colleagues studied the effects of cannabis upon human testosterone levels for a second time. On this occasion, the investigation was more rigorous. Plasma testosterone levels were significantly reduced at 30, 120 and 180 minutes after smoking cannabis, compared to levels measured in the same individuals during a non-smoking period. However, a study by Mendelson and co-workers in 1978, using a similarly rigorous design, again failed to reproduce these results. It is unclear why Kolodny and associates have consistently reported that cannabis can reduce testosterone levels whilst other groups have not...

Diet Infertility

In men, poor nutrition - a diet high in refined carbohydrates, saturated fat, and processed foods and low in important micronutrients -may reduce sperm number and motility. To help increase sperm quality, the diet should emphasize high-quality protein, whole grains, and fresh fruits and vegetables. Heavy alcohol consumption (more than 3 drinks per day) can impair fertility.6 Overweight men are more likely to have low testosterone levels and lower numbers of sperm.

Menstrual disorders

A combination of an oestrogen and a progestogen induces a hormonal pseudo-pregnancy. The oral contraceptive is used either continuously or cyclically (21 active pill followed by 7 days of placebo). Both regimens are effective the amenorrhea of continuous administration is advantageous for women with dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists diminish the secretion of follicle-stimulating hormone and luteinising hormone, resulting in hypo-gonadotropic hypogonadism, endometrial atrophy and amenorrhea. The GnRH agonist can be given

Changes With Aging

Testosterone levels decline with aging and may affect both libido and sexual function. Erection becomes more dependent on tactile stimulation and less responsive to erotic cues. Pubic hair may decrease and become gray. The penis decreases in size and the testicles drop lower in the scrotum. Although the testes often decrease in size with protracted illnesses, they do not necessarily change size with aging per se.

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