PEAK TESTOSTERONE

Can HCG Increase Pregnenolone?

Many men on TRT (testosterone therapy) are using HCG (human chorionic gonadotropin) as a complementary therapy for a variety of reasons:

  • Improved libido
  • Improved fertility
  • Restored testicular volume
  • Another not-so-well-known potential advantage of HCG is its ability to increase pregnenolone, the "master hormone" that is at the top of our production line. Virtually all of the well-known hormones, many of which help us mentally and sexually, start with pregnenolone, including DHEA, testosterone, estradiol, DHT, progesterone and cortisol. Considering that many men are often low in one or more of these key hormones, stimulating pregnenolone may be a good thing for these men.  The theory is that pregnenolone can "trickle down" and increase other downstream hormones as the body sees fit.

    Now that is largely a theory, because, as far as I know, there is no study on men showing that HCG significantly and consistently increases anyof those hormones.  However, let me provide you with some reasonable evidence that this can often be the case:

    1. Stimulation of the P450 Side Chain Cleavage Enzyme.  The enzyme, sometimes written as P450scc, is responsible for converting cholesterol into pregnenolone.  The name may be casual but this enzyme is about as important as it gets.  In vitro studies show that HCG stimulates the activity of this enzyme, which should result in increased pregnenolone levels:

    a)  One study on female granulosa cells found that "elevation of P450 SCC [Side Chain Cleavage] alone was evident following FSH and HCG stimulation." [1]

    b) One study on adrenal cells revealed similar findings:

    "Double immunostaining revealed that LH/hCG receptors are present in the same cells that contain cytochrome P450 side chain cleavage enzyme, suggesting that the receptor containing cells are steroidogenic." [2]

    2. Mitochondrial Connection.  Scientists even know where this conversion of cholesterol into pregnenolone occurs:  the mitochondria (of certain cells). [3] One study described this as follows:

    "Taken together, these results indicate that LH induces neuronal pregnenolone production by modulating the expression of the LH receptor, increasing mitochondrial cholesterol transport and increasing P450scc-mediated cleavage of cholesterol for pregnenolone synthesis and secretion." [4]

    3. Luteinizing Hormone.  HCG attaches to the same receptor as LH (luteinizing hormone).  LH also activates the P450scc enzyme: "LH treatment caused a rapid and transient increase in the hybridization of P450scc mRNA which was sevenfold greater than that of saline-treated controls when the animals were killed 1 h after the last injection but fell to control levels within 24 h of cessation of treatment." [5]  (There are key differences between these two hormones, something I discuss in my page on Potential Risks of High Dose HCG.)

    4. My Own Labs.  Here were my labs pre-HCG after starting on 25 mg daily of pregnenolone and DHEA. 

    2/24/2016@10:30 am: DHEA-S=407.4 ug/dl; Progesterone=1.01 ng/ml; Cortisol=8.9 ug/dl

    Keep in mind that I was taking compounded DHEA/pregnenolone and so the quanity should be very accurate.

    Then on 3/8/2016 I started on HCG and a couple weeks later I pulled similar labs and notice the results:

     3/18/2016@8:30 am :  DHEA-S=491.2 ug/dl; Progesterone=1.45 ng/ml; Cortisol=9.1 ug/dl

    Notice that both DHEA-S and progesterone had risen.  Of course, it would have been nice if I had pulled pregnenolone directly, but I did not simply to save money. However, the downstream hormones of DHEA and progesterone appear to have risen significantly from the HCG even after a relatively short time period of taking it.

    NOTE:  I actually do not want my DHEA-S or progesterone that high and am going to discuss lowering my dose of DHEA and pregnenolone shortly.

    REFERENCES:

    1)  Molecular Human Reproduction, 1996, 2(6):391-400, "Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of cell death in long-term cultures of human granulosa cells."

    2) The Journal of Clinical Endocrinology & Metabolism, 1996, 81(6), "Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands"

    3) Reproductive Endocrinology: A Molecular Approach, edited by P. Jorge Chedrese, p. 175

    4) J Neurochem, 2007, 100:1329-1339, "Luteinizing hormone receptor mediates neuronal pregnenolone production via up-regulation of steroidogenic acute regulatory protein regulation"

    5) J Endocrinol, 1990 Apr;125(1):131-8, "Effect of LH injections on testicular steroidogenesis, cholesterol side-chain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice"