I thought that I'd help out and post my ongoing research into the issue of erectile function and libido in regard to the HPT, including testosterone, estrogen, and prolactin. Long story short, you need to have your estrogen (estradiol, ultra sensitive) and prolactin checked, in addition to your free testosterone and SHBG/albumin.
To me, it sounds like estrogen is out-competing testosterone at your androgen receptors, or your prolactin is antagonizing your testosterone. In either case, get them checked.
Here you go:
We conclude that 5 a-reductase inhibitors do not lead to erectile dysfunction to a significant degree, and we support the position that dihydrotestosterone is less relevant than testosterone in erectile function.
J Androl 2008;29:514–523
The results suggest that anabolic steroids can act via muscle glucocorticoid receptors,
thereby antagonizing the catabolic activity of endogenous glucocorticoids, rather than via muscle
androgen receptors.
J. steroid Bioehem.V ol. 29, No. 6, pp. 575-581, 1988
Although the role of androgens in erectile function in men is controversial, primary or secondary hypogonadism is considered key in the pathophysiology of erectile dysfunction (ED) (Korenman et al, 1990; Aversa et al, 2004; Yassin and Saad, 2007). Androgens exert not only genomic effects, for example, by stimulating the expression of the neuronal isoform of nitric oxide (NO) synthase (Reilly et al, 1997; Park et al, 1999), but also nongenomic effects, for example, by relaxing the smooth musculature of coronary arteries and the aorta (Yue et al, 1995; Deenadayalu et al, 2001).
J Androl 2008;29:514–523
T is important for modulating the central and peripheral regulation of ED. Erectile function depends on a normal penile anatomy and a functioning venoocclusive mechanism, which implies integrity of the
structural and cellular components. It was demonstrated that T deprivation causes apoptosis of cells from cavernosal and spongiosal tissues, which can be prevented by androgen administration (Podlasek et al, 2005).
J Androl 2008;29:514–523
Smooth muscle, a vital component of the penile anatomy, is a critical structure for tumescence. Using a
rat model, investigators established that experimental castration caused significant reduction in trabecular smooth muscle and a significant increase in connective tissue deposition concomitant with loss of erectile function, indicating that T is vital for smooth muscle integrity (Traish et al, 2003). Further support for the androgenic requirement for penile erection derives from scientific knowledge of the molecular basis for NO function in the penis. It was shown that the NO pathway plays a critical role in initiation and maintenance of erectile function (Burnett, 2004). In animals, the expression of NO synthase (NOS) isoforms in the Canguven and Burnett N 5 a-reductase Inhibitors on Erection 515 corpus cavernosum is regulated by androgens. Researchers found that NOS activity is decreased in
erectile tissues of castrated animals, as is the erectile response to pelvic nerve stimulation (Lugg et al, 1995; Park et al, 1999; Baba et al, 2000). These investigators further established that T restores the erectile response and normalizes NOS protein expression and activity. On the whole, the mechanism of penile erection is a function of corporal smooth muscle relaxation required for blood filling and engorgement of the penis in response to sexual excitement, exerted at the molecular level by cGMP by way of its effector cGKI (Andersson, 2001). Type 5 phosphodiesterase enzyme (PDE5), the predominant phosphodiesterase expressed in the corpus cavernosum, has regulatory control of penile vasorelaxant actions. In the animal model, castration resulted in reduced protein expression and activity of PDE5, although androgen treatment up-regulated the expression of PDE5 activity (Morelli et al, 2004). In addition, the efficacy of PDE5 inhibitors to elicit erections induced by electrostimulation of the cavernous nerves following castration was decreased. After castrated animals were treated with T, the tissue relaxation caused by PDE5 inhibitors was successfully restored (Traish et al, 1999; Morelli et al, 2004). Clinical studies also indicate the direct influence of androgens on erectile responses to PDE5 inhibitors. Investigators carrying out clinical trials in androgen deficient men confirmed these observations and found that with androgen substitution these men displayed enhanced responses to the ED treatment (Aversa et al, 2004; Shabsigh et al, 2004; Morelli et al, 2007). These studies strongly suggest that T exerts vital physiological actions in erectile function.
J Androl 2008;29:514–523
The data suggested that DHT is the active androgen that prevents erectile failure in castrated rats.
With recent discoveries of PDE5 inhibitors as well NOS signaling in the penis, Park et al (1999) examined whether DHT influences the erectile response and the mRNA expressions of NOS isoforms in the penile corpus cavernosum of castrated rats. For this purpose, rats were separated into 5 groups: sham, castrated alone, and castrated receiving T, DHT, or T with the 5ARI finasteride. Both T and DHT effectively restored the erectile response to normal. NOS activity and the amount of neuronal NOS (nNOS) mRNA were also reduced in castrated rats but restored by both T and DHT replacement.
J Androl 2008;29:514–523
Finasteride, DHT, Testosterone, Atrophy of Corpus Cavernosum
The T and DHT levels in castrated rats and the DHT level in finasteride-treated groups were significantly lower than those in the control group. In the castrated animals, there was a high degree of
fibrosis in the corpus cavernosum with irregularly arranged collagenous fibers and a marked decrease in smooth muscle fibers, while in the DHT-inhibited group (finasteride-treated), the corpus cavernosum comprised a substantial amount of thick and irregularly arranged collagenous fibers, but the degree of fibrosis was less than that of the castration group (Shen et al, 2000). This work suggests that because finasteride inhibits the action of DHT but not T on the corporal cavernosal tissue, the degree of fibrosis was less in the DHT-inhibited group than in the castration group. In the castration group, the thickness of tunica albuginea decreased significantly and the elastic fibers were mostly supplanted by collagenous fibers, and in the DHT-inhibited group, the elastic fibers were replaced by disorganized and thick collagenous fibers. Since the tunica albuginea plays a major role in the erectile mechanism of the penis, the latter results offer an explanation for the presentation of ED in patients treated with 5ARIs.
J Androl 2008;29:514–523
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
Only one androgen receptor cDNA has been identified and cloned, despite the two different ligands (22, 23, 24, 25). The concept of two hormones and one receptor to explain the different actions of androgens has been generally accepted and, according to the information available from the human genome project, it is very unlikely that additional genes exist coding for a functional nuclear receptor with androgen receptor-like properties (17).
Chapter 3. Androgen Physiology: Receptor and Metabolic Disorders
Albert O. Brinkmann, Ph.D. Assoc. Professor of Biochemistry, Endocrinology, and Reproduction, Departmentsyntherol of Reproduction and Development ,ErasmusMC, University Medical Center Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands HOME
Revised November, 2009
Bromocriptine, Dostinex, for elavated prolactin levels that are a big problem... for some reason the hpta gets out of whack and the problem can linger for years. Expecially with a deca cycle.
**broken link removed**
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.
Toxicological Sciences 70, 202-211 (2002)
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 H. D. MEYER
Deca is very inhibitory due to progestagenic effect and for good recovery use should be ended well before the end of the cycle, if used at all. There seems to be a quite long-lasting effect to inhibition resulting from this mechanism.
TESTOSTERONE NATION | Tren & Progesterone Receptor Activation - Page 1
Hyperprolactinemia induces hypogonadism by interfering with the secretion of gonadotropinreleasing
hormone (GnRH) from the hypothalamus (Figure 2).4,5 The resulting decrease in serum T is believed
to be the cause of the erectile dysfunction, although there may be an end-organ effect of prolactin on
the penis.4 Surprisingly, not everyone with hyperprolactinemia has a low serum T level or complains of erectile dysfunction.6,7 However, when the serum prolactin is corrected in patients with an elevated prolactin level and a low serum T level, the serum T level usually returns to a normal value, and erectile function is usually restored (if erectile dysfunction was present).2 Simply treating the patient with exogenous T does not usually correct the erectile dysfunction (unless the prolactin levels are returned to normal). Hyperprolactinemia is a very rare cause of impotence in a general population
of men with impotence.8 However, men who have hyperprolactinemia have a high incidence of
sexual dysfunction, and the erectile dysfunction appears more likely to resolve in patients with the most
severe hyperprolactinemia once this glandular disorder is corrected.7
Main Points
• The prolactin level should be measured in men presenting with a complaint of
erectile dysfunction who have a low serum testosterone level.
• Hypogonadism is almost always the cause of an endocrinopathy that affects
erectile function.
• In hyperprolactinemia, which induces hypogonadism, the excess prolactin
interferes with secretion of gonadotropin-releasing hormone, resulting in
decreased testosterone and erectile dysfunction.
• Hyperprolactinemia caused by a pituitary tumor can be managed with surgery
and/or a dopamine agonist.
Hyperprolactinemia and Erectile Dysfunction
Scott I. Zeitlin, MD, Jacob Rajfer, MD
University of California, Los Angeles, School of Medicine
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1476085/pdf/RIU002001_0039.pdf
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
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.
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.
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
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
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
(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
1) Smooth Muscle Dysfunction.syntherolResearchers 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.syntherol 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]syntherol 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.syntherol
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.syntherol "Did it do permanent damage?" is the natural question to ask yourself.
The answer is probably 'yes' to some degree.syntherol However, the good news is that studies show that if testosterone is restored, normal erectile function usually goes with it.syntherol 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.syntherol
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.syntherol And, yes, Sex is Good For You.
syntherol 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"syntherol
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
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
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