Anbolic technologies

[Haritec]

Some literature - this is part of what I gave to my doc to justify him putting me on 5 mg Cialis a day. When that goes through I will let you know the results. I usually get Testosterone tests regularly with my naturopath ( he is awesome about testing) and he knows I do 25 mg Chlomid EOD - so will be interesting to see the effects of this. Anyways here is some literature - sorry all the links broke when I cut and pasted from Word but a google search with the title of the paper in the search (cut and paste) will bring it up on pubmed.

Selected Literature – Tadalafil

Cardio Protective and Cardiomyopathy effects

This is a fascinating paper and the one that made me want to consider daily tadalafil
Cardiac role of cyclic-GMP hydrolyzing phosphodiesterase type 5: from experimental models to clinical trials.
Kass DA.
Curr Heart Fail Rep. 2012 Sep;9(3):192-9. doi: 10.1007/s11897-012-0101-0. Review.

Selected quotation
Quick jump to 2012, and we can see how far the field has changed [20]. Many groups now
report a potent role of PDE5 in regulating cardiac remodeling in heart disease and benefits
from its inhibition; small clinical trials are finding benefits in heart failure patients related to
multi-organ-targeting, including the heart; and multicenter studies in HF patients with
preserved ejection fraction (eg, Phosphodiesterase-5 Inhibition to Improve Quality of Life
and Exercise Capacity in Diastolic Heart Failure [RELAX]) are nearing completion, while
others are about to start.

Emerging new uses of phosphodiesterase-5 inhibitors in cardiovascular diseases.
Kukreja RC, Salloum FN, Das A, Koka S, Ockaili RA, Xi L.
Exp Clin Cardiol. 2011 Winter;16(4):e30-5.

ABSTRACT
Phosphodiesterase type-5 (PDE-5) is an enzyme that catalyzes the hydrolytic degradation of cyclic GMP - an essential intracellular second messenger that modulates diverse biological processes in living cells. Three selective inhibitors of PDE-5 - sildenafil, vardenafil and tadalafil - have been successfully used by millions of men worldwide for the treatment of erectile dysfunction. Also, sildenafil and tadalafil are currently approved for the treatment of pulmonary hypertension. Recent powerful basic science data and clinical studies suggest potential nonurological applications of PDE-5 inhibitors, including ischemia/reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, stroke, neurodegenerative diseases and other circulatory disorders including Raynaud's phenomenon. Future carefully controlled clinical trials would hopefully expedite their expanding therapeutic use in patients with cardiovascular disease.


The beneficial effects of tadalafil on left ventricular dysfunction in doxorubicin-induced cardiomyopathy.
Jin Z, Zhang J, Zhi H, Hong B, Zhang S, Guo H, Li L.
J Cardiol. 2013 Aug;62(2):110-6. doi: 10.1016/j.jjcc.2013.03.018. Epub 2013 May 31.


Anti-inflammatory and cardioprotective effects of tadalafil in diabetic mice.
Varma A, Das A, Hoke NN, Durrant DE, Salloum FN, Kukreja RC.
PLoS One. 2012;7(9):e45243. doi: 10.1371/journal.pone.0045243. Epub 2012 Sep 21.

[Clinical use of phosphodiesterase-5 inhibitors in cardiopulmonary diseases: from experimental evidence to clinical application].
Guazzi M, Vicenzi M, Samaja M.

Article in Italian but Abstract pertinent
Phosphodiesterases are a class of proteins that primarily modulate intracellular levels of cyclic nucleotides such as cGMP and cAMP. Phosphodiesterase-5 (PDE5) is mainly involved in the smooth muscle cell cGMP inactivation. Chemical inhibition of PDE5 has recently become a valid therapeutic option of nitric oxide pathway potentiation via cell cGMP availability. More specifically, PDE5 inhibition appears successful for the treatment of idiopathic pulmonary arterial hypertension. Additional intriguing therapeutic properties are a protective effect on the myocardium through antihypertrophic and antiapoptotic mechanisms and on vascular function by improving endothelial responsiveness and tolerance to myocardial ischemia-reperfusion injury. These effects imply a potential usefulness in the treatment of coronary artery disease and heart failure. Evidence currently available for considering PDE5 inhibition an additional therapeutic opportunity in cardiovascular disorders is provided.
Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide.
Salloum FN, Chau VQ, Hoke NN, Abbate A, Varma A, Ockaili RA, Toldo S, Kukreja RC.
Circulation. 2009 Sep 15;120(11 Suppl):S31-6. doi: 10.1161/CIRCULATIONAHA.108.843979. Erratum in: Circulation. 2009 Oct 13;120(15):e139.

Blood Pressure / Hypertension
All PDE5 inhibitors are associated with lowering blood pressure. There is a lot of research on Right Ventricle dysfunction and pulmonary hypertension – which I don’t have but it shows that it is a cardioprotective drug with beneficial effects. CARE HAS TO BE TAKEN RE BLOOD PRESSURE – MINE CAN ALREADY GET LOW
More has been done with Sildenafil than Tadalfil in this area. Some of these papers are about Sildenafil (Viagra) versus Tadalafil (Cialis) but is pertinent nonetheless.
Pharmacokinetic evaluation of sildenafil as a pulmonary hypertension treatment.
Chaumais MC, Perrin S, Sitbon O, Simonneau G, Humbert M, Montani D.
Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1193-205. doi: 10.1517/17425255.2013.804063. Epub 2013 Jun 12.

Sildenafil citrate has multiple advantages, it is one of the treatments of choice for all
ages and whether it is first-line treatment alone or in combination for the mild form of the

Tadalafil: a long-acting phosphodiesterase-5 inhibitor for the treatment of pulmonary arterial hypertension.
Arif SA, Poon H.
Clin Ther. 2011 Aug;33(8):993-1004. doi: 10.1016/j.clinthera.2011.06.008. Epub 2011 Jul 16. Review.
Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of pulmonary arterial hypertension (PAH).
By selectively inhibiting PDE-5, tadalafil causes nitric oxide-mediated vasodilation in the pulmonary vasculature. Tadalafil has a greater affinity (10,000-fold) for PDE-5 compared with the other PDE inhibitors and has a t(½) of 17.5 hours.

Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia

Tadalafil for benign prostatic hyperplasia.
[No authors listed]
Drug Ther Bull. 2013 Aug;51(8):93-6. doi: 10.1136/dtb.2013.8.0199.

Tadalafil is a phosphodiesterase type-5 (PDE5) inhibitor licensed for the treatment of erectile dysfunction (ED) in adult males (Cialis-Lilly) and for the management of pulmonary arterial hypertension (Adcirca-Lilly).(1) The 5mg tablet was licensed in November 2012 for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) in adult males (Cialis 5mg-Lilly).(2) In this article, we consider the evidence for tadalafil and how its use fits with current management strategies for BPH.

It is well tolerated and multiple advantages
Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study.[J Sex Med. 2012]
Works as well whether patients have ED or not
Tadalafil once daily in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in men without erectile dysfunction.
Brock G, Broderick G, Roehrborn CG, Xu L, Wong D, Viktrup L.
BJU Int. 2013 Nov;112(7):990-997. doi: 10.1111/bju.12251. Epub 2013 Aug 13.

Efficacy and Safety of Tadalafil 5 mg Once Daily for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Subgroup Analyses of Pooled Data From 4 Multinational, Randomized, Placebo-controlled Clinical Studies.
Porst H, Oelke M, Goldfischer ER, Cox D, Watts S, Dey D, Viktrup L.
Urology. 2013 Sep;82(3):667-73. doi: 10.1016/j.urology.2013.05.005. Epub 2013 Jul 19

Phosphodiesterase inhibitors in clinical urology.
Ückert S, Kuczyk MA, Oelke M.
Expert Rev Clin Pharmacol. 2013 May;6(3):323-32. doi: 10.1586/ecp.13.16.

Testosterone Levels

Efficacy and Safety of Tadalafil 5 mg Once Daily for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Subgroup Analyses of Pooled Data From 4 Multinational, Randomized, Placebo-controlled Clinical Studies.
Porst H, Oelke M, Goldfischer ER, Cox D, Watts S, Dey D, Viktrup L.
Urology. 2013 Sep;82(3):667-73. doi: 10.1016/j.urology.2013.05.005. Epub 2013 Jul 19

CONCLUSION:
In these pooled data analyses, tadalafil 5 mg improved LUTS/BPH across subgroups of age, LUTS severity, testosterone levels, and prostate volume. Rates of AEs were similar across the subgroups assessed.
Tadalafil improves total testosterone, IIEF score and SEP in old and middle-aged males with late-onset hypogonadism].
Wang XK, Luo L, Wang S, Li J, Li WX.
Zhonghua Nan Ke Xue. 2012 May;18(5):475-7. Chinese.



Sexual Function

An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors.
Bruzziches R, Francomano D, Gareri P, Lenzi A, Aversa A.
Expert Opin Pharmacother. 2013 Jul;14(10):1333-44. doi: 10.1517/14656566.2013.799665. Epub 2013 May 16.

EXPERT OPINION:
All PDE5-i are equally effective and safe for the treatment of ED. On-demand use of any PDE5-i is also safe for patients with comorbid conditions. Tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients. Preliminary data suggest that the use of vardenafil may also be beneficial in cases of ED associated with premature ejaculation. Daily treatment is another option in men with ED and documented vascular or prostate disease