TRT Dosing And Frequency Breakdown With Dr. Peter Attia
Summary
TLDRThe 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
💉 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.
🌡 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.
📦 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.
Mindmap
Keywords
💡Dosing frequency
💡Testosterone cypionate
💡Half-life
💡Steady-state serum concentrations
💡Injection adherence
💡Aromatization
💡5 Alpha reduction
💡Pharmacokinetics
💡Nesto
💡Subcutaneous vs. Intramuscular
💡Gynecomastia
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
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