Aveed (Nebido- Testosterone Undecanoate) Long Acting Testosterone Dosing

The dose used in the US study for Aveed was 750 mg, not the usual 1000 mg approved in most countries. Below is the document submitted to the FDA to explain the coughs issue, etc. The pic shows the dosing in the studies. There was a loading phase and then injections became less frequent. Between 21 and 40 days total T would be under 500 ng/ml. The goal is to be above 300 ng/ml, which will not be enough for most men unless you inject every 750 mg once a month.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM348092.pdf

Testosterone Injections Helped Obese Men Lose Weight

Introduction: Abdominal adipose tissue suppresses testosterone production by various mechanisms affecting the hypothalamic–pituitary–gonadal axis. Hypogonadism leads to further accumulation of fat mass thus creating a vicious circle. This study analysed the effects of restoring testosterone in obese hypogonadal men.

Methods: Cumulative, prospective, registry study of 181 men (mean age: 59.11±6.06 years) with testosterone levels below 12.1 nmol/l and a BMI of ≥30 kg/m². All men received parenteral testosterone undecanoate 1000 mg/12 weeks following an initial 6-week interval. 89 men were treated 5 years, 114 4 years, 133 3 years, 159 2 years, 181 1 year. The changing numbers do not reflect drop-out rates but are a result of the design as new patients are added once they have received at least 1 year of treatment.

Results: At the end of the observation period, mean weight (kg) decreased from 114.71±11.59 (minimum 87.0, maximum 139.00) to 93.24±8.49 (min 80.0; max 115.0). This decrease was statistically significant vs baseline .

Waist circumference (cm) as a measure of abdominal fat decreased from 111.2±7.54 (min 89.00; max 129.00) to 100.47±7.11 (min 84.00; max 117.00), BMI from 36.72±3.72 (min 30.10; max 46.51) to 30.22±2.6 (min 25.66; max 36.71).

Fasting glucose decreased from 5.84±0.84 to 5.41±0.12 mmol/l, total cholesterol from 7.63±0.95 to 4.9±0.28, LDL from 4.47±1.03 to 2.94±0.93, triglycerides from 3.31±0.56 to 2.17±0.13 mmol/l. Systolic blood pressure decreased from 159.17±15.9 to 139.08±10.99 mmHg, diastolic blood pressure from 96.5±11.01 to 80.39±7.51 mmHg (P<00001 p="">

Conclusion: Normalising testosterone produced loss of weight/waist circumference and improved metabolic profile. These improvements were progressive over 5 years.

http://www.endocrine-abstracts.org/ea/0032/ea0032p740.htm

Results from a 15 year study using a long acting testosterone injection (Nebido) show great improvements in several parameters in men

More from the ENDO meeting happening now in Houston :

Results from a 15 year study using Nebido injections (it will be called Aveed when it is hopefully approved in the US).  I am amazed on how HDL increased since that kind of dose is usually associated with decreases in HDL cholesterol.  Almost too good to be true but  it was probably due to the weight loss and reduction in metabolic syndrome in those men.

http://www.abstracts2view.com/endo/view.php?nu=ENDO12L_SAT-117

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study.

Aging Male. 2012 Mar 23. [Epub ahead of print] Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study. Aversa A, Bruzziches R, Francomano D, Greco EA, Fornari R, Luigi LD, Lenzi A, Migliaccio S. Source Department of Experimental Medicine, Medical Pathophysiology, Food and Science and Endocrinology Section, "Sapienza" University of Rome , Rome , Italy.


Abstract

 We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T equal or less than 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD = 0.989 ± 0.109; p <0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2) = 0.66, p < 0.0001) and femoral (r(2) = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.




Comment from Nelson Vergel (author of  Testosterone: A Man's Guide- available on www.testosteronewisdom.com ) 




 Testosterone undecanoate injections are known as the brand name Nebido around the world. In the United States it will be called Aveed. Aveed is currently under review for approval by the FDA. This ester may stay longer in your system so that less frequent injections may be needed. The injection is usually given once every 10 to 14 weeks, though the frequency will depend on your individual testosterone levels. After your first injection you may be asked to come back for another injection at week six. For use in the United States, the company claims that only five injections a year are needed (compared to 48 injections per year for a 100 mg per week regimen).

 In other countries, a large injection dose of 1000 mg are allowed. The FDA did not allow the manufacturer to use this dose in studies done in this country due to fears of side effects. In an open-label study which enrolled 130 hypogonadal men with blood total testosterone levels below 300 ng/dL at study entry, Aveed was dosed as an intramuscular injection (750 mg) at baseline, at week four, and then every 10 weeks throughout the remainder of the 21-month study. Approximately 70 percent of patients completed all injections and 94 percent of them had total testosterone from 300 to 1,000 nanograms/ml through the entire study. After Nebido was approved in Europe a small number of European patients experienced respiratory symptoms immediately following an intramuscular injection of 1000 mg in a 4 cc injection volume, (versus the 750 mg, 3 cc injection volume used in the United States). The makers of Nebido believe, and the FDA concurs, that the reaction is likely the result of a small amount of the oily solution immediately entering the vascular system from the injection site. This known yet uncommon complication of oil-based depot injections may be related to inappropriate injection technique or site. The problem is characterized by short-term reactions involving an urge to cough or a shortness of breath. In some rare cases the reaction had been classified as serious or the patient had experienced other symptoms such as dizziness, flushing or fainting.

In U.S. clinical trials of Nebido 750 mg (3 cc injection volume), the proposed dose in the U.S., there was a single, mild, non-serious case of oil-based coughing. The U.S. manufacturer, Endo Pharmaceuticals, is gathering data to address concerns about the respiratory symptoms. It is not known how much longer it will take the get this product approved in the United States as of June 2010. And even if it gets approved, it may not be widely available for people to buy through private health insurance if the company decides to price it as high as gels.