ADT 's effect on body fat and muscle mass from Life on ADT blog by Richard Wassersug

[Scout4answers]

ADT’s impact on Muscle and Fat

October 23, 2023

Standard ADT with either LHRH agonist or antagonist drugs (like Lupron or Firmagon, respectively) cause a loss of lean muscle mass and weight gained as fat. Those are among the most common side effects of ADT. Patients experience this as fatigue for they have more weight to move and less muscle to do it with. It is also part of a suite of features associated with an increased risk of diabetes and heart disease.

So, how does the situation change when one adds either Zytiga (abiraterone ) or Xtandi (enzalutamide) to standard ADT? This is an important question since patients are increasingly being offered doublet therapy to control prostate cancer. Doublet therapy typically entails adding either a second-generation anti-androgen, like enzalutamide, or abiraterone (Zytiga) to a standard LHRH treatment. Do these combined therapies improve the situation or make it worse?

According to a new paper that asks these very questions the combinations typically, but not always, make matters worse. The data come from 229 patients, with 120 on an LHRH drugs alone, and just over 50 patients on either enzalutamide or abiraterone.

In terms of muscle loss, there was greater loss with the doublet therapies particularly after 18 months when enzalutamide was the secondary agent. This is consistent with a common complaint for patients of a lot of fatigue when enzalutamide is added to the LHRH drugs.

As for the amount of fat gained, the authors distinguished between subcutaneous fat and the deeper fat packed in the body around the viscera. The LHRH drugs alone show minimal change in the visceral fat. In fact, there can even be a loss of visceral fat, but insignificantly so. Adding in abiraterone, however, significantly increased the visceral fat after just six months by an average almost 5%.

The situation is quite different when it comes to the subcutaneous fat. Here the increase is substantial; i.e., a 8.6% at six months with the LHRH drugs alone, although that can decrease over the following year to an average increase of 4.7% at 18 months.

This increase in subcutaneous fat is consistent with the extra belly roll of fat that men at ADT typically acquire—unless they aggressively commit to burning off more calories than they are ingesting.

In that regard, the authors do not say anything about how lifestyle may influence the results related to fat distribution and weight gain. One suggestion we have is that patients, who find the weight gain, belly roll, and fatigue bothersome, make lifestyle changes to slow down the progressive loss of muscle and gain in fat. There is no evidence though that the authors of the paper collected data on how exercise or diet might have influenced their findings.

Perhaps what's most interesting in this paper is the differences between these drugs affects on visceral versus subcutaneous fat, and how this is associated with a different level of diabetic risk with the different doublet combinations. It turns out that adding abiraterone to standard ADT increases the diabetic risk slightly, while adding enzalutamide reduces that risk for some men on ADT. This can be partly understood by changes in the androgen receptor, which is targeted by enzalutamide. Those receptors are indeed more prominent in visceral than subcutaneous fat.

From the patients’ perspective this has important implications to personalized oncological care and diabetic risk. If a patient is already overweight and diabetic, the paper suggests that, of the two options, they may be better treated with an anti-androgen, like enzalutamide, then with abiraterone. The authors also acknowledged that since abiraterone must be taken with a steroid, the steroid can also affect the body’s composition.

So, what is the bottom line? In general, for patients, who need to be on hormonal therapy, adding in these new agents can improve cancer control. But overall, they increase the risk of loss of muscle mass, and they have complicated and disparate effects on the body’s fat distribution. Overall, they're more likely to increase serious side effects, which need to be managed. That can be done in part with appropriate lifestyle interventions.

Reference:

Blow, T. A., Murthy, A., Grover, R., Schwitzer, E., Nanus, D. M., Halpenny, D., ... & Goncalves, M. D. (2023). Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy. European Urology Open Science, 57, 1-7.

[mrscruffy]

The positive side of this is fat loss and muscle loss can be reversed in the gym with proper nutrition and supplements

[Scout4answers in reply to mrscruffy]

We agree

[timotur]

The best way I found to beat fat accumulation on ADT was to exercise in the morning before breakfast— i .e. using stored energy before intake energy—and wait an hour or two after the workout to eat to feel hungry. I made it through ADT ok, but oddly found after it was over my appetite increased as T recovered to normal. That was another challenge in proportion control.

[TryGuyCP]

I've been on low-carb way of eating since 1999, exercising regularly (10h/week) since 2009 and kept at my usual weight of 167 lbs since start of ADT in March 2022 but lost muscle (and conversely gained fat to the tune of 21%) and bone density (-2.7 T-score at femur neck).

Since August 2023 started keto with intermittent fasting plus aggressive heavy lifting and now lost fat and gained a little muscle. Now at 155 lbs with 13% fat. I'm 6' tall.

I plan on doing OsteoStrong to address osteoporosis once I return to the states.

[Scout4answers in reply to TryGuyCP]

plus aggressive heavy lifting I am using the Body by Science method - slow lifts- heavy weights- done to muscle failure. once a week. 3 months in it seems to be working very well. slowly increasing the weight. the whole work out takes less than 30 minutes.

[TryGuyCP in reply to Scout4answers]

Same basics here!

I use X3 Bar system: single set to failure with 15-40 reps. 2-3 seconds to move.

I tried 6 times a week but it was too much combined with tons of cycling so reduced it to 4 times a week.

jaquishbiomedical.com/x3-pr...

[Scout4answers in reply to TryGuyCP]

3X looks interesting, I go to my local club and use the machines. I started with the "Big 5" core exercises and have now added 5 additional focused on arms and legs. Followed by 5 minutes in the hot tub, (more if the scenery is good) and then a cold shower like the Wim -Hof method advocates.

[TryGuyCP in reply to Scout4answers]

I used to go to local Planet Fitness (5min walk from our house) but then realized I need portable home GYM that's always at hand and got a set of resistance band loops and tubes with handles and used that at home or on any trip. I did not like the fact that heavy flat bands caused a lot of stress on my hands, tried gloves but then discovered X3 and realized how ingenious it was to use bar with bands. I got DASKING bar, 20x15x1 cutting board as footplate from Amazon and follow same exact X3 12-week program. There is tons of videos on how to perform exercises with correct form and rationale behind it all.

[dhccpa in reply to TryGuyCP]

On your historical diet since 1999, how many total calories per day? And how did that break out into grams of carbs, fat, and protein, on an average day? Thanks.

[TryGuyCP in reply to dhccpa]

I started Atkins WOE (Way Of Eating as he insisted calling it rather than "diet") in 1999 and never counted calories which is the key principle of it (or for that matter that of modern day Keto or Carnivore, Paleo). Our bodies due to million years of eating only meat and low-carb vegetation have great auto feedback mechanism where you feel satiated once you had what's enough for you. Did our ancestors from count calories? I simply eat until I feel full and then stop.

For all this years I used simple rule: step on the scales after waking up and if I see weight trends up I reduce carbs in my food (as in don't allow any!) for next days. Eventually you figure out what amount of carbs is acceptable for you.

In August I started keto and intermittent fasting with OMAD (one meal a day). I noticed the hunger is much reduced so I ate too little and my morning routine changed: now when I weigh in the morning and see trend down I make conscious effort to eat more. I do inexpensive body-comp DEXA monthly and by end August I noticed loss of even more muscle and so changed from OMAD to reduced feeding window (i.e. 12pm and 4pm) as its hard to get enough protein in one sit. So by trial and error I'm getting there. I use body-comp bathroom scales for some guidance realizing they're way off DEXA but ok for comparison.

[dhccpa in reply to TryGuyCP]

Thanks

[London441]

‘In that regard, the authors do not say anything about how lifestyle may influence the results related to fat distribution and weight gain.’

‘May’ influence the results? LOL.

In the US, 77% of the entire population do not exercise. For those over 65 with a cancer diagnosis, 85%. Exercise is the primary intervention for all ADT side effects, along with caloric restriction, especially carbohydrates.

ADT induced sarcopenia presents a challenge which unfortunately is not met by most men. Whether it’s LHRH alone or in combination with abiraterone enzalutamide etc. matters far less than the degree of intervention . Cardiovascular and weight bearing exercise- along with eating well (and less) comprises that intervention, quite simply.

Someday this will be ‘proven’. One would do well to forget about waiting on that.

[Scout4answers in reply to London441]

We are on the same page

[TryGuyCP in reply to London441]

In retrospect, I wish my oncologist before starting ADT :

1. insisted I started heavy lifting to counter both sarcopenia and osteoporosis.

2. ordered bone density DEXA before start of ADT and then every year after.

I only found out just how serious my osteoporosis was after innocent bike fall (lost balance and fell on my left side at 5 mph) that led to fractured left hip joint and complete left hip replacement. Only then I asked for DEXA bone density and it came up with -2.7 T-score on remaining right hip.

[timotur in reply to TryGuyCP]

Just for reference, my DEXA was -2.1 before 18 months of Lupron/six months Abi, and it decreased to -2.4 after. I didn’t take any calcium supplements, but did eat calcium-friendly foods like broccoli, sesame seeds, and sardines/anchovies. Lifted light weights 3x/wk, ran 12 miles/wk, tennis 2x/wk, swam 1 miles/wk. Still had bone loss of about 12.5%.

[dhccpa in reply to London441]

Don't forget, though, that here in USA both TV watching and video game playing are recognized as strength building and aerobic exercises. The rest of the world is, of course, lagging behind.

[Derf4223]

Add creatine supplementation before exercise. I also use taurine and HMB. Gaining muscle albeit at 1/2 the rate if I wasn't on lupron and abi. My Dexa scores were osteopenic. I get Prolia every 6 months. The trial below is going to evaluate creatine and is based on an earlier small study.

healthcare.utah.edu/huntsma...

[TryGuyCP in reply to Derf4223]

What dose of creatine do you take? Only before exercise? what about on rest days?

Is'n there a danger of promoting cancer growth by activating mTOR?

[Derf4223 in reply to TryGuyCP]

A fairly high dose -- 2x/day, with breakfast and dinner (before exercise). About 20 grams total. Exercise is daily. I pace myself accordingly. Approximately 1 hour walking in hilly woods, 1 hour evening resistance training, and 1 hour aerobics and stretches and crunches.

Here is a quote from the first linked article.

"This is of particular relevance given that dietary creatine supplementation has been implicated to have multiple health benefits, including potential anticancer activities (18). In patients with prostate cancer receiving androgen deprivation therapy, creatine supplementation has been suggested to enhance the positive effects of resistance training on patient performance and quality of life (19, 20)."

aacrjournals.org/cancerres/...

Also see this uclahealth.org/news/creatin...

And about this prospective study news-medical.net/news/20231...

I am actually _building_ muscle. Also taking HMB, L Theanine, and Taurine.

Living with APCa and the SE's of LT androgen blockade treatment frequently involves forced trade-offs. We face bone and muscle loss and _must_ do stuff to address them, diet, and on and on.

[cigafred in reply to Derf4223]

Citations greatly appreciated. Thanks.

[TryGuyCP in reply to Derf4223]

Thanks a lot on more details Derf!

Totally agree we must address SE's of ADT considering all the trade-offs.

I looked at design of that 12-week original study form 2019 (By the way, could not find its results anywhere only plan of it) and they used 20g/day for only day preloading period and then 5g/day after that. Looks like you take 20g daily. For how long by now?

After reading your first reply I ordered creatine tablets and started taking 10(g) twice a day: first 30m before (usually) morning exercise, then with dinner.

I did find the first article but it talks about "cyclocreatine, a creatine analog" which got me confused.

[Derf4223 in reply to TryGuyCP]

The amount of creatine needed is a function of age and diet. Vegetarians need to add some. It also is said to help mental health. As for how long I've been taking 20 g/day, about 3 months with no intention of stopping. I keep my MO in the loop about this and all other supplements, vitamins and medicines I take.

ncbi.nlm.nih.gov/pmc/articl...

[j-o-h-n]

The best way I found to beat fat accumulation on ADT, was to make it out of bed all by myself in the morning.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 10/25/2023 9:29 PM DST