Nandrolone Data (including joint pain relief mechanisms [by Type-IIx])

[Type-IIx]

Nandrolone Data (including joint pain relief mechanism(s))
Author: Type-IIx

19-nortestosterone; 19-nor-4-androsten-17β-ol-3-one; 17β-hydroxyestr-4-en-3-one; Nandrolone; Deca; NPP

Removal of the methyl group at C-19 yields a product that is 20% as susceptible to aromatization as T (Vida (227)). Its C-4,5 double bond does render it susceptible to 5α-reduction, however, its 5α-reduced product, dihydronandrolone (DHN) is a weak AR ligand, thus its action in prostrate, scalp is relatively weakened. [1]


Unlike Trenbolone, Nandrolone has no effect on GR number (glucocorticoid receptor expression) in rat muscle (40). [2]


Erythropoiesis
Markedly augments erythropoiesis (>Oxymetholone) [3] (decanoate > phenylpropionate)


Bloodwork
600mg Deca only:

E2 8.1 pg/mL (low-normal)

IGF-I 327 µg/L (high)

Source: withheld; off-site reference



Potency for muscle anabolism
[4] 200mg 8 weeks ND yielded +2.6 kg FFM

[5] 300mg ND vs. 300mg TE * 6 weeks, skinfold caliper measures, insignificant between-group differences (n=8 or 9)
(consider inaccuracies inherent to caliper use and inter- subject & inter- & intra- practitioner variation in measurement technique; small group sizes & high likelihood of type II error [statistics])


Psychological effects of Nandrolone

Hannan et al. (1988) have examined plasma homovanillic acid changes following 6 weekly intramuscular injections of 100 or 300mg of testosterone enanthate or nandrolone decanoate administration in 25 males and found significant increases in homovanillic acid for both of the nandrolone but neither of the testosterone treatments. Since a large proportion of plasma homovanillic acid originates from CNS metabolism of dopamine, the demonstrated change associated with nandrolone administration confirms an anabolic-androgenic steroid-induced alteration in CNS neurotransmitter metabolism and suggests a mechanism to explain reported altered behaviour in some anabolic-androgenic steroid users. Interestingly in this regard the deletion of the 19-methyl group in nandrolone produces a more planar steroid than testosterone that thus, like 5α-dihydrotestosterone, has altered receptor binding affinities, as well as unique metabolites. It must be added that estrogens are also known to alter central nervous system neurotransmitters through inhibition of monamine oxidase activity, so aromatisation of testosterone to estrogen could also play a role (Klaiber 1972).
[6]

[7]

* Serum homovanillic acid (HVA) changed significantly in ND 100 mg weekly (+17.6 ± 7.7 pmol/L) and ND 300 mg weekly (+11.0 ± 3.3 pmol/L) but not in TE 100mg nor TE 300mg groups. That is, even therapeutic/replacement doses of nandrolone produced significant changes in dopamine metabolism.

Dopamine metabolism changed by nandrolone but not by testosterone... could have originated from both intra- and extra- cerebral sources. The difference in effect may reside in differences in the biologically active metabolites, but high TE (300mg) producing by far the greatest change in estrogen concentration while not producing any change in HVA argues against a role for estrogen alone in dopaminergic activity of androgens. [7]

- The proposed dynamic interaction of changing concentrations of estrogen metabolites with ND (half-life, 8 days) and its metabolite DHN may be implicated in changes in the number of dopamine receptors that are dependent on the timing of exposure to estrogens and on the presence of other steroid hormones (Hruska, 1980; Fernandez-Ruiz, et al., 1989) [7].


Aromatization
After 6 weeks, serum E₂ was reduced to 11 ± 9 pg/mL (100mg ND) and 14 ± 4 pg/mL (200mg ND) [7]


Molecular modeling of predicted activity

Swiss Target Prediction:



Pharmacokinetics & Pharmacodynamics



NPP (nandrolone phenylpropionate; Durabolin [sans Deca]): duration of activity of 10 days vs. Deca-Durabolin's duration of activity of 21-28 days. The phenylpropionate ester is characterized by a relative molecular weight of 1.46 & relative parent hormone content of 0.69 (comparable to cypionate & enanthate).


HPG axis suppression

- Testosterone suppression: complete suppression between 5-10 days with a single 100mg bolus:



- "Plasma testosterone concentrations were most rapidly and completely suppressed within the first week after injections of the phenylpropionate ester, but this suppression was sustained for the shortest time. The duration of suppression was significantly longest after the gluteal 1-ml injection. Plasma testosterone concentrations returned to base line by day 13 after the phenylpropionate ester but required >20 days to return to base-line levels after the decanoate ester." [10]

- FSH suppression occurred rapidly (day 3 or 4) but returned to base-line practically immediately after phenylpropionate (IM gluteal) and after about a week with decanoate (Table 6, Inhibin, p. 100) [10]

 

[Type-IIx]

Joint Pain Relief
Mechanisms in improved joint pain symptoms:

- increased collagen synthesis & deposition in tendon & ligament
- synovial joint fluid retention


Collagen synthesis
Supraphysiological AAS (primarily Nandrolone & T):

- ↑ serum PIIINP [dose-dependently]
- ↑ urine HP:LP

High AAS doses enhance soft tissue collagen metabolism, with no change in bone resorption [8]

Withdrawal ↓ serum ICTP [time-dependently] [8]

* procollagen Type III N-terminal propeptide (PIIINP): a marker of interstitial fibril biosynthesis in soft tissues
- highly relevant to sport; this is what is stimulated by fast movement/velocity training in tendon, where stiffness benefits velocity, whereas muscular strength adaptations must compensate for the heightened risk of muscular strain due to excessive tendon stiffness

Urinary markers:

* HP (PYD): hydroxylysylpyridinoline; reflects turnover of collagens Type I (bone), II, III & IX; present in tendon, cartilage, bone, vessel walls & dentine

* LP (DPD): lysylpyridinoline; reflects turnover of collagen Type I (bone); present in bone & dentine

- There is an age-associated decline in HP (↓), LP (↓), and HP/LP ratio (↓)

- HP:LP (urine) excludes skin metabolism (useful)

- The urinary HP and LP are potentially more useful markers of the catabolism of collagen fibres from skeletal tissues than urinary hydroxyproline. The latter has a lower specificity profile since it is found in all collagen types of all connective tissues (including skin). Moreover, it may also be released from collagen molecules prior to their incorporation into fibrils, and a large proportion of hydroxyproline is metabolized in the liver, thereby evading quantitative analysis of the resorption of mature collagen by urinary measurements (9- 12). [9]

- Lower HP:LP may reflect higher relative proportion of bone resorption vs. collagen & cartilage turnover since bone collagen is the primary LP source whereas HP reflects soft tissues generally (except skin)...suggests that resorption of Type III collagen (more HP than Type I) also decreases with age [9]

- Peak bone mass & HP:LP occurs at age 27 [9]

crosslinked telopeptide of Type I collagen (ICTP): released into circulation during the osteoclastic phase of bone modeling and remodeling (bone/collagen breakdown). ICTP constitutes pyridinoline crosslinks formed in mature collagen type I, and their concentrations in serum and urine reflect bone resorption.

RAS (fluid retention & collagen deposition in tendon)
Both mechanisms (increased collagen production in i.e. flexor tendon) and synovial joint fluid retention may be positively acted upon by the renin-angiotensin system (RAS). The RAS regulates water and electrolyte balance, connective tissue cell growth, and the metabolism of loose and dense connective tissue and sites of tissue repair [11] . Pathologically, RAS activation increases vascoconstriction, cardiac hypertrophy, and fibrosis (resulting in myocardial infarction, fibrosis of the liver) [11]. Therefore, it is important to consider the duality of the potential joint (i.e., knee extensor tendon) augmentation while on nandrolone: you may have a transient benefit in tendon remodeling (i.e., extensor tendon), but via this same mechanism, may be accruing fibrotic or cardiac/left ventricular maladaptations.

So, to the potential transient benefits: Angiotensin-I converting enzyme (ACE) is a marker positively correlated with collagen type I mRNA activity, and may reflect ECM remodeling wherein collagen synthesis outstrips degradation.

Whereas AAS generally decrease matrix metalloproteases (MMP), collagen gene expression, nandrolone increases ACE activity and increases matrix type I collagen deposition. The results of [11] showed Nand + jump training >> Nand > jump training > sedentary in ACE activity in tendon (i.e., knee extensor). Consider, however, that this same pathway is implicated in cardiac tissue remodeling and pathological action.

__________
References:
[1] Bergink, E. W., et al. “Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions.” Journal of steroid biochemistry 22.6 (1985): 831-836.
[2] Herbst, K. L., & Bhasin, S. (2004). Testosterone action on skeletal muscle. Current Opinion in Clinical Nutrition and Metabolic Care, 7(3), 271–277. doi:10.1097/00075197-200405000-00006
[3] Gorshein, D., Murphy, S., & Gardner, F. H. (1973). Comparative study on the erythropoietic effects of androgens and their mode of action. Journal of Applied Physiology, 35(3), 376–378. doi:10.1152/jappl.1973.35.3.376
[4] van Marken Lichtenbelt WD, Hartgens F, Vollaard NB, Ebbing S, Kuipers H.
Bodybuilders' body composition: effect of nandrolone decanoate. Med Sci Sports Exerc. 2004 Mar;36(3):484-9. doi: 10.1249/01.mss.0000117157.06455.b0. PMID: 15076791.
[5] Friedl, K. E., Dettori, J. R., Hannan, C. J., Patience, T. H., & Plymate, S. R. (1991). Comparison of the effects of high dose testosterone and 19-nortestosterone to a replacement dose of testosterone on strength and body composition in normal men. The Journal of Steroid Biochemistry and Molecular Biology, 40(4-6), 607–IN6. doi:10.1016/0960-0760(91)90283-b
[6] Bahrke, M. S., Yesalis, C. E., & Wright, J. E. (1990). Psychological and Behavioural Effects of Endogenous Testosterone Levels and Anabolic-Androgenic Steroids Among Males. Sports Medicine, 10(5), 303–337. doi:10.2165/00007256-199010050-00003
[7] Hannan, C.J., Friedl, K., Zold, A., Kettler, T., & Plymate, S. (1991). Psychological and serum homovanillic acid changes in men administered androgenic steroids. Psychoneuroendocrinology, 16(4), 335–343. doi:10.1016/0306-4530(91)90019-p
[8] Pärssinen, M., Karila, Kovanen, & Seppälä. (2000). The Effect of Supraphysiological Doses of Anabolic Androgenic Steroids on Collagen Metabolism. International Journal of Sports Medicine, 21(6), 406–411. doi:10.1055/s-2000-3834
[9] Açil, Y., Brinckmann, J., Notbohm, H., Müller, P. K., & Bätge, B. (1996). Changes with age in the urinary excretion of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). Scandinavian Journal of Clinical and Laboratory Investigation, 56(3), 275–283. doi:10.3109/00365519609088617
[10] Minto CF, Howe C, Wishart S, Conway AJ, Handelsman DJ. Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: effects of ester, injection site and injection volume. J Pharmacol Exp Ther. 1997 Apr;281(1):93-102.
[11] Marqueti, R. de C., Hashimoto, N. Y., Durigan, J. L. Q., Batista e Silva, L. L., Almeida, J. A. de, Silva, M. da G. da, … Araújo, H. S. S. de. (2015). Nandrolone increases angiotensin-I converting enzyme activity in rats tendons. Revista Brasileira de Medicina Do Esporte, 21(3), 173–177. doi:10.1590/1517-869220152103143667

 

[luki7788]

great fast - so what weekly dose of nandrolone (let's say, for example, decanoate) will give quite a clear collagen synthesis effect - 100 mg per week?

 

[Type-IIx]

great fast - so what weekly dose of nandrolone (let's say, for example, decanoate) will give quite a clear collagen synthesis effect - 100 mg per week?

Yes, I believe even as low as 50 mg weekly can confer joint pain benefits.

 

[luki7788]

This is what I do, keep 100mg a week all year round and I definitely feel a huge difference than when I didn't

 

[carbs]

This is what I do, keep 100mg a week all year round and I definitely feel a huge difference than when I didn't

any deca dick with that dosage?

 

[luki7788]

any deca dick with that dosage?

lol I don't use nandrolone without testosterone so it's not possible, after that I even tried 2000mg of nandrolone per week and never had anything like a dick deck

 

[junker]

Yes, I believe even as low as 50 mg weekly can confer joint pain benefits.

good post, i was gonna ask this too. ive seen it as low as 50mg but also seen studies where nd was given at half the dose of test on trt and pain relief was universal pretty much. id like to use minimum effective dose so ill try 50 first

 

[Mufasa123]

This is what I do, keep 100mg a week all year round and I definitely feel a huge difference than when I didn't

Same here 100mg during cruises and minimum in any blast. I think the joint fluid is the main thing. It's like an anti inflammatory. Promotes an environment where you are less likely to have issues and any issues you do have seem to heal faster in that environment. Not a miracle drug but my God it's a night and day difference.

 

[Performance Based]

Nandrolone Data (including joint pain relief mechanism(s))
Author: Type-IIx

19-nortestosterone; 19-nor-4-androsten-17β-ol-3-one; 17β-hydroxyestr-4-en-3-one; Nandrolone; Deca; NPP

Removal of the methyl group at C-19 yields a product that is 20% as susceptible to aromatization as T (Vida (227)). Its C-4,5 double bond does render it susceptible to 5α-reduction, however, its 5α-reduced product, dihydronandrolone (DHN) is a weak AR ligand, thus its action in prostrate, scalp is relatively weakened. [1]


Unlike Trenbolone, Nandrolone has no effect on GR number (glucocorticoid receptor expression) in rat muscle (40). [2]


Erythropoiesis
Markedly augments erythropoiesis (>Oxymetholone) [3] (decanoate > phenylpropionate)


Bloodwork
600mg Deca only:




Source: withheld; off-site reference



Potency for muscle anabolism
[4] 200mg 8 weeks ND yielded +2.6 kg FFM

[5] 300mg ND vs. 300mg TE * 6 weeks, skinfold caliper measures, insignificant between-group differences (n=8 or 9)
(consider inaccuracies inherent to caliper use and inter- subject & inter- & intra- practitioner variation in measurement technique; small group sizes & high likelihood of type II error [statistics])


Psychological effects of Nandrolone


[7]

* Serum homovanillic acid (HVA) changed significantly in ND 100 mg weekly (+17.6 ± 7.7 pmol/L) and ND 300 mg weekly (+11.0 ± 3.3 pmol/L) but not in TE 100mg nor TE 300mg groups. That is, even therapeutic/replacement doses of nandrolone produced significant changes in dopamine metabolism.

Dopamine metabolism changed by nandrolone but not by testosterone... could have originated from both intra- and extra- cerebral sources. The difference in effect may reside in differences in the biologically active metabolites, but high TE (300mg) producing by far the greatest change in estrogen concentration while not producing any change in HVA argues against a role for estrogen alone in dopaminergic activity of androgens. [7]

- The proposed dynamic interaction of changing concentrations of estrogen metabolites with ND (half-life, 8 days) and its metabolite DHN may be implicated in changes in the number of dopamine receptors that are dependent on the timing of exposure to estrogens and on the presence of other steroid hormones (Hruska, 1980; Fernandez-Ruiz, et al., 1989) [7].


Aromatization
After 6 weeks, serum E₂ was reduced to 11 ± 9 pg/mL (100mg ND) and 14 ± 4 pg/mL (200mg ND) [7]


Molecular modeling of predicted activity

Swiss Target Prediction:
View attachment 155980


Pharmacokinetics & Pharmacodynamics
View attachment 155981


NPP (nandrolone phenylpropionate; Durabolin [sans Deca]): duration of activity of 10 days vs. Deca-Durabolin's duration of activity of 21-28 days. The phenylpropionate ester is characterized by a relative molecular weight of 1.46 & relative parent hormone content of 0.69 (comparable to cypionate & enanthate).


HPG axis suppression

- Testosterone suppression: complete suppression between 5-10 days with a single 100mg bolus:

View attachment 155983

- "Plasma testosterone concentrations were most rapidly and completely suppressed within the first week after injections of the phenylpropionate ester, but this suppression was sustained for the shortest time. The duration of suppression was significantly longest after the gluteal 1-ml injection. Plasma testosterone concentrations returned to base line by day 13 after the phenylpropionate ester but required >20 days to return to base-line levels after the decanoate ester." [10]

- FSH suppression occurred rapidly (day 3 or 4) but returned to base-line practically immediately after phenylpropionate (IM gluteal) and after about a week with decanoate (Table 6, Inhibin, p. 100) [10]

Thank you kindly for taking your time to compile this data for us mate.

 

[xpoc]

2 biggest concerns. Cardiovascular impact. I read a study that showed it was over 10x more damaging on the heart than straight testosterone. And then the erectile issues. Any input on these?

 

[Vanilla Thunder]

Yes, I believe even as low as 50 mg weekly can confer joint pain benefits.

I run 70-100mg / wk when I'm lean and lifting heavy and it really helps

 

[Type-IIx]

2 biggest concerns. Cardiovascular impact. I read a study that showed it was over 10x more damaging on the heart than straight testosterone. And then the erectile issues. Any input on these?

I do mention the duality of RAS activation (vascoconstriction, cardiac hypertrophy, and fibrosis, despite water and electrolyte balance, connective tissue cell growth, and the connective tissue metabolism & tissue repair): it's a double-edged sword. But if you can share some study showing this "10x more damaging to the heart than straight testosterone?" Is it this study by chance? D’Ascenzo, S., Millimaggi, D., Di Massimo, C., Saccani-Jotti, G., Botrè, F., Carta, G., … Dolo, V. (2007). Detrimental effects of anabolic steroids on human endothelial cells. Toxicology Letters, 169(2), 129–136. doi:10.1016/j.toxlet.2006.12.008

With respect to erectile issues and "deca dick," consider testosterone as it is the anabolic agent you'd want to use for preserving (and augmenting) sexual function.

 

[Biggerp73]

Brother I appreciate your posts, you are an intelligent guy, and you are trying to be helpful, but the mark of intelligence is making a complex subject simple, and the way you are currently approaching sharing information is the opposite of that, and really works against your ability to be of any help. It would be better if you wrote out your posts with more explanations, quotation marks, etc

 

[Type-IIx]

Brother I appreciate your posts, you are an intelligent guy, and you are trying to be helpful, but the mark of intelligence is making a complex subject simple, and the way you are currently approaching sharing information is the opposite of that, and really works against your ability to be of any help. It would be better if you wrote out your posts with more explanations, quotation marks, etc

Yeah, OTH is working with me on a more important quasi-article with a simplified section. Honestly, to me, this is rather simplified (as much as I believe it can be reduced without losing granularity). Sorry if it's incomprehensible, perhaps if there's enough demand (I didn't think this as much more than just a dump from my notes on Nandrolone) a guy like OuchThatHurts can put out a simplified version that preserves important detail.

 

[Type-IIx]

Thank you kindly for taking your time to compile this data for us mate.

You're welcome brother.

 

[Biggerp73]

Yeah, OTH is working with me on a more important quasi-article with a simplified section. Honestly, to me, this is rather simplified (as much as I believe it can be reduced without losing granularity). Sorry if it's incomprehensible, perhaps if there's enough demand (I didn't think this as much more than just a dump from my notes on Nandrolone) a guy like OuchThatHurts can put out a simplified version that preserves important detail.

You just need to put your copy/paste notes in quotes and introduce them with a few sentences of explanation.

 

[supermofo]

lol I don't use nandrolone without testosterone so it's not possible, after that I even tried 2000mg of nandrolone per week and never had anything like a dick deck

You're lucky, Luki. Even 50mg of NPP weekly with testosterone still negatively impacted my erection quality and even lowered my libido after just a few weeks. I want to like nandrolone for the joint comfort and muscle fullness that it gave me but I just can't because of the sexual sides and depressed mood that it gives me. I'd love to give nandrolone another chance alongside my TRT if I could offset those negative side effects.

 

[Mufasa123]

I do mention the duality of RAS activation (vascoconstriction, cardiac hypertrophy, and fibrosis, despite water and electrolyte balance, connective tissue cell growth, and the connective tissue metabolism & tissue repair): it's a double-edged sword. But if you can share some study showing this "10x more damaging to the heart than straight testosterone?" Is it this study by chance? D’Ascenzo, S., Millimaggi, D., Di Massimo, C., Saccani-Jotti, G., Botrè, F., Carta, G., … Dolo, V. (2007). Detrimental effects of anabolic steroids on human endothelial cells. Toxicology Letters, 169(2), 129–136. doi:10.1016/j.toxlet.2006.12.008

With respect to erectile issues and "deca dick," consider testosterone as it is the anabolic agent you'd want to use for preserving (and augmenting) sexual function.

I hear the 10x or multiples of test on cardiac all the time. I would REALLY like to know the issue as I've not found it either. I've heard it suggested that lack of enough E2 (on pure nandrolone vs test) was the cause and if a decent amount of E2 is present then it's a negating or mitigating factor. I've also heard the single one source study is shit as well.

That said, I've never seen or seen quoted that actually study or info. As someone who benefits greatly from nandrolone, had it prescribed and ran it for years alongside trt test with zero negative impact on blood markers (can't say that about even primo), understand it is one of the most studied anabolic out there with long term approval in US for human use - I'd love it get up to date on this one.

 

[rippedyearround]

Thanks for the research, TypeII!

Uneducated question: Would Telmisartan be useful in mitigating the effect nandrolone has on the RAS?