2. Testosterone and Aging

Size: px
Start display at page:

Download "2. Testosterone and Aging"

Transcription

1 2. Testosterone and Aging Shalender Bhasin, MD Thomas G. Travison, PhD Ravi Jasuja, PhD Carlo Serra, PhD Thomas W. Storer, PhD Shehzad Basaria, MD Case 2-1 A 78-year-old man requests evaluation for weakness, fatigue, and difficulty in walking and climbing stairs. He suffers from hypertension and diabetes mellitus. Since incurring a myocardial infarction six years ago, he has experienced chest pain during heavy exertion once or twice a month. He urinates three times each night, and reports poor urine stream and some urgency. His medications include metformin 500 mg twice daily, lisinopril 10 mg daily, and metoprolol 50 mg once daily. Heart rate is 62 per minute, blood pressure 142/82 mm Hg. No jugular venous distension or edema. Testes are soft and measure 20 ml bilaterally. Hemoglobin 11.5 g/dl, hematocrit 0.34 L/L, blood glucose 121 mg/dl, A1C 6.7%, creatinine 1.5 mg/dl, total testosterone 210 ng/dl, luteinizing hormone (LH) 14 U/L, follicle-stimulating hormone (FSH) 12 U/L. His primary care provider asks whether he should receive testosterone therapy. Case 2-2 A 62-year-old man with diabetes mellitus and hypertension requests evaluation for inability to achieve or maintain erections during intercourse. His early morning erections are weak. He reports leg cramps on walking two blocks. He uses sublingual nitroglycerine several times each week for angina pectoris that he experiences when he walks more than one block. He also takes an alpha adrenergic blocker for lower Dr. Shalendar Bhasin participated in writing the chapter entitled "Testosterone and Aging" but did not participate in developing the CME questions in consideration of his role as Chair of the American Board of Internal Medicine Endocrinology and Metabolism subspecialty examination board. Translational Endocrinology & Metabolism, Volume 2, Number 2,

2 urinary tract symptoms, an angiotensin converting enzyme inhibitor for hypertension, and metformin for diabetes. Physical examination reveals BP 155/92, HR 80/min, and symmetric pulses bilaterally. Fasting blood glucose 105 ng/dl Total testosterone 320 ng/dl. He asks if testosterone therapy could improve his sexual function. Age-Related Decline in Testosterone Levels The practicing endocrinologist is frequently consulted for consideration of testosterone therapy in older men with age-related symptoms such as fatigue, weakness, sexual dysfunction, and physical dysfunction. The debate over this issue is often polarizing and clouded by the failure to distinguish classical hypogonadism in men resulting from known diseases of the testes, pituitary Total and free testosterone and the hypothalamus from the age-related levels decline progressively with decline in testosterone. Even though there aging, but neither the clinical are few large, long term randomized trials benefits nor the long term risks of of testosterone therapy in older men with testosterone therapy are known classical hypogonadism, there is general in older men with age related agreement based largely on 70 years of decline in testosterone levels. clinical experience and open-label trials that testosterone therapy of men with androgen deficiency due to known diseases of the hypothalamus, pituitary, and the testes has many beneficial effects and is associated with a low frequency of adverse events. In contrast, neither the clinical benefits nor the long-term risks of testosterone therapy are known in older men with age-related decline in testosterone levels. Total testosterone levels are lower in older men than in young men (1 7). There is no identifiable inflection point an andropause at which there is an abrupt cessation of androgen production in men; longitudinal studies have confirmed that testosterone levels peak in the second and the third decade of life and then decline gradually throughout life (1 3). The trajectory of age-related decline is affected by the degree of adiposity, co-morbid conditions, medications, and poorly understood genetic factors (8 9). The term Late Onset Hypogonadism has been used to reflect the view that in some middle-aged and older men, the age-related decline in testosterone is associated in a syndromic constellation with a cluster of symptoms and signs of androgen deficiency; indeed, in an analysis of the European Male Aging Study (EMAS), sexual symptoms poor morning erection, low sexual desire, and erectile dysfunction were associated with testosterone levels below 320 ng/dl (11 nmol/l) (6). 40 Translational Endocrinology & Metabolism: Aging Update

3 In contrast to testosterone levels which decline with age, the sex-hormone binding globulin (SHBG) concentrations increase with age and are higher in older men than in young men (1 7). Consequently, free and bioavailable testosterone levels decline to a greater extent and with a sharper trajectory than total testosterone levels. Epidemiologic Studies The estimates of the prevalence of low testosterone concentrations vary greatly among epidemiologic studies, reflecting differences in the study population, ethnic composition, thresholds used to define low testosterone levels, and the assays used to measure testosterone levels. In the Massachusetts Male Aging Study (2), 4% of community dwelling men, years of age, had serum total testosterone concentration below 150 ng/dl (5.2 nmol/l), in association with elevated LH concentration. In the Baltimore Longitudinal Study of Androgen deficiency is a Aging (BLSA) (1), 30% of men over the age syndrome characterized by signs of 60 and 50% of men over the age of 70 had and symptoms in association with total testosterone concentration below the unequivocally low testosterone lower limit of the normal range for healthy levels. The presence of low young men (<325 ng/dl, 11.3 nmol/l). testosterone by itself should The prevalence was even higher when not be viewed as diagnostic of these investigators used a free testosterone androgen deficiency syndrome. index to define androgen deficiency (1). As androgen deficiency is a syndrome characterized by a constellation of signs and symptoms in association with unequivocally low testosterone levels (10), the presence of low testosterone levels by itself should not be viewed as diagnostic of androgen deficiency syndrome. The prevalence of symptomatic androgen deficiency is substantially lower than that of low testosterone levels alone (6, 11). For instance, in the EMAS, while 23.5% of communitydwelling men, years of age, had low testosterone levels, only 2.1% had symptomatic androgen deficiency (6). Pathophysiologic Basis of Age-Related Decline in Testosterone Levels The age-related decline in circulating testosterone concentrations results mostly from decreased testicular testosterone production in older men; abnormalities at all levels of the hypothalamic-pituitary-testicular axis contribute to decreased testosterone production (12 18). The ability of LH to stimulate synchronous testosterone secretion from the Leydig cells (feed forward) is impaired (12) and hypothalamic pulsatile GnRH secretion is perturbed Testosterone and Aging 41

4 (13). Serum LH and FSH concentrations are higher in older men than in young men (1 7); however, serum LH concentrations do not increase in proportion to the age-related decline in circulating testosterone levels, likely reflecting the alterations in hypothalamic GnRH secretion and in the gonadal steroid feedback relationships (13). The estimated half-lives of LH, FSH, Testosterone production rates as or alpha-subunit are not significantly different between young and older men (14). are decreased in older men. well as its plasma clearance rates The orderliness of LH pulses and the synchrony between LH and testosterone pulses are perturbed in older men (15), and the LH pulse frequency, amplitude, and secretory mass exhibit considerably greater variability in older men, in comparison to young men (15). The diurnal rhythm of testosterone secretion is dampened in older men (16). The GnRH content, prepro-gnrh mrna expression level, and the number of neurons expressing prepro GnRH mrna are lower in older male rats than in young rats (17). The decreased levels of hypothalamic excitatory amino acid glutamate and gamma-aminobutyric acid (GABA) and the reduced responsiveness of GnRH neurons to N-methyl-d-aspartate contribute to decreased GnRH secretion in old rats (17). Plasma clearance rates of testosterone are lower in older men than in younger men (18); thus, testosterone levels in older men receiving testosterone therapy are higher than in young men after adjusting for testosterone dose. The older men are more sensitive to the inhibitory feedback effects of testosterone (13, 19). Estradiol administration in older men also is associated with a greater decrease in LH pulse frequency in older men than young controls (19). With advancing age, inhibin B levels remain largely unchanged even in the face of rising FSH levels suggesting some degree of Sertoli cell resistance in older men (20). Age-Related Decline in Circulating Testosterone and Health Outcomes in Older Men Circulating testosterone levels have been related with a number of health outcomes in middle-aged and older men (Table 2-1). Low bioavailable testosterone levels have been associated with low skeletal muscle mass in the upper and lower extremities, and decreased upper and lower extremity strength (21 22). Low testosterone levels also have been associated with decreased self-reported as well as performancebased measures of physical function, such as gait speed (22 23). The 42 Translational Endocrinology & Metabolism: Aging Update

5 Table 2-1. Relationship of Endogenous Testosterone with Outcomes in Epidemiologic Studies Directionality of association Outcome category Associated outcomes Positive Association Negative Association Inconsistent or no association Muscle Mass, muscle performance, and physical function Sexual Function Cognition Bone Erythropoeisis Cardiometabolic outcomes Fat-free mass, Appendicular skeletal muscle mass, Upper and lower extremity strength, Self-reported physical function, Walking speed, Mobility limitation, Falls, Frailty Libido, Early morning erections Verbal memory, Visuospatial cognition, Executive function Bone mineral density, Trabecular architecture, Bone quality, Bone geometry, Volumetric density Fracture,Osteoporosis Hemoglobin and hematocrit Whole body fat mass, abdominal fat mass, metabolic syndrome; Weak negative association with cardiovascular disease in men over 75, but inconsistent or no association in middle-aged men, diabetes mellitus, HDL cholesterol Lower urinary tract symptoms, Aging-related symptoms, Overall health-related quality of life, Erectile dysfunction, Depression men with low free testosterone levels are more likely to suffer from incident mobility limitation, frailty, and falls than those with normal free testosterone levels (23 25). In the EMAS, the men with low total testosterone levels were more likely to report decreased morning erections; additionally, the men with low free testosterone were more likely to report decreased morning erections, erectile dysfunction and decreased frequency of sexual thoughts (6). In the Massachussetts Male Aging Study, decreased libido, but not erectile dysfunction, was associated with very low testosterone levels (26). The prevalence of low testosterone levels is not significantly different in middle-aged men with erectile dysfunction and those without erectile dysfunction (27). Testosterone and Aging 43

6 Verbal memory, visual memory, spatial ability, and executive function have been associated with testosterone levels, although these associations are weak (28 32). Low total and bioavailable testosterone levels also have been associated with increased risk of mild cognitive impairment and Alzheimer s disease (33 35). The association of testosterone levels with depression has been inconsistent across studies (36 38). Low testosterone levels in older men appear to be associated more with subsyndromal depression than with major depression (37 38). Testosterone levels are lower in older men with dysthymic disorder than in those without any depressive symptoms (38). Testosterone levels have been associated with bone mineral density, bone geometry, and bone quality (39 44); bioavailable testosterone and estradiol are more strongly associated with these bone outcomes than total testosterone. In the MrOS Study, the odds of osteoporosis in men with a total testosterone less than 200 ng/dl were 3.7 fold higher than in men with normal testosterone level (43); free testosterone was an independent predictor of prevalent osteoporotic bone fractures (43). Testosterone levels are not related with aging-related psychological and somatovegetative symptoms, assessed by an Aging Males Symptoms scale (45), or with lower urinary tract symptoms. Testosterone and Cardiometabolic Outcomes Total testosterone levels are associated consistently with the risk of prevalent diabetes mellitus and metabolic syndrome (46-48); the association of free testosterone with the risk of prevalent diabetes and metabolic syndrome is weaker than that of total testosterone. Furthermore, the association of total testosterone with diabetes is attenuated after adjusting for SHBG concentrations (48). In longitudinal analyses, SHBG, but neither total nor free testosterone, is associated significantly with diabetes risk (Figure 2-1) (48). Polymorphisms in the SHBG gene have been linked to diabetes risk. As SHBG is affected by obesity, insulin sensitivity, and inflammation, it is possible that SHBG is a marker of metabolic risk. It is also possible that age, adiposity, and insulin resistance may independently affect both SHBG levels and the metabolic risk. Further research is needed to determine whether SHBG is a marker or a contributor to metabolic risk. SHBG levels have also been associated with fracture risk. The risk of cardiovascular events is increased in men with prostate cancer who receive androgen deprivation therapy. A number of cross-sectional studies found no difference in serum testosterone levels between men who had 44 Translational Endocrinology & Metabolism: Aging Update

7 4 3 Hazard Ratio Total Testosterone Free Testosterone Quartile SHBG FIG Sex-hormone binding globulin (SHBG), but not total or free testosterone levels are associated prospectively with diabetes risk in longitudinal analysis of the Massachusetts Male Aging Study. Total T quartiles: 1=<409 ng/dl; 2= ng/dl; 3= ng/dl; 4>624 ng/dl Free T quartiles: 1<8.5 pg/ml; 2= pg/ml; 3= ng/dl; 4>13.6 ng/dl SHBG quartiles: 1<22 n,ol/l; 2=22 26 nmol/l; 3=28 38 nmol/l; 4>38 nmol/l Derived from Reference 48. coronary artery disease and those who did not have coronary artery disease; other studies have reported testosterone levels or to be lower in men with coronary artery disease than in men without coronary artery disease (49 52). Several, but not all, epidemiologic studies have reported higher allcause mortality, particularly cardiovascular mortality, in men with low testosterone levels than in those with normal testosterone levels (53 55). In the Rancho Bernardo Study, men in the lowest quartile of testosterone levels (<241 ng/dl) were 40% more likely to die over the next 20 years than those in the higher quartiles, independent of multiple risk factors, including age, adiposity, and lifestyle (55). Testosterone and Lifespan The relationship of testosterone and human lifespan has not been investigated rigorously. Studies of castrati singers or of castrated institutionalized men with behavioral problems have found no significant differences in their lifespan compared to eugonadal men. Interesting as these studies are, their small sample size and the susceptibility to bias in the selection of historical samples detract from Testosterone and Aging 45

8 Table 2-2. A Qualitative Summary of Intervention Trials of the Effects of Testosterone on Physical Function, Bone Health, and Anemia in Middle-Aged and Older Men Outcomes Subject Populations Summary Findings Caveats Physical Function Bone Anemia Mostly community dwelling, healthy older men with low or low normal testosterone levels; Only a few trials in older men with physical dysfunction, mobility limitation, or frailty Community-dwelling, healthy older men Mostly healthy older without anemia. No trials specifically in anemic older men. Consistent increases in lean body mass and self-reported physical function, and decrease in fat mass; Less consistent increase in maximal voluntary strength and power; Inconsistent or no changes in performance-based measures of physical function Increase in lumbar bone mineral density, but no significant effect on femoral bone density. Consistent increases in hemoglobin and hematocrit Trials characterized generally by small size, inclusion of subjects without functional limitations, heterogeneity of subject populations, testosterone dose and formulations, and measures of muscle performance and physical function; the use of physical function tests with low ceiling or floor. No trials in men with osteoporosis. No trials with fracture as the primary outcome Focus on erythrocytosis as an adverse event rather than on treatment of anemia. No trials in older men with anemia This table presents the authors qualitative assessment of the data from randomized testosterone trials and meta-analyses of randomized testosterone trials in middle-aged and older men. the strength of the inferences that can be drawn from such historical studies. It is remarkable that all models of life span extension that have been investigated, including caloric restriction, have low levels of sex hormones and growth factors. Causality cannot be inferred from epidemiologic studies, which can only suggest guilt by associations. In fact, reverse causality cannot be excluded from cross-sectional studies. Furthermore, the associations between testosterone levels and health-related outcomes are weak, and confounded by the colinearity of age-related co-morbidities and low testosterone levels. It is unclear whether the age-related decline in testosterone is a cause or a consequence of these age-related conditions that have been associated with low testosterone levels. It is possible that testosterone levels are a marker of general health. 46 Translational Endocrinology & Metabolism: Aging Update

9 Table 2-3. A Qualitative Summary of Intervention Trials of the Effects of Testosterone on Sexual Function, Cognitive Function, and Health-related Quality of Life in Middle-Aged and Older Men Outcomes Subject Populations Summary Findings Caveats Sexual Function Cognitive Function Healthrelated Quality of Life Healthy middle-aged and older men; hypogonadal men; middle-aged and older men with sexual dysfunction Mostly healthy older men with low or low normal testosterone; very few trials in Alzheimer s disease or mild cognitive impairment Healthy communitydwelling older men; Few trials in men with symptomatic clinical conditions Improvements in sexual thoughts and motivation; frequency, duration, and amplitude of nocturnal erections; number of successful intercourses, and overall sexual satisfaction in men with low testosterone. No effect on erectile function in men with normal testosterone level. Inconsistent effects on response to PDE5 inhibitors. Inconsistent improvements in some aspects of memory and visuospatial cognition in older men in some trials but not in others. Inconsistent results in men with Alzheimer s disease or mild cognitive impairment. No significant change in overall healthrelated quality of life scores; significant improvements in the physical function domain score Heterogeneity of subject population, inclusion of subjects without sexual dysfunction, wide age range, and varying testosterone doses and formulations. Trials generally characterized by short duration and small sample size, and inclusion of healthy older men. No longterm trials in men with mild cognitive impairment Heterogeneity of subject population; varying testosterone doses, formulations, and treatment durations. HRQOL assessed using generic instruments This table presents the authors qualitative assessment of the data from randomized testosterone trials and meta-analyses of randomized testosterone trials in middle-aged and older men. The Effects of Testosterone Therapy on Muscle Performance and Physical Function In healthy hypogonadal men, testosterone therapy increases fat-free mass and decreases fat mass (10, 56 61), and improves maximal voluntary strength. The administration of supraphysiologic doses of testosterone to Testosterone and Aging 47

10 eugonadal men increases fat-free mass, muscle size, and maximal voluntary strength (62 64). Resistance exercise training augments the anabolic response to androgens (64). The effects of testosterone on fat-free mass, muscle size, and maximal voluntary strength are strongly related to the dose and the on-treatment testosterone concentrations (62 63). Testosterone effects on muscle performance are domain-specific: testosterone administration increases maximal voluntary strength and leg power, but does not affect fatigability (63). Unlike resistance exercise training, which improves the contractile properties of the skeletal muscle, testosterone administration does not change specific force (63). Meta-analyses (56, 67) of placebo-controlled, randomized trials in middle-aged and older men with low or low normal testosterone levels that used testosterone or its esters in replacement doses for >90 days have revealed Testosterone administration that testosterone therapy is associated increases skeletal muscle mass with a significantly greater increase in fatfree mass and grip strength, and a greater but has not been shown to and maximal voluntary strength reduction in fat mass than placebo (65 76). consistently improve performancebased measures of physical Self-reported physical function, as assessed by the SF-36 questionnaire, improved to a function or health outcomes. greater extent in men assigned to testosterone arm than in those assigned to placebo arm (69). Changes in lower extremity muscle strength and performance-based measures of physical function have been inconsistent across trials (65 76). Three recent trials are notable because they recruited older men with physical dysfunction; two trials recruited men with one or more frailty characteristics (e.g., 73, 77), while a third trial recruited men with mobility limitation (76). Srinivas-Shankar et al (73) randomized prefrail or frail older men to either 50-mg testosterone gel or placebo gel for 6 months. The men randomized to testosterone arm experienced greater improvements in isometric knee extension peak torque, lean body mass, and somatic and sexual symptoms than those randomized to placebo arm. Although measures of physical function did not differ significantly between the two arms, they improved in the subgroup of older and frail men (73). In a recent Testosterone in Older Men with Mobility Limitation (The TOM Trial), Basaria et al (76) randomized subjects to either placebo or 10 g testosterone gel daily for 6 months. The testosterone dose was adjusted to achieve testosterone levels between 500 and 1000-ng/dL. The men randomized to testosterone arm experienced greater improvements in leg-press strength, chestpress strength and power, and loaded stair-climbing speed and power than those assigned to placebo arm. A greater proportion of men in the testosterone arm 48 Translational Endocrinology & Metabolism: Aging Update

11 improved more than the minimal clinically important difference for leg-press and chest-press strength and stair-climbing speed than that in the placebo arm. The men in the testosterone arm also experienced a higher frequency of adverse events and cardiovascular-related events than those in the placebo arm, leading the trial s Data and Safety Monitoring Board to recommend enrollment cessation and further administration of study medication (Figure 2-2) (76). The application of testosterone as a function promoting anabolic therapy is based on the premise that its administration will increase muscle mass, that muscle mass gains will translate into proportional gains in muscle strength and power, and that the strength gains will translate into improvements in measures of physical functions that are dependent on muscle strength and power, such as walking and stair climbing. Randomized trials reviewed above are in agreement that testosterone increases muscle mass and strength. However, even substantial increases in lean body mass and leg-press strength during testosterone administration have not been associated with consistent improvements in measures of physical function, such as walking speed (56, 65 77). Additionally, the findings of the TOM Trial have raised concern that frail older persons with high burden of chronic disease may be susceptible to increased risk of adverse events during testosterone administration, especially at high testosterone concentrations Cardiovascular-related Dermatologic Necessating referral Hazard Ratio (95% Cl) FIG Cardiovascular-related events, dematologic events, and medical referrals due to adverse events in a randomized trial of testosterone in older men with mobility limitation. In a randomized testosterone trial in older men with mobility limitation, the frequency of cardiovascular-related events, the dermatologic events, medical referrals for adverse events was significantly higher in men assigned to testosterone arm of the trial than in those assigned to the placebo arm. The numbers of men at risk at various time points are shown at the bottom. Derived from Reference 76. Testosterone and Aging 49

12 (76). Therefore, the therapeutic application of testosterone as a function promoting anabolic therapy is predicated crucially upon the development of strategies, which facilitate the translation of muscle mass and strength gains into functional improvements at lower testosterone concentrations that can be administered safely. Such adjunctive strategies might include physical exercise interventions that emphasize cognitive and behavioral training, or combined administration of testosterone with other anabolic agents such as recombinant human growth hormone. Empiric experience in athletes suggests that task-specific training is necessary for translating the muscle mass and strength gains induced by androgen administration into improvements in performance. Further studies are needed to determine whether physical activity interventions can facilitate the translation of testosterone-induced increases in muscle mass and strength into clinically meaningful gains in physical function and health-related outcomes at lower testosterone doses that can be administered safely. The Effects of Testosterone on Sexual Function Testosterone administration in young hypogonadal men improves many domains of sexual function, including sexual desire, intensity of sexual feelings, sexual fantasies, attentiveness to erotic stimuli, nocturnal penile erections, number of successful intercourses, and overall sexual activity and satisfaction (77 82). Testosterone administration has no significant effect on Testosterone administration erectile function in men with normal testosterone levels (78-80). Although spontane- sexual function in hypogonadal improves many domains of ous erections are testosterone-responsive, men but has no significant effect androgen deficient men are able to achieve on erectile function in men with erections in response to erotic stimulus (81). normal testosterone levels. Testosterone administration increases the amplitude, frequency, and duration of nocturnal erections (82). Androgen deficiency and erectile dysfunction are two separate disorders with distinct pathophysiology which often co-exist in middle-aged and older men (27). Androgen-deficient men also may experience delayed orgasm and low ejaculatory volume. It is possible that androgen deficiency may worsen erectile dysfunction, and normal testosterone levels might be required for achieving optimal penile rigidity (82 86). Testosterone increases penile blood flow, regulates nitric oxide synthase activity in the cavernosal smooth muscle, exerts trophic effects on the cavernosal smooth muscle and ischiocavernosus and bulbospongiosus muscles, and is necessary for the veno-occlusive response (83-86). These data have led to the hypothesis that testosterone therapy would augment erectile response to the administration of selective phosphodiesterase 50 Translational Endocrinology & Metabolism: Aging Update

13 5 inhibitors in men with erectile dysfunction, who have low testosterone levels (84 85). A few trials that have tried to address this question have been inconclusive because of the inclusion of men with normal testosterone concentrations, small trial size, the use of low testosterone doses in some trials which resulted in only small increments in testosterone concentrations, or the failure to exclude men with severe erectile dysfunction. Testosterone Effects on Mood Anecdotally, hypogonadal men report marked improvements in mood, wellbeing and energy after initiation of testosterone therapy. Testosterone therapy of healthy hypogonadal men improves positive aspects of mood and attenuate negative aspects of mood (87). Testosterone trials in men with refractory depression taking anti-depressants have revealed conflicting results (88 89), although some trials have reported benefits in patients with mild depression and dysthymia (90 91). Effects of Testosterone on Cognition Young hypogonadal men have lower scores in verbal fluency, spatial ability, and working memory than eugonadal men (28, 30). Similarly, androgen deprivation therapy in men with prostate cancer is associated with impairments in verbal memory, visual memory, spatial ability, and executive function (92). The few trials that have examined the effects of testosterone on cognitive function in older men, have been characterized by small sample size, variable testosterone levels, varying doses and regimens of testosterone administration, short treatment durations, and the use of a limited battery of cognitive tests (93 97). The results of these trials have generally been inconsistent. In one trial in men with Alzheimer s disease or minimal cognitive impairment, relatively high-dose testosterone improved spatial memory, constructional ability, and verbal memory (97). In other studies of men with mild cognitive impairment and Alzheimer s disease, lower doses of testosterone had little effect on cognitive function (98). Testosterone Effects on the Bone There are no randomized trials data on the effects of testosterone therapy on fracture risk in men. Meta-analyses of relatively small trials of one to three years duration have reported significantly greater increase in lumbar bone mineral density in testosterone arm than in the placebo arm of these trials, but no significant difference in femoral bone density between arms (10, Testosterone and Aging 51

14 99). In general, the trials that used testosterone esters have shown greater increases in bone mineral density than those that used transdermal formulations, presumably due to the higher doses of testosterone delivered by the injections of testosterone esters. The heterogeneity in the results of these trials may reflect differences in study population, testosterone doses and formulations, study duration, and baseline testosterone levels. The aromatization of testosterone to estradiol may be important in mediating the effects of testosterone on the bone; older men treated with a CYP19aromatase inhibitor had lower bone mineral density than those treated with placebo in spite of the higher testosterone levels in anastrozole-treated men (100). Testosterone Effects on Fatigue/Vitality Fatigue is a prevalent symptom amongst older persons. Anecdotally, hypogonadal men report marked improvements in energy and wellbeing after initiation of testosterone therapy (101). Similarly, small trials in HIV-infected men have reported improvements in fatigue (102). The data on the effects of testosterone therapy on fatigue are inconsistent for non-hiv-infected men and need confirmation in large randomized trials. Testosterone Effects on Quality of Life Very few trials have been conducted to determine the effects of testosterone therapy on health-related quality of life in persons with clinical conditions. Metaanalyses of a small number of randomized trials have revealed no significant effects of testosterone therapy on overall health-related quality of life, but have found greater improvements in the physical function domain scores in men assigned to testosterone arm than in those assigned to the placebo arm (10, 56). Testosterone Effects on Anemia Anemia affects ~10-11% of men and women over the age of 65 and 20% of people 85 years of age or older (102), and is associated with fatigue and reduced survival. Although testosterone therapy increases hemoglobin and hematocrit, no randomized trials have been conducted with anemia as the primary outcome (10). Testosterone-induced increases in hemoglobin and hematocrit are greater in older men than in young men (103). The mechanisms by which testosterone increases hematocrit are incompletely understood. Testosterone increases erythropoietin levels, but these increases are transient. The effects of testosterone on erythroid progenitor cells have been inconsistent. Recent studies suggest that testosterone suppresses hepcidin levels and might thereby increase iron availability for erythropoiesis (104). 52 Translational Endocrinology & Metabolism: Aging Update

15 Adverse Effects Associated with Testosterone Therapy in Older Men The adverse events associated with testosterone administration include erythrocytosis, acne, oily skin, and breast tenderness. Meta-analyses of randomized testosterone trials in men with a variety of conditions have found that testosterone administration is associated with greater increases in hemoglobin, hematocrit, and prostate-specific antigens (PSA), and a greater decrease in high-density lipoprotein (HDL) cholesterol level than those associated with placebo (Figure 2-3) (10, ). These effects were most marked in trials enrolling older men using intramuscular tes- Prostate Cancer PSA > 4 Biopsies Prostate Events Hct > 50% Cardiac Events Death Odds Ratio (95% Cl) FIG Meta-analyses of adverse events in randomized testosterone trials in middleaged and older men. A meta-analysis of randomized placebo-controlled, testosterone trials in middle-aged and older men found a significantly higher risk of erythrocytosis and prostate events in men randomized to testosterone arm of the trials than in those randomized to placebo arm. The frequency of prostate cancer or individual prostate events was not significantly different between placebo and testosterone groups. Derived from Reference 105. Testosterone and Aging 53

16 tosterone preparations, presumably due to the typically higher dose of testosterone when testosterone esters are used in comparison to transdermal gels or a patch. Erythrocytosis is the most frequent adverse event associated with testosterone therapy (105). The rates of cardiovascular events, sleep apnea, overall mortality, prostate cancer, lower urinary tract symptom scores, and systolic and diastolic blood pressure did not differ among testosterone- and placebo-treated men (106). The small size of most trials, inconsistent results across trials, and the incomplete reporting of adverse events lower the quality of the evidence. In a separate meta-analysis of randomized testosterone trials in middleaged and older men (105), the men assigned to testosterone arm experienced a higher frequency of prostate events than those assigned to the placebo arm (Figure 2-3). Rates of prostate cancer, PSA >4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between the groups were not individually statistically significant (105). In testosterone trials, the men randomized to testosterone arm are at higher risk of the detection of prostate events, partly because of increased surveillance (10, 105). This is because PSA increments are more likely in testosterone-treated men than in placebo-treated men, and PSA increments may trigger a prostate biopsy (10). Thus, men receiving testosterone are at a greater risk of undergoing prostate biopsy (105) and more likely to be diagnosed with a subclinical prostate disorder than placebo-treated men. A standardized monitoring plan is necessary to minimize the risk of unnecessary prostate biopsy (10). Testosterone Therapy and the Risk of Cardiovascular Events A recent report of increased frequency of cardiovascular events in a testosterone trial in older men with mobility limitation has heightened concern about the long-term effects of testosterone therapy on cardiovascular health in older men with a high burden of chronic conditions (Figure 2-2) (76). As discussed earlier, many, though not all, epidemiologic studies have reported a negative association between testosterone levels and the risk of coronary artery disease and mortality (49 56). Clinical trials data on the effects of testosterone on cardiovascular events are limited. Testosterone undecanoate administration has been reported to improve angina pectoris in men with coronary heart disease (107). Testosterone infusion has been reported to improve coronary blood flow (101). These vasodilatory effects of testosterone are mediated through L type calcium channels (108). The effects of testosterone therapy on vascular reactivity have been inconsis- 54 Translational Endocrinology & Metabolism: Aging Update

17 tent. The recent TOM Trial was stopped early due to a higher frequency of cardiovascular events in men assigned to the testosterone arm than in those assigned to the placebo arm (76). The participants in the TOM Trial were older men (mean age 74) with high prevalence of chronic conditions, such as heart disease, diabetes, obesity, hypertension, and hyperlipidemia. The men assigned to the testosterone arm experienced significantly higher frequencies of total adverse events, and cardiac, respiratory, and dermatologic events than those assigned to the placebo group; these differences persisted after adjustment for baseline risk factors (76). Men 75 years of age or older and men with higher on-treatment testosterone levels appeared to be at greater risk of cardiovascular events. Meta-analyses of randomized testosterone trials have not demonstrated a statistically increased risk of cardiovascular events in men randomized to testosterone than in those assigned to the placebo arm (Table 2-4) ( ). However, these metaanalyses are limited by the small size of most trials, heterogeneity of subject populations, poor quality of adverse event reporting, and short treatment duration in many trials. Most trials recruited healthy older men. Prostate volume is lower in androgen-deficient men than in eugonadal men and testosterone therapy increases prostate volumes to that observed in age matched controls (10). In men with severe lower urinary tract symptoms due to benign prostatic hypertrophy, even small increases in prostate volume during testosterone administration may exacerbate obstructive symptoms. Table 2-4. Meta-analysis of Cardiovascular Events in Randomized Testosterone Trials Trial OR Confidence Intervals Copenhagen Study 1986 (129) to English et al 2000 (107) to Snyder et al 2001 (130) to 5.91 Amory et al 2002 (131) to Amory et al 2004 (132) to Svartberg et al 2004 (133) to Pooled OR to 4.23 A meta-analysis of cardiovascular events in randomized testosterone trials. Most trials did not use standardized definitions of cardiovascular events nor blinded adjudication of the events. Derived from: Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007;82: The numbers in parentheses refer to the citation in the reference list. Testosterone and Aging 55

18 Testosterone and Prostate Cancer Risk There has not been a consistent relationship between testosterone levels and the risk of prostate cancer (109), and there is no evidence that testosterone causes prostate cancer. However, many older men harbor microscopic foci of cancer in their prostates, and there is concern that testosterone therapy might make these subclinical cancers grow (10). Androgen administration also may promote the growth of metastatic prostate cancer (110). Therefore, testosterone therapy is contraindicated in men with metastatic prostate cancer (10). A high prevalence of biopsy-detectable prostate cancer has been reported in men with low testosterone levels, but these studies did not have a control group. As discussed above, the men receiving testosterone therapy are at increased risk of undergoing a prostate biopsy than those assigned to the placebo arm (105). The increase in PSA levels during testosterone therapy and more intensive PSA screening and follow-up of men receiving testosterone might lead to increased number of prostate biopsies and detection of subclinical prostate cancers (10, 105). Dissociating Beneficial Effects from Adverse Effects: Achieving Selectivity of Testosterone s Action Two important insights have emerged from testosterone trials; first, very substantial gains in skeletal muscle mass and strength are achievable with supraphysiologic doses of testosterone, but that the administration of higher doses is limited by the potential for adverse events, especially in older men with high burden of chronic conditions. Therefore, strategies to achieve greater selectivity of action are necessary to realize the beneficial anabolic effects without the undesirable adverse effects. Second, remarkable gains in skeletal muscle mass and strength induced by testosterone administration have not been associated consistently with improvements in physical function measures. Therefore, adjunctive strategies, such as physical activity interventions, or cognitive and behavioral training, might be needed to induce neuromuscular and behavioral adaptations that are necessary for translating muscle strength gains into clinically meaningful improvements in physical function. Three approaches have been used historically to achieve increased selectivity of hormone action: the elucidation of molecular targets in the signaling cascade of hormone action that might provide greater tissue selectivity, the development of selective hormone receptor modulators, and the tissue-specific delivery of hormone. All three strategies are being investigated to achieve increased selectivity of testosterone action. 56 Translational Endocrinology & Metabolism: Aging Update

19 Mechanisms of Androgen Action on the Muscle Elucidation of signaling mechanisms can unveil novel targets for drug discovery, which might provide greater selectivity of action than testosterone. Testosterone-induced increase in muscle mass is largely due to the hypertrophy of type I and II muscle fibers ( ) and associated with dosedependent increases in the number of myonuclei and satellite cells (112). The prevalent view is that testosterone increases muscle mass by stimulating muscle protein synthesis (58, 65 66, 113). Testosterone administration increases nitrogen retention in eunuchoidal men, but not in eugonadal men. Furthermore, the changes in muscle protein synthesis during testosterone administration in men have been inconsistent across trials. Testosterone also has been reported to reduce muscle protein degradation and Testosterone increases skeletal improve the reutilization of amino acids muscle mass by inducing muscle (66). Indeed, in one study, while muscle fiber hypertrophy and by protein synthesis was transiently stimulated after short term testosterone therapy, satellite cells. increasing the number of muscle the net gains in muscle mass at 6-months were associated with significant inhibition of muscle protein degradation, but no change in muscle protein synthesis (66). In a mouse model, orchiectomy was associated with upregulation of muscle atrophy genes (127). The changes in muscle protein metabolism alone do not easily explain the reciprocal loss of fat mass and the increase in satellite cell number observed during testosterone administration, suggesting that additional mechanisms that regulate the proliferation and differentiation of muscle progenitor cells might also be operative (Figure 2-4). To explain the increase in the number of muscle progenitor cells and the reciprocal decrease in whole body and inter-muscular fat mass, we hypothesized that testosterone promotes the differentiation of mesenchymal progenitor cells into the myogenic lineage and inhibits their differentiation into adipogenic lineage. In multipotent C3H10T1/2 cells that express androgen receptor (AR) protein at low levels, co-incubation with testosterone induces AR expression, up regulates the expression of MyoD and myogenin, and promotes the formation of myotubes ( ). Testosterone also promotes myogenic differentiation of human skeletal muscle progenitor cells (116). Testosterone inhibits the adipogenic differentiation of C3H10T1/2, 3T3-L1, and human marrowderived mesenchymal stem cells cells into Oil Red O+ adipocytes, and down regulates the expression of key adipogenic differentiation factors, C/EBP-alpha, peroxisome proliferator-activated receptor gamma (PPARG), ap2 and leptin (114, 117). Testosterone and Aging 57

20 Pluripotent progenitor cell Mesenchimal multipotent stem cell Fat cell lineage Pre-adipocyte progenitor cell β catenin Muscle cell lineage Satellite cell Testosterone IGF-I Pre-adipocyte IGF-I Myoblast Adipocyte Myotube Muscle Protein Synthesis Muscle Protein Degradation Testosterone FIG A Model of Androgen Action on the Skeletal Muscle. Testosterone can potentially affect skeletal muscle mass through multiple mechanisms. Testosterone has been shown to promote myogenic differentiation of multipotent progenitor cells by promoting the association of liganded androgen receptor with beta-catenin and activating Wnt target genes including follistatin. Testosterone also stimulates satellite cell proliferation as well as differentiation; intramuscular IGF-1 and its receptor play an important role in mediating testosterone s effects on satellite cell proliferation and differentiation. Additionally, there are some data, albeit inconclusive, that suggests that testosterone may regulate muscle protein synthesis and protein degradation pathways in differentiated myotubes. Testosterone inhibits adipogenic differentiation of mesenchymal multipotent progenitor cells as well as preadipocytes. Testosterone effects on myogenic differentiation are mediated through an AR-mediated pathway, as they are blocked by bicalutamide. Testosterone requires beta-catenin to increase myogenic differentiation of mesenchimal multipotent cells (115). Testosterone promotes the association of AR with beta-catenin, and the translocation of the AR:beta-catenin complex into the nucleus, where it associates with TCF-4/LEF and activates a number of Wnt-target genes, including follistatin (115). 58 Translational Endocrinology & Metabolism: Aging Update

21 Follistatin is essential for mediating the effects of testosterone on myogenic differentiation, and it cross-communicates the AR-Wnt signal to the TGF-beta// SMAD pathway (115). Follistatin blocks the actions of a number of TGF-beta family members, including myostatin, a powerful inhibitor of muscle growth. In a post-mitotic myocyte-specific AR knockout (marko) mouse, lean body mass is lower than in control mice (118). The weight of the androgensensitive levator ani is significantly reduced ( 46%), whereas the weights of other muscle groups were slightly reduced in marko mice (118). These findings suggest that in addition to its effects on muscle progenitor cells, testosterone affects post-mitotic myocytes. The Role of Growth Hormone and Insulin-Like Growth Factor I in Mediating Anabolic Effects of Testosterone on Androgen-Responsive Muscle Testosterone administration increases circulating growth hormone (GH) and insulin-like growth factor I (IGF-I) and intramuscular IGF-I mrna expression; however, circulating GH and IGF-1 are not essential for mediating testosterone s effects on the muscle (116). Testosterone stimulates the proliferation of human skeletal muscle cells (hskmcs) in vitro, an effect blocked by small interference RNA targeting human IGF-I receptor (sihigf- IR) (116). In differentiation conditions, testosterone promotes the fusion of hskmcs into larger myotubes, an effect attenuated by sihigf-ir. Notably, MKR male mice that express a dominant negative form of the IGF-IR in skeletal muscle fibers, treated with a GnRH antagonist (acycline) to suppress endogenous testosterone, respond to testosterone administration by an attenuated increase in the levator ani muscle mass (116). Thus, intramuscular IGF-I signaling plays an important role in mediating testosterone s effects on skeletal muscle progenitor cell growth and differentiation. Role of Steroid-5-alpha-reductase and CYP19aromatase Testosterone serves as a substrate for conversion to dihydrotestosterone and estradiol by the steroid 5 alpha-reductase and CYP19aromatase, respectively. Experimental models of estrogen deficiency, humans with natural mutations of estrogen receptor-alpha and the CYP19aromatase, and knockout mice harboring null mutations of estrogen receptor-alpha, estrogen receptor-beta, and CYP19aromatase, are characterized by decreased muscle mass and increased adiposity, indicating the important role of estrogens in regulation of body composition (119). Testosterone and Aging 59

Insight into male menopause'

Insight into male menopause' Insight into male menopause' Dr Mark Vanderpump MD FRCP Consultant Endocrinologist Clinics: Tuesday PM Mark Vanderpump Consultant Physician and Endocrinologist Introduction Serum total and free testosterone

More information

Donald W. Morrish, MD, PhD, FRCPC Presented at Mountain Man: Men's Health Conference, May Terry s Testosterone

Donald W. Morrish, MD, PhD, FRCPC Presented at Mountain Man: Men's Health Conference, May Terry s Testosterone Focus on CME at University of Alberta ADAM: Dealing with the Decline Donald W. Morrish, MD, PhD, FRCPC Presented at Mountain Man: Men's Health Conference, May 2005 We now know there is a decline in total

More information

Issues. What is a low testosterone? Who needs testosterone therapy? Benefits/adverse effects of testosterone replacement Treatment options

Issues. What is a low testosterone? Who needs testosterone therapy? Benefits/adverse effects of testosterone replacement Treatment options Male Hypogonadism Jauch Symposium Waterloo, IA May 17, 2013 Janet A. Schlechte, M.D. Disclosure of Financial Relationships Janet A. Schlechte, M.D. has no relationships with any proprietary entity producing

More information

Secrets of Abang Sado : Effects of testosterone therapy. Azraai Nasruddin

Secrets of Abang Sado : Effects of testosterone therapy. Azraai Nasruddin + Secrets of Abang Sado : Effects of testosterone therapy Azraai Nasruddin + Testosterone Testosterone : Steroid hormone - Made primarily by the testicles in males - Small amounts produced by the adrenal

More information

Adverse effects of anabolic androgenic steroids abuse on gonadal function, glucose homeostasis and cardiovascular function

Adverse effects of anabolic androgenic steroids abuse on gonadal function, glucose homeostasis and cardiovascular function Adverse effects of anabolic androgenic steroids abuse on gonadal function, glucose homeostasis and cardiovascular function Associate Professor Caroline Kistorp, Ph.D Department of Internal Medicine, Herlev

More information

The Science of. NUTRICULA Longevity Journal

The Science of. NUTRICULA Longevity Journal 32 December, 2011 The Science of 33 NUTRICULA Longevity Journal As men age, there is often a decline in libido and sexual function. This decline frequently interferes in intimacy within romantic relationships,

More information

Elements for a Public Summary. Overview of disease epidemiology

Elements for a Public Summary. Overview of disease epidemiology VI.2 VI.2.1 Elements for a Public Summary Overview of disease epidemiology Benign prostatic hyperplasia (BPH) (an increase in size of the prostate that is not cancerous) is the most prevalent of all diseases

More information

The Testosterone Quandary. Beth Crowder, PhD, APRN

The Testosterone Quandary. Beth Crowder, PhD, APRN The Testosterone Quandary Beth Crowder, PhD, APRN Objectives Define testosterone, the hypothalamic-pituitary-gonadotrophic axis, and normal blood levels List functions of testosterone and symptoms of low

More information

Jeremiah Murphy, MD Mercy Urology Clinic. October 21, 2017

Jeremiah Murphy, MD Mercy Urology Clinic. October 21, 2017 Jeremiah Murphy, MD Mercy Urology Clinic October 21, 2017 Describe an appropriate strategy for the evaluation and diagnosis of male hypogonadism Endocrine Society Clinical Practice Guideline-2010 Review

More information

UnitedHealthcare Pharmacy Clinical Pharmacy Programs

UnitedHealthcare Pharmacy Clinical Pharmacy Programs UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2017 P 2018-9 Program Prior Authorization/Medical Necessity Topical Androgens Medication Axiron*, Androderm, Androgel*, Fortesta*, Natesto*,

More information

Natural Hair Transplant Medical Center, Inc Dove Street, Suite #250, Newport Beach, CA Phone

Natural Hair Transplant Medical Center, Inc Dove Street, Suite #250, Newport Beach, CA Phone Natural Hair Transplant Medical Center, Inc. 1000 Dove Street, Suite #250, Newport Beach, CA 92660 Phone-949-622-6969 Finasteride (PROPECIA ) Acknowledgement Finasteride is an oral medication, manufactured

More information

Original Research Declining testicular function in aging men

Original Research Declining testicular function in aging men (2003) 15, Suppl 4, S3 S8 & 2003 Nature Publishing Group All rights reserved 0955-9930/03 $25.00 www.nature.com/ijir Original Research 1 * 1 Wesley Woods Health Center, Atlanta, Georgia, USA Age-related

More information

Testosterone Hormone Replacement Drug Class Prior Authorization Protocol

Testosterone Hormone Replacement Drug Class Prior Authorization Protocol Testosterone Hormone Replacement Drug Class Prior Authorization Protocol Line of Business: Medicaid P&T Approval Date: February 21, 2018 Effective date: April 1, 2018 This policy has been developed through

More information

Testosterone Hormone Replacement Drug Class Prior Authorization Protocol

Testosterone Hormone Replacement Drug Class Prior Authorization Protocol Line of business: Medi-Cal Effective Date: August 16, 2017 Revision Date: August 16, 2017 Testosterone Hormone Replacement Drug Class Prior Authorization Protocol This policy has been developed through

More information

TREATMENT OPTIONS FOR MALE HYPOGONADISM

TREATMENT OPTIONS FOR MALE HYPOGONADISM TREATMENT OPTIONS FOR MALE HYPOGONADISM Bruce Biundo, RPh, FACA PCCA Pharmacy Consulting Department Updated July 2012 Hypogonadism in men is primarily a state involving lower than expected levels of testosterone,

More information

Drug Class Monograph

Drug Class Monograph Drug Class Monograph Class: Testosterone Hormone Replacement Drug: Androderm (testosterone transdermal system), Androgel (testosterone topical gel), Axiron (testosterone topical solution), Aveed (testosterone

More information

M0BCore Safety Profile. Pharmaceutical form(s)/strength: 5 mg SE/H/PSUR/0002/006 Date of FAR:

M0BCore Safety Profile. Pharmaceutical form(s)/strength: 5 mg SE/H/PSUR/0002/006 Date of FAR: M0BCore Safety Profile Active substance: Finasteride Pharmaceutical form(s)/strength: 5 mg P-RMS: SE/H/PSUR/0002/006 Date of FAR: 16.05.2014 4.3 Contraindications Finasteride is not indicated for use in

More information

Risks and benefits of testosterone therapy in older men. Matthew Spitzer, Grace Huang, Shehzad Basaria, Thomas G. Travison and Shalender Bhasin

Risks and benefits of testosterone therapy in older men. Matthew Spitzer, Grace Huang, Shehzad Basaria, Thomas G. Travison and Shalender Bhasin Risks and benefits of testosterone therapy in older men Matthew Spitzer, Grace Huang, Shehzad Basaria, Thomas G. Travison and Shalender Bhasin Abstract In young men (defined as age

More information

Androgenes and Antiandrogenes

Androgenes and Antiandrogenes Androgenes and Antiandrogenes Androgens The androgens are a group of steroids that have anabolic and/or masculinizing effects in both males and females. Testosterone [tess-toss-terone], the most important

More information

Associate Professor Geoff Braatvedt

Associate Professor Geoff Braatvedt Associate Professor Geoff Braatvedt Endocrinologist Diabetologist and Physician Green Lane and Auckland City Hospitals Auckland 14:00-14:55 WS #145: Approach to Low Testosterone Values 15:05-16:00 WS #157:

More information

TESTOFEN HUMAN CLINICAL TRIAL GENCOR PACIFIC, INC. Copyright 2006 by Gencor Pacific, Inc.

TESTOFEN HUMAN CLINICAL TRIAL GENCOR PACIFIC, INC. Copyright 2006 by Gencor Pacific, Inc. GENCOR PACIFIC, INC. 920 E. Orangethorpe Avenue, Suite B, Anaheim, CA 92801 Ph: 714.870.8723 714.870.8724 efax: 732.875.0306 drjit@gencorpacific.com gita@gencorpacific.com www.gencorpacific.com TESTOFEN

More information

MI Androgen Deficiency Hypogonadism

MI Androgen Deficiency Hypogonadism MI Androgen Deficiency Hypogonadism WADA TUE Expert Group John A Lombardo, MD October 2014, Columbus, Ohio USA Hypothalamic-Pituitary-Gonadal Axis / 2 Hypogonadism/Androgen Deficiency Clinical syndrome:

More information

Elements for a public summary

Elements for a public summary VI.2 VI.2.1 Elements for a public summary Overview of disease epidemiology Prostate gland enlargement is a common condition as men get older. Also called benign prostatic hyperplasia (BPH) and prostatic

More information

PRODUCT INFORMATION TESTOVIRON DEPOT. (testosterone enanthate)

PRODUCT INFORMATION TESTOVIRON DEPOT. (testosterone enanthate) PRODUCT INFORMATION TESTOVIRON DEPOT (testosterone enanthate) NAME OF THE MEDICINE Testosterone enanthate is designated chemically as 17 beta-heptanoyloxy-4-androstene-3- one. The empirical formula of

More information

Androgens and Anabolic Steroids Prior Authorization with Quantity Limit - Through Preferred Topical Androgen Agent

Androgens and Anabolic Steroids Prior Authorization with Quantity Limit - Through Preferred Topical Androgen Agent Androgens and Anabolic Steroids Prior Authorization with Quantity Limit - Through Preferred Topical Androgen Agent Androgens/Anabolic Steroids Prior Authorization with Quantity Limit Through Preferred

More information

FINASTERIDE (PROPECIA, PROSCAR) SIDE EFFECT & CONSENT FORM

FINASTERIDE (PROPECIA, PROSCAR) SIDE EFFECT & CONSENT FORM 750 West Broadway Street Suite 905 Vancouver, BC M5Z 1K1 FAX: (604) 648-9003 vancouveroffice@donovanmedical.com FINASTERIDE (PROPECIA, PROSCAR) SIDE EFFECT & CONSENT FORM What is finasteride? Finasteride

More information

1001 West Broadway, Vancouver, BC V6H 4B1. Topical Finasteride

1001 West Broadway, Vancouver, BC V6H 4B1. Topical Finasteride 1001 West Broadway, Vancouver, BC V6H 4B1 Topical Finasteride 1 Topical finasteride is a solution containing the drug finasteride typically sold under the brand names Propecia and Proscar. The Finasteride

More information

Robert Perlstein, M.D. Medical Officer. Center for Drug Evaluation and Research. U.S. Food & Drug Administration

Robert Perlstein, M.D. Medical Officer. Center for Drug Evaluation and Research. U.S. Food & Drug Administration -------------------- Robert Perlstein, M.D. Medical Officer Center for Drug Evaluation and Research U.S. Food & Drug Administration -------------------- Sentencing of Food and Drug Offenses Before the

More information

FINCAR Tablets (Finasteride)

FINCAR Tablets (Finasteride) Published on: 10 Jul 2014 FINCAR Tablets (Finasteride) Composition FINCAR Tablets Each film-coated tablet contains: Finasteride USP - 5 mg Dosage Form Tablet Pharmacology Pharmacodynamics Mechanism of

More information

September 17, FDA background documents for the discussion of two major issues in testosterone replacement therapy (TRT):

September 17, FDA background documents for the discussion of two major issues in testosterone replacement therapy (TRT): JOINT MEETING FOR BONE, REPRODUCTIVE AND UROLOGIC DRUGS ADVISORY COMMITTEE (BRUDAC) AND THE DRUG SAFETY AND RISK MANAGEMENT ADVISORY COMMITTEE (DSARM AC) September 17, 2014 FDA background documents for

More information

Nutrition, supplements, and exercise

Nutrition, supplements, and exercise Nutrition, supplements, and exercise Walter R. Frontera, MD, PhD Professor and Chair Department of Physical Medicine and Rehabilitation Vanderbilt University School of Medicine And Medical Director of

More information

Testosterone Effects in Transmen

Testosterone Effects in Transmen Transmen Testosterone Effects in Transmen EFFECT Skin oiliness/acne Facial/body hair growth Scalp hair loss Increased muscle mass/strength Fat redistribution Cessation of menses Clitoral enlargement Vaginal

More information

Chapter 5. General discussion

Chapter 5. General discussion Chapter 5. General discussion 127 Chapter 5 In 2003, two review papers concluded that endogenous androgens do not show any consistent association with cardiovascular disease (CVD) risk 1,2. Apparently,

More information

Medical Policy Testosterone Therapy

Medical Policy Testosterone Therapy Medical Policy Testosterone Therapy Subject: Testosterone Therapy Effective Date: April 2015 Overview: Testosterone cypionate, testosterone enanthate, testosterone undecanoate, and testosterone pellet

More information

Reproductive DHT Analyte Information

Reproductive DHT Analyte Information Reproductive DHT Analyte Information - 1 - DHT Introduction Dihydrotestosterone (DHT) together with other important steroid hormones such as testosterone, androstenedione (ASD) and dehydroepiandrosterone

More information

Dr Tarza Jamal Pharmacology Lecture 2

Dr Tarza Jamal Pharmacology Lecture 2 Contraceptives and androgen hormone Contraceptives: Currently, interference with ovulation is the most common pharmacologic intervention for preventing pregnancy. Major classes of contraceptives 1. Combination

More information

Testosterone Use and Effects

Testosterone Use and Effects Parkland College Natural Sciences Poster Sessions Student Works 2013 Testosterone Use and Effects Brandon Mills Parkland College Recommended Citation Mills, Brandon, "Testosterone Use and Effects" (2013).

More information

PRODUCT INFORMATION PROVIRON

PRODUCT INFORMATION PROVIRON PRODUCT INFORMATION PROVIRON NAME OF TE MEDICINE Mesterolone is a white to yellowish crystalline powder and is practically insoluble in water. The chemical name for mesterolone is 17 beta-ydroxy-1 alpha-methyl-5

More information

Male pattern baldness is the most common type of balding among males. It affects roughly, 50% of men by the age of 50,

Male pattern baldness is the most common type of balding among males. It affects roughly, 50% of men by the age of 50, Dihydrotestosterone (DHT) Male pattern baldness is the most common type of balding among males. It affects roughly, 30% of men by the age of 30, 50% of men by the age of 50, 57% of men by the age of 60.

More information

What is the difference with Whey, Casein, BCAA's, Glutamine, NO products?

What is the difference with Whey, Casein, BCAA's, Glutamine, NO products? Charles Glass - Mr. World / IFBB PRO Senior Executive Vice President Personal Trainers Association (PROPTA) PROPTA Master Trainer about Recov Bipeptides This is the best protein supplement I ever tried

More information

LEUCINE. - A major driving force for Muscle Protein Synthesis

LEUCINE. - A major driving force for Muscle Protein Synthesis LEUCINE - A major driving force for Muscle Protein Synthesis An article by Professor Don MacLaren, 2016. Leucine is one of the 9 essential amino acids that are required to be ingested by the body since

More information

DUPROST Capsules (Dutasteride)

DUPROST Capsules (Dutasteride) Published on: 10 Jul 2014 DUPROST Capsules (Dutasteride) Composition Each soft gelatin capsule contains: Dutasteride... 0.5 mg Dosage Form Capsule Pharmacology Pharmacodynamics Mechanism of Action Dutasteride

More information

PRODUCT INFORMATION PRIMOTESTON DEPOT. (testosterone enantate)

PRODUCT INFORMATION PRIMOTESTON DEPOT. (testosterone enantate) PRODUCT INFORMATION PRIMOTESTON DEPOT (testosterone enantate) NAME OF THE MEDICINE Testosterone enantate is designated chemically as 17 beta-heptanoyloxy-4-androstene-3- one. The empirical formula of testosterone

More information

Laboratoires Dom AVMM (Suisse) Inc. New Innovation in Peptide Therapy for Slimming

Laboratoires Dom AVMM (Suisse) Inc. New Innovation in Peptide Therapy for Slimming Laboratoires Dom AVMM (Suisse) Inc New Innovation in Peptide Therapy for Slimming Globally, Fat Facts 1 billion overweight adults 300 million obese adults A major risk for chronic diseases: Type 2 diabetes

More information

Affirming Care of the Transgender Patient

Affirming Care of the Transgender Patient Mountain West AIDS Education and Training Center Affirming Care of the Transgender Patient Jessica Rongitsch, MD, FACP This presentation is intended for educational use only, and does not in any way constitute

More information

PHYSICIANS CIRCULAR FINASTERIDE PROSCAR. Tablet 5-Alpha Reductase Inhibitor

PHYSICIANS CIRCULAR FINASTERIDE PROSCAR. Tablet 5-Alpha Reductase Inhibitor PHYSICIANS CIRCULAR FINASTERIDE PROSCAR Tablet 5-Alpha Reductase Inhibitor FINASTERIDE (PROSCAR) a synthetic 4-azasteroid compound, is a specific inhibitor of Type II 5α-reductase, an intracellular enzyme

More information

TESTOFEN. Anabolic & Androgenic Activity GENCOR PACIFIC, INC. Fenugreek Extract standardized for FENUSIDE TM. Copyright 2005 by Gencor Pacific, Inc.

TESTOFEN. Anabolic & Androgenic Activity GENCOR PACIFIC, INC. Fenugreek Extract standardized for FENUSIDE TM. Copyright 2005 by Gencor Pacific, Inc. GENCOR PACIFIC, INC. 920E. Orangethorpe Avenue, Suite B, Anaheim, CA. 92801 Ph: 714.870.8723 714.870.8724 efax: 732.875.0306 drjit@gencorpacific.com manu@gencorpacific.com www.gencorpacific.com TESTOFEN

More information

Mens Health Post Puberty. Nayan Patel PharmD

Mens Health Post Puberty. Nayan Patel PharmD Mens Health Post Puberty Nayan Patel PharmD Definition of Androgen Deficiency * Consistently low testosterone * Associated signs/symptoms * Evidence based review of literature * Data is weak at best Definition

More information

CHAPTER XVI PDL 101 HUMAN ANATOMY & PHYSIOLOGY. Ms. K. GOWRI. M.Pharm., Lecturer.

CHAPTER XVI PDL 101 HUMAN ANATOMY & PHYSIOLOGY. Ms. K. GOWRI. M.Pharm., Lecturer. CHAPTER XVI PDL 101 HUMAN ANATOMY & PHYSIOLOGY Ms. K. GOWRI. M.Pharm., Lecturer. Muscle Cell Metabolism Muscle Cells Provide ATP to Drive the Crossbridge Cycle The sources of ATP: Available ATP in the

More information

HGH for Sale Natural Anti-Aging Human Growth Hormone

HGH for Sale Natural Anti-Aging Human Growth Hormone HGH for Sale Natural Anti-Aging Human Growth Hormone Human growth hormone is one of the hottest supplement trends on the market, and now you can purchase top-quality HGH to be delivered right to your home!

More information

Testosterone Topical/Buccal/Nasal

Testosterone Topical/Buccal/Nasal BENEFIT APPLICATION Testosterone Topical/Buccal/Nasal DRUG POLICY Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations

More information

HARVARD PILGRIM HEALTH CARE RECOMMENDED MEDICATION REQUEST GUIDELINES

HARVARD PILGRIM HEALTH CARE RECOMMENDED MEDICATION REQUEST GUIDELINES Generic Brand HICL GCN Exception/Other METHYL ANDROID METHITEST METHYL TESTRED 01404 ROUTE MISCELL. CYPIONATE ENANTHATE GUIDELINES FOR USE ANDRODERM ANDROGEL AXIRON FORTESTA NATESTO STRIANT TESTIM VOGELXO

More information

Growth Hormone & Somatotropin are an Ergogenic Aid

Growth Hormone & Somatotropin are an Ergogenic Aid Growth Hormone & Somatotropin are an Ergogenic Aid BPK 312 MARCH 28 2017 MICHAEL MORKOS PAUL SOURIAL DEL INGVALDSON Table of Contents 1. Hypothesis 2. Clinical Use 3. Mechanism of Action 4. Growth hormone

More information

Leader: Anne Coble Voss, PhD, RD, LD, Abbott Nutrition, Columbus, OH

Leader: Anne Coble Voss, PhD, RD, LD, Abbott Nutrition, Columbus, OH Discussion Leader: Anne Coble Voss, PhD, RD, LD, Abbott Nutrition, Columbus, OH Dr Tisdale: Dr Bosaeus, you suggested that the drive to synthesize acute-phase proteins by the liver was actually driving

More information

SELECT WHEY SOME THOUGHTS ON WHY WHEY PROTEIN CONTINUES TO BE CLINICALLY IMPORTANT

SELECT WHEY SOME THOUGHTS ON WHY WHEY PROTEIN CONTINUES TO BE CLINICALLY IMPORTANT SELECT WHEY SOME THOUGHTS ON WHY WHEY PROTEIN CONTINUES TO BE CLINICALLY IMPORTANT Certainly, a legitimate concern about whey protein supplementation is allergenicity. However, while this concern is warranted,

More information

Chapter 37 (pages ): Hereditary Angioedema and Bradykinin-Mediated Angioedema Prepared by: Sarah Spriet, DO

Chapter 37 (pages ): Hereditary Angioedema and Bradykinin-Mediated Angioedema Prepared by: Sarah Spriet, DO FIT Board Review Corner May 2017 Welcome to the FIT Board Review Corner, prepared by Tammy Peng, MD, and Amar Dixit, MD, senior and junior representatives of ACAAI's Fellows-In-Training (FITs) to the Board

More information

Antiduretic Hormone, Growth. Hormone & Anabolic Steroids

Antiduretic Hormone, Growth. Hormone & Anabolic Steroids Goudarz Sadeghi, DVM, PhD, DSc Associate Professor of Pharmacology University of Tehran Faculty of Veterinary Medicine Veterinary Pharmacology Endocrine System Antiduretic Hormone, Growth Hormone & Anabolic

More information

AFTER nearly six decades of intense controversy (1),

AFTER nearly six decades of intense controversy (1), Journal of Gerontology: MEDICAL SCIENCES 2003, Vol. 58A, No. 12, 1103 1110 Copyright 2003 by The Gerontological Society of America Review Article The Mechanisms of Androgen Effects on Body Composition:

More information

Testosterone as a Therapeutic Tool

Testosterone as a Therapeutic Tool 330 Medicine Update 56 Testosterone as a Therapeutic Tool SV MADHU INTRODUCTION Testosterone preparations have been available for many years and have been used by physicians primarily to treat sexual problems.

More information

MODULE #8 - Lesson 3

MODULE #8 - Lesson 3 MODULE #8 - Lesson 3 21st Century Man: Testosterone and Andropause Module 8 - Lesson 3 21st Century Man: Testosterone and Andropause Testosterone and andropause are 2 pressing issues for men in the 21st

More information

Updates on Anti-doping and TUE Management in Paralympic Sport

Updates on Anti-doping and TUE Management in Paralympic Sport International Paralympic Committee Updates on Anti-doping and TUE Management in Paralympic Sport Matthew Fedoruk, Ph.D. March 15, 2018 PyeongChang 2018 IPC Medical / Sports Science Committee Workshops

More information

Growth Hormone s Impact as a Safe Ergogenic Aid to Increase Body Size

Growth Hormone s Impact as a Safe Ergogenic Aid to Increase Body Size Growth Hormone s Impact as a Safe Ergogenic Aid to Increase Body Size Point Argument: Growth Hormone is a Safe Ergogenic Aid to Increase Body Size Monica Chauhan Carissa Eastwood Emily Lefler Mar. 28,

More information

Relationship between Aerobic Training and Testosterone Levels in Male Athletes

Relationship between Aerobic Training and Testosterone Levels in Male Athletes Relationship between Aerobic Training and Testosterone Levels in Male Athletes Siu Yuen Ng Biology 493 13 th December, 2010 Abstract Salivary testosterone levels of 11 athletes and 15 non athletes were

More information

Male Hormone Replacement Therapy. Punita Dhindsa D.O PGY 2

Male Hormone Replacement Therapy. Punita Dhindsa D.O PGY 2 Male Hormone Replacement Therapy Punita Dhindsa D.O PGY 2 Physiology of Testosterone & Causes of Hypogonadism in Males The use of testosterone therapy is very common in the US, with an estimated 2.3 million

More information

SUMMARY and OBJECTIVES. LOW T- I m half the man I used to be. Prevalence of Low-T. Definition of Hypogonadism 9/19/ Million men in the US

SUMMARY and OBJECTIVES. LOW T- I m half the man I used to be. Prevalence of Low-T. Definition of Hypogonadism 9/19/ Million men in the US SUMMARY and OBJECTIVES LOW T- I m half the man I used to be A discussion of male hypogonadism David Doriguzzi, PA-C Valley Endocrine & Diabetes Consultants Definition Prevalence Causes Signs & Symptoms

More information

Clinical Study Synopsis

Clinical Study Synopsis Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace

More information

Pharmacotherapy of Metabolic Modulation in Acute Burns Mitchell J Daley, PharmD, FCCM, BCPS

Pharmacotherapy of Metabolic Modulation in Acute Burns Mitchell J Daley, PharmD, FCCM, BCPS Pharmacotherapy of Metabolic Modulation in Acute Burns Mitchell J Daley, PharmD, FCCM, BCPS Clinical Pharmacy Specialist, Critical Care Dell Seton Medical Center at the University of Texas and Seton Healthcare

More information

Exam Key. NROSCI/BIOSC 1070 and MSNBIO 2070 Exam # 2 October 28, 2016 Total POINTS: % of grade in class

Exam Key. NROSCI/BIOSC 1070 and MSNBIO 2070 Exam # 2 October 28, 2016 Total POINTS: % of grade in class NROSCI/BIOSC 1070 and MSNBIO 2070 Exam # 2 October 28, 2016 Total POINTS: 100 20% of grade in class 1) An arterial blood sample for a patient at sea level is obtained, and the following physiological values

More information

PRODUCT INFORMATION. Testosterone Phenylpropionate: Testosterone Phenylpropionate is 3-oxoandrost-4-en-17β-yl

PRODUCT INFORMATION. Testosterone Phenylpropionate: Testosterone Phenylpropionate is 3-oxoandrost-4-en-17β-yl PRODUCT INFORMATION SUSTANON '250' NAME OF THE MEDICINE Sustanon '250' ('250' mg/ml for injection): testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, testosterone decanoate.

More information

The ICL Insider. Lab Testing: Testosterone. In This Issue. The Debate

The ICL Insider. Lab Testing: Testosterone. In This Issue. The Debate The ICL Insider February 2017 Volume 2, Issue 2 Lab Testing: Testosterone In This Issue Testosterone shashtilak@iclabs.ca Next Issue: Expected Release April 2017 The Debate Aging is accompanied by various

More information

Use of Performance Enhancing Substances Good Chemistry Gone Bad. Evan M. Klass, M.D., F.A.C.P.

Use of Performance Enhancing Substances Good Chemistry Gone Bad. Evan M. Klass, M.D., F.A.C.P. Use of Performance Enhancing Substances 2017 Good Chemistry Gone Bad Evan M. Klass, M.D., F.A.C.P. Doping the use of banned athletic performance-enhancing drugs by competitors Performance enhancing substances

More information

Icd-10 low levels of testosterone

Icd-10 low levels of testosterone Icd-10 low levels of testosterone The Borg System is 100 % Icd-10 low levels of testosterone 1-10-2017 if your hormone levels are too high or too low, you may have a hormone disorder. Hormone diseases

More information

Female testosterone level chart

Female testosterone level chart Female testosterone level chart The Borg System is 100 % Female testosterone level chart Mar 23, 2015. Male, Female. Age: T Level (ng/dl):, Age: T Level (ng/dl):. 0-5 mo. 75-400, 0-5 mo. 20-80. 6 mos.-9

More information

Package Leaflet: Information for the patient. Sustanon 250, 250 mg/ml, solution for injection (testosterone esters)

Package Leaflet: Information for the patient. Sustanon 250, 250 mg/ml, solution for injection (testosterone esters) Package Leaflet: Information for the patient Sustanon 250, 250 mg/ml, solution for injection (testosterone esters) Read all of this leaflet carefully before you start using this medicine because it contains

More information

Copyright 2009 by UniScience Group Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form.

Copyright 2009 by UniScience Group Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form. Copyright 2009 by UniScience Group Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form. This book is intended to give general information, not personal, one-on-one

More information

Proviron. Proviron Functions & Traits: (Mesterolone)

Proviron. Proviron Functions & Traits: (Mesterolone) Proviron (Mesterolone) Proviron represents one of the oldest anabolic androgenic steroids on the market. A product of the giant pharmaceutical company Schering, it would first appear in 1934. Officially

More information

XYOSTED (testosterone enanthate) injection, for subcutaneous use CIII Initial US approval: 1953 IMPORTANT SAFETY INFORMATION

XYOSTED (testosterone enanthate) injection, for subcutaneous use CIII Initial US approval: 1953 IMPORTANT SAFETY INFORMATION ANTARES PHARMA ANNOUNCES THE COMMERCIAL AVAILABILITY OF XYOSTED (TESTOSTERONE ENANTHATE) INJECTION A NEW TREATMENT FOR ADULT MEN DIAGNOSED WITH TESTOSTERONE DEFICIENCY XYOSTED - A Novel Subcutaneous Testosterone

More information

Medication Policy Manual

Medication Policy Manual Independent licensees of the Blue Cross and Blue Shield Association Medication Policy Manual Topic: Non-preferred, non-transdermal testosterone replacement therapy products (Android, Aveed, Androxy, Methitest,

More information

Protein: Nutrient Timing & Distribution MATT CARLIN & MELANIE MARSHALL

Protein: Nutrient Timing & Distribution MATT CARLIN & MELANIE MARSHALL Protein: Nutrient Timing & Distribution MATT CARLIN & MELANIE MARSHALL Introduction: Nutrient Timing Strategy: maximize exercise-induced muscular adaptations and facilitate repair of damaged tissue Pre-

More information

Anavar For Sale Oxandrolone

Anavar For Sale Oxandrolone Anavar For Sale Oxandrolone Anavar (oxandrolone C 19 H 30 O 3 ) is an anabolic steroid that provides outstanding results. The Anavar steroid is a synthesized version of testosterone that boosts lean muscle

More information

Monitoring Hormone Therapy Mark Newman, M.S. President of Precision Analytical Inc.

Monitoring Hormone Therapy Mark Newman, M.S. President of Precision Analytical Inc. Mr Mark Newman Monitoring Hormone Therapy Mark Newman, M.S. President of Precision Analytical Inc. 2 Avoiding Pitfalls in (B)HRT Monitoring and Picking the Right Lab Test Objectives: Outline how expected

More information

Clinical impact of type I and type II 5 alpha-reductase inhibition in prostatic disease: review and update 아주대학교김선일

Clinical impact of type I and type II 5 alpha-reductase inhibition in prostatic disease: review and update 아주대학교김선일 Clinical impact of type I and type II 5 alpha-reductase inhibition in prostatic disease: review and update 아주대학교김선일 Development of 5ARI Discovery of 5AR type I and type II Pharmacodynamic and pharmacokinetic

More information

DEPO-Testosterone Injection is available in two strengths, 100 mg/ml and 200 mg/ml testosterone cypionate.

DEPO-Testosterone Injection is available in two strengths, 100 mg/ml and 200 mg/ml testosterone cypionate. Depo -Testosterone testosterone cypionate injection, USP CIII DESCRIPTION DEPO-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)- cyclopentylpropionate

More information

Treatment of androgen deficiency in the aging male

Treatment of androgen deficiency in the aging male Treatment of androgen deficiency in the aging male The Practice Committee of the American Society for Reproductive Medicine Birmingham, Alabama Although guidelines for androgen replacement therapy for

More information

New Directions in Aplastic Anemia: What is on the Horizon

New Directions in Aplastic Anemia: What is on the Horizon Case Presentation #1 New Directions in Aplastic Anemia: What is on the Horizon Gabrielle Meyers, MD 62 y/o male, with hypertension, who presented to his PCP for evaluation of fatigue, shortness of breath

More information

Inappropriate Testosterone Billings

Inappropriate Testosterone Billings Inappropriate Testosterone Billings Carla Patrick-Fagan March 30, 2015 Truven Health Analytics Inc. All Rights Reserved. 1 Agenda Proposed in the 2015 analytic plan Steroid prescriptions Code of Federal

More information

Natural estrogens estradiol estrone estriol

Natural estrogens estradiol estrone estriol Estrogens Natural estrogens estradiol estrone estriol Nonsteroidal synthetic Diethylstilbestrol Chlorotrianisene Methallenestril Steroidal synthetic Ethinyl estradiol Mestranol Quinestrol To decrease some

More information

Creatine Versus Anabolic Steroids. Over the past few years, many athletes have been using performance-enhancing

Creatine Versus Anabolic Steroids. Over the past few years, many athletes have been using performance-enhancing Hester 1 Kyle Hester Instructor s Name ENGL 1013 Date Creatine Versus Anabolic Steroids Over the past few years, many athletes have been using performance-enhancing supplements on a regular basis. Two

More information

Lung Volumes and Capacities

Lung Volumes and Capacities Lung Volumes and Capacities Normally the volume of air entering the lungs during a single inspiration is approximately equal to the volume leaving on the subsequent expiration and is called the tidal volume.

More information

This is an English translation of the original Chinese instruction leaflet generated by Google Translate. No amendments were made.

This is an English translation of the original Chinese instruction leaflet generated by Google Translate. No amendments were made. Approved Date: December 26, 2006 Revision Date: September 12, 2012 Modify Date: December 1, 2013 Finasteride tablets instructions Please read the instructions carefully and use under the guidance of a

More information

Gynaecomastia. Benign breast conditions information provided by Breast Cancer Care

Gynaecomastia. Benign breast conditions information provided by Breast Cancer Care Gynaecomastia This booklet tells you about gynaecomastia. It explains what gynaecomastia is, what causes it, how it s diagnosed and what will happen if it needs to be treated or followed up. Benign breast

More information

LIFETIME FITNESS HEALTHY NUTRITION. UNIT 2 Lesson 14 FLEXIBILITY LEAN BODY COMPOSITION

LIFETIME FITNESS HEALTHY NUTRITION. UNIT 2 Lesson 14 FLEXIBILITY LEAN BODY COMPOSITION LIFETIME FITNESS HEALTHY NUTRITION MUSCULAR STRENGTH AEROBIC ENDURANCE UNIT 2 Lesson 14 FLEXIBILITY LEAN BODY COMPOSITION MUSCULAR ENDURANCE Created by Derek G. Becher B.P.E., B. Ed., AFLCA Resistance

More information

Health Products Regulatory Authority

Health Products Regulatory Authority 1 NAME OF THE VETERINARY MEDICINAL PRODUCT Myodine 25 mg/ml solution for injection for dogs and cats 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active substance: Nandrodine laurate 25

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 20 June 2012

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 20 June 2012 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 20 June 2012 CINRYZE 500 units, 2100 IU, powder and solvent for solution for injection B/2 bottles (CIP code: 218

More information

AndroGel. (testosterone gel) 1% H 3 C

AndroGel. (testosterone gel) 1% H 3 C 1 AndroGel (testosterone gel) 1% 500122/500127 Rev Dec 2004 DESCRIPTION AndroGel (testosterone gel) is a clear, colorless hydroalcoholic gel containing 1% testosterone. AndroGel provides continuous transdermal

More information

Month/Year of Review: September 2013 Date of Last Review: December 2009

Month/Year of Review: September 2013 Date of Last Review: December 2009 Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119 Copyright 2013 Oregon State University. All Rights

More information

Dietary supplements and nutrition in sports and exercices performance

Dietary supplements and nutrition in sports and exercices performance Dietary supplements and nutrition in sports and exercices performance Nutrition for endurance sports The most likely contributors to fatigue during an endurance exercise are dehydration and carbohydrates

More information

Skin metabolism of steroid hormones as endogenous compounds?

Skin metabolism of steroid hormones as endogenous compounds? Skin metabolism of steroid hormones as endogenous compounds? Van Luu-The Department of Molecular Medicine Laval University Québec, Canada This work has been supported by L Oréal Research Steroid hormones

More information

Medical Policy An independent licensee of the Blue Cross Blue Shield Association

Medical Policy An independent licensee of the Blue Cross Blue Shield Association Androgens and Anabolic Steroids Page 1 of 57 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Androgens and Anabolic Steroids Prime Therapeutics will review Prior

More information

Buy The Complete Version of This Book at Booklocker.com:

Buy The Complete Version of This Book at Booklocker.com: Maintain youthful libido, sexual function, cardiovascular, bone, muscle, overall health. The Gentleman's Guide to the Fountain of Youth Buy The Complete Version of This Book at Booklocker.com: http://www.booklocker.com/p/books/2056.html?s=pdf

More information