Testosterone and Aging Clinical Research Directions (2004) / Chapter Skim
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2 Testosterone and Health Outcomes
2 Testosterone and Health Outcomes
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From page 32... ...
· What are the health benefits and risks of testosterone therapy? While the questions may seem simple, determining how and to what extent changes in testosterone levels cause or influence clinical outcomes is a complex research challenge.
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From page 33... ...
Additionally, whether total testosterone, free testosterone, bioavailable testosterone, or some combination is the most appropriate measure has been debated. This section highlights the results of several large cohort studies that have compared endogenous testosterone levels among various age groups (Box 2-1~.
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use, others MMAS. Group 1: Stratified by 415 nonobese men obesity with no excess alcohol consumption, self-reported chronic illness, prostatic hypertrophy, history of prostate surgery, prescription meds; Group 2: 1,294 men with at least one of the above as true Cross-sectional analysis: total T decreased linearly with age Longitudinal analysis: significant downward progression of T at every age; no significant differences in rate of decline in T by decade of age T and free T negatively correlated with age (rTotal T = - 0 23; rf T = - 0 30' Age and relative weight were independent predictors of T and free T in multivariable analysis Hormones declined with age at similar slope in 2 groups Free T 1~1.2%/yr; albumin-bound T 1' 1%/yr; total T 1' 0.4%/yr; SHBG 1~ 1.2%/yr T levels significantly and consistently lower in Group 2 Continued
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From page 36... ...
810 men, ratio, cigarettes, ages 24 to 90 in alcohol, caffeine, 1984-1987 exercise, sera storage time; 5-year age groups Hormone levels differed by apparent good health, but trends did not Cross-sectional: SHBG 1~ 1.6%/yr; Total T 1' 0.8%/ yr; Free T and albuminbound T 1' about 2%/yr Within subject: SHBG 1~ 1.3%/yr; Total T 1' 1.6%/ yr; Bioavailable T 1' 2%3/yr Apparent good health added 10%-15% to level of several hormones Total T 1' 1.9 pg/ml/yr age; Bioavailable T 1' 18.5 pg/ml/yr age; Total E 1'0.03 pg/ml/yr age; Bioavailable E2 1' 0.12 pg/ml/yr age NOTE: BLSA = Baltimore Longitudinal Study of Aging; BMI = body mass index; E2 = estradiol; MMAS = Massachusetts Male Aging Study; MRFIT = Multiple Risk Factor Intervention Trial; SHBG = sex hormone binding globulin; T = testosterone.
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From page 37... ...
Numbers in parentheses represent the number of men in each cohort. With the exception of free T index in the ninth decade, segments show significant downward progression at every age, with no significant change in slopes for T or free T index over the entire age range (Herman et al., 2001~.
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From page 38... ...
Apparent good health was associated with higher levels of several hormones, including total testosterone by 10 percent to 15 percent. Among participants in the Multiple Risk Factor Intervention Trial (MRFIT)
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From page 39... ...
. Total testosterone concentrations decreased by approximately 0.19 ng/dL per year of age, and bioavailable testosterone decreased by 1.85 ng/dL per year of age.
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From page 40... ...
outcome sections discusses results from studies of endogenous testosterone levels, followed by a discussion of results from placebo-controlled randomized trials of testosterone therapy in older men. The overview of the literature on endogenous testosterone draws from extensive reviews on this topic and provides tables on selected studies.
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From page 41... ...
Many of the trials assessed multiple outcomes and are discussed in several of the health outcome sections. In subsequent tables in the chapter the results for the placebo-controlled clinical trials are sorted by the mean baseline total testosterone level of study participants and by testosterone preparation used in the trial.
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From page 42... ...
For instance, androgen deprivation therapy for the treatment of prostate cancer has been shown to result in rapid bone loss, and osteopenia and osteoporosis are common in men undergoing this therapy (Dawson, 2003; Smith, 2003~. Despite this clear clinical effect, the mechanisms that underlie bone loss in hypogonadal men are uncertain.
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From page 43... ...
Clinical Trials of Testosterone Therapy and Bone-Related Outcomes Four published, placebo-controlled trials have reported the effect of testosterone therapy on bone turnover markers and bone density in older community-dwelling men with low to low-normal baseline testosterone levels (Table 2-4~. These trials included 13 to 108 men treated from 3 to 36
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From page 44... ...
All but 13 white. 280 controls Some analyses stratified by age; multivariable analyses control for other hormone levels Age, BMI, alcohol and cigarette use, other variables Center et al., 1999 437 community-dwelling Age, weight, men over age 60 other hormones followed for approximately 4 years Fractures Barrett-Connor Rancho Bernardo study.
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From page 45... ...
One trial found that testosterone therapy decreased urinary excretion of hydroxyproline, a nonspecific marker of bone resorption, but did not change measures of nine other bone turnover markers (Tenover, 1992~. Kenny and colleagues (2001)
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aDoses are physiologic, unless otherwise noted. bThis column is intended to provide an overall summary of whether testosterone therapy had positive changes on bone density or bone turnover markers A; no significant changes (+/-~; or negative changes (-)
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From page 47... ...
There are terminology and measurement issues regarding body composition that deserve careful consideration in future clinical trials of testosterone therapy. At the molecular level, two main components of body weight are recognized: fat and fat-free mass.
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T also negatively men age 50 or correlated with body fat older in waist, hip, but not with visceral adipose tissue NOTE: BMI = body mass index; MMAS = Massachusetts Male Aging Study; T = testosterone. free mass.
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From page 49... ...
For example, a small cross-sectional study conducted in Finland compared strength measures and testosterone levels in 9 men 44 to 57 years of age with 11 men 64 to 73 years of age and did not find an association between testosterone levels and muscle strength (Hakkinen and Pakarinen, 1993~. Clinical Trials of Testosterone Therapy and Body Composition and Strength Body Composition Twelve placebo-controlled trials have examined body composition measures in response to exogenous testosterone.
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, 44 12 months Decrease healthy, all received vitamin Two 2.5 mg patches in lean bc D and calcium daily no differs groups Snyder et al., l999b Age >65, (mean 73) , healthy 108 36 months Increase i 6 mg scrotal patch mass (am daily significan measures
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From page 51... ...
and decrease in fat + mass (arms and legs) compared to controls; no significant differences in changes in strength measures (knee extension or flexion, hand grip strength)
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aDoses are physiologic, unless otherwise noted. bThis column is intended to provide an overall summary of whether there were positive improvements in body composition measures with testosterone therapy A; no significant changes (+ /-~; or negative changes (-)
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From page 53... ...
Decrease in uptake and significant increase in turnover rate of triglycerides in abdominal but not femoral subcutaneous adipose tissue + Increase in grip strength compared with baseline in NA T-treated group NA This column is intended to provide an overall summary of whether there were positive improvements in strength measures with testosterone therapy (id; no significant changes (+/-~; or negative changes (-) as compared with placebo controls.
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From page 54... ...
Ten placebo-controlled trials assessed changes in muscle strength with testosterone treatment, including many of the clinical trials discussed above. Thus, the populations, sample sizes, duration of treatment, and types of interventions were similar to those that examined body composition outcomes (Table 2-6~.
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There is increasing evidence to suggest that declines or dysregulation TABLE 2-7 Physical Functioning in CommunityDwelling Men, 70 Years and Older, U.S. Perform with Unable to Difficulty (%)
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Clinical Trials of Testosterone Therapy and Physical Function Five placebo-controlled trials have examined physical function outcomes in studies of testosterone therapy in older men (Table 2-8~. Three of TABLE 2-8 Randomized Placebo-Controlled Trials of Testosterone Therapy and Physical Function in Older Men Reference Population; Age (years)
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The results of the randomized trials are mixed. The two trials noting improvement in the testosterone-treated group, as compared with placebo controls, were in men with low testosterone levels at baseline or men who were ill.
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From page 58... ...
Physical function is an area that has not been widely studied in relationship to testosterone therapy, and although the results of the few randomized trials to date are inconsistent, this is an area that deserves further exploration as it is an important outcome to aging men and is related to several potential intermediates of the effects of testosterone such as strength (as well as many other risk factors)
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From page 59... ...
Clinical Trials of Testosterone Therapy and Cognitive Function Five placebo-controlled trials in older men have examined the effect of treatment with testosterone on cognitive function (Table 2-10~. The trials were small and of short duration, including 19 to 56 participants followed for 12 months or less.
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. No randomized trials have evaluated the effect of testosterone therapy among men with impaired cognitive function or at risk for developing dementia.
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From page 61... ...
of therapy required to produce optimal beneficial effects on cognitive function remain to be determined. MOOD AND DEPRESSION Although depression is not a normal part of aging, certain medical conditions such as stroke, cancer, diabetes, heart disease, and Parkinson's disease are associated with increased risk for depression (NIMH, 2003b)
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From page 62... ...
was reported with decreasing bioavailable testosterone after controlling for age, change in body weight, and regular exercise; however, no significant associations were found between BDI scores and total testosterone. In the Massachusetts Male Aging Study, Gray and colleagues (199lb)
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From page 63... ...
and anger expression measures; positive correlation between dominance and albumin-bound T and free T NOTE: MMAS = Massachusetts Male Aging Study; T = testosterone. Clinical Trials of Testosterone Therapy and Mood and Depression Eleven placebo-controlled trials in older men have examined the effect of testosterone therapy on mood and depression (Table 2-12~.
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From page 64... ...
IM weekly Pope et al., 2003 Age 30-65 (mean 47) with treated 19 8 weeks but refractory depression 10 g 1% g adjusted Studies of Men with Normal Baseline Total Testosterone Levels Schiavi et al., 1997 Age 46-67 (median 60)
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From page 65... ...
TESTOSTERONE AND HEALTH OUTCOMES one 65 Duration; Dosage a Results fob 22 19 77 70 29 19 12 29 5 months 100 mg or 400 mg TE IM every 4 weeks 12 months 200 mg TC IM every 14-17 days 1 month 150 mg TE IM weekly No change in mood measured by POMS No effects on Yesavage Geriatric Depression Scale No significant change in measures of mood 6 week discontinuation trial Participants randomized to placebo after 4 200 mg TC IM once, then 400 weeks of T treatment showed decrements in mg TC IM biweekly, adjusted depression measures compared with during as needed T treatment 6 weeks 200 mg TC IM once, then 400 mg TC IM biweekly, adjusted as needed 6 weeks 200 mg TE IM weekly 8 weeks 10 g 1% gel daily, then adjusted 6 weeks 200 mg TE IM biweekly 8 weeks 120 mg TU orally daily +/— Significant improvement in measures of + depression (Ham-D score and BDI) No difference in depression measures (Ham-D)
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From page 66... ...
IM weekly Janowsky et al., 1994 Age 60-75 (mean 67) , healthy 56 3 months 15 mg scrap 16 hours/c NOTE: BDI = Beck Depression Inventory; CGI = Clinical Global Impression score; GDS-SF = Geriatric Depression Score, Short Form; Ham-D = Hamilton Depression Rating Scale; HIV = human immunodeficiency virus; IM = intramuscular; POMS = Profile of Mood States; T = testosterone; TC = testosterone cypionate; TE = testosterone enanthate; TU = testosterone undecanoate.
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From page 67... ...
In the analysis of this survey, sexual dysfunction was generally associated with poor physical and emotional health. Erectile dysfunction (ED)
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From page 68... ...
Studies of Endogenous Testosterone Levels and Sexual Function As mentioned above, the testosterone concentrations needed to maintain normal sexual activity appear to be low, and it is therefore not unexpected that only a weak correlation has been found between testosterone levels and libido or sexual activity in many studies of healthy men (reviewed in Matsumoto, 2002~. In general, studies report stronger associations between measures of sexual frequency, desire, and erections with aging, than with sex hormone levels (including total testosterone and free testosterone)
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From page 69... ...
Clinical Trials of Testosterone Therapy and Sexual Function Measures of sexual function have been studied in 10 placebo-controlled trials of testosterone therapy (Table 2-14~. Eight of the trials administered testosterone for five months or less.
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From page 70... ...
, 23 8 months slightly to moderately obese 80 mg ora`^ NOTE: HIV = human immunodeficiency virus; IM = intramuscular; T = testosterone; TC = testosterone cypionate; TE = testosterone enanthate; TU = testosterone undecanoate. aDoses are physiologic, unless otherwise noted.
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From page 71... ...
TESTOSTERONE AND HEALTH OUTCOMES one 71 Duration; Dosage a Results fob 5 months 100 mg or 400 mg TE IM every 4 weeks 4 months 80 mg TU orally twice daily 10 70 29 13 108 12 29 12 weeks 200 mg TC IM every 2 weeks 6 weeks 200 mg TC IM once, then 400 mg TC IM biweekly, adjusted as needed 6 weeks 200 mg TE IM weekly 3 months 100 mg TE IM weekly 36 months 6 mg scrotal patch daily 6 weeks 200 mg TE IM biweekly 8 weeks 120 mg TU orally daily 8 months 80 mg oral TU twice daily Increase in frequency of erection + Improvement in sexual activity and desire + increase in reported sexual activity, urge for sex, morning/sleep erections, potency, and libido Increased libido and morning erections + + Marginal improvement in sexual function, + activity, and satisfactory measures 12 of 13 patients correctly predicted T therapy, +/ in part because of an increase in libido No significant difference in responses to sexual function questionnaire between groups Increase in reported ejaculation frequency; + no effects on erection or sexual satisfaction No significant difference in reported erectile dysfunction Increased sexual desire reported by 5 of 11 in T-treated group versus 1 of 12 on placebo improvements in sexual function with testosterone therapy (+~; no significant changes (+/-~; or negative changes (-) as compared with placebo controls.
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From page 72... ...
Since both trials are small and used different testosterone interventions, it is not possible to reach definitive conclusions on the effect of testosterone therapy on erectile dysfunction. A number of additional studies have found increases in measures of sexual interest, arousal, and other aspects of sexual function with testosterone therapy (Appendix C)
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From page 73... ...
Several additional studies in hypogonadal males using comparison with baseline measures found improvements in quality of life indicators, but did not use placebo controls (Appendix C; Wang et al., 1996; Snyder et al., 2000; Cutter, 2001~. The randomized trials that found positive results were conducted in populations of men with chronic health concerns or low baseline testosterone levels.
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From page 74... ...
, healthy 44 12 month Two 2.5 ~ Snyder et al., l999b Age >65, mean 73, healthy 108 36 month 6 mg scrot Studies of Men with Normal Baseline Total Testosterone Levels Marin et al., 1992 Age >45 (mean52C) , 23 8 months abdominally obese 80 mg ora`^ NOTE: HRQoL = Health-related Quality of Life; HIV = human immunodeficiency virus; IM = intramuscular; PGWB = Psychological General Well Being scale; PSDI = Positive Symptom Distress Index; Q-LES-Q = Endicott Quality of Life Enjoyment and Satisfaction Questionnaire; SF-36 = Short Form 36 item; T = testosterone; TE = testosterone enanthate; TU = testosterone undecanoate.
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From page 75... ...
+/Improvement in 1 of 8 SF-36 domains: perception of physical function; no significant change in perception of energy + Increase in "well-being," trend toward + "feeling of improved energy" bThis column is intended to provide an overall summary of whether there were positive improvements in the assessment of health-related quality of life with testosterone therapy (+~; no significant changes (+/-~; or negative changes (-) as compared with placebo controls.
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From page 76... ...
Studies of Endogenous Testosterone Levels and Cardiovascular and Hematologic Outcomes Studies of endogenous testosterone levels have looked at a variety of cardiovascular risk factors with mixed results (Table 2-16~. A number of epidemiologic studies have found positive correlations between total or free testosterone levels in the physiologic range and high density lipoprotein (HDL)
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From page 77... ...
with no variables included levels; SBP, cholesterol, coronary artery age, BMI, total age differentiated groups disease, compared cholesterol, with 46 men with hormone levels CAD (age 41-92) Zmuda et al., 1997 MRFIT.
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From page 78... ...
per -1 SD 40-70, followed 7-10 years Cross-Sectional Study Barrett-Connor, 1992 Rancho Bernardo Tobacco and Diabetic men had study. 44 cases alcohol use; significantly lower total T noninsulin controls matched and free T controlling for dependent DM; on age and time tobacco and alcohol use 88 controls of visit 1984-1987 NOTE: BLSA = Baltimore Longitudinal Study of Aging; bp = blood pressure; BMI = body mass index; CAD = coronary artery disease; DBP = diastolic blood pressure; DM = diabetes mellitus; IMT = intima-media thickness; MMAS = Massachusetts Male Aging Study; MRFIT = Multiple Risk Factor Intervention Trial; OR = odds ratio; SHBG = sex hormone-binding globulin; SOP = systolic blood pressure; SD = standard deviation; T = testosterone.
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From page 79... ...
(Khaw and Barrett-Connor, 1988~. Clinical Trials of Testosterone Therapy and Cardiovascular and Hematologic Outcomes The higher prevalence of heart disease in men compared to premenopausal women has led to an historical identification of the lack of estrogen and the presence of testosterone as risk factors for coronary artery disease.
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From page 80... ...
Lipid Profile Thirteen randomized trials have compared various measures of cholesterol levels in older men treated with testosterone or placebo with mixed results. Eight of the 13 trials found no effect on the lipid profile in comparisons of the testosterone-treated group with their baseline measures or with controls.
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From page 81... ...
PROSTATE OUTCOMES Concerns regarding the risks of testosterone therapy have focused primarily on the potential for increased incidence of prostate cancer and benign prostatic hyperplasia (BPH)
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From page 82... ...
82 TESTOSTERONE AND AGING TABLE 2-17 Randomized Placebo-Controlled Trials of Testosterone Therapy and Cardiovascular or Hematologic Outcomes in Older Men Reference Population; Age (years) N Duration; Dosage a Results Studies of Men with Frankly Low Baseline Total Testosterone Levels Sihet al., 1997 Mean age 65,healthy 22 12 months No effect 200 mg TC LDL, HD IM every 14-17 days Bhasin et al., 1998b Age 18-60, HIV positive 32 12 weeks No signif Two 2.5 mg patches from bass daily and hems Simon et al., 2001 Mean age 53 18 3 months No effect 125 mg gel at first, increase i then adjusted T-treated Studies of Men with Low to Low-Normal Baseline Total Testosterone Levels Amory et al., 2002 Age 58-86 (mean 70)
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From page 83... ...
; increase in hematocrit and hemoglobin from baseline in T-treated group +/— No significant change in total cholesterol, LDL; trend +/ toward decreased HDL after 14 days; increase in hematocrit No significant hematocrit change in either group NA No effect on total cholesterol; increase in hemoglobin in +/ T-treated group compared to baseline 2 of 8 men in T-treated group developed hematocrits >51% NA No effect on lipid profile (total cholesterol, HDL, LDL) ; +/ increased hematocrit Significant decrease in total cholesterol and LDL; nonsignificant trend to decreased HDL; increase in hematocrit, hemoglobin, red cell count at 3 months (2 men's hematocrit >50%)
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From page 84... ...
bThis column is intended to provide an overall summary of whether there were positive improvements in cardiovascular risk factors (most often lipid profiles) with testosterone therapy (+~; no significant changes (+/-~; or negative changes (-~.
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From page 85... ...
; increase in hematocrit and hemoglobin at 6 months, then stable (3 men's hematocrit >52%) in T-treated group +/ - +/— Decrease in total cholesterol in T-treated group compared + NA to baseline; no significant change in HDL or TG compared vice daily to baseline in either group Decrease in TG and total cholesterol in T-treated group + NA daily" compared to baseline, no effect on HDL eeks No elevation in hemoglobin >15 mg/dL NA E Decrease in sum of ST segment depression in multiple + IM weekly leads in T-treated group; increase in hematocrit and hemoglobin at 4 and 8 weeks in T-treated group CThis column is intended to provide an overall summary of whether there were positive improvements in hematocrit with testosterone therapy I; no significant changes (+/-~; or negative changes (-I.
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From page 86... ...
Autopsy studies have documented the histological prevalence of prostate carcinoma in more than 30 percent of men older than 60 years, and higher rates with advancing age (Holund, 1980; Sakr et al., 1993; Etzioni et al., 2002; NCI, 2003~. The complexities that subclinical prostate cancers present for conducting clinical trials of testosterone therapy in older men are discussed in Chapter 3.
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From page 87... ...
the vast majority of prostate carcinoma cells require androgens for their continued growth and avoidance of programmed cell death. At diagnosis, the majority of prostate cancers are dependent on androgens for growth, and the elimination of AR ligands by surgical or chemical castration leads to marked tumor regression through a mechanism of apoptosis (Denmeade et al., 1996~.
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From page 88... ...
Population-based studies clearly document the relationship between aging and both increases in prostate cancer incidence rates and decreases in circulating testosterone levels. While this relationship does not equal causality, the findings do raise intriguing hypotheses regarding the influence of testosterone on inhibiting prostate carcinogenesis (Prehn, 1999~.
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From page 89... ...
These results support the need for continued research aimed toward a clear delineation of the positive and negative effects of testosterone and testosterone metabolites on prostate carcinoma. Studies of Endogenous Testosterone Levels and Prostate Outcomes A number of epidemiological studies have examined the risk of prostate cancer associated with a variety of factors, including serum hormone levels (Table 2-18~.
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From page 90... ...
or approximately albumin-bound T and 9 years prostate cancer at p = 0.01 Carter et al., 1995 BLSA. Of men over Age No differences in age 60,16 men measures and with no prostatic development of prostate disease; 20 with diseases BPH; 20 with prostate cancer Barrett-Connor Rancho Bernardo Age, BMI No association found et al., 1990 study.
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From page 91... ...
T; no trend of risk with increasing T levels NOTE: BLSA = Baltimore Longitudinal Study of Aging; BMI = body mass index; BPH = benign prostatic hypertrophy; E2 = estradiol; MMAS = Massachusetts Male Aging Study; OR = odds ratio; PSA = prostate-specific antigen; RR = relative risk; SBP = systolic blood pressure; SHBG = sex hormone-binding globulin; T = testosterone. the Physicians Health Study identified 520 cases of prostate cancer by 1992, of which 222 men had plasma samples stored that were sufficient for sex hormone determination.
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From page 92... ...
No significant increase was seen in the placebo group. Three men receiving testosterone therapy and one receiving placebo had persistent increases in PSA levels above 4.0 ng/mL and required a biopsy.
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From page 93... ...
Several noncontrolled studies of hypogonadal men found some evidence of increases in disordered breathing events during testosterone therapy but with wide variability in the extent of sleep disturbances between individuals (Appendix C)
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From page 94... ...
IM every Clague et al., 1999 Age 60+, healthy; normal PSA, 14 12 weeks rectal exam, and urine flow rate 200 mg T] IM every Ferrando et al., 2002 Age 64-71, healthy; PSA<4.0, no 12 6 months history of prostate cancer TE IM we then biwee Tenover, 1992 Age 57-76, healthy; no history of 13 3 months prostate disease 100 mg T]
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From page 95... ...
TESTOSTERONE AND HEALTH OUTCOMES one 95 Duration; Dosagea Results fib 22 32 18 22 74 14 12 13 37 46 44 12 months 200 mg TC IM every 14-17 days 12 weeks Two 2.5 mg patches daily 3 months 125 mg gel at first, then adjusted 4 weeks 600 mg TE IM 21, 14, 7, and 1 day(s) before surgery 26 weeks 100 mg TE IM every 2 weeks 12 weeks 200 mg TE IM every 2 weeks 6 months TE IM weekly for 1 month, then biweekly, adjusted doses 3 months 100 mg TE IM weekly 2 months 120 mg TU orally daily 12 weeks Two 2.5 mg patches daily 12 months Two 2.5 mg patches daily No significant change in PSA levels compared + /to controls; no nodules detected No significant change in PSA levels in either group; no difference between groups No significant change in PSA levels compared to controls; 1 case of benign nodular hypertrophy No significant change in PSA level in either group; no increase in symptoms of urinary retention No significant change in PSA levels in either groups; no significant change in IPSS scores or reports of prostatism symptoms +/— +/— No significant change in PSA levels in either +/group No significant change in PSA levels in either group; no change in prostate volume or urinary flow rate Increase in PSA from baseline in T-treated group; no significant change in prostate size or urine postvoiding residual measurements No patients complained of changes in urination patterns No significant change in PSA levels in either group Increase in PSA levels in T-treated group vs.
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From page 96... ...
prostate cancer IM weekly Holmang et al., 1993 Age 40-65 (median 52) , slightly 23 8 months to moderately obese 80 mg ore Marin et al., 1992 Age >45 (mean 526, abdominally 23 8 months obese; no enlarged prostate 80 mg oral TU to Marin et al., 1993, 1995 Mean age 58, abdominally obese; 27 9 months prostate not enlarged, PSA < 3.0 ,ug/1 125 mg ge' Studies in Which the Baseline Testosterone Level Is Not Reported Bakhshi et al., 2000 Age 65-90, ill, admitted to rehab 15 up to 8 w unit; PSA <4.5, no recurrent prostatitis 100 mg T]
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From page 97... ...
eOne patient's PSA increased from 3.5 to 4.1 ng/mL and was discontinued from the study. fMean age for the testosterone-treated group.
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From page 99... ...
Testosterone treatment increases hematocrit, but there is no definitive evidence of other risks. The potential for testosterone therapy to increase risk for symptomatic prostatic hypertrophy and prostate cancer is of major concern, but quantifying these risks will require randomized trials that include large numbers of men followed for multiple years.
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From page 100... ...
2003. What Are the Key Statistics About Prostate Cancer?
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From page 101... ...
1995. Longitudinal evaluation of serum androgen levels in men with and without prostate cancer.
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From page 102... ...
2002. The role of androgens and the androgen receptor in prostate cancer.
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From page 103... ...
1999. Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies.
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From page 104... ...
1996. Prospective study of sex hormone levels and risk of prostate cancer.
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From page 105... ...
1993. Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer.
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From page 106... ...
2003. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy.
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From page 107... ...
Prediagnostic serum hormones and the risk of prostate cancer. Cancer Research 48~12~:3515-3517.
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From page 108... ...
1999. Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism.
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From page 109... ...
2000. Hormonal predictors of prostate cancer: a meta-analysis.
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From page 110... ...
1997. Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.
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From page 111... ...
1993. Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3)
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