Testosterone The Double Edged Sword (LH/neurosteroids)

[madman]

Testosterone deficiency can be a devastating condition associated with adverse emotional and physical conditions, but it should not be the first answer to the problem. Understanding that trauma induced neuroinflammation and medication such as Ibuprofen can cause testosterone deficiency. A thorough medical and medication history followed by a 28-point biomarker panel can help to identify the causation and thereby the treatment. This presentation will explain why not to use Testosterone until a deeper understand of the cause for the deficiency is elucidated.

 

[madman]

Effect of TRT vs hCG/FSH on upstream hormone pathways.

The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways -insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement SUMMARY Objective: To delineate the role of gonadotropins in male androgen biosynthesis pathways...

www.excelmale.com

*Take-home point:

A replacement regimen with combined hCG/rFSH mimics physiologic steroid hormone profiles better than a substitution with exogenous testosterone. The documented differences in steroid profiles on testosterone replacement in hypogonadal males with absent or severely reduced endogenous LH and FSH secretion may have long-term consequences for health and well-being. Specifically, body composition, bone health, glucose, and lipid metabolism, salt and water balance, cognition, mood, sleep, and sexual function could be affected. The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

 

[Nelson Vergel]

The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

I agree, but I doubt anyone is looking at this in the era known for testosterone promotion.

 

[madman]

The role of neurosteroids in post-traumatic stress disorder and alcohol use disorder

Abstract Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited...

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Allopregnanolone: Regenerative therapeutic to restore neurological health

Allopregnanolone: Regenerative therapeutic to restore neurological health (2023) Gerson D. Hernandez, Roberta D. Brinton ABSTRACT Chronic stress has been proposed as a driver of altered brain structure and function, including the pathogenesis of neurodegenerative diseases, and a driver of...

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Progestogen-mediated neuroprotection in central nervous system disorders

Progestogen-mediated neuroprotection in central nervous system disorders (2022) Bassani TB, Bartolomeo CS, Oliveira RB, Ureshino RP Abstract Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens...

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Major Depressive Disorder: Next-Generation Neurosteroids

PPD: Postpartum depression MDD: Major Depressive Disorder This webcast features presentations that examine the diverse pathophysiologic mechanisms that may contribute to MDD and PPD and the resultant implications for therapeutic targeting, including the GABAergic signaling pathway.

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Development of neuroactive steroids for the treatment of postpartum depression

Abstract Postpartum depression (PPD) is a common major depressive episode surrounding childbirth, with estimated rates ranging from 5.5% to 23.5% of all live births across Europe and the USA based on the presence of key symptoms. PPD has been associated with significant impairments in both...

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Allopregnanolone in mood disorders

ABSTRACT The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAAR), and the down-regulation of its biosynthesis has been attributed to the development of mood disorders, such as depression, anxiety, and post-traumatic stress...

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Sex Neurosteroids: hormones made by the brain for the brain

ABSTRACT In general, hippocampal neurons are capable of synthesizing sex steroids de novo from cholesterol, since the brain is equipped with all the enzymes required for the synthesis of estradiol and testosterone, the end products of sex steroidogenesis. Regarding estradiol, its synthesis in...

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Post-finasteride syndrome: a surmountable challenge for clinicians

Post-finasteride syndrome: a surmountable challenge for clinicians Abdulmaged M. Traish, Ph.D. Department of Urology, Boston University School of Medicine, Boston, Massachusetts Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical...

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[Nelson Vergel]

"
Neurosteroid Levels
Baseline serum levels of pregnenolone did not differ between groups (mean [SE], 585.26 [48.85] pg/mL for placebo vs 585.26 [48.85] pg/mL for pregnenolone; P = .99) (eTable 4 in Supplement 2). Serum pregnenolone levels more than doubled after 1 week of 100 mg of pregnenolone (mean [SE], 599.68 [54.70] pg/mL vs 1352.50 [107.57] pg/mL; P < .001), further increased after a week of 300 mg of pregnenolone (mean [SE], 684.04 [63.02] pg/mL vs 2443.89 [216.11] pg/mL; P < .001), and increased to a level almost 5 times greater than placebo after 2 weeks of 500 mg of pregnenolone (mean [SE], 616.73 [51.20] pg/mL vs 2786.24 [285.94] pg/mL; P < .001).

Allopregnanolone, a pregnenolone metabolite with analgesic properties, exhibited a pattern similar to pregnenolone. Allopregnanolone levels did not differ between groups at baseline (mean [SE], 62.22 [5.10] pg/mL for placebo and 67.96 [9.83] pg/mL for pregnenolone; P = .95); however, participants receiving pregnenolone had significantly increased allopregnanolone levels after 1 week of 100 mg of pregnenolone (6.5-fold increase; mean [SE], 59.73 [5.64] pg/mL vs 508.98 [55.31] pg/mL; P < .001). Allopregnanolone levels markedly increased again after participants received 1 week of 300 mg of pregnenolone (14.3-fold increase; mean [SE], 71.22 [11.07] pg/mL vs 1036.50 [108.04] pg/mL; P < .001) and continued to increase after 2 weeks of 500 mg (17.6-fold increase; mean [SE], 61.32 [6.00] pg/mL vs 1263.10 [136.90] pg/mL; P < .001). Changes in pregnanolone, another positive GABAA receptor modulator, were similar, showing no difference at baseline (mean [SE], 32.75 [2.02] pg/mL for placebo vs 34.98 [25.19] pg/mL for pregnenolone; P = .98), but increasing significantly after 2 weeks of 500 mg of pregnenolone (mean [SE], 32.84 [2.28] pg/mL vs 883.87 [166.57] pg/mL; P < .001). Serum levels of androsterone, a neurosteroid that also positively modulates GABAA receptors, did not differ at baseline between groups (mean [SE], 177.60 [10.92] pg/mL for placebo vs 171.67 [14.06] pg/mL for pregnenolone; P = .70) and decreased slightly in the pregnenolone group (mean [SE], 148.93 [11.07] pg/mL) compared with the placebo group (mean [SE], 186.26 [12.32] pg/mL) at visit 6 (P = .02)."

Source: Pregnenolone vs Placebo for Chronic Low Back Pain Among US Military Veterans

 

[Nelson Vergel]

I am going to start pregnenolone again after reading this study.

 

[seppuku]

I am going to start pregnenolone again after reading this study.

What caused you to stop using it before though Nelson?

 

[Seagal]

Effect of TRT vs hCG/FSH on upstream hormone pathways.

The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways -insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement SUMMARY Objective: To delineate the role of gonadotropins in male androgen biosynthesis pathways...

www.excelmale.com

*Take-home point:

A replacement regimen with combined hCG/rFSH mimics physiologic steroid hormone profiles better than a substitution with exogenous testosterone. The documented differences in steroid profiles on testosterone replacement in hypogonadal males with absent or severely reduced endogenous LH and FSH secretion may have long-term consequences for health and well-being. Specifically, body composition, bone health, glucose, and lipid metabolism, salt and water balance, cognition, mood, sleep, and sexual function could be affected. The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

To what extent this hypothesis is true, should be addressed in future clinical studies.

 

[Seagal]

Effect of TRT vs hCG/FSH on upstream hormone pathways.

The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways -insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement SUMMARY Objective: To delineate the role of gonadotropins in male androgen biosynthesis pathways...

www.excelmale.com

*Take-home point:

A replacement regimen with combined hCG/rFSH mimics physiologic steroid hormone profiles better than a substitution with exogenous testosterone. The documented differences in steroid profiles on testosterone replacement in hypogonadal males with absent or severely reduced endogenous LH and FSH secretion may have long-term consequences for health and well-being. Specifically, body composition, bone health, glucose, and lipid metabolism, salt and water balance, cognition, mood, sleep, and sexual function could be affected. The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

However, Δ5 biosynthesis of 17-OH-pregnenolone, DHEA(S) seems fully gonadotropin-independent, and the production of androstenedione is largely gonadotropin-independent. Thus, an “adrenal-peripheral tissues-testicular collaboration” regarding androgen synthesis by classic or alternative pathways seems possible.

 

[Nelson Vergel]

What caused you to stop using it before though Nelson?

Blood pressure increase, but I am now on better meds.