UNIVERSITY PEDs Cycle Progression: 19Nortestosterone Derivatives Lesson Overview Cycle Progression after a Testosterone and DHT Why 19-Nor as Next Step? Gynecomastia Primer Nandrolone Deployment Trenbolone Deployment Sample Cycle Design Cycle Progression Established testosterone is a base growth anchor in our cycle to support optimal estrogen and DHT levels DHT derivatives (primobolan, masteron, proviron, anavar) have been deployed a secondary compounds to continue to grow and modulate side effects The need for escalating the dosage to continue to grow might be present and we need a compound to bring about greater anabolism and limit androgenic effects from higher testosterone Higher DHT derivatives are not longer producing the outcomes needed The next compound to introduce into the cycle would be a 19-nor derivative Why 19-Nortestosterone as a Third Compound 19-Nortestosteorne is also known as nandrolone and this in fact is naturally occurring in the body as an intermediate in the aromatization of testosterone These compounds are more tissue selective than testosterone, however, can interact on other receptor sites, making them for experience users Also 19-Nors are very suppressive and should be reserved for those planning to stay on TRT These compounds are progestogenic and can interact with the estrogen receptor themselves Interesting fact, Levonorgestrel, a progestin birth control, is analog of nandrolone Removal of the methyl group at position 19 of the steroid backbone significantly reduces the susceptibility of 19-nor androgens to aromatize as well as undergo 5α-reduction Some aromatize, some not Some are effected by alpha reductase, some are not Will drastically enhance the anabolic to androgenic ratio in your cycle Gynecomastia Input Understanding Figure from: Swerdloff 2019 Nandrolone (19-Nortestosterone) Clinical Application Came to market in 1962 Application in advanced breast cancer, osteoporosis, anemia, pituitary-deficit growth hormone, HIV wasting Still in clinical use today, 100-200mg per week Properties Aldosterone Interaction: agonist (increased sodium retention, monitor BP and take an ARB, remove close to show) Estrogen Interaction: can interact with the ER, making aromatase inhibitor less effective in nandrolone induced gyno Can induce increased aromatase activity especially in combination with GH/IGF1 Also, greater aromatization to estrone over estradiol (not enough estrogen for protective health roles, therefore test is our base) Progesterone Interaction: Can interact with the progesterone receptor producing estrogen like effects and augment the stimulatory effects of estrogen, also reason why it is so much more suppressive on the HPTA than other compounds Promotes GH production 5-alpha reductase interaction: 5-alpha reduced to a weak androgen Dihydronandrolone (terrible for libido and erectile function and brain if not enough DHT present) Likely one driver in “deca dick” Cardiovascular: 600mg of nandrolone per week can have greater detriment on HDL than the equivalent amount of testosterone, 12 weeks post cycle still not fully restored Liver: Not c17aa, low liver toxicity; decanoate or phenyl propionate ester for IM usage Gynecomastia: Lab work for prolactin, E2, SHBG, IGF1, Testosterone (identify the source and treat) ED: Nandrolone suppresses test levels, provides weak estrogen form and weak DHN Likely need an increase in testosterone, DHT, or more or less estrogen (check your labs) Nandrolone (19-Nortestosterone) Bodybuilding Application Offseason: 200-400mg is common dosing Step Wise approach to dosing based on need for growth Advanced users may take this to 600-800mg Recommend starting with phenyl propionate ester as dosage changes will be impact quicker than decanoate ester if problems arise If user is experienced and need for lower shot volume is a factor the decanoate ester has application *Proviron as aid for ED with NPP for lack of DHT and modulate estrogen for gyno *Masteron as aid to modulate prolactin and estrogen if this is the issue *Nolvadex on hand if nandrolone direct action on ER is problematic over increased aromatization and nonresponsive to AI *Cabergoline last resort strategy for gyno as Dopamine withdrawal syndrome is a health risk with this type of product, first line strategy is lower nandrolone dosage Contest Prep: Compound may be used in initial phase of prep of the need to hold high levels of muscle development is present Remove it later stages of prep, 10 weeks out as the aldosterone interaction can increase water retention, also this may be further complicated with need to manage estrogen, prolactin and progesterone activity On prep only use the phenyl propionate ester, same offseason dosage applies Trenbolone Clinical Application SARM not designed for human usage, within drawn from human use in 1990s Growth promoter i n l ivestock FDA approved 1992, i ncreased feed efficacy Ca strated steers have move fat mass and lower wei ght gain Tren + E2 i nduces greater weight gain l ikely vi a the GH/IGF-1 axis Cl i nical interest i n enhancing s keletal muscle mass and BMD in individuals with muscle or bone wasting conditions or with a ndrogen deficiency s yndromes Properties Es trogen Interaction: Ca n not aromatize a nd very l ow affinity to the Estrogen receptor i tself (test base recommended) Proges terone Interaction: Ca n i nteract with the progesterone receptor (137% that of progesterone i tself) augmenting the s ti mulatory effects of estrogen, also reason why i t is so much more s uppressive on the HPTA than other compounds Al so potential a ctiva tion of BAT and increased night s weats Prol a ctin: Ca n ca use direct increase i n prolactin l evels Gl ucocorticoid interaction: Tren decreases Glucocorticoid binding capacity a nd lower GRs in s keletal muscle and suppress ACTH s ti mulated cortisol s ynthesis i n the adrenals, significantly reducing protein degradation, excellent during calorie res tri ction Potential enhanced glucose uptake 5-a l pha reductase i nteraction: Not s usceptible to 5alpha reductase vi a the 3-oxotriene s tructure, less androgenic tha n tes tosterone Androgen receptor interaction: 3x i ncreased affinity compared to testosterone, *this does NOT mean i t is 3x s tronger hypertrophy ga ins Ca rdi ovascular: ts given 2mg/kg of trenbolone for weeks s howed i mproved lipid profiles (serum TAG 62%, HDL 57%, LDL 78% reducti ons) Also i ncrease in prostate hyperplasia 34% decrease in fat mass and 11% i ncrease in l ean mass No cha nge in liver markers 38% reduction i n s erum insulin Li polysis: Decreases Visceral fat and whole-body fa t Decrease l ipid uptake in fat cells a nd i ncrease in Beta-adrenergic receptors Pairs well with Beta receptor a gonist Li ver: Not c17a a, l ow liver toxi city Gynecomastia: La b work for prolactin, E2, SHBG, IGF1, Testosterone (identify the source and treat) ED: Trenbolone s uppresses test a nd DHT levels, l owers estrogen, suppresses LH and FSH (check your labs) Sl eep: In a surrogate model, melatonin alleviated abnormal sleep behaviors i nduced by trenbolone GI di stress: Potential i ncrease in histamine levels i nduce nausea, loss appetite, acid reflux *l imits offseason application for thi s reason Thyroi d a xis: Trenbolone alone decreases T3 and T4 i n ca ttle, but when provi ded estradiol along with tren increase of T4 to T3 convers ion is present Brain: Male rats showed elevated Aβ42 levels in the brain within 48 hours of trenbolone injection, in a dosedependent manner, highest does was 5mg/kg (0.85mg/kg human equivalent) Trenbolone Bodybuilding Application Offseason: Limit application as tren is more advantageous in caloric restriction due to glucocorticoid reduction and beta upregulation Trenbolone disadvantageous in the offseason for many due to decreased appetite and GI issues Not human approved; From a safety standpoint has high potential for neurotoxicity Testosterone and nandrolone in offseason will be primary growth anchors Contest Prep: Large advantage in caloric restriction 100mg is a starting point 400mg is reaching to the point of diminishing returns, last 6-12 weeks of contest prep *Daily administration of the acetate ester can stabilize serum levels and lessen side effects *pairs very well with growth hormone and clenbuterol *Masteron use can modulate prolactin increases, *Cabergoline last resort strategy for gyno as Dopamine withdrawal syndrome is a health risk with this type of product, first line strategy is lower trenbolone dosage *Melatonin use to aid in sleep disruption *GI distress should be treated by symptom, Zinc Carnosine and digestive enzymes Sample Cycle Progression Offseason *on hand: Nolvadex, Arimidex/Aromasin, Cabergoline Cycle Test cypionate 400mg/wk Masteron or Primobolan 400mg/wk Proviron 25mg/day Cycle Test cypionate 400mg/wk Masteron or Primobolan 400mg/wk Nandrolone Phenyl Propionate 200mg/wk Proviron 25mg/day Cycle Test cypionate 400mg/wk Masteron or Primobolan 500mg/wk Nandrolone Phenyl Propionate 350mg/wk Proviron 25mg/day Sample Cycle Progression Contest Prep Intermediate *on hand: Nolvadex, Arimidex/Aromasin, Cabergoline 16 weeks out Test cypionate 300mg/wk Primobolan 200mg /wk Nandrolone Phenyl Propionate 200mg/wk 10 weeks out Test cypionate 300mg/wk Masteron 300mg/wk Trenbolone Acetate 200mg/wk weeks out Test cypionate 300mg/wk *drop test weeks out if needed for water retention Masteron 300mg/wk Trenbolone Acetate 200mg/wk Anavar 30mg/day Summary Testosterone is our established base growth anchor A DHT derivative like Proviron, Anavar, Primobolan and/or Masteron are secondary compounds to deploy Our next deployed drug will be a nandrolone derivative Nandrolone for offseason usage and Trenbolone reserved in contest prep We have some special phase compounds that can be deployed with limited usage that we will be reviewing Also we are reaching a point in cycle progression that moving into aggressive dosing likely will require an Aromatase Inhibitor, Selective Estrogen Receptor Modulator and/or a Dopamine Agonist to advance more Before we deploy these compounds and in higher dosages, I think we can get more out our current AAS stack by implementing Growth Hormone and Insulin, we will cover these items next References Nandrolone Sirianni R, Capparelli C, Chimento A, Panza S, Catalano S, Lanzino M, Pezzi V, Andò S Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation Mol Cell Endocrinol 2012 Nov 5;363(1-2):100-10 doi: 10.1016/j.mce.2012.08.002 Epub 2012 Aug 10 PMID: 22906881 Chowdhury P, Mahanta R Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration and Serum Na+/K+ Levels in Albino Mice Cardiovasc Hematol Agents Med Chem 2017;14(3):160-166 doi: 10.2174/1871525715666161121152116 PMID: 27875951.Masteron Reel JR, Humphrey RR, Shih YH, Windsor BL, Sakowski R, Creger PL, Edgren RA Competitive progesterone antagonists: receptor binding and biologic activity of testosterone and 19nortestosterone derivatives Fertil Steril 1979 May;31(5):552-61 doi: 10.1016/s0015-0282(16)44003-3 PMID: 446780 Sattler FR, Schroeder ET, Dube MP, Jaque SV, Martinez C, Blanche PJ, Azen S, Krauss RM Metabolic effects of nandrolone decanoate and resistance training in men with HIV Am J Physiol Endocrinol Metab 2002 Dec;283(6):E1214-22 doi: 10.1152/ajpendo.00189.2002 Epub 2002 Aug 27 PMID: 12388173 Bijlsma JW, Duursma SA, Thijssen JH, Huber O Influence of nandrolondecanoate on the pituitary-gonadal axis in males Acta Endocrinol (Copenh) 1982 Sep;101(1):108-12 doi: 10.1530/acta.0.1010108 PMID: 6812344 Bovee TF, Helsdingen RJ, Rietjens IM, Keijer J, Hoogenboom RL Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types J SteroidBiochem Mol Biol 2004 Jul;91(3):99-109 doi: 10.1016/j.jsbmb.2004.03.118 PMID: 15276617 Van der Gugten AA The effect of I-(morpholinomethyl)-4-phtalimido-piperidindione-2,6 and drostanolone propionate on the plasma prolactin concentration of oestrone-treated orchidectomized R-Amsterdam rats Eur J Cancer 1971 Dec;7(6):581-2 doi: 10.1016/0014-2964(71)90066-1 PMID: 5172331 Trenbolone: Donner DG, Beck BR, Bulmer AC, Lam AK, Du Toit EF Improvements in body composition, cardiometabolic risk factors and insulinsensitivity with trenbolone in normogonadic rats Steroids 2015 Feb;94:60-9 doi: 10.1016/j.steroids.2014.12.017 Epub 2014 Dec 30 PMID: 25554582 Spranger B, Metzler M Disposition of 17 beta-trenbolone in humans Journal of Chromatography 1991 Apr;564(2):485-492 Ma F, Liu D 17β-trenbolone, an anabolic-androgenic steroid as well as an environmental hormone, contributes to neurodegeneration.Toxicol Appl Pharmacol 2015 Jan 1;282(1):68-76 doi: 10.1016/j.taap.2014.11.007 Epub 2014 Nov 25 PMID: 25461682 Le Guevel R, Pakdel F Assessment of oestrogenic potency of chemicals used as growth promoter by in-vitro methods Hum Reprod 2001 May;16(5):1030-6 Bauer ER, Daxenberger A, Petri T, Sauerwein H, Meyer HH Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor APMIS 2000 Dec;108(12):838-46 Thomas KM, Rodway RG Effects of trenbolone acetate on adrenal function and hepatic enzyme activities in female rats J Endocrinol 1983 Jul;98(1):121-7 Baxa TJ, Hutcheson JP, Miller MF, Brooks JC, Nichols WT, Streeter MN, Yates DA, Johnson BJ Additive effects of a steroidal implant and zilpaterol hydrochloride on feedlot performance, carcass characteristics, and skeletal muscle messenger ribonucleic acid abundance in finishing steers JAnim Sci 2010 Jan;88(1):330-7 Yarrow JF, McCoy SC, Borst SE Tissue selectivity and potential clinical applications of trenbolone (17beta-hydroxyestra-4,9,11-trien-3-one): A potent anabolic steroid with reduced androgenic and estrogenic activity Steroids 2010 Jun;75(6):377-89 doi: 10.1016/j.steroids.2010.01.019 Epub 2010 Feb PMID: 20138077 Books: Llewellyn W Anabolics Jupiter, FL: Molecular Nutrition LLC; 2017 Bond P Book on Steroids: A complete evidence based reference PeterBond.org; 2020 Swerdloff RS, Ng CM Gynecomastia: Etiology, Diagnosis, and Treatment [Updated 2019 Jul 7] In: Feingold KR,Anawalt B, Boyce A, et al., editors Endotext [Internet] South Dartmouth (MA): MDText.com, Inc.; 2000- Available from: https://www.ncbi.nlm.nih.gov/books/NBK279105/ ... training in men with HIV Am J Physiol Endocrinol Metab 20 02 Dec ;28 3(6):E 121 4 -22 doi: 10.11 52/ ajpendo.00189 .20 02 Epub 20 02 Aug 27 PMID: 123 88173 Bijlsma JW, Duursma SA, Thijssen JH, Huber O Influence... MCF-7 breast cancer cell proliferation Mol Cell Endocrinol 20 12 Nov 5;363(1 -2) :100-10 doi: 10.1016/j.mce .20 12. 08.0 02 Epub 20 12 Aug 10 PMID: 22 906881 Chowdhury P, Mahanta R Effect of Administration... 20 15 Feb;94:60-9 doi: 10.1016/j.steroids .20 14. 12. 017 Epub 20 14 Dec 30 PMID: 25 5545 82 Spranger B, Metzler M Disposition of 17 beta-trenbolone in humans Journal of Chromatography 1991 Apr;564 (2) :485-492