Dear Mark: TRT Edition

Inline_DM_092517Last week’s post on testosterone replacement therapy generated a lot of comments and questions, so for today’s edition of Dear Mark I’ll be answering some of them.

From the prostate and heart disease issues to the high T/low free T phenomenon to the question of women and TRT to keto’s effect on testosterone to chronic cardio’s, you folks came up with some good ones.

First, Polyphemus made a suggestion:

Probably worth addressing the worry about heart and prostate issues. The prostate is SUCH a classic issue for the same population that might want TRT. (including me)


Let’s look at prostate cancer first.

The most recent studies (and many of the older ones) suggest that TRT is safe, or even protective, for the prostate.

In May of this year, a study found that while TRT patients had an increased diagnosis of favorable-risk (less deadly) prostate cancer, they had a decreased incidence of aggressive prostate cancer. Furthermore, the authors suggested that the increased incidence of favorable-risk prostate cancer was an artifact of detection bias.

A February study of men with low testosterone found that those receiving TRT were just as likely as those not receiving TRT to develop prostate cancer.

Even men at a high risk for prostate cancer don’t get prostate cancer at any greater rate when they take TRT.

Same goes for men with a history of prostate cancer. Taking testosterone has no impact on their risk of recurrence.

Now let’s look at heart health and TRT.

First of all, testosterone deficiency is a widely-recognized risk factor for heart disease. It’s linked to poor glucose control, endothelial dysfunction, insulin resistance, atherosclerosis, and poor lipid markers.

If anything, heart patients do better with TRT. One study found that a combo of resistance training and TRT helped heart failure patients halt muscle wasting and recover lost strength and functionality. Another study found that men with androgen deficiency saw fewer heart attacks when they took TRT.

The trick is achieving testosterone normalcy. Getting things back to normal is protective; steroid abuse is dangerous.

The human studies are enough to give me confidence, but the mechanistic animal studies put me over the top. A 2015 study found that giving testosterone-deprived rats TRT protected them against induced cardiac arrest by limiting mitochondrial dysfunction. Mitochondria are the lynchpin for almost everything that goes on and goes wrong in our bodies. If testosterone deficiency negatively impacts mitochondrial function, TRT is essential.

KTT requests:

I’m 46 and my total testosterone is in the 800’s but my free testosterone is very low, 40’s or .6%, can you address this scenario.

I can’t give out medical advice of course, but I’d suggest looking into the possibility of high sex hormone-binding globulin, or SHBG. SHBG binds to testosterone to modulate its transmission to tissues, but this has the effect of nullifying the bioactivity of any bound testosterone.

All else being equal, older men tend to have higher levels of SHBG than younger men. This throws off test results and explains why many older men can have “normal” testosterone while suffering from deficiency symptoms.

Boron reduces SHBG and increases free T. In one study, subjects took 10 mg of boron per day.

Make sure you’re eating enough zinc. There’s a “specific decrease in the affinity of human SHBG for C18 steroids in the presence of a zinc ion.”

Get a handle on stress, as cortisol opposes free testosterone. Chronic stress, remember, can also come from too much or too little exercise, inadequate calorie intake, and just about too much of anything

Statins can reduce free T, but they also tend to reduce total testosterone. You don’t suffer from that problem, nor did you mention taking statins, so it’s probably not that (but anyone reading for whom this does ring true should consider it).

Amanda asked:

what about for women with T lower than is ideal for women

As I’ve written in the past, women need testosterone. A lower than ideal testosterone level causes problems in women, too:

It lowers libido. If a doctor prescribes testosterone to a woman, it’s usually to correct a libido deficiency.

Older women with very low testosterone levels are at a greater risk for urinary incontinence and elevated stress, perhaps because of atrophied pelvic floor muscles. In low T rats, TRT cures urinary incontinence.

It can exacerbate anxiety. Socially anxious women may benefit from T supplementation, as it can lower reactivity to angry faces and decrease threat avoidance.

Note, though, that testosterone assays are notoriously unreliable in women. Some research shows that “guessing” women’s T levels based on symptoms is “nearly as good” as direct testosterone assays.

Matt asked:

Hey Mark,

Did all of this happen while you were in ketosis? Perhaps prolonged ketosis can lower testosterone

No, this was well before my keto experiment. I was eating low-carb in range of 50-150g/day, so not classically ketogenic, though I did drift in and out of ketosis due to fasting, training, and the general variation of my day-to-day carb intake. But it wasn’t a concerted effort to get into and remain in ketosis.

David asked:

Mark, two questions:
1) Do you think your chronic cardio years contributed to low T later in life?
2) There are a ton of herbal supplements that purportedly improve T. Any chance of a post reviewing some of the more legitimate ones? (Personally, I’d rather spend money on steak and eggs, and do resistance training and sprinting, but if there is a legit supplement, I’m willing to experiment)
Thanks for this post and thanks for all you do!

  1. Chronic cardio absolutely tanks testosterone. That’s not in question. Those days are long past, however. I haven’t done any serious endurance training for almost two decades, which is plenty of time for testosterone levels to recover from overtraining.
  2. Sure. That sounds like a good idea for a post. I’ll add it to the docket.

Gary wondered:

My total testosterone is over 800 but I don’t know the free count. Will supplementing at my level increase free. I have read proper level is 25. My age is 73.

TRT supplies testosterone. It’s up to your body to render it bioavailable. As I understand it, TRT is meant to increase testosterone directly and free T indirectly. If you have 800 at age 73, that’s plenty (and very impressive) of substrate. Any low free T readings you experience won’t have anything to do with the amount of raw testosterone your body produces. That’s covered. That’s adequate.

It’s better to focus on lowering SHBG (see my answer to KTT’s question for ideas), which binds testosterone and reduces free T.

Thanks for reading, everyone. Take care and keep the questions coming!


About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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16 thoughts on “Dear Mark: TRT Edition”

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  1. Hi Mark – thank you for addressing the keto / testosterone issue!

    What do you think about eating whole roasted coffee beans versus brewing it for coffee? Seems way more convenient – and maybe more nutritious because you are consuming it whole?

  2. Wow, a ton of in-depth information here. Good job, Mark. I usually take rat studies with a grain of salt since I’m not a lab rat, but the info is probably worth knowing about. Thanks for putting it out there.

  3. How about the use of a SERM, such as clomiphene, to induce the body to produce more testosterone endogenously? This strategy has been gaining acceptance amongst those endocrine doctors specializing in andrology for treating centrally-mediated hypogonadism. What do you see as the pros and cons of such an approach?

    1. While we await Mark’s views, here are a few thoughts from having researched this extensively and having done it myself:

      – Uses most of your body’s natural HPTA functioning
      – Some prefer pills to shots or creams/gels
      – Fairly easy recovery if you stop since it does not shut down your natural production
      – Works very well for a minority of people
      – Fairly cheap

      – creates mood problems for many people
      – most doctors oversdose clomid…12 mg every other day seems to be the dose that works best for the people who can tolerate it. There are studies that claim 25mg every day is a workable dose, but this rarely seems to work in the real world
      – creates temporary eye floaters for some people
      – oftens raises SHBG which potentially negates the rise in T
      – Clomid is a very tricky drug to “dial in”; it is made of two isomers that have different half-lives and affects, so finding the sweet spot is very difficult
      – Tamixifen is also a SERM that seems simpler to dose, but again, seems to treat a piece of paper better than it treats symptoms
      – SERMS will not work if your body cannot produce enough T, they only work if your “set point” is too low

      So…IMO, SERMs are a very good thing to try as a first step, and they will work well for some people, but the majority of people will do much better on a good TRT program

  4. Mark,
    I listened to a Podcast with guest from Master Your T and he said that once you start on a T supplement your body only produces what is required to maintain that level. Once you start you are on for life unless you want to go through the drop after you stop taking the supplement. He recommended doing everything naturally before trying the supplements. What are your thoughts on that?

  5. I’m a woman who on bioidentical hormone replacement for testosterone and progesterone. I have noticed a huge difference in my energy levels as well as my libido. I’m 44 and in perimenopause and my energy has been horrid as a result. The testosterone makes a big difference in my day to day functionality.

  6. Thank you, as always, for tons of helpful, research backed information. I would also be interested in your suggestions for herbs/supplements to increase testosterone, so I look forward to reading more in a future post!

  7. I’ve been following all of this and find it very interesting. As people are asking about natural supplements it got me thinking about maca, which was covered last month. But it appears that maca somehow works without affecting hormonal levels. Anyway, love the interesting topics and questions that come up!

  8. For KTT’s question of high total and low free. I had this problem, I had very high SHBG (130). It was due to liver function from me having Hereditary Hemochromatosis and iron overload. So if you have normal total T and low free, might be worth checking your ferritin levels.

    1. Simon, thanks so much for this post. I left you a comment on your blog, but this info was seriously eye-opening for me. I’ve recently found out I have very high SHBG levels (113 nmol/L) and high ferritin (230 mg/dl). I thought they were two separate issues, but was totally unaware of the link between high ferritin and high SHBG. It was just by chance that I had the two tests done at the same time. Did your SHBG naturally come down to normal levels when you addressed the ferritin issue?

  9. Thank you Mark! TBH, didn’t really think you would take the time to answer my question, and not only did you, but you gave a very thoughtful response (glad the $200 I just spent on Primal Nutrition products went to a company that gave me value). Not on statins and I suspect my low free T might be due to high cortisol levels stemming from too much exercise, am a recovering 10-hour ironman athlete, who has a hard time not exercising too much. But I retired from ironman racing 4 years ago with the goal of putting my health before my fitness. Though I’m not averaging 15-20 hour training weeks now, I still do about 10-12 hours of exercise per week. So hard to let go because it feels so good. Thanks again.

  10. Hey Mark, I’m 25 and have no reason to believe I have low T, so I won’t be doing TRT. But I would love a post on herbal supplements that can increase testosterone. Also would love to learn more about boron and whether it makes sense for a healthy, young male to supplement with. And if so, at what dosage and how much Zinc to take in conjunction. And how to weigh that against the boron and zinc we get from our diets Thanks!

  11. Is there any long-term studies on the use of Boron? I’m 52 and have total testosterone levels around 600 my/dL and free 7 pg/ml. I’ve tried about everything to increase my free with no success. 8 weeks ago I started supplementing with 9mg of Boron. I just had labs done this week and my total increased from 603 to 913 and free went from 7.9 to 15.3. I’m just wondering on long term effects or if Boron should be cycled?