SERM/SARM combo: the real trick to an effective jumpstart?

  1. Jumpstarting HPTA using combo SERM + Avodart/SARM

    As I understand it, the mechanism of HPTA shutdown is as follows...

    Androgens/estrogens from an exogenous source increase in the hypothalamus, which responds by increasing expression of androgen/estrogen receptors.

    Even when the exogenous source of androgens/estrogens is removed, this increased level androgen/estrogen receptors continues to produce significant negative feedback (as it amplifies even low levels of stimulation), such that GnRH, LH, and ultimately testosterone are never produced in abundance.

    SERMS work by acting as 'partial agonists' at hypothalamus (as well as pituitary) estrogen receptors, thereby causing the hypothalamus to sense a lower level of estrogens, and in turn downregulate estrogen receptors. Less estrogen receptors means less negative feedback, and so testosterone levels increase.

    We can perhaps imagine that a 'SARM' might one day be available, which could act in a similar partially agonistic fashion in order to likewise decrease hypothalamic AR.

    This would in effect solve the other half of the puzzle, leading the way to a much higher success rate in restoring the HPTA.

    Any thoughts?

  2. Or, instead of a SARM, I imagine that avodart might fit the bill.

    Avodart (dutasteride) is a 5AR type I inhibitor, that would work specifically in the brain to inhibit the production of DHT.

    As is noted in this article (which I pulled from this site)...
    A {gamma}-Aminobutyric AcidB Agonist Reverses the Negative Feedback Effect of Testosterone on Gonadotropin-Releasing Hormone and Luteinizing Hormone Secretion in the Male Sheep -- Jackson et al. 141 (11): 3940 -- Endocrinology

    "TESTOSTERONE (T) ACTS primarily within the hypothalamus via its metabolites, estradiol or dihydrotestosterone, to reduce the frequency of GnRH and LH pulses (1, 2, 3, 4)."

    Tamoxifen, as you are all aware, acts as an anti-estrogen. By blocking estrogen in the hypothalamus, it reduces negative feedback, and increased production of GnRH.

    The combination of dutasteride and tamoxifen would effectively knock out both major sources of negative feedback, DHT and E2, resulting in a much more significant GnRH surge.

    Also note that tamoxifen would counteract any potential duesteride estragonic side effects (i.e. gyno, penile AR downregulation, etc).

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