Why is Deca so suppressive ?

[Madball99]

What is it about Deca that makes it so suppressive as compared to other anabolics and what makes recovery from it so hard and slow ?

[DLMCBBB]

Originally Posted by Madball99

What is it about Deca that makes it so suppressive as compared to other anabolics and what makes recovery from it so hard and slow ?

Madball99,

Here is a copy of what Nandi had to say about this subject before his passing.

Enjoy

Wannabebig: Why do you think Deca has been touted as one of, if not the most suppressive androgen?

Nandi: Deca's reputation as being highly suppressive to the Hypothalamic-Pituitary-Testicular Axis (HPTA) is probably deserved, but Trenbolone may be even more suppressive. Unfortunately there is not much research to rely on here so we are forced to speculate to some degree. There are several reasons that could explain Deca's ability to shut down the HPTA relatively strongly. First, the decanoate ester is very long lived. By this I mean because of its hydrophobicity (insolubility in water or plasma) it has a tendency to diffuse very slowly out of the injection site into the plasma where the ester is removed from the nandrolone molecule. I like to refer people to the study by Minto et al to see this depicted graphically in Figure 1 from the Pharmacology website.

As Fig.1 shows, it takes over a month for nandrolone plasma levels to return to zero after a single injection of Deca. Figure 3 in the same study shows that plasma levels of endogenous testosterone levels are a virtual mirror image of plasma nandrolone levels, with testosterone taking a month to return to baseline. And bear in mind this is after just one injection of Deca. The second reason Deca may be so suppressive is that besides being an androgen, it also has progestigenic properties, meaning it binds to the human progesterone receptor at relatively low concentrations where it acts as an agonist (1). As an example of the relative binding affinities of androgens to the progesterone receptor (PR), if progesterone itself is given an arbitrary relative binding affinity (RBA) of 100, testosterone's RBA is 1.1; DHT's is 0.9; nandrolone's RBA is 20; trenbolone's is 60 (2). So we see that nandrolone binds to the PR with about 20% of the strength of progesterone. The significance of this to our discussion is that progesterone, as well as synthetic progestins can act on the HPTA to reduce luteinizing hormone (LH) production (3). Most of our readers are aware that LH secreted from the pituitary is what drives testicular testosterone production. So by acting as a progesterone receptor agonist, nandrolone is contributing to the suppression of the HPTA. This is in addition to the ability of androgens in general to suppress pituitary LH production by interfering with the Gonadatropin Releasing Hormone (GnRH) signal sent from the hypothalamus to the pituitary, which drives LH secretion.

The above mentioned ability of Deca and other androgens to suppress natural testosterone production by acting to disrupt GnRH signaling is the third reason Deca is quite suppressive. The presence of androgen receptors in the GnRH secreting neurons has been demonstrated in a number of studies (see 4,5 for example) and it is believed that androgens act directly on these receptors to disrupt GnRH pulse signaling. As most readers are aware, nandrolone binds to the AR with a greater affinity than does testosterone, so this may be another factor in nandrolone being more suppressive than other steroids. However, as (4) points out, DHT could possibly be the active androgen in the hypothalamus. If this is the case, one might expect testosterone, via its conversion to DHT, to be more suppressive at the hypothalamic level. This clearly requires more research.

Deca also aromatizes to some degree, and since estrogens are quite suppressive, this certainly could contribute to Deca's ability to shut a person down compared to nonaromatizing steroids. On the other hand, testosterone aromatizes quite readily and the resulting elevated estrogen levels contribute significantly to HPTA suppression. Moreover, by suppressing testosterone production, which is a superior substrate for aromatase, Deca has been shown to either lower estrogen levels or leave them unchanged. So aromatization is the least likely mechanism for Deca's HPTA suppression.

In a recent issue of Mind & Muscle I described in an article entitled Understanding Androgen Actions how different androgens and anabolic steroids, after binding to the androgen receptor, preferentially bind to different genes:

Quoting from the article,

"[There is] evidence for the existence of distinct steroid specific target gene transcription profiles following AR activation (3). In other words, the structures of androgen responsive genes vary in such a way that some genes are more readily activated by certain androgens than by others. The set of genes readily switched on by a given androgen determines the net physiological effect of that androgen."

This is most likely the best explanation for the suppressive nature of Deca: due perhaps simply to the shape or charge distribution of the molecule, after binding to the androgen receptor (AR), the Deca/AR complex preferentially binds to genes that regulate LH and/or GnRH production, the net result being a decrease in the production of either or both of those hormones.

1) Methods Find Exp Clin Pharmacol 1997 May;19(4):215-22
Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays.
Markiewicz L, Gurpide E.

(2) Cancer Res 1978 Nov;38(11 Pt 2):4186-98
Unique steroid congeners for receptor studies.
Ojasoo T, Raynaud JP.

(3) Clin Endocrinol (Oxf) 2003 Apr;58(4):506-12 Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male.
Brady BM, Anderson RA, Kinniburgh D, Baird DT

(4) J Neuroendocrinol 2001 Apr;13(4):353-7
5Alpha-reductase type 2 and androgen receptor expression in gonadotropin releasing hormone GT1-1 cells.
Poletti A, Rampoldi A, Piccioni F, Volpi S, Simeoni S, Zanisi M, Martini L

(5) Endocrinology 1998 Mar;139(3):1108-14
Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alpha-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons.
Belsham DD, Evangelou A, Roy D, Duc VL, Brown TJ.

[chris gordon]

very good info here....Nandi definitely knew his shit