American Urological Association (AUA) 2014 Annual Scientific Meeting Abstracts
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American Urological Association Meeting Abstracts
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Exercise improves the effect of testosterone replacement therapy and the durability of response after cessation of treatment
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-02
Introduction and Objectives - The effect of the combination of exercise and testosterone replacement therapy (TRT) on the symptoms of late-onset hypogonadism (LOH) and the durability of response after cessation of TRT was investigated.
Methods - Total 50 ED patients who had sedentary lifestyle with low serum total testosterone levels were consecutively enrolled and followed for 20 weeks. The patients were randomly divided into two groups and all of them received testosterone (T) gel once daily for 12 weeks and then, it was discontinued for 8 weeks. The 25 patients assigned to group II were offered supervised physical activity program over 3 times per week for 20 weeks combined with TRT. Measurement of BMI and serological tests were performed during the first visit, followed by another measurement after 12 weeks and 8 weeks after cessation of treatment (at 20th week). Self-assessment questionnaires (IIEF and AMS) were used to evaluate the symptom severity and the GAQ (Has there been any improvement in your erectile function since the start of therapy?) was asked.
Results - The baseline characteristics and the initial symptom scores showed no significant difference between two groups. In group II, BMI was decreased significantly at 12th week and maintained until 20th week. But, there was no significant decrease of BMI in group I. Serum total T levels were significantly increased at 12 weeks in both groups. Increase of T levels in group II was greater than group I. There was significant decrease of T levels at 20 weeks compared to the 12th week in both groups and the T levels of group II was significantly higher than group I. Decrease of total T level after cessation of treatment was greater in group I than group II. Mean total scores of IIEF and AMS scale were significantly improved after 12 weeks of treatment in both groups. In comparison between two groups, group II showed better symptom score than group I. At 20th week, both groups showed worsened symptom scores compared to the 12th week. In comparison between two groups, group II showed better symptom scores than group I. On the GAQ, 77.3% of group I and 94.4% of group II stated the improvement of erectile function. At 20th week, the ratio of both groups decreased into 45.5% and 72.2%, respectively with significant difference between two groups.
Conclusions - The combination of exercise and TRT showed significant improvements in serum T level and LOH symptoms compared to the monotherapy group. Additionally, these improvements were well sustained in the combination group with continuous exercise, even after the cessation of TRT.
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-02
Introduction and Objectives - The effect of the combination of exercise and testosterone replacement therapy (TRT) on the symptoms of late-onset hypogonadism (LOH) and the durability of response after cessation of TRT was investigated.
Methods - Total 50 ED patients who had sedentary lifestyle with low serum total testosterone levels were consecutively enrolled and followed for 20 weeks. The patients were randomly divided into two groups and all of them received testosterone (T) gel once daily for 12 weeks and then, it was discontinued for 8 weeks. The 25 patients assigned to group II were offered supervised physical activity program over 3 times per week for 20 weeks combined with TRT. Measurement of BMI and serological tests were performed during the first visit, followed by another measurement after 12 weeks and 8 weeks after cessation of treatment (at 20th week). Self-assessment questionnaires (IIEF and AMS) were used to evaluate the symptom severity and the GAQ (Has there been any improvement in your erectile function since the start of therapy?) was asked.
Results - The baseline characteristics and the initial symptom scores showed no significant difference between two groups. In group II, BMI was decreased significantly at 12th week and maintained until 20th week. But, there was no significant decrease of BMI in group I. Serum total T levels were significantly increased at 12 weeks in both groups. Increase of T levels in group II was greater than group I. There was significant decrease of T levels at 20 weeks compared to the 12th week in both groups and the T levels of group II was significantly higher than group I. Decrease of total T level after cessation of treatment was greater in group I than group II. Mean total scores of IIEF and AMS scale were significantly improved after 12 weeks of treatment in both groups. In comparison between two groups, group II showed better symptom score than group I. At 20th week, both groups showed worsened symptom scores compared to the 12th week. In comparison between two groups, group II showed better symptom scores than group I. On the GAQ, 77.3% of group I and 94.4% of group II stated the improvement of erectile function. At 20th week, the ratio of both groups decreased into 45.5% and 72.2%, respectively with significant difference between two groups.
Conclusions - The combination of exercise and TRT showed significant improvements in serum T level and LOH symptoms compared to the monotherapy group. Additionally, these improvements were well sustained in the combination group with continuous exercise, even after the cessation of TRT.
Predictors of Poor Response to Transdermal Testosterone Therapy in Men with Metabolic Syndrome
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-04
Introduction and Objectives - Testosterone replacement therapy (TRT) is approved for treatment of male hypogonadism, but TRT may be beneficial in hypogonadal men with metabolic syndrome. Anecdotal observations indicate that adiposity is associated with a reduced frequency of men reaching a eugonadal state. We have collected metabolic data on a cohort of men receiving transdermal TRT (T-TRT) to identify predictors of response to T-TRT.
Methods - We reviewed 58 consecutive patients with metabolic data and hypogonadism presenting to a male reproductive medicine practice. Patients received a physical examination and a full hormonal evaluation including total testosterone (TT) measured using liquid chromatography–mass spectrometry (LC/MS). All men initiated 50mg daily transdermal testosterone. Multivariate logistic regression assessed predictors of failure to reach eugonadal (TT=350ng/dL or free testosterone(FT)=65 pg/mL) status at most recent follow-up (median 21.2 months). Non-obese patients had BMI<30 (Group 1, n=32). Obesity was defined as BMI>30 (Group 2, n=26).
Results - Baseline age, primary diagnosis, and blood pressure were similar in each group (P>0.05). Initial FT, TT, follicle-stimulating hormone (FSH), cholesterol, and hemoglobin A1c (HbA1c) were also similar between groups (P>0.05). At the end of the study period, more non-obese men attained eugonadal testosterone levels than obese men (FT-81% vs 52% (P=0.03) and TT-81% vs 54% (P=0.018)). On multivariate logistic regression, age and obese BMI were predictive of final FT <65pg/mL (P=0.03 and 0.043). HbA1c >6.4 (diagnostic criteria for diabetes mellitus) predicted TT<350ng/dL (P=0.042). Response to therapy (final TT) was independent of baseline FT and TT in both univariate and multivariate models.
Conclusions - Hypogonadal men with diabetes and obesity are less likely to achieve normal free and total testosterone levels on topical testosterone therapy relative to non-obese, non-diabetic men. This relationship occurred independent of baseline hormone profile. The underlying mechanisms and optimal management of failure to respond to T-TRT needs to be determined. Health care practitioners and patients should aware of predictors of response.
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-04
Introduction and Objectives - Testosterone replacement therapy (TRT) is approved for treatment of male hypogonadism, but TRT may be beneficial in hypogonadal men with metabolic syndrome. Anecdotal observations indicate that adiposity is associated with a reduced frequency of men reaching a eugonadal state. We have collected metabolic data on a cohort of men receiving transdermal TRT (T-TRT) to identify predictors of response to T-TRT.
Methods - We reviewed 58 consecutive patients with metabolic data and hypogonadism presenting to a male reproductive medicine practice. Patients received a physical examination and a full hormonal evaluation including total testosterone (TT) measured using liquid chromatography–mass spectrometry (LC/MS). All men initiated 50mg daily transdermal testosterone. Multivariate logistic regression assessed predictors of failure to reach eugonadal (TT=350ng/dL or free testosterone(FT)=65 pg/mL) status at most recent follow-up (median 21.2 months). Non-obese patients had BMI<30 (Group 1, n=32). Obesity was defined as BMI>30 (Group 2, n=26).
Results - Baseline age, primary diagnosis, and blood pressure were similar in each group (P>0.05). Initial FT, TT, follicle-stimulating hormone (FSH), cholesterol, and hemoglobin A1c (HbA1c) were also similar between groups (P>0.05). At the end of the study period, more non-obese men attained eugonadal testosterone levels than obese men (FT-81% vs 52% (P=0.03) and TT-81% vs 54% (P=0.018)). On multivariate logistic regression, age and obese BMI were predictive of final FT <65pg/mL (P=0.03 and 0.043). HbA1c >6.4 (diagnostic criteria for diabetes mellitus) predicted TT<350ng/dL (P=0.042). Response to therapy (final TT) was independent of baseline FT and TT in both univariate and multivariate models.
Conclusions - Hypogonadal men with diabetes and obesity are less likely to achieve normal free and total testosterone levels on topical testosterone therapy relative to non-obese, non-diabetic men. This relationship occurred independent of baseline hormone profile. The underlying mechanisms and optimal management of failure to respond to T-TRT needs to be determined. Health care practitioners and patients should aware of predictors of response.
HYPOGONADAL MEN TAKING CLOMIPHENE CITRATE REPORT SIMILAR SATISFACTION COMPARED TO MEN ON TESTOSTERONE REPLACEMENT THERAPY
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-06
Introduction and Objectives - The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism has been reported. We compared satisfaction and treatment efficacy in men with symptomatic hypogonadism taking CC, testosterone gel (T gel), and testosterone injections (T injections).
Methods - Men receiving CC or T gel or T injections for symptomatic hypogonadism (total testosterone < 300 ng/dl) were asked to report satisfaction with their current treatment regimen with ADAM and qADAM scores. Serum testosterone levels were collected on the same day that men filled out the ADAM questionnaire. Treatment efficacy was evaluated using pre- and post-treatment serum testosterone, and satisfaction was assessed using androgen deficiency in aging male (ADAM) and quantitative ADAM (qADAM) questionnaire scores
Results - The charts of 451 men on testosterone supplementation (51 on CC, 265 on T injections, and 135 on T gel) were reviewed. The mean serum total T levels in men on CC (525 ng/dL) was lower (p<0.01) than men taking T injections (1015 ng/dL), but similar to serum total T in men on gels (453.3 ng/dL, p=0.07). Post-treatment testosterone levels were higher in men taking CC, T injections and T gels compared to pre-treatment levels (227 ng/dL, 221 ng/dL, 211 ng/dL p<0.01)
Despite differences in serum T, men on CC, T injection, and T gel reported similar satisfaction levels. Both the ADAM scores (2.37, 2.81, and 3.17) and quantitative ADAM scores (37.2, 36.8, and 35.6) for the men on different testosterone supplementation regimens were similar. Men taking CC were younger (38.5y) than men taking T injections (46.8y) or T gels (59.4, p< 0.01).
Conclusions - Testosterone supplementation regimens including CC, T gels and T injections are efficacious in improving serum total testosterone levels. However, men taking clomiphene citrate or testosterone gels report similar satisfaction levels compared to men taking testosterone injections despite lower serum total testosterone levels.
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-06
Introduction and Objectives - The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism has been reported. We compared satisfaction and treatment efficacy in men with symptomatic hypogonadism taking CC, testosterone gel (T gel), and testosterone injections (T injections).
Methods - Men receiving CC or T gel or T injections for symptomatic hypogonadism (total testosterone < 300 ng/dl) were asked to report satisfaction with their current treatment regimen with ADAM and qADAM scores. Serum testosterone levels were collected on the same day that men filled out the ADAM questionnaire. Treatment efficacy was evaluated using pre- and post-treatment serum testosterone, and satisfaction was assessed using androgen deficiency in aging male (ADAM) and quantitative ADAM (qADAM) questionnaire scores
Results - The charts of 451 men on testosterone supplementation (51 on CC, 265 on T injections, and 135 on T gel) were reviewed. The mean serum total T levels in men on CC (525 ng/dL) was lower (p<0.01) than men taking T injections (1015 ng/dL), but similar to serum total T in men on gels (453.3 ng/dL, p=0.07). Post-treatment testosterone levels were higher in men taking CC, T injections and T gels compared to pre-treatment levels (227 ng/dL, 221 ng/dL, 211 ng/dL p<0.01)
Despite differences in serum T, men on CC, T injection, and T gel reported similar satisfaction levels. Both the ADAM scores (2.37, 2.81, and 3.17) and quantitative ADAM scores (37.2, 36.8, and 35.6) for the men on different testosterone supplementation regimens were similar. Men taking CC were younger (38.5y) than men taking T injections (46.8y) or T gels (59.4, p< 0.01).
Conclusions - Testosterone supplementation regimens including CC, T gels and T injections are efficacious in improving serum total testosterone levels. However, men taking clomiphene citrate or testosterone gels report similar satisfaction levels compared to men taking testosterone injections despite lower serum total testosterone levels.
COMBINATION THERAPY WITH AN AROMATASE INHIBITOR IS NEEDED IN ONE OUT OF SIX HYPOGONADAL MEN TREATED WITH CLOMIPHENE CITRATE
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-05
Introduction and Objectives - Clomiphene citrate (CC) is a selective estrogen receptor modulator used off label to stimulate endogenous testosterone production in hypogonadal men. In some patients, CC leads to elevated estradiol levels, necessitating combination therapy with an aromatase inhibitor, such as anastrozole (AZ).
The objectives of this project were to
(1) determine the previously unreported rate of conversion from CC monotherapy to combination therapy with CC+AZ in hypogonadal men, and
(2) test the hypothesis that men needing combination therapy with CC+AZ would have higher body mass index (BMI) compared to men maintained on CC monotherapy.
Methods - We obtained institutional review board approval and performed a retrospective chart review of hypogonadal men treated with CC by a single urologist at our institution between 2006 and 2013. Response to CC therapy was monitored with serum hormones; when estradiol became elevated above the reference range, AZ therapy was added.
Results - We identified 271 hypogonadal men treated with CC and followed for an average of 28 months (SD = 19). Following initiation of CC therapy, 46 (17%) patients required combination therapy with CC+AZ due to elevated estradiol levels. While age and race were similar between groups, the average BMI of patients who converted to CC+AZ combination therapy was significantly higher than those patients who remained on CC monotherapy (Table 1, p < 0.001).
Conclusions - Following initiation of therapy with CC, 17% of hypogonadal men developed elevated estradiol levels, necessitating combination therapy with an aromatase inhibitor. Men requiring the addition of AZ were obese (BMI > 30 kg/m2), implicating increased peripheral aromatization of androgens to estrogens as a contributor to elevated estradiol levels in these men during CC therapy.
Table 1. Demographic information for hypogonadal men treated with CC monotherapy versus CC+AZ
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP48-05
Introduction and Objectives - Clomiphene citrate (CC) is a selective estrogen receptor modulator used off label to stimulate endogenous testosterone production in hypogonadal men. In some patients, CC leads to elevated estradiol levels, necessitating combination therapy with an aromatase inhibitor, such as anastrozole (AZ).
The objectives of this project were to
(1) determine the previously unreported rate of conversion from CC monotherapy to combination therapy with CC+AZ in hypogonadal men, and
(2) test the hypothesis that men needing combination therapy with CC+AZ would have higher body mass index (BMI) compared to men maintained on CC monotherapy.
Methods - We obtained institutional review board approval and performed a retrospective chart review of hypogonadal men treated with CC by a single urologist at our institution between 2006 and 2013. Response to CC therapy was monitored with serum hormones; when estradiol became elevated above the reference range, AZ therapy was added.
Results - We identified 271 hypogonadal men treated with CC and followed for an average of 28 months (SD = 19). Following initiation of CC therapy, 46 (17%) patients required combination therapy with CC+AZ due to elevated estradiol levels. While age and race were similar between groups, the average BMI of patients who converted to CC+AZ combination therapy was significantly higher than those patients who remained on CC monotherapy (Table 1, p < 0.001).
Conclusions - Following initiation of therapy with CC, 17% of hypogonadal men developed elevated estradiol levels, necessitating combination therapy with an aromatase inhibitor. Men requiring the addition of AZ were obese (BMI > 30 kg/m2), implicating increased peripheral aromatization of androgens to estrogens as a contributor to elevated estradiol levels in these men during CC therapy.
Table 1. Demographic information for hypogonadal men treated with CC monotherapy versus CC+AZ
Attachments
Intra-Individual Variations In Serum Total Testosterone Among Men Presenting For Evaluation Of Hypogonadism
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP32-13
Introduction and Objectives - Medical society guidelines recommend confirmation of the diagnosis of low total testosterone (TT) with a repeat measurement. We aim to describe the intra-individual variation in serum T levels and analyze the impact of duration between TT measurements on such variability.
Methods - Patient population consisted of consecutive men who (1) were high-risk for testosterone deficiency syndrome (TDS) or presented with symptoms of TDS or (2) had low or low normal serum TT levels on presentation to an andrology clinic and(3) had 2 early morning TT levels within 90 days of one another and (4) had hormone testing conducted at a single laboratory. TT was measured using liquid chromatography mass spectroscopy. Patient records were reviewed for demographics, comorbidities, and serum hormone profiles. Age, diabetes, and chemotherapy as predictors of change were analyzed, and change in TT levels between tests was analyzed based on duration between tests.
Results - Average age of the 109 men was 58±14 (range 23-87) years. Mean TT at the initial visit = 270±99 ng/dl and free testosterone (FT) = 48±31 pg/ml. Mean change in TT between the two lab tests = 38±127 (range -333 to 648 ng/dl), while mean change in FT was 1±20 (range -85 to 50). 18% moved from TT <300 to TT >300, with half of them increasing by ?100. 9% moved from TT >300 to TT <300, with one third decreasing ?100. 3% moved from initial TT <200 to repeat TT >400, while 1% moved from initial TT >400 to repeat TT <200. Change in TT by time between tests is listed in Table 1 (no difference between groups, p = 0.67). There were no significant predictors of TT change in either univariate or multivariable models (p=0.29 to 0.84). The average variability as a percentage of the initial lab value was 24% in the group overall, with a range of -88% to 476%. For the 0-30d group, the variability was 11% (-41% to 268%), 31-60 was 33% (-60% to 476%) and 61-90 was 33% (-88% to 386%).
Conclusions - Although the majority of patients had confirmatory TT within 100 ng/dL of the initial value, over 20% had a greater than 100 ng/dL on repeat examination. While these data support the value of repeat testing in men with low TT levels, the variability in lab findings illustrates the importance of symptom assessment in the diagnosis of hypogonadism. Repeat levels should be measured within 30 days of initial testing.
Percent of Patients with Change in Total Testosterone (ng/dl) Stratified by Days between Tests
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP32-13
Introduction and Objectives - Medical society guidelines recommend confirmation of the diagnosis of low total testosterone (TT) with a repeat measurement. We aim to describe the intra-individual variation in serum T levels and analyze the impact of duration between TT measurements on such variability.
Methods - Patient population consisted of consecutive men who (1) were high-risk for testosterone deficiency syndrome (TDS) or presented with symptoms of TDS or (2) had low or low normal serum TT levels on presentation to an andrology clinic and(3) had 2 early morning TT levels within 90 days of one another and (4) had hormone testing conducted at a single laboratory. TT was measured using liquid chromatography mass spectroscopy. Patient records were reviewed for demographics, comorbidities, and serum hormone profiles. Age, diabetes, and chemotherapy as predictors of change were analyzed, and change in TT levels between tests was analyzed based on duration between tests.
Results - Average age of the 109 men was 58±14 (range 23-87) years. Mean TT at the initial visit = 270±99 ng/dl and free testosterone (FT) = 48±31 pg/ml. Mean change in TT between the two lab tests = 38±127 (range -333 to 648 ng/dl), while mean change in FT was 1±20 (range -85 to 50). 18% moved from TT <300 to TT >300, with half of them increasing by ?100. 9% moved from TT >300 to TT <300, with one third decreasing ?100. 3% moved from initial TT <200 to repeat TT >400, while 1% moved from initial TT >400 to repeat TT <200. Change in TT by time between tests is listed in Table 1 (no difference between groups, p = 0.67). There were no significant predictors of TT change in either univariate or multivariable models (p=0.29 to 0.84). The average variability as a percentage of the initial lab value was 24% in the group overall, with a range of -88% to 476%. For the 0-30d group, the variability was 11% (-41% to 268%), 31-60 was 33% (-60% to 476%) and 61-90 was 33% (-88% to 386%).
Conclusions - Although the majority of patients had confirmatory TT within 100 ng/dL of the initial value, over 20% had a greater than 100 ng/dL on repeat examination. While these data support the value of repeat testing in men with low TT levels, the variability in lab findings illustrates the importance of symptom assessment in the diagnosis of hypogonadism. Repeat levels should be measured within 30 days of initial testing.
Percent of Patients with Change in Total Testosterone (ng/dl) Stratified by Days between Tests
Attachments
Baseline Correction in Testosterone Bioequivalence Study
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP32-10
Introduction and Objectives - For applicants seeking approval of a drug product, a bioequivalence (BE) study may be required if an application relies on FDA’s finding of safety and/or effectiveness for the reference listed drug (RLD). Testosterone (T), an anabolic steroid, is approved to treat men with hypogonadism.
For approval of a T product, an endogenous substance drug product, the demonstration of BE against an RLD is complicated by endogenous T production. To rule out the influence of endogenous T, baseline T concentrations are subtracted from the total T concentrations for each subject after the drug product is administered. Pharmacokinetic and statistical analyses are performed on both uncorrected and corrected data as appropriate.
Determination of BE between a test and RLD is based on the baseline-corrected T data. BE assessment may be complicated if an individual’s endogenous T concentrations change day-to-day or exhibit a circadian pattern. Currently, there are no consistent or data-driven approaches to assessing and reporting baseline T concentrations.
The objectives of this study was to use FDA in-house data to assess baseline T characteristics and to determine the optimal baseline correction method for evaluation of BE of T products.
Methods - FDA in-house data from T clinical trials (pivotal BE and phase 1 studies) were collected and analyzed for baseline T concentrations in hypogonadal men. We assessed the presence of a circadian rhythm in hypogonadal men and intra-subject variability of endogenous T between treatment periods.
Results - A total of 266 hypogonadal men from 4 new drug applications submitted to FDA were analyzed. Data were obtained from 3 BE studies and 3 relative bioavailability studies. The age and body mass index in hypogonadal men ranged from 18 to 80 years and 15 to 35 kg/m2, respectively.
Preliminary results show that, in general, baseline T concentrations in hypogonadal men fluctuated less than 100 ng/dL over a 12- to 24-hour period pre-treatment. Up to 200% intra-subject variability was seen when endogenous T concentration measurements were taken at the same time of the day with several days of separation (i.e., 108 versus 325 ng/dL taken at 10 am on Days 1 and 8).
Conclusions - Correction of baseline T concentration is needed for the assessment of BE of T products. Circadian rhythm is not significant in hypogonadal men compared to intra-subject variability. Therefore, the need to take extensive blood samples over 24 hours to characterize baseline T concentrations may not be necessary. However, due to the intra-subject variability, assessment of baseline T is needed before each treatment period.
http://www.aua2014.org/abstracts/abstractprint.cfm?id=MP32-10
Introduction and Objectives - For applicants seeking approval of a drug product, a bioequivalence (BE) study may be required if an application relies on FDA’s finding of safety and/or effectiveness for the reference listed drug (RLD). Testosterone (T), an anabolic steroid, is approved to treat men with hypogonadism.
For approval of a T product, an endogenous substance drug product, the demonstration of BE against an RLD is complicated by endogenous T production. To rule out the influence of endogenous T, baseline T concentrations are subtracted from the total T concentrations for each subject after the drug product is administered. Pharmacokinetic and statistical analyses are performed on both uncorrected and corrected data as appropriate.
Determination of BE between a test and RLD is based on the baseline-corrected T data. BE assessment may be complicated if an individual’s endogenous T concentrations change day-to-day or exhibit a circadian pattern. Currently, there are no consistent or data-driven approaches to assessing and reporting baseline T concentrations.
The objectives of this study was to use FDA in-house data to assess baseline T characteristics and to determine the optimal baseline correction method for evaluation of BE of T products.
Methods - FDA in-house data from T clinical trials (pivotal BE and phase 1 studies) were collected and analyzed for baseline T concentrations in hypogonadal men. We assessed the presence of a circadian rhythm in hypogonadal men and intra-subject variability of endogenous T between treatment periods.
Results - A total of 266 hypogonadal men from 4 new drug applications submitted to FDA were analyzed. Data were obtained from 3 BE studies and 3 relative bioavailability studies. The age and body mass index in hypogonadal men ranged from 18 to 80 years and 15 to 35 kg/m2, respectively.
Preliminary results show that, in general, baseline T concentrations in hypogonadal men fluctuated less than 100 ng/dL over a 12- to 24-hour period pre-treatment. Up to 200% intra-subject variability was seen when endogenous T concentration measurements were taken at the same time of the day with several days of separation (i.e., 108 versus 325 ng/dL taken at 10 am on Days 1 and 8).
Conclusions - Correction of baseline T concentration is needed for the assessment of BE of T products. Circadian rhythm is not significant in hypogonadal men compared to intra-subject variability. Therefore, the need to take extensive blood samples over 24 hours to characterize baseline T concentrations may not be necessary. However, due to the intra-subject variability, assessment of baseline T is needed before each treatment period.
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