TRT Dosing And Frequency Breakdown With Dr. Peter Attia

Summary

The video script discusses optimal dosing and injection frequency for testosterone replacement therapy (TRT). It highlights the importance of patient adherence and the impact of half-life on steady-state serum concentrations. The conversation explores different dosing strategies, including once weekly, twice weekly, and daily injections, and their effects on hormone levels and side effects. The script also touches on the use of different testosterone esters, administration routes (subcutaneous vs. intramuscular), and the benefits of more frequent dosing to mimic natural hormone fluctuations and reduce side effects.

Takeaways

• 😀 The script discusses the advantages of different dosing frequencies for hormone therapy, particularly for testosterone.
• 🤔 The half-life of a drug, such as testosterone cypionate with a half-life of 10 days, plays a significant role in determining dosing schedules for steady state serum concentrations.
• 💉 Injecting more frequently can be beneficial for patient adherence and achieving a more stable hormone level, but it also depends on individual preferences and habits.
• 📉 The script suggests that more frequent injections can lead to less hormone fluctuation and potentially lower side effects.
• 🚀 Daily injections, while difficult to administer, can result in less suppression of FSH and LH, indicating a possible link between peak hormone levels and suppression.
• 📚 The literature often assesses dose response a week after injection, which may not reflect the optimal dosing for hormone optimization.
• 🔍 Personal observations and experiences suggest that more frequent injections can reduce aromatization spikes and 5-alpha reduction.
• 🌡️ The script mentions the use of nesto, a nasal formulation of testosterone with a short half-life, requiring a tid dosing schedule.
• 🏥 The FDA-approved formulations, like nesto, are preferable for their safety and standardized dosing compared to compounding.
• 🌟 The goal of hormone therapy should be to replicate natural hormone fluctuations as closely as possible to minimize side effects and optimize health.
• 💊 Differences between cypionate and enanthate are discussed, with enanthate having a half-life intermediate between cypionate and propionate, and the convenience of pre-loaded pens for some patients.

Q & A

What is the main topic of discussion in the provided transcript?

The main topic of discussion is the dosing frequency and methods of administering testosterone replacement therapy (TRT), including the advantages and disadvantages of different dosing schedules and injection techniques.

What is the half-life of testosterone cypionate as mentioned in the transcript?

The half-life of testosterone cypionate is mentioned as approximately 10 days.

What is the significance of achieving steady-state serum concentrations in the context of TRT?

Achieving steady-state serum concentrations is important as it indicates a stable level of the hormone in the blood, which helps to minimize fluctuations and potential side effects, thus more closely mimicking natural hormone levels.

Why might a patient prefer a more frequent injection schedule for TRT?

A more frequent injection schedule can help maintain a more stable hormone level, reduce the spike in hormone levels that can lead to side effects, and potentially improve the quality of life by more closely replicating the body's natural hormone rhythm.

What is the 'sweet spot' for TRT dosing frequency according to the discussion?

The 'sweet spot' for TRT dosing frequency is suggested to be twice a week, which provides a balance between maintaining stable hormone levels and patient adherence.

What is the difference between daily injections and weekly injections in terms of hormone suppression?

Daily injections of testosterone can result in less suppression of FSH and LH compared to weekly injections, suggesting that the peak hormone levels associated with larger doses may have more impact on hormone suppression.

What are the potential side effects of a large, infrequent dose of testosterone?

A large, infrequent dose of testosterone can lead to super-physiological levels of the hormone and its metabolites, which may cause an aggressive spike in free androgenic signaling, potentially impairing sleep quality, increasing red blood cell production, and activating the sympathetic nervous system.

What is the significance of the FDA formulation of a nasal testosterone product mentioned in the transcript?

The FDA formulation of a nasal testosterone product is significant because it offers a short half-life, allowing for more frequent dosing and potentially fewer side effects. It also provides a convenient, pre-loaded option for those who are squeamish about injections.

How does the pharmacokinetics of subcutaneous (subq) injection compare to intramuscular (IM) injection according to the transcript?

Subcutaneous injection may provide a more sustained release of the hormone due to its absorption through fat tissue, potentially leading to higher total testosterone levels when measured a week after injection compared to intramuscular injection.

What is the difference between testosterone cypionate and enanthate in terms of dosing and administration?

Testosterone enanthate is considered to have a shorter half-life compared to cypionate, making it more suitable for more frequent dosing. It is also available in a pre-loaded pen, which may be more convenient for some patients, but may limit the ability to adjust dosages.

What is the potential impact of more frequent TRT dosing on aromatization and 5-alpha reduction?

More frequent TRT dosing can potentially lower the spikes in aromatization and 5-alpha reduction, which are processes that convert testosterone into other hormones, thus helping to manage side effects related to these conversions.

Outlines

00:00

💉 Optimal Testosterone Injection Frequency and Dosage

The paragraph discusses the benefits of different dosing frequencies for testosterone injections. It mentions that dividing a weekly dose into two halves for bi-weekly injections or even daily doses can be more beneficial for steady hormone levels. The half-life of testosterone cypionate, commonly prescribed in the US, is highlighted as being 10 days, which affects the time to reach steady state serum concentrations. The speaker suggests that injecting twice a week is the minimum for good hormone optimization, and daily injections can lead to less suppression of FSH and LH, potentially reducing side effects. The paragraph also touches on the physiological impact of high peak levels of testosterone and the benefits of more frequent injections to avoid such spikes.

05:00

🌡 Stability in Hormone Levels and FDA Formulations

This section delves into the importance of maintaining stable hormone levels to mimic natural function and reduce side effects. It contrasts the rapid fluctuation of testosterone levels from less frequent injections with the more natural diurnal rhythm of hormone release. The discussion includes the benefits of FDA-approved formulations like the nasal testosterone product 'nesto', which has a short half-life and allows for more frequent dosing without the risks associated with large spikes in hormone levels. The paragraph also addresses the challenges of finding the right dosing regimen to optimize hormone therapy and the potential for different testosterone esters to have varying half-lives and effects.

10:01

📦 Convenience and Cost of Pre-Loaded Testosterone Pens

The final paragraph focuses on the practical aspects of hormone replacement therapy, including the convenience and cost associated with pre-loaded testosterone pens like Zad. It discusses the limitations of these pens in terms of dosage flexibility and the potential for patients to not be optimizing their hormone levels if they are only injecting once a week. The paragraph also compares the pharmacokinetics of subcutaneous (subq) versus intramuscular (IM) injections, suggesting that subq injections might offer a more sustained release and potentially better mimic natural hormone levels. The speaker emphasizes the importance of frequency in administration to achieve a more stable hormone profile and improve quality of life.

Keywords

💡Dosing frequency

Dosing frequency refers to how often a medication is administered. In the context of the video, it discusses the advantages of different dosing schedules for hormone therapy, such as once weekly, twice weekly, or daily dosing. The script mentions that more frequent dosing can lead to steadier hormone concentrations and potentially lower side effects, which is a central theme of the discussion.

💡Testosterone cypionate

Testosterone cypionate is a medication used for hormone replacement therapy, specifically for conditions like hypogonadism. It has a half-life of about 10 days, meaning it takes this long for half of the drug to be eliminated from the body. The script notes that this medication is commonly prescribed in the US and is used to illustrate the concept of steady-state serum concentrations.

💡Half-life

The half-life of a drug is the time it takes for the concentration of the substance in the body to decrease by half. The script discusses the half-life of testosterone cypionate and how it relates to achieving steady-state levels in the blood, which is crucial for understanding the effects of different dosing frequencies on hormone levels.

💡Steady-state serum concentrations

Steady-state serum concentrations refer to the point at which the amount of drug being absorbed is equal to the amount being eliminated, resulting in stable levels in the blood. The script explains that achieving this state can take about 50 days for testosterone cypionate and is an important factor in the effectiveness and side effects of hormone therapy.

💡Injection adherence

Injection adherence is the consistency with which patients follow their prescribed injection schedule. The script mentions that the frequency of injections can be influenced by patient adherence, with some individuals preferring less frequent injections despite the potential for less optimal hormone levels.

💡Aromatization

Aromatization is the process by which androgens like testosterone are converted into estrogens. The script discusses how more frequent injections can lower the aromatization spike, which can help reduce side effects like gynecomastia and maintain more natural hormone levels.

💡5 Alpha reduction

5 Alpha reduction refers to the conversion of testosterone to dihydrotestosterone (DHT), another androgen. The script suggests that more frequent dosing can reduce this conversion, potentially leading to fewer side effects and a more balanced hormone profile.

💡Pharmacokinetics

Pharmacokinetics is the study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion. The script uses pharmacokinetics to explain why certain dosing frequencies and methods of administration, such as subcutaneous (subq) versus intramuscular (IM), may be more effective or have different effects on hormone levels.

💡Nesto

Nesto is a nasal formulation of testosterone that has a very short half-life, requiring a three-times-a-day dosing schedule. The script mentions Nesto as an example of how different administration methods and dosing frequencies can affect hormone levels and side effects, with the added benefit of being an FDA-approved product.

💡Subcutaneous vs. Intramuscular

Subcutaneous (subq) and intramuscular (IM) are two methods of drug administration. Subq involves injecting into the fatty tissue under the skin, while IM involves injecting directly into muscle tissue. The script discusses the pharmacokinetic differences between these methods, suggesting that subq may provide a more sustained release and potentially fewer side effects.

💡Gynecomastia

Gynecomastia is a condition in which male breast tissue develops, often due to an imbalance of hormones. The script mentions gynecomastia as a potential side effect of testosterone therapy, particularly when there is a high spike in estrogen levels due to aromatization, and how adjusting dosing frequency can help manage this side effect.

Highlights

Dosing hormone therapy once a week is the bare minimum but not optimal.

Twice a week dosing is recommended for better steady hormone concentrations.

Daily injections can lead to less suppression of FSH and LH compared to weekly doses.

Higher peaks in hormone levels can cause more FSH suppression.

Frequent injections can lower aromatization spikes and 5 Alpha reduction.

150 mg testosterone injections daily are challenging due to the small volume required.

Nesto, a nasal testosterone formulation, has a short half-life and requires tid dosing.

Nesto avoids hematopoiesis issues and is FDA approved for women's use.

Intravaginal use of certain formulations can enhance women's orgasmic function.

FDA-formulated products are preferable to avoid the risks associated with compounding.

More frequent hormone administration can lead to a lower side effect burden.

Daily dosing can help some patients avoid gynecomastia and the need for aromatase inhibitors.

The standard dosing every two weeks may not be ideal for hormone optimization.

Differences between cypionate and enanthate may be age-specific and related to metabolism.

Zad, a pre-loaded pen for enanthate, offers convenience but less flexibility in dosing.

SubQ administration might provide a more sustained release effect than IM.

Pharmacokinetic profiles can vary significantly with different administration routes.

The choice between subQ and IM depends on individual factors and dosing frequency.

Transcripts

any advantage to dosing it once weekly

taking that dose and dividing it by two

and doing it twice a week taking that

dose and dividing it by seven and doing

it every day yeah it's and I don't

necessarily know that like for example

when patients come to you I'm sure

they're looking for the highest level of

optimization hence why they're with you

so maybe it's more reasonable to expect

them to pin more frequently say pin I

mean inject but there is a halflife

associate like with the drug depending

on the estr chosen typically

testosterone cypionate will be

prescribed at least in the US that's the

most prescribed one which is a halflife

of 10 days if I recall off the top of my

head depends on the person of course

where it's injected blah blah blah

but that halflife you could you know

extrapolate out from that okay it's

going to take 50 days to achieve steady

state serum concentrations in the blood

and that's going to look on like a

steroid plotter you could check online

and see this kind of like you know

spiking until all of a sudden there is

the same amount of dropping of the drug

clearing out of your system you're

getting an equal amount of Spike back up

like there is no accumulation of drug

burden after you've achieved steady

state serum

concentrations so the advantage to

injecting more

frequently and this is going to be

determined largely by patient adherence

more than anything because some people

simply refuse to inject even more than

I've seen some in like insane stuff

where people will let themselves drop to

literally hypogonadal territory and then

remember based on their dick not working

I'm going to okay now I take my test but

in general once a week is like bare

minimum I would say but that's certainly

not optimal and I would say that two

times a week at least for somebody

seeking good quality oversight you know

preventative medicine whatever if

they're coming to you or to somebody who

believes in the same things you do

twice a week I think is kind of minimum

for decent steady hormone concentrations

yeah we've sort of arrived at the same

conclusion that that's The Sweet Spot we

do have a couple patients who do daily

injections and interestingly in these

patients we see much less for the same

dose of testosterone so you take oh like

15 milligrams injected a day which is

actually very difficult to do you have

to be very thoughtful about what kind of

needles you're using to actually get

such a small volume in but they they

will have much less FSH LH suppression

hm which suggests to me that the bigger

the the higher the peak the more the

fshh suppression I don't know that

there's anything physiologically

relevant to that other than I think it's

the studies is when you look at trough

level T levels and I say trough I mean

like the lowest point of hormone

concentrations after an injection often

times these studies assessing dose

response will look a week after your

injection so what you see in the

literature isn't necessarily reflective

of what's going to be in patients trying

to optimize anyways but what I see

personally and in meral and through all

my blood work that I've seen over the

years

Etc the more frequent you get there's a

diminishing returns for sure but you can

lower the

aromatization spike and 5 Alpha

reduction by going more frequent so if

you have a bullus administration of I

don't know 150 Mig once a week you are

literally spiking your tea into Super

physiological territory acutely and

concurrently you are getting super

physiologic conversion to estradi DHT

you also have a very very aggressive

Spike and free androgenic signaling

which can crank your sympathetic nervous

system up impair your Sleep Quality like

there's so many consequences people

don't and you'll see more hematopoesis

yeah so when I had Mo Cara on here he

was talking about nesto which is the

nasal formulation which has such a short

halflife that it's actually a tid dosing

schedule wild so it's 7 milligrams of

testosterone injected inally three times

a day for more than a year and still

tell me it's cool and fun to

take so if you end up doing that for trt

you I probably will not but what his

point was two two two interesting points

with with Testo the first is they don't

have the hematopoesis

so you know you these are not people who

are making too many red blood cells that

you have to actually be careful of and

have to go and get them therapeutically

photomizer gets over 50 um secondly it's

a FDA formulation that women can use

right because if a guy is taking seven

milligrams in each nostril three times a

day clearly a woman could take one of

those every other day and and by the way

it's sort of an OnDemand libido uh tool

for women in particular so so there are

lots of interesting things around that

also they're doing a clinical study and

we're sort of observing what they're

doing where women are using intravaginal

use one you know one application of that

intravaginally before sex to enhance

orgasmic function nice so again pretty

pretty it's always desirable to have an

FDA formulated product when you can kind

of avoid the the the the dark side of

compounding is my view I think the best

way to conceptualize for The Listener

too why this frequent protocol or

getting a more stable level is even why

is it result in a lower side effect

burden to it's the most the closest you

can replicate natural function the more

you will replicate natural side effect

profile which you know should be nothing

if you were a physiologic so with you

know nesto which is like in and out

acutely like so fast you were not

getting this huge Spike to like you

know, 1500 2,000 nagram per deciliter

Total Tea there is no situation ever in

which your testes would just blast you

once a week with a hammer of test and

all of the associated metabolites and

back end and consequences of that you

would have little pulsations over you

know a dial Rhythm and this is why you

you know you would test your blood as a

natural in the morning when your

testosterone is spiking and it's going

to EB and flow over the day your test

level in the morning will not could be

300 NS per deciliter higher than later

in the day like it fluctuates so to

expect that it's reasonable to jam

yourself with an absurd amount of test

in one go and then hang on that as it

declines at your body and then crank it

to the stratosphere again once a week

it's just not representative of a

physiologic state whatsoever so the more

you can replicate that dial Rhythm

through the synthetic Administration

route the closer you're going to get to

a

Lower Side effect burden like I've seen

some guys that get gynecomastia from trt

dosages go to Ed everyday dosing and get

off their AI like that's how significant

yeah so just to translate that into

English you've seen guys you've seen

guys who can take a weekly dose of

testosterone and in doing so they make

so much estrogen that they have to take

an androgen inhibitor pardon me an

aromatase inhibitor to prevent them from

getting breast tissue gynecomastia and

if they take that same dose and divide

it daily they can come off their

aromatase inhibitor alt together yeah

and some people it's it's problematic

because they will give feedback to their

doctor or just give a state a give a

judgment to what hormone therapy was

like for them based on what is maybe a

not the right dose but also just not

even close to an ideal dosing regimen

and injection frequency when we you know

when I got back into the practice of

medicine and was learning about HRT I

couldn't find doctors who weren't

prescribing anything different than

twice every two weeks that was the

standard have you seen the European

susten on I mean it's just no I have not

but but so standard was 200 milligrams

every two weeks and um which immediately

I I was actually I remember going

through lewellen's pharmacology and

looking at the pharmacokinetics and

being like this is an awful idea um so

yeah uh any difference

clinically between cypionate and ananth

eight um obviously one of the advantages

of an anate is there's a commercial

product called zad for people who are

squeamish about injecting that comes in

a pre-loaded pen so we have some

patients who just don't like the idea of

having to draw up a syringe and they

just kind of want something that's a

little more TurnKey so Z which is a

slightly different uh form of

testosterone but but clinically I I sort

of remember at one point there was some

difference that might be age specific

but I don't recall now yeah the halflife

ananth is often thought to be a long

Ester which it is relative to like

propionate or phenol propionate but it's

kind of like an in between of cypionate

and propionate it's like a half life of

could be as short as like four and a

half to 5 days I believe off the top of

my head where a could be twice as long

in some people so it depends on your

individual metabolism of the drug um

often so and also if you're pinning subq

or IM like you could kind of like bleed

out the effect more so with I would say

if you're injecting frequently enough

it's essentially irrelevant but with

these auto injector pens which is

typically the auto injector the the zad

protocol from the FDA is once weekly oh

is it which is actually I mean we still

recommend people do it twice a week just

use a lower dose the difference of not

using your what you're supposed to take

versus using it like obviously frequency

is of a lesser concern than you walking

around with no test so if the if it's

the difference between a guy taking it

versus not you know okay take your you

know once a week if that's what it's

going to take I don't know if it's is

the pre-loaded dose you can't can you

modulate you can't meter it that's

what's so annoying about it such yeah

it's such a racket because and I tell

patients I'm like look if if you're

completely cost insensitive I guess fine

but otherwise like getting you know

cenate in a jar is a fraction of the

cost if you're just willing to be the

guy that meters it out um but the

enanthate I think only comes in three

loaded doses of zad so you also you also

have less wiggle room if you're not

happy with the output I would assert

with near certainty that you are not

optimizing your hormone status if you

are I want say optimize I mean just like

dialing in the stability of it and the

side effect profile and potentially

quality of life as much as you could if

you did a more frequent schedule

especially with an anate so once a week

is a little bit meaning you you you you

the more frequent you're giving it the

better yeah like I think the diminished

returns are there's a significant drop

off when you go from every other day to

every day but like one week to twice a

week like I'd say there's a pretty

dramatic difference that's worthwhile to

Y um let's talk about the difference

between subq and I am um again I

I I have always advised patients to do

subq um for the belief that it has as

you point out kind of you bleed out the

effect a little bit longer uh but I I

have to be honest I don't think I've

seen data to support that I have seen

and I think this is an extrapolation but

I believe it to be true is when you look

at subq dosing you'll notice the total T

levels are higher and then people take

away from that oh subq is like you get

more out of your test but the reality is

when they measure total test levels it's

often a week after your shot to it just

lasts longer so I think you are almost

giving yourself a sustained release kind

of through administering into the fat

tissue rather than intramuscular which

is more readily absorbed

quicker blood flow Etc just like if you

did like an IV Administration it would

be like in your blood immediately not

that you would do that of course but

yeah the difference in pharmacokinetic

profile of like IV to IM to subq like

you can change the same drug

dramatically in onset of action through

that so you think that subq is probably

a better Administration and so if you

were I think once you get to every other

day dosing it's almost it doesn't almost

matter yeah but I think especially for

people who are doing and again it

depends on the amount because if you're

doing once a week is that going to be

too much of a a Bolis like to sit in

stomach fat depends on the person yeah

but you know I would say especially for

infrequent you'd be better you know subq

ideally if the volume of oil isn't

significant enough that it's like

creating lumps and stuff