Testicle Size: Testosterone Injections vs hCG vs T gel

[Nelson Vergel]

Effects of Three Different Medications on Metabolic Parameters and Testicular Volume in Patients With Hypogonadotropic Hypogonadism

3-Year Experience


Clin Endocrinol. 2013;79(2):243-251.

Abstract
Introduction The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH).

Subjects design and methods Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment.

Results Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers.

Conclusion hCG treatment resulted in favourable effects particularly on Testicular Volume and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.

Note: Dosing of hCG, injectable testosterone and testosterone gel were not "standard" as shown:

25 patients treated with hCG (Pregnyl® Organon hCG 5000 IU; Organon USA Inc., Roseland, NJ, USA) 5000 IU twice weekly, 28 patients treated with IM injections of oil-based blend of four esterized testosterone (TE) compounds (Sustanon® 250 mg Organon; Organon Schering-Plough Corporation, Istanbul, Turkey; 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate and 100 mg testosterone decanoate) once every 3 weeks, and 24 patients treated with daily transdermal testosterone gel (TG; Testogel® Testosterone 50 mg/5 g-Schering, Schering Health Care Ltd, Burgess Hill, West Sussex) were enrolled.

This graph shows the changes in HDL, triglycerides, testosterone, and testicular volume. It is surprising that 5000 IU of hCG twice per week hardly increased T levels. hCG looks good in all other parameters.



This graph shows the same parameters before and after each treatment option. You can see how all patients were undertreated (total T levels did not increase beyond 300 ng/dL)




The authors admit that their dosing regimen was not the best:

"Successful testosterone replacement treatment is guided by the hormone levels remaining above the lower limit of normal range just before the next application of drug.[SUP][16][/SUP] In this respect, we found only TG treatment achieved the target and hCG was the least effective. Similar to our result, IHH was previously found poorly responsive to hCG therapy in terms of normalization of serum testosterone.[SUP][17][/SUP]However, some other studies showed that serum testosterone increased to normal ranges after hCG treatment at a dose of 5000 IU.[SUP][18, 19][/SUP] Our subjects received 5000 IU hCG twice weekly. This regimen resulted in a significant increase in tanner scores, but the magnitude of change was lesser in comparison with the other two options. It is likely that serum testosterone increased to an effective level after hCG treatment, but this period remained relatively short, and testosterone level turned nearly to baseline values before the next injection time. Although some improvements were evident in tanner scores in this study, this treatment regimen may not optimal for obtaining basal testosterone level, also suggesting that smaller doses with shorter intervals may be more favourable. After injection of the commonly administered dose of 200 or 250 mg, TE has the disadvantage that it produces supraphysiological serum testosterone levels during the days immediately following administration, with a slow decline to the lower limit of normal within the following 10–14 days. Patients frequently dislike these swings in serum testosterone levels, which they experience as ups and downs in vigour, mood and sexual activity.[SUP][20][/SUP] Our study showed that serum testosterone falls to the levels lower than the normal just before the next injection. As a result, also for TE treatment, smaller doses with narrow intervals may be tried to reach physiological testosterone levels."

http://www.medscape.com/viewarticle/808683

 

[Nelson Vergel]

More on HCG here:
The Use of HCG to Prevent / Reverse Testicular Shrinkage and Preserve Fertility

 

[Seth]

Effects of Three Different Medications on Metabolic Parameters and Testicular Volume in Patients With Hypogonadotropic Hypogonadism

3-Year Experience


Clin Endocrinol. 2013;79(2):243-251.

Abstract
Introduction The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH).

Subjects design and methods Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment.

Results Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers.

Conclusion hCG treatment resulted in favourable effects particularly on Testicular Volume and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.

Note: Dosing of hCG, injectable testosterone and testosterone gel were not "standard" as shown:

25 patients treated with hCG (Pregnyl® Organon hCG 5000 IU; Organon USA Inc., Roseland, NJ, USA) 5000 IU twice weekly, 28 patients treated with IM injections of oil-based blend of four esterized testosterone (TE) compounds (Sustanon® 250 mg Organon; Organon Schering-Plough Corporation, Istanbul, Turkey; 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate and 100 mg testosterone decanoate) once every 3 weeks, and 24 patients treated with daily transdermal testosterone gel (TG; Testogel® Testosterone 50 mg/5 g-Schering, Schering Health Care Ltd, Burgess Hill, West Sussex) were enrolled.

This graph shows the changes in HDL, triglycerides, testosterone, and testicular volume. It is surprising that 5000 IU of hCG twice per week hardly increased T levels. hCG looks good in all other parameters.

View attachment 1064

This graph shows the same parameters before and after each treatment option. You can see how all patients were undertreated (total T levels did not increase beyond 300 ng/dL)

View attachment 1065


The authors admit that their dosing regimen was not the best:

"Successful testosterone replacement treatment is guided by the hormone levels remaining above the lower limit of normal range just before the next application of drug.[SUP][16][/SUP] In this respect, we found only TG treatment achieved the target and hCG was the least effective. Similar to our result, IHH was previously found poorly responsive to hCG therapy in terms of normalization of serum testosterone.[SUP][17][/SUP]However, some other studies showed that serum testosterone increased to normal ranges after hCG treatment at a dose of 5000 IU.[SUP][18, 19][/SUP] Our subjects received 5000 IU hCG twice weekly. This regimen resulted in a significant increase in tanner scores, but the magnitude of change was lesser in comparison with the other two options. It is likely that serum testosterone increased to an effective level after hCG treatment, but this period remained relatively short, and testosterone level turned nearly to baseline values before the next injection time. Although some improvements were evident in tanner scores in this study, this treatment regimen may not optimal for obtaining basal testosterone level, also suggesting that smaller doses with shorter intervals may be more favourable. After injection of the commonly administered dose of 200 or 250 mg, TE has the disadvantage that it produces supraphysiological serum testosterone levels during the days immediately following administration, with a slow decline to the lower limit of normal within the following 10–14 days. Patients frequently dislike these swings in serum testosterone levels, which they experience as ups and downs in vigour, mood and sexual activity.[SUP][20][/SUP] Our study showed that serum testosterone falls to the levels lower than the normal just before the next injection. As a result, also for TE treatment, smaller doses with narrow intervals may be tried to reach physiological testosterone levels."

Three Different Medications in Hypogonadotropic Hypogonadism

I can't understand the charts above. Which bar graphs related to testicle size?

 

[madman]

I can't understand the charts above. Which bar graphs related to testicle size?

Table 1. Baseline anthropometric, biochemical, tanner stages and testicular volume in patients and controls

Table 2. Anthropometric and biochemical parameters, and testicular volume before and after esterized testosterone (TE), human chorionic gonadotropin (hCG) and testosterone gel (TG) treatments

Table 3. Comparisons of anthropometric and biochemical parameters, and testicular volume changes after treatment with esterized testosterone (TE), human chorionic gonadotropin (hCG) and testosterone gel (TG)

Fig. 1 Biochemical parameters and testicular volume before and after treatment with TE, hCG, and TG. C, cholesterol; HDL, high-density lipoprotein; TRG, Triglyceride; TV, testicular volume; TE, esterized testosterone; hCG, human chorionic gonadotropin; TG, testosterone gel (*P < 0.05, **P < 0.005).

Fig. 2 Comparison of biochemical parameters and testicular volumes changes with TE, hCG, and TG treatments. C, cholesterol; HDL, high density lipoprotein; TRG, triglyceride; TV, testis volumes; TE, esterized testosterone; hCG, human chorionic gonadotropin; TG, testosterone gel (*P < 0.05, **P < 0.005)

 

[madman]

*TV was determined with ultrasound (General Electric, Wauwatosa, WI, USA linear transducer 7.5-MHz), and calculated as the mean volume of the left and right sides.14 A normal testicular size is defined as 15–25 ml.

 

[Seth]

*TV was determined with ultrasound (General Electric, Wauwatosa, WI, USA linear transducer 7.5-MHz), and calculated as the mean volume of the left and right sides.14 A normal testicular size is defined as 15–25 ml.

Thanks, but I still can't understand those charts. It looks like size increased, but by how much? It shows a number followed a + and another number. Doesn't make any sense to me.

 

[madman]

Thanks, but I still can't understand those charts. It looks like size increased, but by how much? It shows a number followed a + and another number. Doesn't make any sense to me.

*Increase in TV was higher in the hCG group compared with both TE and TG groups; but, there was no difference between TE and TG groups regarding a change in TV.








Results

Baseline characteristics T

The demographic and biochemical features of patients (n = 77) and healthy controls (n = 42) are displayed in Table 1. The two groups were similar with regard to age and BMI. Fasting plasma glucose and HOMA-IR levels were higher, whereas serum haemoglobin, haematocrit, creatinine, FSH, LH, TT, TS and mean TV were significantly lower in patients with IHH (P < 0.05, for all). LDL-cholesterol level of the control group was significantly higher than the patient group (P = 0.003). Of the 77 men in the study population, 17 (22.4%) had anaemia at baseline, with no evident cause. However, leucocyte counts, platelet count, total cholesterol, HDL cholesterol, triglyceride, AST, ALT and urea levels were similar in the two groups (Table 1). Among the three subgroups of treatment, baseline values for BMI and age, biochemical parameters and mean TV were also similar (Table 1).




Baseline vs post-treatment demographics, biochemical parameters, TS and TV

Subjects treated with TE were found to have significantly increased BMI, haemoglobin, haematocrit, triglyceride, TT, creatinine, TS and mean TV, and decreased urea and HDL cholesterol levels by the 24th week (P < 0.05, for all) (Table 2; Fig. 1).

Mean plasma triglyceride decreased, whereas LH, TS and TV increased significantly after hCG treatment (P < 0.05, for all) (Table 2; Fig. 1). No significant changes in BMI or other biochemical parameters were observed in this group after 24 weeks.

Application of TG was associated with a significant increase in TT level, but within the normal range. Besides, BMI, LH, TS and mean TV increased, and total cholesterol and HDL cholesterol levels decreased significantly in the same subgroup (P < 0.05, for all). Other tested parameters were similar before and after treatment (Table 2).




Comparisons for the magnitude of the alterations in tested parameters among the study groups by the 24th week

The number of changes in each tested parameter before and after the treatment was simply calculated by subtracting the pretreatment values from post-treatment ones. Then, intergroup differences were determined statistically (Table 3; Fig. 2).

The number of changes in each tested parameter before and after the treatment was simply calculated by subtracting the pretreatment values from post-treatment ones. Then, intergroup differences were determined statistically (Table 3; Fig. 2). Leucocyte count reduced in TG-treated individuals, while it was found increased in the other two treatment types, and the difference between the TG and TE groups was significant. Haematocrit count increased much lower in the hCG-treated group, which was significant when compared with TE-treated group. hCG treatment resulted in a decrease in plasma triglyceride level, whereas it was found higher in the other two groups, and the differences were significant. TG treatment caused a significant increase in FSH, LH and testosterone levels compared with TE treatment. Increase in testosterone level was significantly higher in the TG-treated group in comparison with the other two groups. Increase in TS was significantly higher in the TE and TG treatment groups. Increase in TV was higher in the hCG group compared with both TE and TG groups; but, there was no difference between TE and TG groups regarding a change in TV.

 

[madman]

Keep in mind the piss poor protocol used for the patients injecting esterified T.


*28 patients treated with IM injections of an oil-based blend of four esterized testosterone (TE) compounds (Sustanon 250 mg Organon; Organon Schering-Plough Corporation, Istanbul, Turkey; 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate) once every 3 weeks





Treatment of hypogonadotropic hypogonadism is required to initiate androgenization and fertility. While the former can be achieved by testosterone replacement, the latter can only be succeeded by gonadotropins or pulsatile GnRH treatment.39 In either condition, testicular growth is highly important. One of the major findings in this study was that TV increased significantly after either gonadotropin or testosterone treatment, being more remarkable in the hCG-treated group. Our results with hCG treatment is in accordance with the previous data.40,41 However, several authors reported reduced testicular size after testosterone treatment.42 It should be emphasized that the patients included in these studies were older in comparison with our patients. Moreover, in our study, both TE and TG treatments caused increases in TV, suggesting that the resultant effect was not accidental. In younger patients, testosterone treatment was not shown to cause a negative effect on the hypothalamic-pituitary-testicular axis and to increase growth hormone and IGF1 levels.43 GH upregulates IGF-I secretion, IGF-I receptor numbers, and LH receptors in Leydig cells in vivo. 44 Absolute or testosterone adjuvant effect of GH may increase TV in patients treated with testosterone. Nevertheless, the long-term effects of testosterone treatment on TV are unknown. Administration of hCG increases intratesticular testosterone level via a direct effect on the Leydig cells,4 which can cause enlargement of the testes. Burris et al. 40 found a two-fold increase in TV after hCG treatment. In another study, satisfactory responses were achieved even in patients with very small initial testicular size.39 On the other hand, in our study, the efficacy of hCG treatment was inferior to the previous results reported in most of these studies; however, low responsiveness to hCG treatment in terms of testicular growth was also reported in IHH.17 Interestingly, a predictive role for initial TV in terms of achieving optimal testicular size on gonadotropin administration was also described in several investigations.39,40,45,46 Nevertheless, sample size, heterogeneous pretreatment TV values, ethnicity, and differences in the duration of treatment might have caused discrepant results in clinical trials. Although there were significant differences in TV after testosterone and hCG treatments, the magnitude of these differences is quite small, and the clinical importance of these differences is not completely known. The low patient number seems to be the main limitation of this study. Due to narrow selection criteria, the overall sample size remained small to represent all subjects with hypogonadotropic hypogonadism treated for hormone replacement. However, most previous studies had the same drawback; therefore, evaluation of the past and present data collected is required to make clearer comments. Also, a 6-month follow-up period may not be optimal to examine the long-term effects of these treatments, but we were not able to extend this course due to certain official issues. Probably some changes, mainly with hCG, may/will occur later.