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

History of Testosterone Product Commercialization

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

Testosterone Therapy Helps Obese Men Lose Weight

Results of a study were presented at the 2012 European Congress on Obesity in Lyon , France  by Dr Bradley Anawalt, M.D. from The Endocrine Society and the University of Washington Medical Center, Seattle that followed 251 obese men aged 38 to 83 with low testosterone levels. Among these men, 214 were followed for two years and 115 were followed for five years.

The men were given 1,000 milligrams of testosterone by injection when the study started, again at six weeks and then every 12 weeks until the end of the trial. The product used was Nebido (possible upcoming name in the US: Aveed)

The men who were followed for five years lost an average of 35 pounds. Their average body-mass index — a measurement that takes height and weight into account — dropped from 34 to 29, moving them from the obese category into the overweight category. In addition, they also saw improvements in their cholesterol and triglyceride levels, along with their blood pressure.

In addition, there was no increase in the risk of prostate cancer, researchers noted.

Prior studies in conditions like HIV have shown testosterone replacement to decrease fat mass and increase lean body mass.

Testosterone replacement also increases energy levels, so men can exercise more frequently.

Spanish Translation: Monitoreando la Terapia de Reemplazo de Testosterona

Este capitulo fue extraido del libro "La Testosterona" (puede ser comprado en www.testosteronewisdom.com o en amazon.com)

El primer paso para la correcta evaluación de la terapia de reemplazo de testosterona es facilitarle a su médico un historial médico minucioso.  Los pacientes que deseen ser proactivos, pueden llevar este formulario y entregarles una copia a sus médicos. Se espera que cada médico tenga un formulario similar, aunque la mayoría de ellos no formulan preguntas relacionadas con la función sexual o el uso de andrógenos. Hágale saber a su médico acerca de todos los medicamentos que toma para poder descartar la disfunción sexual inducida por fármacos antes de iniciar la testosterona.

También considero firmemente que si un paciente acude al médico para obtener una prescripción de Viagra, Cialis o Levitra, el médico debería revisar los niveles de testosterona en la sangre del paciente para asegurarse que esa no es la raíz del problema. Es probable que los hombres hipogonadales no respondan muy bien a estos medicamentos si no se normalizan primero sus niveles de testosterona. Los estudios que combinan la testosterona y fármacos orales para aumentar la sexualidad han mostrado efectos sinérgicos en beneficios sexuales. Los siguientes consejos para evaluar el reemplazo de testosterona son recomendados por varios grupos de médicos y practicantes:

1.   Usted debería ser evaluado después del primer mes de terapia para medir sus niveles de testosterona en la sangre. Si su médico no le pregunta, hágale saber usted sobre su calidad de vida. Asegúrese que su médico esté al tanto de sus niveles de energía, humor y función sexual, así como también cualquier efecto secundario potencial (mamas sensibles, disminución en el flujo urinario, malhumor y acné).

2.   Cuando esté usando testosterona, su médico querrá medir sus niveles de testosterona total en la sangre justo antes de la próxima inyección correspondiente después del primer mes (toma tiempo para que los niveles sanguíneos se estabilicen). Si la testosterona se encuentra por arriba de 900-1000 ng/dl (24,5 nmol/litro) o menos de 350 ng/dl (12,3 nmol/litro), su médico ajustará la cantidad o la frecuencia de su dosis. Mencioné esto previa- mente en el libro, pero es necesario repetirlo aquí: Algunos hombres necesitan niveles de testosterona total por encima de 500 ng/dl para poder experimentar cualquiera de los beneficios sexuales que se espera de la testosterona. Es importante ser honesto cuando su médico le pregunte sobre su desempeño sexual.

3.   Su médico revisará sus hematocritos (la proporcion de celulas rojas en la sangre) antes de iniciar la testosterona, después de 3 meses y luego cada año después de eso. Si su hematocrito están por encima de 54%, puede que usted necesite una flebotomía terapéutica o donar sangre para bajar este numero.  Alto hematocrito es peligroso para el corazon ya que la sangre se convierte mas espeza (lea la sección “Revisando el Incremento del Espesor de la Sangre (Policitemia)” para mayores detalles).

4.   Esté preparado para hacerse un examen rectal digital y un examen sanguíneo de antígeno prostático específico (APE) antes de iniciar la testosterona, y repetirlo a los 3 meses. No sería irracional realizarlo también una vez cada 6 meses, especialmente en hombres mayores. Un APE por encima de 4 ng/ml puede ser razón para preocuparse y referirlo a un urólogo. Si se observa un incremento en los niveles de APE encima de lo normal, es necesario detener el reemplazo de testosterona. Nota: al inicio del reemplazo de testosterona en hombres mayores, cuando los niveles de testosterona están en rápido aumento, también es probable que incremente el APE. Esto sucede especialmente cuando se emplean geles de testosterona, ya que elevan la DHT más que las demás opciones. Una vez que se hayan estabilizado los niveles de testosterona, el APE disminuye casi hasta el valor base. Es importante esperar hasta alcanzar un “estado seguro” después de las fluctuaciones de la testosterona antes de medir el APE; un mes aproxi- madamente debería ser suficiente. Tambien hay que recordar que infecciones de la prostata tambien pueden subir el antigeno prostatico.

5.   Si usted comienza a experimentar sensibilidad, dolor o crecimiento en las mamas, pídale a su médico que mida su nivel de estradiol en sangre realizando un análisis sensible (no el examen regular usado para mujeres). El valor normal de estradiol en hombres es 20-54 pg/ml (30-200 pmol/litro). Los hombres que presenten alto estradiol pueden ser tratados con inhibidores del receptor de estrógeno como el anastrozole o tamoxifen (más detalles en “Evitando el agrandamiento de mamas (ginecomastia)”).

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.