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    Thread: Pregnenolone: The overlooked hormone

    1. #1
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      Pregnenolone: The overlooked hormone

      One of the hormones that is greatly overlooked is pregnenolone. Now, I know you’re thinking, “why would I want to get pregnant…I’m a guy?!” Look, this hormone doesn’t make you ovulate.

      Pregnenolone is actually the parent hormone to all other steroid hormones such as testosterone, estradiol, cortisol, DHEA, DHT, and progesterone. Pregnenolone is considered a neurosteroid. Neurosteroid essentially translates to a 1) hormone that can be synthesized by the brain and/or; 2) can be synthesized by an endocrine gland that subsequently reaches the brain and exerts its effects.

      Pregnenolone is synthesized from cholesterol and is highly lipophilic meaning that it can cross the blood brain barrier (BBB) readily. Furthermore, being lipophilic means that pregnenolone can have widespread distribution quite well.

      In terms of pregnenolone’s place in TRT we must consider the pathways of steroid hormones. Pregnenolone is the precursor to DHEA, testosterone, estradiol, cortisol, progesterone, and DHT, respectively. When taking exogenous testosterone (i.e. injection, cream) we have a negative feedback system that shuts down endogenous production. In other words, your body senses that you are getting enough from an external source, thus it produces less and less of testosterone internally. This is called hypothalamic pituitary axis (HPA) shutdown.

      Since pregnenolone is the precursor hormone we can “backfill” the pathways by supplementing with pregnenolone while on TRT. Will this attenuate HPA shutdown? No, you’ll still have deficits in FSH and LH however your body will have the parent hormone to thus self-regulate the other steroid hormones. I coined the term “autofilling.” Compare this to a plinko game; pretend pregnenolone is the ball you drop into the top. Wherever it is needed it will distribute down the stream and fall into the appropriate hormone “slot” that needs it.

      Furthermore, newer literature is emerging showing that pregnenolone has efficacy in improving the symptoms of anxiety, depression, ADHD/ADD, Alzheimer’s disease, along with other psychiatric illnesses. Pregnenolone has been shown to modulate the GABA-A receptors in the brain, which are inhibitory receptors (calming effect). Drugs like benzos (i.e. *****, Klonopin) and antidepressants often exert their effects on GABA-A receptors. Other areas that pregnenolone can enhance are cognition, memory, learning, and even relieving arthritic joint pain!

      Cai et al (2018). Neurosteroids in schizophrenia: pathogenic and therapeutic implications.

      Esder et al (2006). Neuroactive steroids as modulators of depression and anxiety.

      Ogino et al (2016). Handbook of Hormones: Subchapter 94E – Testosterone/Dihydrotesterone.

      Vallee, M (2016). Neurosteroids and potential therapeutic targets: Focus on pregnenolone.

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      Good read!

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      Quote Originally Posted by quadzilla View Post
      Good read!
      I always test my pregnenolone 1-2x a year. About a $70 lab but worth it.

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      Quote Originally Posted by *XXL View Post
      I always test my pregnenolone 1-2x a year. About a $70 lab but worth it.
      Same here.

      I'll never forget when starting TRT, my TRT Doc kept increasing my TC dose because Total and Free test values stayed the same. He then checked Pregnenolone and DHEA numbers - they were abysmally low.

      After Pregnenolone and DHEA supplementation, my values climbed significantly.

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