Fertility and Injecting Testosterone - Dr. Cameron Sepah

Can you explain the. The mechanism behind why when you inject testosterone, it basically makes you less likely to have a baby? Because some people would almost think the opposite.

Right.

You're gonna have a bunch of libido and go out there and populate the planet.

Yeah, it's a great question. So there's something called the HPG axis, the hypothalamus pituitary gonadal axis, where essentially the hypothalamus produces a hormone called GnRH, or gonadotropin releasing hormone, which stimulates the pituitary to release two hormones. One is lh, or luteinizing hormone. The other is fsh, or follicle stimulating hormone. FSH stimulates the gonads or the testes, where the word testosterone comes from. To produce testosterone, FSH stimulates the gonads or testes to produce sperm. And so what happens is when you're getting exogenous testosterone, it creates a negative feedback loop up at the hypothalamus and pituitary. And so the brain thinks, ah, I'm getting enough testosterone. You know, the body tries to maintain homeostasis or balance. Right. And so it shuts down the production of GnRH. If you actually do your blood work, your LH and FSH basically go to near zero. So you can tell you're essentially shut down. And so as a result, there's no signal going to the testes. And what happens is essentially the testes, because there isn't sort of gas in the gas tank. It's almost like having a dead car battery. So they're not producing, they actually will atrophy, they'll shrink. Most people will notice essentially a decrease in what's called testicular volume, the size of the testes. Right, right.

The famous ball shrinkage.

Exactly. So it's basically analogous to what type 1 diabetics do who are insulin dependent. Right. Their pancreas can no longer produce insulin, so they inject it exogenously and it's life saving. But the analogy that I make is most people aren't type 1 diabetic. Most people are pre diabetic. They're on the type 2 diabetes spectrum. Right. Which is what my first company worked on for those people. They should really, to your point, focus on diet, exercise, sleep, maybe take a low dose of a metformin or a glucose reducing agent and. And really focus on changing their lifestyle rather than hopping on insulin. Insulin is really the treatment of last resort for uncontrolled type 2 diabetes that I used to see when I was.

Working at the va. And unfortunately, sadly, it's also an easy way out. There's a lot of people going to the Cheesecake Factory with their insulin syringe.

Exactly. Instead of obviously reducing their carbohydrate intake. I think injectable TRT is analogous. It is, there's definitely a place for injectable trt. But increasingly, I think if you talk to clinicians, including the top urologists and med school professors in the country, who are my colleagues and advisors, they really think TRT should be a treatment of. Injectable TRT should be a treatment of last resort, because you're essentially going to become dependent on it for the rest of your life.

Okay, got it. Now backpedal here just a little bit because I think what you were explaining there regarding the hypogonadal issues and the LH and FSH relates to two ways that testosterone can be low. There's primary and secondary hypogonadism. Do I have that right?

Yes. Yeah, that's a really important differentiation and that's analogous to essentially the type 1 and type 2 diabetes. So in primary hypogonadism, the testes essentially no longer function correctly, just as in type 1 diabetes, the pancreas no longer functions correctly. So basically, no matter how much LH or FSH stimulation you're getting from the pituitary, if you're primary hypogonadal, your testicles are not able to essentially respond to that signal and they're essentially shut off. For those folks, injectable trts, absolutely, they're correct solution because yeah, your testes no longer work.

Right. There's no feedback loop to shut down.

Exactly right.

And with, with primary, what's the reason that something like primary would happen where the signal isn't even being sent? Is that just a bunch of stress? Is that being born with some kind of genetic issue or what causes that?

Yeah, sometimes people have testicular injury, testicular cancer, or other sort of very major medical problems. It's actually uncommon. I wouldn't say the majority of folks actually have primary hypogonadism. Just like the majority of folks, probably single digit percentages have type 1 diabetes. It's much more the type 2 diabetes and secondary hypogonadism. Secondary hypogonadism, you're still, your testicles still work. It's just that they're not as responsive. Just like in type 2 diabetes, your pancreas still works. It's just that you're insulin resistant and your body's not responding to the insulin as well. Just like the Testicles aren't responding to the LH and FSH as well. So you're getting the signal, but it's not producing as much testosterone. It's not producing as much sperm, generally due to poor lifestyle and health, which is unfortunately, as you point out, ubiquitous these days.

So how would you test for primary versus secondary hypogonadism? Would it be someone who's not on testosterone and you're measuring their LH and FSH levels and if they were not on testosterone and those levels were low, that could give you a clue that they might have primary?

Yeah. So in both cases, both individuals would have low testosterone. Right. Now, traditionally, what people do is they do look at the LH and fsh. So sometimes people who are primary hypogonadal have very high LH levels and so they'll use that because it's like the pituitary, the testicles aren't responding. So it's almost like trying to send more gas in order to turn it on. We find, however, that's not a perfect prognostic sign of whether you're primary hypogonadal. I think the best way to actually know conclusively is to actually put people on a cm. So traditionally there's something called the Clomid challenge. So Clomid is a selective estrogen receptor modulator, or cirm. It basically, not everywhere in the body, but in selective places, including at the hypothalamus level, blocks the estrogen receptor. It's an estrogen receptor antagonist is also an agonist as well because it's two different drugs, technically speaking. But basically what it does is it tricks the body into thinking, I don't have enough estrogen or estradiol that's derived actually from testosterone. And so the body will produce more.

Testosterone in response to it because estrogen is being blocked. The body thinks, okay, I need to make more estrogen. And the only way that you can efficiently do that as a male is to go through the testosterone pathway.

Exactly. So you'll produce more testosterone. So Clomid has been an FDA approved drug since 1967. It's used for female fertility. It's been used off label for men's infertility actually for many decades as well. It works pretty well. And what will happen is if you are secondary hypogonadal, it will restart your system and get you to produce more testosterone. If you're primary hypogonadal, it won't work if you're. And so you can do this pretty efficiently. You do that for like A week or two and you can tell if you're responsive. Great. Your testicles still function, essentially. And then you should probably figure out ways of increasing your endogenous or natural production. If you don't, you can go right to injectable trt.

Okay, and you call that the Clomid challenge.

That's typically what's been called in the, in the academic research literature when we've analyzed LH and fsh, by the way. And in terms of what predicts treatment response to a serum, it's actually usually when people. It's not when their LH is too high, contrary to popular opinion, it's when their LH or FSH are below one or they're almost zero. Those folks, essentially, they either have had a testicular injury, their testicles aren't working, or they've been suppressed because they've been on injectable testosterone so long that they're essentially no longer able to really produce.

Oh, so you can basically self induce primary hypogonadism absent of something like testicular injury from using something like repeated testosterone injection, for example.

Yeah, that's kind of the irony of trt, right? Is it essentially, well, can induce primary hypogonadism now? Not always. There are some folks who, they go on it and when they decide, hey, it's time to have a baby, they can go off of it and they can recover. There's a little bit of individual variability in terms of that. And you can use, in fact, a CIRM or HCG to restart the system. It does work, but basically, in clinical observation, it depends on how long you were on TRT and what the dose was. Because if you were on it for too long and too strong, essentially, then it may not totally come back. That's why conservative clinicians basically tell people, if you at any point in the future would like to still have children, it's probably not wise to mess with your fertility. In fact, Jim Hoatling, who's on my podcast, basically argued that really, like, if you're under 50 or you still want to maintain your fertility, you should consider other options before jumping on injectable testosterone hit.

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