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Dear Mark: TRT Edition

Last week’s post on testosterone replacement therapy [1] generated a lot of comments and questions, so for today’s edition of Dear Mark [2] 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)

Absolutely.

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 [3] 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 [4] 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 [5] when they take TRT.

Same goes for men with a history of prostate cancer. Taking testosterone has no impact [6] 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 [7] for heart disease. It’s linked [8] to poor glucose control, endothelial dysfunction, insulin resistance, atherosclerosis, and poor lipid markers.

If anything, heart patients do better with TRT. One study [9] found that a combo of resistance training and TRT helped heart failure patients halt muscle wasting and recover lost strength and functionality. Another study [10] found that men with androgen deficiency saw fewer heart attacks when they took TRT.

The trick is achieving testosterone normalcy [11]. 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 [12] 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 [13] 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 [14], 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 [15].”

Get a handle on stress, as cortisol opposes free testosterone. Chronic stress [16], 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 [17]. A lower than ideal testosterone level causes problems in women, too:

It lowers libido [18]. 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 [19] for urinary incontinence and elevated stress, perhaps because of atrophied pelvic floor muscles [20]. In low T rats, TRT cures urinary incontinence [21].

It can exacerbate anxiety. Socially anxious women may benefit from T supplementation, as it can lower reactivity to angry faces and decrease threat avoidance [22].

Note, though, that testosterone assays are notoriously unreliable [23] in women. Some research [24] 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 [25] in range of 50-150g/day [26], so not classically ketogenic [27], 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 [28].

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 [29] absolutely tanks testosterone [30]. That’s not in question. Those days are long past, however. I haven’t done any serious endurance training [31] for almost two decades, which is plenty of time for testosterone levels to recover from overtraining [32].
  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!