TRT Peaks and troughs or steady levels. Which is correct?

busydad

New Member
I'm a bit confused. I'm considering starting TRT. I'm trying to decide on injecting or oral. My doctor prescribes either one but says he prefers sub-q injection 2x per week. Where I'm confused is I see arguments for both therapies. Some folks say the peaks and troughs of orals is best cause it mimics our body's natural rhythm. The I see others stating it's good to have steady state of higher test at all times.

The reason I'm considering the oral is because E2 is always very high. I've been having labs done going back 15 years and my Estradiol has never been in range. It's usually between 50 - 80. I really don't want to go on a aromatase inhibitor so it seems like the oral may be my best option.

Would daily injections work the same as the oral?

Thanks
 
I'm a bit confused. I'm considering starting TRT. I'm trying to decide on injecting or oral. My doctor prescribes either one but says he prefers sub-q injection 2x per week. Where I'm confused is I see arguments for both therapies. Some folks say the peaks and troughs of orals is best cause it mimics our body's natural rhythm. The I see others stating it's good to have steady state of higher test at all times.

The reason I'm considering the oral is because E2 is always very high. I've been having labs done going back 15 years and my Estradiol has never been in range. It's usually between 50 - 80. I really don't want to go on a aromatase inhibitor so it seems like the oral may be my best option.

Would daily injections work the same as the oral?

Thanks
We have a few threads on oral testosterone. You may find this one interesting.

 
It's a good question, without a definitive answer. There's too much individual variation to say whether you'd find the differences to be subtle or profound. Neither modality produces a natural-looking diurnal rhythm in serum testosterone. However, men can have good results with either. Twice-weekly injections of testosterone cypionate actually do yield pronounced peaks and troughs, with a 50% reduction from peak to trough being typical. It's only when you get to daily or EOD injections that levels can become fairly static.

Personally I have come to favor having intra-day variation, though I have not used oral testosterone to attain it. Also, my point of comparison is static levels from EOD testosterone enanthate.

With your concerns about estradiol it does seem as though oral testosterone is the better choice. However, I'd encourage you to start with something even faster acting if possible, such as testosterone nasal gel, before resorting to a form of TRT that results in significant suppression of the HPTA.
 
Is there any new information (e.g., studies) regarding trying to replicate the natural daily fluctuation of testosterone of an adult male at peak health?

I'm asking because a few months back I switched to daily injections of testosterone phenylpropionate (based on the bits and pieces of relevant info. in this forum).
 
Is there any new information (e.g., studies) regarding trying to replicate the natural daily fluctuation of testosterone of an adult male at peak health?

I'm asking because a few months back I switched to daily injections of testosterone phenylpropionate (based on the bits and pieces of relevant info. in this forum).

I'm not aware of anything new on the subject. The successes of testosterone nasal gel and oral testosterone seem likely to reduce interest in finding ways to more precisely mimic a normal diurnal rhythm in serum testosterone. You may have seen a study referenced by @madman showing that a particular form of topical testosterone—maybe a patch?—produced the best likeness. Nonetheless, I think a testosterone propionate/cypionate blend for injection is preferable to this because then you have an approximation of a natural daily rhythm without the excessive DHT of a transdermal. Because phenylpropionate is between cypionate and propionate it may act like a reasonable blend on its own. How are you finding it? I see you said you were doing quite well on testosterone acetate prior to this, though at very high doses.
 
Thanks for the update. Hopefully, more will come out, especially regarding long-term effects/differences, if any.

When I started TRT about 15 years ago, it didn't go well through my PCP. I got frustrated, couldn't afford to go outside of insurance, so I researched how to brew testosterone on my own. I've been completely on my own since then.
 
I only responded to oral testosterone. Turns out I didn’t need it. My original health problem was T2 diabetes, which caused iron and vitamin D deficiency.

The treatment was TRT! I don’t know how TRT is supposed to correct iron and vitamin D deficiency. If anything, TRT is going make the iron deficiency worse.

If only I knew 9 years ago, all I needed was carnivore diet and vitamin D supplements and my iron deficiency would’ve corrected itself.

You might want to cross your T’s and dot your I’s before starting to your TRT.
 
Is there any new information (e.g., studies) regarding trying to replicate the natural daily fluctuation of testosterone of an adult male at peak health?

I'm asking because a few months back I switched to daily injections of testosterone phenylpropionate (based on the bits and pieces of relevant info. in this forum).

No T formulation other than the T-patch (Androderm®) applied before bed would be the closest to achieving this!

It was discontinued 2018 in Canada and 2023 in the US by its manufacturer, AbbVie (formerly Allergan).

As I have stated numerous times on the forum over the years when it comes to most closely mimicking the 24 hr natty circadian rhythm of a healthy young male the transdermal T-patch (Androderm®) applied before bed holds the title!

Even then when we are speaking in terms of natty healthy young men those peak T levels achieved are a daily short-lived peak to boot!

Natural endogenous testosterone secretion is pulsatile and diurnal.

During the natural 24-hour circadian rhythm of a healthy young male T levels will start rising gradually overnight reaching a peak (highest point) in the early AM followed by lower levels in the late afternoon and reaching trough (lowest point) in the evening.

Fluctuations from peak--->trough would be around 20-25% (higher in some cases).

One daily peak/trough.

They have a healthy hpta to boot!

Drastic difference here compared to the majority of the men on TTh who are running high FT levels 24/7 and top it off that many are hitting a high/absurdly high trough FT whether injecting daily, EOD, twice-weekly (every 3.5 days), M/W/F or god forbid once weekly!

Strong suppression of the hpta and throw in HAMMERING the shit out of your DOPAMINE and CNS to boot!

The human body was never meant to be amped up on T let alone 24/7!





This is key here!


(i) elevated and near peak TT level during nighttime sleep, (ii) peak TT level around the time of morning awakening, (iii) moderately elevated TT level during the initial hours of wakefulness, (iv) reduced TT level in the late afternoon, and (v) lowest TT level in the evening. Based upon these criteria, only the Androderm® transdermal patch (Figure 3D), when applied in the evening (∼22:00 h) as recommended, closely mimics the TT circadian rhythm of normal young adult males.


* The TT concentration produced by the Androderm® transdermal patch applied to the skin of the back, stomach, upper arms, or thighs nightly before retiring to sleep more closely reproduces the normative TT circadian pattern of young adult males than any of the other marketed PA-TRTs. Following application, TT concentration progressively rises during sleep and peaks around the time of morning awakening; it progressively declines during late morning and afternoon, reaching its nadir (Cmin) in the evening before the next scheduled patch application (Figure 3D).


* The TT level produced by the Androderm® transdermal patch system when applied as recommended in the evening before bedtime most closely simulates the normal physiologic pattern. In this regard, the high and low limits of normal TT in the graph of this PA-TRT found in the package insert are unique (Figure 3D); they are depicted in a time-varying cyclic, rather than a time invariable constant, manner that takes into consideration the normal high-amplitude TT circadian variation of diurnally active healthy young men(https://www.accessdata.fda.gov/ drugsatfda_docs/label/2011/020489s025lbl.pdf). This is in distinct contrast to the manner in which the high and low limits of normal are depicted in the package insert of all the other PA-TRTs (Figure 2A-2F and Figure 3A-3C), that is, as constant values consistent with the presumed homeostatic perspective of human biology and endocrinology. Such a homeostatic perspective drives the recommended procedures of dose assessment and titration, although with inconsistencies between the different PA-TRTs in the recommended time of day when to conduct them (Table 2).













 
The human body was never meant to be amped up on T let alone 24/7!

Natty diurnal rhythm of a healthy young male!


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Again!

(i) elevated and near peak TT level during nighttime sleep, (ii) peak TT level around the time of morning awakening, (iii) moderately elevated TT level during the initial hours of wakefulness, (iv) reduced TT level in the late afternoon, and (v) lowest TT level in the evening.


If you pluck out those natty outliers in the 95th percentile hitting that FT 25 ng/dL this is a f**king short-lived daily peak we are talking about here!

Many men on exogenous T therapy especially those knumbskulls pushing that more T is better mentality on those so called mens health/HRT forums are running around with absurdly inflated FT levels and this is at the f**king trough to boot!

Complete S**T SHOW at its finest!
 
"The human body was never meant to be amped up on T let alone 24/7!"
"Natural endogenous testosterone secretion is pulsatile and diurnal."
Natty diurnal rhythm of a healthy young male!


View attachment 53032
This is an inarguable fact that is often overlooked or brushed aside. You cannot improve on the natural cycle. It's the ebb and flow that creates balance.
 
Natural testosterone production and fluctuations
  • Daily cycle (diurnal rhythm): For most men, testosterone levels are highest in the morning and gradually decline throughout the day, reaching their lowest point in the evening.
  • Aging: After a man's peak testosterone production in his late teens to early adulthood, his levels gradually decrease by about 1% to 2% each year after age 30 or 40.
  • Lifestyle factors: Natural fluctuations are also affected by sleep, stress, diet, and physical activity. Chronic stress, sleep deprivation, and obesity can all contribute to lower testosterone levels.
  • Average ranges: Normal testosterone levels vary widely among individuals and with age, typically falling between 270 and 1,070 nanograms per deciliter (ng/dL) for males.
 
Remember that an oral is going to be hard on your liver so some degree. I've been OK AST/ALT with Oxandrolone (Anavar) but all out of whack on Stanozolol (Winstrol). I'm not too versed in oral Test how that impacts the liver but something to consider.
 
"Natural endogenous testosterone secretion is pulsatile and diurnal."

You cannot improve on the natural cycle.
We don't know what nature was optimizing for. I seem to do better with cypionate (although I have not tried every combination) but I think we can be confident that nature was not trying to have 60 Y/O's optimized for having lots of kids since that would not be historically optimal for the species.
 
We don't know what nature was optimizing for. I seem to do better with cypionate (although I have not tried every combination) but I think we can be confident that nature was not trying to have 60 Y/O's optimized for having lots of kids since that would not be historically optimal for the species.
I'm not certain what you were referring to exactly. The statement is referring to the daily ebb and flow of testosterone, not stating that TRT doesn't have its purpose. I have been on bi weekly T Cyp for 20 years with excellent results. But if we could replicate the natural diurnal cycle with the same ebb and flow of natural production, that would be optimum.

The statement was referring to the cycle itself, that is how it is intended to function. Cypionate most definitely doesn't work for that purpose, too long of a half-life. T Gel would appear to be the best option, but unfortunately for me, I don't absorb it very well. I see guys doing daily T Cyp injections as if they think it's going to replicate the natural diurnal cycle. The half-life is the same regardless of the dosage. At some point you reach saturation and your levels are static.

Of course, age is a factor, along with others that cause a decline, or malfunction of testosterone production. My point is that it would be optimal if the delivery system mimicked the natural rise and fall of T levels.
 
I'm not certain what you were referring to exactly. The statement is referring to the daily ebb and flow of testosterone, not stating that TRT doesn't have its purpose. I have been on bi weekly T Cyp for 20 years with excellent results. But if we could replicate the natural diurnal cycle with the same ebb and flow of natural production, that would be optimum.

The statement was referring to the cycle itself, that is how it is intended to function. Cypionate most definitely doesn't work for that purpose, too long of a half-life. T Gel would appear to be the best option, but unfortunately for me, I don't absorb it very well. I see guys doing daily T Cyp injections as if they think it's going to replicate the natural diurnal cycle. The half-life is the same regardless of the dosage. At some point you reach saturation and your levels are static.

Of course, age is a factor, along with others that cause a decline, or malfunction of testosterone production. My point is that it would be optimal if the delivery system mimicked the natural rise and fall of T levels.
I'll try to clarify. I've seen a lot of people assume that the natural rise and fall is "better" and go to extreme lengths to try to mimic it, however I have never seen logic or evidence that it would be optimal for the individual or the modern human species. I mean no disrespect to nature or the creative forces, however what is optimal for the species where people rarely lived past 40 yeas of age is likely not optimal for most on TRT. For example, if the natural rhythm was timed for peak sexual performance when being distracted from predators was least likely to be a threat, that would no longer apply. It may also have been that the natural cycle was merely good enough, but not optimal.

Of more relevance is that there is an IMO compelling theory of aging which says that aging is largely a programmed function whereby the body essentially tries to kill itself in order to prevent old, injured individuals from becoming a drag on the species. Josh Mittledorf has written extensively on this topic and his blog post entitled "There is no such thing as Natural Anti-aging" is a good summary.

I see a lot of bad health decision-making in general based on assuming what's natural is automatically best. People who think they can avoid supplements because they are not "natural" or who say adult humans should not drink milk are examples of this kind of flawed logic.
 
As @BadassBlues pointed out, the ebb and flow is what creates balance.

For example, quite a few of us here have experimented with blends of medium and fast acting esters to create a spike in the morning with a trough at night instead of a constant state of CNS arousal 24 hours a day.

I need that trough at night to cobble together a decent night's sleep. I have no idea how some guys sleep well on supra-physiological doses. If I'm at top end of TT range overnight, I am lucky to get 4 hours of sleep. If you can get away with it, bless you.

Same thing with dopamine. You need a low to experience a high. Otherwise your body will simply downregulate.
 
It's funny you would think injecting a blend at bedtime would be closer to the natural state where t starts going up once you enter sleep...but rarely you ever hear of anyone doing that.
 
I'll try to clarify. I've seen a lot of people assume that the natural rise and fall is "better" and go to extreme lengths to try to mimic it, however I have never seen logic or evidence that it would be optimal for the individual or the modern human species. I mean no disrespect to nature or the creative forces, however what is optimal for the species where people rarely lived past 40 yeas of age is likely not optimal for most on TRT. For example, if the natural rhythm was timed for peak sexual performance when being distracted from predators was least likely to be a threat, that would no longer apply. It may also have been that the natural cycle was merely good enough, but not optimal.

Of more relevance is that there is an IMO compelling theory of aging which says that aging is largely a programmed function whereby the body essentially tries to kill itself in order to prevent old, injured individuals from becoming a drag on the species. Josh Mittledorf has written extensively on this topic and his blog post entitled "There is no such thing as Natural Anti-aging" is a good summary.

I see a lot of bad health decision-making in general based on assuming what's natural is automatically best. People who think they can avoid supplements because they are not "natural" or who say adult humans should not drink milk are examples of this kind of flawed logic.
I follow your logic and agree to a certain extent. However, I do disagree on this particular subject. I believe the natural diurnal rhythm to be ideal. As @madman stated, the body is not supposed to be in a state of elevated testosterone for extended periods of time. That throws off the balance and has effects on other functions, cortisol, neurotransmitters and a variety of other processes are affected.

We can all acknowledge the age-related decline in androgen receptor sensitivity, LH production, Leydig Cell sensitivity which do cause a definite decline in overall male mojo which you referred to above.


Most of these issues can be treated with exogenous products which are definitely not part of the natural process as we are intervening with the normal aging process. To this extent, I wholeheartedly agree with you. But I do disagree that maintaining the natural rhythm is not ideal, it functions like that for very good reasons. It's similar to circadian rhythm in that if it gets out of balance, it has ill effects on homeostasis.

I think we likely agree on most things related to this topic, but I can't help but think that something is being lost in translation.

Your reference to Josh Mittledorfs theory of aging highlights that. I read that as rejecting the natural process of cellular degradation and letting the body die "naturally". Which is different from maintaining natural cycles. Keeping fit, diet and incorporating specific medications and supplements will help to maintain natural cycles. Just like sirolimus accelerates the natural process of autophagy. It is those processes that I am referring to. I dye my hair because I don't look good in grey, that is an example of a natural process that I am all in on in changing.

Interesting article from Josh on anti aging supplements:

 
It's funny you would think injecting a blend at bedtime would be closer to the natural state where t starts going up once you enter sleep...but rarely you ever hear of anyone doing that.

Injectables would never cut it even when using the medium acting esters TC/TE as there will still be a burst release of T within 2 hrs post-injection as T levels will start rising quickly!

Natty endogenous T levels GRADUALLY RISE OVERNIGHT peaking in the early AM!

The closest you could get to mimicking this would be the transdermal T-patch (Androderm) applied before bed.
 

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This tool provides predictions based on statistical models and should NOT replace professional medical advice. Always consult with your healthcare provider before making any changes to your TRT protocol.

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Understanding Your Hormones

Estradiol (E2)

A form of estrogen produced from testosterone. Important for bone health, mood, and libido. Too high can cause side effects; too low can affect well-being.

DHT

Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth, prostate health, and masculinization effects.

Free Testosterone

The biologically active form of testosterone not bound to proteins. Directly available for cellular uptake and biological effects.

Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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