Here is some of my ongoing research:
Systemic Effects:
1. Adrenal Gland
Trenbolone has been implicated in shrinking the adrenal gland in vivo, and antiglucocorticoid activity via inhinbition of dexamethasone-induced transcriptional activity.
The adrenal cortex is regulated by neuroendocrine hormones secreted by the pituitary gland and hypothalamus → Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland, both located at the base of the skull, does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus.
2. Androgen Receptors, Progesterone Receptors
Trenbolone shows strong binding to the androgen receptor, to the progestin receptor and to the glucocorticoid receptor (21). Concerning the androgenic activity, it can be assumed that trenbolone acts like other androgens - in comparison with the most active endogenous hormone dihydrotestosterone (RBA= 100) the affinity of trenbolone-17P is even higher (RBA= 109).
“Biochemistry and physiology of anabolic hormones used for improvement of meat production” Review article, Heinrich Meyer
3. Pituitary, Hypothalamus, Testis
Since trenbolone possesses both estrogenic (ER) or progestogenic (PR) activity, it inhibits LH & FSH by directly down-regulating the GnRH receptors on the pituitary, while also reducing GnRH release from the hypothalamus. Therefore, progestin based AAS such as trenbolone (and nandralone) are “double suppressive” because they are binding to the AR and PR and suppressing LH & FSH by two different mechanisms.
Patterns of LH secretion in castrated bulls during intravenous infusion of androgenic and estrogenic steroids: Pituitary response to exogenous luteinizing hormone-releasing hormone
M.J. D’occhio et al. Biology of reproduction 26, 249-257 (1982)
Studies on the role of sex steroids in the feedback control of FSH concentrations in men.
Sherins RJ, Loriaux DL. 1973 J Clin Endocrinol Metab. 36:886-893
So, What Does This Mean?
1. In terms of Erectile Dysfunction
"On the other hand, T is more relevant than DHT in erectile function, which requires central and peripheral androgenic activity. T exerts both humoral endocrine and local paracrine effects. It is likely that androgens are vital for the development, maintenance and function of penile tissue and regulation of erectile physiology. However, the critical androgenic substance for these effects is most likely T rather than DHT." J Androl 2008;29:514–523
This implies that trenbolone affects and/or displaces testosterone and DHT from androgen receptors, thereby effecting erections.
Further, the increases in prolactin seen on -- and after cessation of -- trenbolone have an adverse, inhibitory effect on testosterone and LH levels. High prolactin is correlated with low libido and erectile dysfunction.
Results of this investigation indicate that oestradiol causes pathophysiological changes in erectile function. These observations provide an indirect evidence for the possible sexual health hazards in man upon inadvertent exposure to environmental oestrogens, ageing and derangement of E2–T ratio.
International Journal of Impotence Research (2003) 15, 38–43. doi:10.1038/sj.ijir.3900945
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In summary, administration of a potent and selective aromatase antagonist reduces estradiol and
elevates mean LH concentrations equivalently in young and older men. The low estrogen-feedback
state in elderly men unmasks diminished incremental LH pulse amplitude and area; absence of further
acceleration of LH pulse frequency; impaired regulation of the orderliness of LH release; and reduced
testosterone to SHBG ratios. Thus, aging alters expected hypothalamopituitary-gonadal adaptations
to short-term partial estrogen depletion in healthy men.
J Clin Endocrinol Metab. 2005 January ; 90(1): 211–218.
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In summary, administration of a selective aromatase antagonist lowers (24-h mean)
concentrations of estradiol by 50% and elevates LH concentrations by 100% in young and
older healthy men. Negative-feedback adaptations to partial estrogen withdrawal differ
significantly by age. In particular, relative estrogen depletion in older, unlike young, men fails
to evoke (further) augmentation of the following: 1) incremental LH peak amplitude and LH
pulse area; 2) daily LH pulse frequency; 3) LH secretory-pattern irregularity; and 4) the molar
ratio of testosterone to SHBG concentrations. These outcomes extend concepts of agingassociated
regulatory defects in the male by hypothalmopituitary gonadal axis to include
estrogen-dependent feedback control.
J Clin Endocrinol Metab. 2005 January ; 90(1): 211–218.
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Results of this investigation indicate that oestradiol causes pathophysiological changes in erectile function. These observations provide an indirect evidence for the possible sexual health hazards in man upon inadvertent exposure to environmental oestrogens, ageing and derangement of E2–T ratio.
International Journal of Impotence Research (2003) 15, 38–43. doi:10.1038/sj.ijir.3900945
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Similar pathophysiological imbalance between androgen and oestrogen is likely to be associated with other clinical states of adult-onset hypogonadism9 as well as hyperoestrogenism.10 Under such circumstances, since E2 is a more potent gonadotropin suppressant than testosterone,4 a vicious cycle that leads to an absolute testosterone deficiency is likely to be precipitated by E2-induced decrements in LH and FSH release.
International Journal of Impotence Research (2003) 15, 38–43. doi:10.1038/sj.ijir.3900945
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Conforming to structural changes in the cavernosum of trans-sexuals exposed to oestrogen,17 the penile morphology demonstrated a reduction in smooth muscle and relative increase in connective
tissue distribution.
International Journal of Impotence Research (2003) 15, 38–43. doi:10.1038/sj.ijir.3900945
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(a) Light micrograph 1: trichrome-stained light micrograph of control rat cavernosum. Scattered sinusoids, smooth muscle fibres and connective tissue show normal architecture (magnification: 50). (b) Light micrograph 2: trichrome-stained light micrograph of cavernosum from E2-(0.01 mg) treated rat at 12 weeks. Some degree of connective tissue proliferation is seen (magnification: 50).
(c) Light micrograph 3: trichrome-stained light micrograph of cavernosum from E2-(0.1 mg) treated rat at 12 weeks. There is extensive loose connective tissue proliferation amidst the distribution of sinusoidal spaces and scanty smooth musculature (magnification: 50).
International Journal of Impotence Research (2003) 15, 38–43. doi:10.1038/sj.ijir.3900945
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1) Smooth Muscle Dysfunction.*Researchers now know that testosterone both maintains smooth muscle and the nerves the fire them in the corpus cavernosum. [1][5] For example, researchers have noted that in castrated animals, the nerve fibers and myelin sheaths around them actually shrink and "wither". And they have also noted that smooth muscle content in the corpus cavernosum decreased as well. [2] Yes, testosterone affects everything in a male!
2) Corpus Cavernosum Integrity. The research points to the fact that low testosterone can actually affect the connective tissue within the corpus cavernosum.* While you are losing smooth muscle, you are also likely gaining more connective tissue, i.e. collagen. [1][2][5] The ECM (extracellelular matrix) changes for the worse, another structure implicated in erectile dysfunction. [6]* This is a sort of "hardening" similar to what causes problems throughout your body. You need for the corpus cavernosum to be flexible and expandable in order to properly compress the outflow.
The bottom line is that researchers have found that in a low testosterone environment, the inside of the penis literally atrophies and is replaced with inelastic, fibrous tissue.*
For some of you that have discovered that you lived in a hypogonadal state for years without knowing it, this may be a scary prospect.* "Did it do permanent damage?" is the natural question to ask yourself.
The answer is probably 'yes' to some degree.* However, the good news is that studies show that if testosterone is restored, normal erectile function usually goes with it.* This means that the damage could not have been too severe from a long term low testosterone environment and indicates that a significant reversal is possible.*
By the way, some of you who may not respond well to PDE5 Inhibitors, such as Viagra or Cialis, may find that restoring your testosterone restores your erections for the above reasons. One study looked at hypogonadal males who did not respond to Viagra and found a significant restoration of erectile function after HRT (Testosterone Therarpy). [3] Very similar results were found in a study of Cialis non-responders as well. [5] In other words, sometimes the problem is nitric oxide and sometimes it is low testosterone (or both).
So the bottom line is that many of you need to either Increase Your Testosterone Naturally or discuss with your doctor Hormone Replacement Therapy if you want your erections back.* And, yes, Sex is Good For You.
* REFERENCES:
1) J Sex Med, 2005, 2:759–770, "The Physiological Role of Androgens in Penile Erection: Regulation of Corpus Cavernosum Structure and Function"
2) Endocrinology, Apr 1 1999, 140(4)1861-1868, "Effects of Castration and Androgen Replacement on Erectile Function in a Rabbit Model"
3) J Urol, 2004 Aug, 172(2):658-63, "Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone"
4) Grape seed
5) Andrologia, 2006, 38:61–68, "Testosterone and erectile function in hypogonadal men unresponsive to tadalafil: results from an open-label uncontrolled study"*
6) Braz. J. Morphol. Sci., 2008, 25(1-4):35-10, "Stereological study of extracellular matrix of penile body in felis domestica: experimental model applied to erectile dysfunction"
Venous Leakage
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Androgens are deemed to be critical for the development, growth, and maintenance of penile tissue as well as for erectile function. Androgens are also reported to inhibit differentiation of stroma progenitor cells into adipocytes and promote differentiation into smooth muscle. The objective of this study was to investigate whether androgen deprivation results in accumulation of adipocytes in the corpus cavernosum. Mature, New Zealand white male rabbits were subjected to sham surgery (control) or orchiectomy. Two weeks after surgery, erectile function was assessed by monitoring changes in intracavernosal blood pressure (ICP) in response to pelvic nerve stimulation. All ICP measurements were normalized to the mean systemic arterial blood pressure. In parallel studies, penile cross sections from control and orchiectomized rabbits were fixed and stained with either Masson's trichrome or hematoxylin and eosin to assess smooth muscle and connective tissue content. Alternatively, tissue sections were stained with Toluidine blue to assess accumulation of fat-containing cells. Orchiectomy resulted in loss of erectile function and penile atrophy, associated with reduced trabecular smooth muscle and increased connective tissue content. Most strikingly, tissue from orchiectomized animals exhibited accumulation of fat-containing cells (adipocytes) in the subtunical region of the corpus cavernosum. We hypothesize that androgen deprivation promotes differentiation of progenitor stroma cells into an adipogenic lineage producing fat-containing cells, thus altering erectile function.
Journal of Andrology, Vol. 26, No. 2, March/April 2005
**This is a work in progress. I'll edit it as my body of research grows.
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