Transcription
Opioids reduce testosterone levels in men and worsen their fertility. And in this video, I'm going to tell you why blocking opiate receptors may increase your testosterone levels, improve your fertility, and be a wonderful add-on for your next post-cycle therapy. Before I do, please like this video, subscribe to the channel, and comment on the video below for the sake of the algorithm. Now, let's begin.
First, there are three opiate receptors in the body, all named after the first letter of the agonist that was first identified to modulate them. So, morphine named the mu opioid receptor. There's also a kappa opioid receptor and a delta opioid receptor. These three receptors respond to endogenous opioids in our bodies. Specifically, endorphins signal at the mu opioid receptors, and keflans signal at the delta opioid receptors, and dinorphins signal the kappa opiate receptors.
Agonism at all three of the opiate receptors inhibits hypothalamic gonadotropin-releasing hormone synthesis. Remember, guys, your hypothalamus releases gonadotropin-releasing hormone, your pituitary releases luteinizing hormone and follicle-stimulating hormone, and in response, your gonads produce testosterone and proliferate and differentiate sperm. Endorphins are thought to inhibit gonadotropin-releasing hormone cell activity in the hypothalamus by modulating levels of nitric oxide in the brain. Interestingly, corticotropin-releasing hormone's effects on luteinizing hormone appear to be modulated via the mu opioid receptors. Now, it's unclear whether the mu opioid receptors directly modulate luteinizing hormone synthesis at the pituitary, but its effect on the hypothalamus is evident and clear. Hypothalamic gonadotropin-releasing hormone neurons also contain delta opioid receptors, and they respond negatively to delta opioid receptor agonism as well. Finally, the endogenous kappa opioid receptor agonists, the dynorphins, are actually thought to terminate the gonadotropin-releasing hormone pulse from the hypothalamus naturally in the pulse cycle. Therefore, agonism at the kappa opioid receptors also inhibits gonadotropin-releasing hormone. Interestingly, estradiol's modulation of kisspeptin neurons in the hypothalamus appears to be modulated via kappa opioid receptors as well.
While there is some evidence that opioid receptor agonism at the pituitary may also worsen luteinizing hormone synthesis, there is also further evidence down the line that opioid receptor agonism worsens the entire process of male fertility. In fact, sperm actually contain opioid receptors, and agonism of the mu opioid receptors worsens sperm motility, while antagonism of the mu opioid receptors improves sperm motility. Conversely, agonism at the delta opioid receptors on sperm actually worsens sperm motility, which is one reason to think that we may want a slightly selective mu opioid receptor antagonist as opposed to an antagonist that has equal potency at the delta and mu opioid receptors.
Now, not only does opioid receptor agonism worsen steroidogenesis across the hypothalamus, potentially the pituitary, and directly in the gonads as well, but opioid receptor antagonism has clearly been shown to improve steroidogenesis. Selective kappa opioid receptor antagonists improve luteinizing hormone synthesis, while non-selective or preferential toward the mu opioid receptor antagonists show an improvement both in frequency of luteinizing hormone pulses as well as amplitude in luteinizing hormone pulses. These two effects are fascinating because, for example, dihydrotestosterone can only decrease frequency of luteinizing hormone secretion, while estradiol, on the other hand, can only decrease, well, mainly decreases amplitude of luteinizing hormone secretion. Naltrexone therapy can undo or attenuate both of those effects. So, there is a profound improvement in steroidogenesis from blocking opioid receptors.
So, how should one go about doing this? What are the considerations? Well, first of all, we talked about this earlier: selectivity. It seems that having an antagonist that's somewhat selective for the mu opioid receptors may be preferential because, as we can see, for example, delta opioid receptors have converse effects in sperm, sperm health, for example. So, naltrexone and naloxone, which are selective a little bit for the mu opioid receptors, especially at lower doses, may be preferential. Further, there's an issue about half-lives also. So, for example, naltrexone was shown to be adapted to by rodents, and it has a much longer half-life than naloxone, which was shown to be not adapted to by rodents. So, potentially a drug with a shorter half-life or less frequent administration may be ideal as well.
Anyway, guys, if any of you try this, please let me know how it goes. I have a feeling that this introduction of opioid receptor antagonists may be almost as valuable for post-cycle therapy and steroidogenesis as aromatase inhibitors. Let me know how it goes, and I hope to see you again soon.
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