The AI dilemma (puberty/height/framemaxxers GTFIH)

[ItsyBitsyJayhawk]

173 cm at 15.25 years old with 15.0 bone age, predicted adult height 178 cm, goal height 185+

173 cm at 15 is pretty decent considering I was only 167 cm at 15 and managed to reach 177 by 17/18. I grew almost 10 cm in a span of two to three years. You might actually accomplish your goal or at least come close to it if you maintain proper nutrition and supplement your diet with hormones. My goal was 185 cm too but sadly I'm coping with LL now since I'm 19. I'm primarily focusing on framemaxxing at the moment because your frame doesn't stop growing up until your mid twenties.
You should look up a peptide analogue called Vosoritide (sold under the brand name Voxzygo). It's literally a magic drug. Expensive as fuck but so potent that it can help pre-pubescent children with dwarfism catch up to their peers in growth. If you pair that shit with AIs and growth hormone peptide analogues in your teen years, in theory the average person could literally achieve the NBA physique.

 

[ItsyBitsyJayhawk]

I'm afraid of wasting my only shot at growth man I wanna hop on hgh+mk asap. I'll ask for a thyroid blood check

Well I'd suggest you to start off with peptide analogues along with MK (since they don't shut off your natural production and have considerably less side effects) and only switch HGH after several months to see how your body responds to drastic increase in serum HGH.

 

[Deleted member 33409]

Well I'd suggest you to start off with peptide analogues along with MK (since they don't shut off your natural production and have considerably less side effects) and only switch HGH after several months to see how your body responds to drastic increase in serum HGH.

Mk doesnt work
Btw to check mild hypothyroidism what hormones do u ask for?

 

[ItsyBitsyJayhawk]

Mk doesnt work

Not on its own it doesn't but pair it with peptides and you will have noticeably stronger spikes of HGH.

Btw to check mild hypothyroidism what hormones do u ask for?

Get blood test done. If you have hypothyroidism, you will have to undergo thyroid replacement therapy in which you will be given synthetic oral thyroxine (T4). While marginal thyroid imbalances don't affect growth that much, significant imbalances in your thyroid levels can be a huge problem.

 

[Deleted member 33409]

Not on its own it doesn't but pair it with peptides and you will have noticeably stronger spikes of HGH.

Get blood test done. If you have hypothyroidism, you will have to undergo thyroid replacement therapy in which you will be given synthetic oral thyroxine (T4). While marginal thyroid imbalances don't affect growth that much, significant imbalances in your thyroid levels can be a huge problem.

Ok but what hormones do i check?

 

[Lemonhead]

173 cm at 15 is pretty decent considering I was only 167 cm at 15 and managed to reach 177 by 17/18. I grew almost 10 cm in a span of two to three years. You might actually accomplish your goal or at least come close to it if you maintain proper nutrition and supplement your diet with hormones. My goal was 185 cm too but sadly I'm coping with LL now since I'm 19. I'm primarily focusing on framemaxxing at the moment because your frame doesn't stop growing up until your mid twenties.
You should look up a peptide analogue called Vosoritide (sold under the brand name Voxzygo). It's literally a magic drug. Expensive as fuck but so potent that it can help pre-pubescent children with dwarfism catch up to their peers in growth. If you pair that shit with AIs and growth hormone peptide analogues in your teen years, in theory the average person could literally achieve the NBA physique.

I have something to ask I haven't grown since 14 years stuck at 172 centimeters and the same height at 19 , never even developed secondary sexual characteristics. I've check MIR scans and x-rays but nothing wrong with my tumor or pituitary gland ( no tumor ) , but my hormonal profile is quited low for Testosterone and basically non existent for hgh and I think it might be due to my recessed air ways as their really recessed and I tend to lack complexion and have acne

 

[truecel12]

Well I'd suggest you to start off with peptide analogues along with MK (since they don't shut off your natural production and have considerably less side effects) and only switch HGH after several months to see how your body responds to drastic increase in serum HGH.

HGH offsets a lot of the muscle / joint-related side effects. im not sure if it would completely offset the osteoblast/osteoclast problem with aromatase inhibitors, but i noticed after i had to abstain from hgh for a month (my parents found it but shipping took 3 weeks), that my joints ached with basketball and high-intensity rowing. my muscles stayed the same strength though.

and the androgen metabolite of exemestane can cause balding, and thats the main reason why im not using aromasin. ascend and i think some other fag was starting to recede because of aromasin

 

[truecel12]

I have something to ask I haven't grown since 14 years stuck at 172 centimeters and the same height at 19 , never even developed secondary sexual characteristics. I've check MIR scans and x-rays but nothing wrong with my tumor or pituitary gland ( no tumor ) , but my hormonal profile is quited low for Testosterone and basically non existent for hgh and I think it might be due to my recessed air ways as their really recessed and I tend to lack complexion and have acne

did your plates fuse at 14 or something

 

[Lemonhead]

did your plates fuse at 14 or something

They are still open from x-ray scans

 

[ItsyBitsyJayhawk]

Ok but what hormones do i check?

It's your T3 and T4 levels, but you don't need to specify anything. Shrinks know how to make medical reports, it's their job. You just need to get a test done and leave the rest to them.

 

[ItsyBitsyJayhawk]

I have something to ask I haven't grown since 14 years stuck at 172 centimeters and the same height at 19 , never even developed secondary sexual characteristics. I've check MIR scans and x-rays but nothing wrong with my tumor or pituitary gland ( no tumor ) , but my hormonal profile is quited low for Testosterone and basically non existent for hgh and I think it might be due to my recessed air ways as their really recessed and I tend to lack complexion and have acne

Correlation and causation are two different things. Recessed airways are caused by improper pubertal or prenatal development which is often a result of abnormal hormonal profile. So I'd argue that it's actually your abnormal hormonal profile which left you with recessed airways and not the other way around.
I could be wrong but this screams of incomplete/delayed puberty. This was me at 17. Shrinks will most likely make you undergo TRT for a few months to trigger another growth spurt (speaking from experience). If that doesn't work they'll prescribe you DHT-derivatives like Proviron while continuing the testosterone replacement therapy. The following part is optional since HGH won't do you much good at 19 but you can inject pharma grade HGH or peptides for framemaxxing at least. And take L-carnitine supplements too (for the upregulation of androgen receptors). While you may not be able to achieve longitudinal growth anymore (unless you're coping with LL like me), lateral growth and development of secondary sexual characteristics is still possible. You've got about 3 or 4 years, hit the gym, take proper nutrition, take hormones and augment your diet with supplements.

 

[ItsyBitsyJayhawk]

HGH offsets a lot of the muscle / joint-related side effects. im not sure if it would completely offset the osteoblast/osteoclast problem with aromatase inhibitors, but i noticed after i had to abstain from hgh for a month (my parents found it but shipping took 3 weeks), that my joints ached with basketball and high-intensity rowing. my muscles stayed the same strength though.

Yeah, HGH does have osteoprotective effects.

and the androgen metabolite of exemestane can cause balding, and thats the main reason why im not using aromasin. ascend and i think some other fag was starting to recede because of aromasin

"Topical" Dutasteride is your friend.

 

[Deleted member 30959]

Exemestane is worse in terms of sides in my case. Also heightmaxxing doesn't work past 16 (except for AI users or super late bloomers/ Lucky 1-2 inch growth spurt)

You have no idea what youre talking about. Northern and eastern european populations grow many inches at ages 17-18 and continue having slight growth until around age 22

 

[truecel12]

Yeah, HGH does have osteoprotective effects.


"Topical" Dutasteride is your friend.

topical dutasteride still goes systemic (not that i have any problems with 5ar inhibitors, im going to hop on one as soon as my development finishes)

its suicide to use one during puberty

 

[truecel12]

Yeah, HGH does have osteoprotective effects.


"Topical" Dutasteride is your friend.

and topical dutasteride wouldnt work that way, it works through stopping 5ar conversion. it doesnt stop anything from binding to the androgen receptor.

if you wanted a topical antiandrogen, something like spiro or breezule would be a better pick

 

[truecel12]

Yeah, HGH does have osteoprotective effects.


"Topical" Dutasteride is your friend.

assuming that topical dutasteride doesnt go systemic, it still doesnt stop the problem with using exemastene.
the androgenic metabolite of aromasin isnt converted through 5ar, inhibiting it wont do shit. it will still bind to the androgen receptors in the scalp and cause balding.

dutasteride will stop hairloss from dht, but if you specifically want to prevent aromsin's metabolites from raping your hair you need to use an antiandrogen to bind to the androgen receptor

and this post doesnt take into account that preventing aromatase increases testosterone (both from it not being converted to estradiol and also the negative feedback loop of estradiol being turned off), where testosterone increases osteoblast count and lifespan

 

[truecel12]

You have no idea what youre talking about. Northern and eastern european populations grow many inches at ages 17-18 and continue having slight growth until around age 22

the average growth velocity bottoms out after 16-17, look at the cdc growth charts. growth plates dont suddenly fuse or fuse, they just slowly ossify.

when you are 16 you can obviously still do heightmaxxing, but dont expect anywhere near the results compared to somebody who started earlier. people who expect entire inches of augmentation are looking for too much imo.

my final height predicted is 181cm, but im not expecting hgh+ai to push me above 185.

 

[ItsyBitsyJayhawk]

topical dutasteride still goes systemic (not that i have any problems with 5ar inhibitors, im going to hop on one as soon as my development finishes)

its suicide to use one during puberty

Topical dut is better than topical fin in this regard. It's unlikely that it will go systemic if your usage is modest.

and topical dutasteride wouldnt work that way, it works through stopping 5ar conversion. it doesnt stop anything from binding to the androgen receptor.

if you wanted a topical antiandrogen, something like spiro or breezule would be a better pick

assuming that topical dutasteride doesnt go systemic, it still doesnt stop the problem with using exemastene.
the androgenic metabolite of aromasin isnt converted through 5ar, inhibiting it wont do shit. it will still bind to the androgen receptors in the scalp and cause balding.

dutasteride will stop hairloss from dht, but if you specifically want to prevent aromsin's metabolites from raping your hair you need to use an antiandrogen to bind to the androgen receptor

17-hydroexemestane while more potent than basic Exemestane isn't nearly as affinitive to the androgen receptors in your scalp as T let alone DHT (which has 5 times the affinity of T to androgen receptors and also the potency/half-life). Hairloss on Exemestane or just AIs in general doesn't result from the androgenic metabolite of Exemestane itself but due to a decline in aromatization. Excess mobile T which was being converted into estrogen before starts being reduced to DHT on AIs. That's what you need a topical 5-ar inhibitor for.

and this post doesnt take into account that preventing aromatase increases testosterone (both from it not being converted to estradiol and also the negative feedback loop of estradiol being turned off), where testosterone increases osteoblast count and lifespan

Well isn't that common sense? While I didn't specify the benefits of enhanced serum androgen levels associated with the use of AIs, I did mention that your androgens will skyrocket on AIs in the very first paragraph.
Also, E2 negative feedback loop is never turned off. Your pituitary gland releases FSH en masse (which accelerates aromatase production) once in a while to make sure of that. E2 levels alternate between baseline and ideal (whatever your ideal is on AIs) every other month or so on average.

 

[ZachS]

With all the studies out there suggesting AI's role in delaying growth cartilage ossification? You can chuck out a couple inches of growth if you start early and consistently follow your routine long enough. I'm talking 2-3 years on AI at least along with consistent exogenous hormonal aid to see significant results.

how expensive is running an ai for that time frame?

 

[Deleted member 78087]

Preface

So I've been scouring the forum for opinions and personal experiences of users on AIs as of late and I found it quite surprising that despite its significance in growthmaxxing, the topic of AIs seems to be one that hasn't been discussed extensively (in detail) on this forum. That hopefully changes with this thread though. All my concerns regarding AIs (based on what I have learnt so far) will be duly addressed in this thread. To whomever this may be of interest, do yourself a favor and read this to the end.

For the newbies to understand the gish gallop that I will be momentarily spitting, we need to cover fundamentals of this topic first. You may skip the following part if you are well acquainted with AIs.

*Skip to the next purple highlight if you know what AIs are and how they work*​

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What is aromatization?​

To understand Aromatase inhibitors, you must first understand the process of aromatization. Aromatization is the process in which certain androgens when in excess amounts, are converted into estrogens which are easier for the body to metabolize. These androgens are called aromatizing androgens (there are non-aromatizing ones too but that's a topic for another thread). Testosterone and androstenedione are two examples of aromatizing androgens that are fairly abundant in the average male human body. This process of aromatization is irreversible and it's a reaction that's catalyzed by an enzyme called Aromatase. ​

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It's also important to know the function of SHBGs (Sex Hormone-Binding Globulins) here. These biological superstructures bind with sex-hormones and regulate the amount of free androgens and estrogens in your tissues that can be used by your body's cells. ​

By facilitating the downregulation of SHBGs you can increase the concentration of androgens and estrogens in your tissues that can be then used by your body's cells to perform various functions. ​

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Now back to aromatization, it's worth noting that mobile aromatizing androgens are aromatized into estrogens wherever the enzyme aromatase is in abundance and these locations in your body can be your gonads, your brain, your bones, your adipose tissues and even the goddamn endothelial walls of your vascular surfaces. ​

As I mentioned earlier, aromatization is simply your body's way of disposing unused androgens since androgens are more taxing on your organs and harder to metabolize than estrogens. It's crucial for you to understand that the abundance of mobile/unused aromatizing androgens in your tissues, is directly proportional to the rate of aromatization. Your objective should be to enable your body to utilize the mobile androgens in your tissues. That way you're not just hindering unnecessary aromatization but also using the free androgens in your tissues to your advantage. Taking effective measures to desensitize and upregulate the amount of androgen receptors in order to allow your body to utilize the free/unused androgens in your tissues would effectively reduce aromatization to some extent by causing a reduction in the concentration of serum androgens with the formation of more hormone-receptor complexes. ​

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It goes without saying that androgens in slightly higher than average amounts are ideal and estrogens in higher concentrations are not. That's not to say that you need to avoid estrogens like the plague. All hormones including estrogens are ESSENTIAL for the ideal functioning of your body and I'll be talking more about this later my post while addressing the adverse effects of estrogen deficiency.​

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The burning question is, what steps must one take to ensure that their serum estrogen levels are ideally minimal? Enter...​

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Aromatase Inhibitors!​

Aromatase inhibitors are a class of compounds which bind with the enzyme aromatase and prevent it from binding with its substrate androgen, thus inhibiting the process of aromatization.​

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To understand how AIs go about inhibiting the action of aromatase, you need to know what enzymes and inhibitors are and how they work. ​

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So enzymes like aromatase are basically biological catalysts which provide their substrates with the necessary activation energy to make or break bonds in order to trigger a chemical reaction. Structurally, they almost entirely consist of proteins, each with their own distinct primary structure which refers to the number or sequence of amino acids in a polypeptide chain. All amino acids being structurally and compositionally different tend to form a variety (potentially near-infinite variations) of bonds and each bond causes the polypeptide chain to fold differently. This folding of proteins gives rise to three-dimensional super structures called tertiary proteins and this is the form in which proteins can function as enzymes (since this folding of peptide chains gives rise to indentations of specific shape in the protein structure which are its active and allosteric sites).​

Since tertiary proteins come in near-infinite variations, every biological compound in the world has an enzyme that complements its shape and can bind with it like lock and key. The chemical compound that complements the shape of an enzyme is its substrate. This makes each enzyme highly specific in nature considering they can only bind with substrates that complement their shape (like lock and key). Substrates bind with enzymes on their active sites and it's these zones in an enzyme that make it highly specific in its action. Androstenedione and testosterone for example are the substrates of the enzyme aromatase.​

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Then there are zones in the protein structure of an enzyme other than its active site which are called allosteric sites. This is where substances besides the enzyme's complementing substrate can attach themselves to, in order to inhibit the activity of enzyme. The binding of substances to the allosteric sites of enzymes induces structural changes into the enzyme's active sites which prevents the formation of enzyme-substrate complexes. No enzyme-substrate complexes equals no chemical reaction.​

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There are competitive enzyme inhibitors and then there are non-competitive enzyme inhibitors. The inhibitors that bind to the enzyme's active sites are competitive inhibitors and they compete with an enzyme's substrate to bind with with its active site. The greater the abundance of substrates will be, the more ineffective a competitive inhibitor will be and vice versa. Non-competitive inhibitors on the other hand are the ones that bind with an enzyme's allosteric site regardless of the substrate concentration. ​

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Inhibitors, regardless of their mode of action can be either reversible or irreversible. Reversible inhibitors are homeostatically controlled and can bind and unbind with an enzyme without disturbing its structure or composition. Irreversible inhibitors on the other hand are disruptive and can cause permanent changes to the protein structure of an enzyme denaturing in the process. There is no intrinsic negative feedback loop to counteract the action of irreversible inhibitors and the factors that offset the reduction of functional enzymes in blood plasma and tissues are all extraneous. Irreversible inhibitors can disrupt serum substrate levels in unoptimized dosages because the process of restoration of functional enzymes takes a while.​

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*The devil is in the details*​

Now if we talk about inhibitors of the enzyme aromatase, there are both irreversible and reversible varieties. Amongst the three most researched selective inhibitors of aromatase, Exemestane (Aromasin) is an irreversible inhibitor, whereas Letrozole (Femara) and Anastrozole (Arimidex) are reversible. Exemestane forms permanent (covalent) bonds with the aromatase enzyme irreparably disrupting its specific shape in doing so. Aanastrozole and Letrozole on the other hand inhibit the synthesis of estrogen via reversible competition.​

These three inhibitors can be further classified into two categories, steroidal and non-steroidal. Exemestane (Aromasin) is a steroidal inhibitor as opposed to Letrozole (Femara) and Anastrozole (Arimidex) which are non-steroidal inhibitors.​

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View attachment 3021991​

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I might be boring some of you to death with all the obvious nonsense that I've been spitting up until this point but I want you all to hang in there for a moment, I promise I'm going somewhere this. I now present to you a number of problems and benefits associated with the use of each of the aforementioned AIs.​

1. Drug properties (Selectiveness/bioavailability/dosage/half-life/pharmacokinetic profile)​

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- Exemestane being a non-competitive aromatase inhibitor is markedly more selective in its action than both Letrozole and Anastrozole since the latter two inhibit estrogen by actively competing with its substrate androgens to bind with the active site of aromatase.​

The rule of thumb is, the more selective a drug, the lower its chances of interacting with other drugs and vice versa.​

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- Being a steroidal inhibitor, Exemestane has its tradeoffs. It is poorly soluble in water (or aqueous mediums in general like all molecular compound that are lipid in nature) and that significantly affects its bioavailability which is extremely low (at about 5%) compared to its non-steroidal (Letrozole and Anastrozole) counterparts. Cyclodextrin are a class of hydrophilic sugar molecules and their complexation enhances solubility and oral bioavailability of poorly soluble drugs. While I don't know if such a variant of Exemestane is commercially available but scientists have previously tried to introduce cyclodextrin complexes in powdered and tablet Exemestane to improve its aqueous solubility.​

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- One standard Aromasin tablet contains about 25 mg of Exemestane to compensate for its poor bioavailability. Each Fermara tablet contains 2.5 mg of Letrozole whereas Arimidex contains only 1 mg of Anastrozole per tablet.​

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It's imperative to note that these clinically administered doses are optimized for female breast cancer patients only. Their hormonal profile is drastically different even from that of the average female let alone the average male or worse a male on different PEDs and supplementation. You need to get your bloodwork done frequently and adjust your dosage in accordance to your hormonal profile. I strongly recommend you to do your own research on the subject matter and also seek professional advice from reputable endocrinologists before devising your drug regimen.​

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- At clinically administered doses, the plasma half-lives of Anastrozole (1 mg once daily), Letrozole (2.5 mg once daily), and Exemestane (25 mg once daily) are between 41-48h, 2-4 days, and 24-27 h, respectively. Letrozole is the most potent AI with the longest half life but is also the least selective amongst the three inhibitors. Triazoles are better at estrogen inhibition than Exemestane in because their inhibitory activity is vast and constant throughout their half-lives. Exemestane tends to have a lasting effect but it is more selective and reserved in its action than Triazoles.​

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- Letrozole and Anastrozole have a better pharmacokinetic profile than Exemestane because they are unlikely to cause a long-lasting estrogen crash. An oral dose of Exemestane is rapidly absorbed and reaches peak plasma concentrations within 2 hours of administration. After 4 hours, the plasma concentration falls to undetectable levels yet the inhibitory activity persists still for at least 5-7 days despite a plasma half-life of only 27 hours.​

This long-lasting inhibitory effect is due to the irreversible aromatase inhibition caused my Exemestane. A new process of enzyme biosynthesis is required to restore estrogen production, leading to a persistent inhibitory effect even after clearance of the drug from plasma and tissues.​

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2. Toxicity profile (lipid profile/renal and hepatic stress/estrogen crash and rebound)​

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- Since both Anastrozole and Letrozole belong to the same class of compounds, called Triazoles their toxicity profiles are similar. Letrozole and Anastrozole had no impact on serum LDL and Triglycerides concentrations in clinically administered doses but the HDL levels were noticeably reduced. Since HDL is considered good cholesterol given that its responsible for the disposal of LDL which is considered bad cholesterol, a reduction in serum HDL may increase the risk of thrombosis (blood clotting) and other cardiovascular morbidities. A low fat (low cholesterol in particular) diet on Anastrozole and Letrozole is essential for those who are already at a high risk for cardiovascular diseases.​

THE USE OF TRIAZOLES IS COMPLETELY OUT OF QUESTION FOR THOSE WHO ALREADY SUFFER WITH CARDIOVASCULAR DISEASES (you'll be paving your way to an early grave). ​

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Exemestane on the other hand has negligible impact on lipid profiles and might reduce Triglycerides and HDL concentrations by 5-7% at most depending on your lifestyle. The reduction of Triglycerides is somewhat beneficial and Exemestane may even improve your lipid profile to a marginal extent.​

All AIs will affect total blood cholesterol levels since estrogen plays a minor role in cholesterol disposal but it will be negligible with Exemestane unless the dosage is unoptimized.​

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- Liver injury is sometimes attributed to Letrozole (rare <1% of occurrences) but it is usually mild, self-limited and typically a transient, asymptomatic elevation in serum enzymes. The impact of Anastrozole and Exemestane on renal and hepatic health is neutral and any complications associated with the usage of the aforementioned drugs isn't commonly reported.​

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- Although all AIs can cause your serum estrogen levels to crash, Exemestane in particular can have lasting effects on your serum estrogen levels if it is administered in unoptimal doses. An estrogen crash caused by the administration of Triazoles will usually resolve as soon as the inhibitory effects of the drug fade, it will however be offset by a homeostatic response from your body which will cause your serum estrogen levels to skyrocket temporarily.​

While this pattern of crash and rebound may not be of significant concern in the short-term, if you miss Letrozole and Anastrozole dosages or administer them in unoptimal doses habitually, this can become a serious problem.​

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3. Other health concerns and side effects (musculoskeletal effects/androgenic effects/neurological and psychological effects)​

- AIs (even the more selective third generation varieties be it Exemestane or Triazoles) are quite notorious for the syndromous effects they tend to have on the musculoskeletal system. Aromatase inhibitor–induced musculoskeletal symptoms (AIMSS) is the term for it.​

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This is because estrogens play a significant role in the growth and maturation of bone as well as in the regulation of bone turnover in adulthood. It's quite ironic that the supposed female sex hormone has such a significant hand in facilitating the development of dimorphic skeletal traits.​

Estrogens play an elaborate role in the formation of osteoblast cells. Its inhibition or deficiency in young skeletons results in decreased osteoblast formation. While the formation of osteoblasts decreases, the formation of osteoclasts is unbothered and since osteoblasts and osteoclasts have antagonistic roles, the reduction in the number of osteoblasts causes osteoclasts to go about their function without osteoblasts to counteract them. This results in bone resorption. These responses inevitably lead to decreased bone mass, disturbed architecture and reduced bone strength. Basically, your bones go from having timber-like consistency to that of bamboo if you're not mindful of your doses or abusing AIs religiously.​

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Heightmaxxing by nature is a double edged sword. You're trading your bone health and integrity for a few inches of longitudinal growth. And it's worth noting that the issues caused by changes that occur in your bones (or the changes that were supposed to occur in your bones during your developmental years but didn't occur) due to hormonal intervention, may very well persist over the long-term. ​

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And it's not just the bones that are affected negatively by estrogen inhibition but also your joints and muscles since the bones and soft tissues in your body connect together to form a kinetic chain. Approximately 47-50% of AI users experience joint stiffness and muscle atrophy besides a perception of heightened pain which results from increases sensitivity of nerves in the region.​

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It's essential to religiously engage in strength training and stretching while taking a balanced diet with loads of supplements while on AIs to manage the adverse musculoskeletal effects of estrogen inhibition.​

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However it's also worth mentioning that in several clinical studies, incidences of bone morbidity were reported to be noticeably greater with the use of non-steroidal AIs like Letrozole and Anastrozole (Triazoles basically) than steroidal ones like Exemestane. This has to do with with the steroidal structure of Exemestane which boasts relatively greater osteoprotective effects. That leads us to our next point.​

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- Exemestane isn't transported in the body in its original form. It is metabolized into another steroidal molecule called 17-Hydroexemestane. This variant of Exemestane is structurally not dissimilar enough from its template molecule to keep it from binding with aromatase. ​

However, 17-hydroexemestane is even more steroidal (read: potent) than basic Exemestane and that allows it to function as an active metabolite which is capable of binding with certain androgenic receptors in your body and promote mild androgenic effects which can compensate for the osteodegenerative effects that result from estrogen inhibition to some extent. ​

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The ability of Exemestane to mimic androgenic behaviour makes it a superior option for those suffering with or concerned about with bone-related issues than non-steroidal aromatase inhibitors. However Exemestane also tends to have osteodegenerative effects in higher doses and it can be even more problematic than Triazoles should that happen habitually because its inhibitory effects are lasting. ​

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- Estrogens like androgens are hormones with anti-oxidative properties which helps with neurological protection in addition to ideal cognitive function since they facilitate/promote synaptic plasticity, neurogenesis and ensure proper glutamate regulation (essential for synaptic transmission), cerebral blood flow, cholinergic flow and maintenance of your cerebral white matter. In other words, you're essentially a few picograms of estrogen less away from becoming a total vegetable. So whether or not you like it, AIs are going to leave you with ADHD-like symptoms (bad short term memory, lack of focus and motivation etc), mood disorders which may affect your sexual performance and even your gut health (if you suffer with gastroenterological issues like IBS) since the gut-brain axis is quite closely linked.​

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- Then again, steroidal AIs like Exemestane are a safer bet than non-steroidal ones since they tend to mimic androgenic behaviour which allows them to compensate for the inhibition of estrogens and minimize its adverse effects to some extent. ​

The potential side effects of Exemestane as I mentioned earlier have the potential to be worse than those of Triazoles should you mess up your dosage and end up with an estrogen crash that spans a week and might even take longer to fully recover from. ​

My advice is to put AIs on the backburner if it's affecting your cognitive function and mood. Specially if it's taxing to your academic performance. ​

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I would also suggest taking nootropics and mood stabilizers to counteract the adverse effects of AIs on cognitive function and mood. I'll admit that I barely know anything about neuroendocrinology and that there are other, more qualified users you can look up to. There are countless threads on this forum that will help you maximize your neurological health as you steer through you growthmaxxing journey. I suggest you look those up.​

Conclusion

There is no definitive AI that will help you breeze through your growthmaxxing journey. What may work for you may not work for someone else and vice versa. The answers to "which AI should I use?" are "all", "none" and "it depends". There are tradeoffs associated with the use of all AIs that you must take into consideration before planning your approach. You need to test out different drugs at different doses and devise an optimal regimen through trial and error.

While this entire thread must have read like a propaganda piece warning you all against the use of AIs, the fact is that this is just the reality of the subject matter. AIs, while manageable are not as safe as most of us like to think they are and biohacking may sound good in theory but it isn't all that practical. Not all of us are blessed with good genetics and there is a cost for those who wish to ascend the limitations that were imposed onto them by nature.

The point of this thread is not just to inform the newcomers but also to ignite a discussion that will allow exchange of valuable information on a topic that isn't discussed in detail very often. Ask whatever you want, I'll try to answer what I can.

TL;DR- There is no summary. Read the whole damn thing (or at least the second half of the thread) you lazy halfwits.



P.S. Although I have been a long time lurker on this forum, this is my first thread. So ​

pardon the atrocious formatting and my overly-rigid style of writing, it'll improve with time.​

 

[SubhumanForever]

All this "pubertymaxing" shit is complete fucking C O P E
And @PubertyMaxxer is proof of that

 

[sb23]

Preface

So I've been scouring the forum for opinions and personal experiences of users on AIs as of late and I found it quite surprising that despite its significance in growthmaxxing, the topic of AIs seems to be one that hasn't been discussed extensively (in detail) on this forum. That hopefully changes with this thread though. All my concerns regarding AIs (based on what I have learnt so far) will be duly addressed in this thread. To whomever this may be of interest, do yourself a favor and read this to the end.

For the newbies to understand the gish gallop that I will be momentarily spitting, we need to cover fundamentals of this topic first. You may skip the following part if you are well acquainted with AIs.

*Skip to the next purple highlight if you know what AIs are and how they work*​

​

What is aromatization?​

To understand Aromatase inhibitors, you must first understand the process of aromatization. Aromatization is the process in which certain androgens when in excess amounts, are converted into estrogens which are easier for the body to metabolize. These androgens are called aromatizing androgens (there are non-aromatizing ones too but that's a topic for another thread). Testosterone and androstenedione are two examples of aromatizing androgens that are fairly abundant in the average male human body. This process of aromatization is irreversible and it's a reaction that's catalyzed by an enzyme called Aromatase. ​

​

It's also important to know the function of SHBGs (Sex Hormone-Binding Globulins) here. These biological superstructures bind with sex-hormones and regulate the amount of free androgens and estrogens in your tissues that can be used by your body's cells. ​

By facilitating the downregulation of SHBGs you can increase the concentration of androgens and estrogens in your tissues that can be then used by your body's cells to perform various functions. ​

​

Now back to aromatization, it's worth noting that mobile aromatizing androgens are aromatized into estrogens wherever the enzyme aromatase is in abundance and these locations in your body can be your gonads, your brain, your bones, your adipose tissues and even the goddamn endothelial walls of your vascular surfaces. ​

As I mentioned earlier, aromatization is simply your body's way of disposing unused androgens since androgens are more taxing on your organs and harder to metabolize than estrogens. It's crucial for you to understand that the abundance of mobile/unused aromatizing androgens in your tissues, is directly proportional to the rate of aromatization. Your objective should be to enable your body to utilize the mobile androgens in your tissues. That way you're not just hindering unnecessary aromatization but also using the free androgens in your tissues to your advantage. Taking effective measures to desensitize and upregulate the amount of androgen receptors in order to allow your body to utilize the free/unused androgens in your tissues would effectively reduce aromatization to some extent by causing a reduction in the concentration of serum androgens with the formation of more hormone-receptor complexes. ​

​

It goes without saying that androgens in slightly higher than average amounts are ideal and estrogens in higher concentrations are not. That's not to say that you need to avoid estrogens like the plague. All hormones including estrogens are ESSENTIAL for the ideal functioning of your body and I'll be talking more about this later my post while addressing the adverse effects of estrogen deficiency.​

​

The burning question is, what steps must one take to ensure that their serum estrogen levels are ideally minimal? Enter...​

​

Aromatase Inhibitors!​

Aromatase inhibitors are a class of compounds which bind with the enzyme aromatase and prevent it from binding with its substrate androgen, thus inhibiting the process of aromatization.​

​

​

​

To understand how AIs go about inhibiting the action of aromatase, you need to know what enzymes and inhibitors are and how they work. ​

​

So enzymes like aromatase are basically biological catalysts which provide their substrates with the necessary activation energy to make or break bonds in order to trigger a chemical reaction. Structurally, they almost entirely consist of proteins, each with their own distinct primary structure which refers to the number or sequence of amino acids in a polypeptide chain. All amino acids being structurally and compositionally different tend to form a variety (potentially near-infinite variations) of bonds and each bond causes the polypeptide chain to fold differently. This folding of proteins gives rise to three-dimensional super structures called tertiary proteins and this is the form in which proteins can function as enzymes (since this folding of peptide chains gives rise to indentations of specific shape in the protein structure which are its active and allosteric sites).​

Since tertiary proteins come in near-infinite variations, every biological compound in the world has an enzyme that complements its shape and can bind with it like lock and key. The chemical compound that complements the shape of an enzyme is its substrate. This makes each enzyme highly specific in nature considering they can only bind with substrates that complement their shape (like lock and key). Substrates bind with enzymes on their active sites and it's these zones in an enzyme that make it highly specific in its action. Androstenedione and testosterone for example are the substrates of the enzyme aromatase.​

​

​

Then there are zones in the protein structure of an enzyme other than its active site which are called allosteric sites. This is where substances besides the enzyme's complementing substrate can attach themselves to, in order to inhibit the activity of enzyme. The binding of substances to the allosteric sites of enzymes induces structural changes into the enzyme's active sites which prevents the formation of enzyme-substrate complexes. No enzyme-substrate complexes equals no chemical reaction.​

​

There are competitive enzyme inhibitors and then there are non-competitive enzyme inhibitors. The inhibitors that bind to the enzyme's active sites are competitive inhibitors and they compete with an enzyme's substrate to bind with with its active site. The greater the abundance of substrates will be, the more ineffective a competitive inhibitor will be and vice versa. Non-competitive inhibitors on the other hand are the ones that bind with an enzyme's allosteric site regardless of the substrate concentration. ​

​

​

Inhibitors, regardless of their mode of action can be either reversible or irreversible. Reversible inhibitors are homeostatically controlled and can bind and unbind with an enzyme without disturbing its structure or composition. Irreversible inhibitors on the other hand are disruptive and can cause permanent changes to the protein structure of an enzyme denaturing in the process. There is no intrinsic negative feedback loop to counteract the action of irreversible inhibitors and the factors that offset the reduction of functional enzymes in blood plasma and tissues are all extraneous. Irreversible inhibitors can disrupt serum substrate levels in unoptimized dosages because the process of restoration of functional enzymes takes a while.​

​

*The devil is in the details*​

Now if we talk about inhibitors of the enzyme aromatase, there are both irreversible and reversible varieties. Amongst the three most researched selective inhibitors of aromatase, Exemestane (Aromasin) is an irreversible inhibitor, whereas Letrozole (Femara) and Anastrozole (Arimidex) are reversible. Exemestane forms permanent (covalent) bonds with the aromatase enzyme irreparably disrupting its specific shape in doing so. Aanastrozole and Letrozole on the other hand inhibit the synthesis of estrogen via reversible competition.​

These three inhibitors can be further classified into two categories, steroidal and non-steroidal. Exemestane (Aromasin) is a steroidal inhibitor as opposed to Letrozole (Femara) and Anastrozole (Arimidex) which are non-steroidal inhibitors.​

​

View attachment 3021991​

​

​

I might be boring some of you to death with all the obvious nonsense that I've been spitting up until this point but I want you all to hang in there for a moment, I promise I'm going somewhere this. I now present to you a number of problems and benefits associated with the use of each of the aforementioned AIs.​

1. Drug properties (Selectiveness/bioavailability/dosage/half-life/pharmacokinetic profile)​

​

- Exemestane being a non-competitive aromatase inhibitor is markedly more selective in its action than both Letrozole and Anastrozole since the latter two inhibit estrogen by actively competing with its substrate androgens to bind with the active site of aromatase.​

The rule of thumb is, the more selective a drug, the lower its chances of interacting with other drugs and vice versa.​

​

- Being a steroidal inhibitor, Exemestane has its tradeoffs. It is poorly soluble in water (or aqueous mediums in general like all molecular compound that are lipid in nature) and that significantly affects its bioavailability which is extremely low (at about 5%) compared to its non-steroidal (Letrozole and Anastrozole) counterparts. Cyclodextrin are a class of hydrophilic sugar molecules and their complexation enhances solubility and oral bioavailability of poorly soluble drugs. While I don't know if such a variant of Exemestane is commercially available but scientists have previously tried to introduce cyclodextrin complexes in powdered and tablet Exemestane to improve its aqueous solubility.​

​

- One standard Aromasin tablet contains about 25 mg of Exemestane to compensate for its poor bioavailability. Each Fermara tablet contains 2.5 mg of Letrozole whereas Arimidex contains only 1 mg of Anastrozole per tablet.​

​

It's imperative to note that these clinically administered doses are optimized for female breast cancer patients only. Their hormonal profile is drastically different even from that of the average female let alone the average male or worse a male on different PEDs and supplementation. You need to get your bloodwork done frequently and adjust your dosage in accordance to your hormonal profile. I strongly recommend you to do your own research on the subject matter and also seek professional advice from reputable endocrinologists before devising your drug regimen.​

​

- At clinically administered doses, the plasma half-lives of Anastrozole (1 mg once daily), Letrozole (2.5 mg once daily), and Exemestane (25 mg once daily) are between 41-48h, 2-4 days, and 24-27 h, respectively. Letrozole is the most potent AI with the longest half life but is also the least selective amongst the three inhibitors. Triazoles are better at estrogen inhibition than Exemestane in because their inhibitory activity is vast and constant throughout their half-lives. Exemestane tends to have a lasting effect but it is more selective and reserved in its action than Triazoles.​

​

- Letrozole and Anastrozole have a better pharmacokinetic profile than Exemestane because they are unlikely to cause a long-lasting estrogen crash. An oral dose of Exemestane is rapidly absorbed and reaches peak plasma concentrations within 2 hours of administration. After 4 hours, the plasma concentration falls to undetectable levels yet the inhibitory activity persists still for at least 5-7 days despite a plasma half-life of only 27 hours.​

This long-lasting inhibitory effect is due to the irreversible aromatase inhibition caused my Exemestane. A new process of enzyme biosynthesis is required to restore estrogen production, leading to a persistent inhibitory effect even after clearance of the drug from plasma and tissues.​

​

2. Toxicity profile (lipid profile/renal and hepatic stress/estrogen crash and rebound)​

​

- Since both Anastrozole and Letrozole belong to the same class of compounds, called Triazoles their toxicity profiles are similar. Letrozole and Anastrozole had no impact on serum LDL and Triglycerides concentrations in clinically administered doses but the HDL levels were noticeably reduced. Since HDL is considered good cholesterol given that its responsible for the disposal of LDL which is considered bad cholesterol, a reduction in serum HDL may increase the risk of thrombosis (blood clotting) and other cardiovascular morbidities. A low fat (low cholesterol in particular) diet on Anastrozole and Letrozole is essential for those who are already at a high risk for cardiovascular diseases.​

THE USE OF TRIAZOLES IS COMPLETELY OUT OF QUESTION FOR THOSE WHO ALREADY SUFFER WITH CARDIOVASCULAR DISEASES (you'll be paving your way to an early grave). ​

​

Exemestane on the other hand has negligible impact on lipid profiles and might reduce Triglycerides and HDL concentrations by 5-7% at most depending on your lifestyle. The reduction of Triglycerides is somewhat beneficial and Exemestane may even improve your lipid profile to a marginal extent.​

All AIs will affect total blood cholesterol levels since estrogen plays a minor role in cholesterol disposal but it will be negligible with Exemestane unless the dosage is unoptimized.​

​

- Liver injury is sometimes attributed to Letrozole (rare <1% of occurrences) but it is usually mild, self-limited and typically a transient, asymptomatic elevation in serum enzymes. The impact of Anastrozole and Exemestane on renal and hepatic health is neutral and any complications associated with the usage of the aforementioned drugs isn't commonly reported.​

​

- Although all AIs can cause your serum estrogen levels to crash, Exemestane in particular can have lasting effects on your serum estrogen levels if it is administered in unoptimal doses. An estrogen crash caused by the administration of Triazoles will usually resolve as soon as the inhibitory effects of the drug fade, it will however be offset by a homeostatic response from your body which will cause your serum estrogen levels to skyrocket temporarily.​

While this pattern of crash and rebound may not be of significant concern in the short-term, if you miss Letrozole and Anastrozole dosages or administer them in unoptimal doses habitually, this can become a serious problem.​

​

3. Other health concerns and side effects (musculoskeletal effects/androgenic effects/neurological and psychological effects)​

- AIs (even the more selective third generation varieties be it Exemestane or Triazoles) are quite notorious for the syndromous effects they tend to have on the musculoskeletal system. Aromatase inhibitor–induced musculoskeletal symptoms (AIMSS) is the term for it.​

​

This is because estrogens play a significant role in the growth and maturation of bone as well as in the regulation of bone turnover in adulthood. It's quite ironic that the supposed female sex hormone has such a significant hand in facilitating the development of dimorphic skeletal traits.​

Estrogens play an elaborate role in the formation of osteoblast cells. Its inhibition or deficiency in young skeletons results in decreased osteoblast formation. While the formation of osteoblasts decreases, the formation of osteoclasts is unbothered and since osteoblasts and osteoclasts have antagonistic roles, the reduction in the number of osteoblasts causes osteoclasts to go about their function without osteoblasts to counteract them. This results in bone resorption. These responses inevitably lead to decreased bone mass, disturbed architecture and reduced bone strength. Basically, your bones go from having timber-like consistency to that of bamboo if you're not mindful of your doses or abusing AIs religiously.​

​

Heightmaxxing by nature is a double edged sword. You're trading your bone health and integrity for a few inches of longitudinal growth. And it's worth noting that the issues caused by changes that occur in your bones (or the changes that were supposed to occur in your bones during your developmental years but didn't occur) due to hormonal intervention, may very well persist over the long-term. ​

​

And it's not just the bones that are affected negatively by estrogen inhibition but also your joints and muscles since the bones and soft tissues in your body connect together to form a kinetic chain. Approximately 47-50% of AI users experience joint stiffness and muscle atrophy besides a perception of heightened pain which results from increases sensitivity of nerves in the region.​

​

It's essential to religiously engage in strength training and stretching while taking a balanced diet with loads of supplements while on AIs to manage the adverse musculoskeletal effects of estrogen inhibition.​

​

However it's also worth mentioning that in several clinical studies, incidences of bone morbidity were reported to be noticeably greater with the use of non-steroidal AIs like Letrozole and Anastrozole (Triazoles basically) than steroidal ones like Exemestane. This has to do with with the steroidal structure of Exemestane which boasts relatively greater osteoprotective effects. That leads us to our next point.​

​

- Exemestane isn't transported in the body in its original form. It is metabolized into another steroidal molecule called 17-Hydroexemestane. This variant of Exemestane is structurally not dissimilar enough from its template molecule to keep it from binding with aromatase. ​

However, 17-hydroexemestane is even more steroidal (read: potent) than basic Exemestane and that allows it to function as an active metabolite which is capable of binding with certain androgenic receptors in your body and promote mild androgenic effects which can compensate for the osteodegenerative effects that result from estrogen inhibition to some extent. ​

​

The ability of Exemestane to mimic androgenic behaviour makes it a superior option for those suffering with or concerned about with bone-related issues than non-steroidal aromatase inhibitors. However Exemestane also tends to have osteodegenerative effects in higher doses and it can be even more problematic than Triazoles should that happen habitually because its inhibitory effects are lasting. ​

​

- Estrogens like androgens are hormones with anti-oxidative properties which helps with neurological protection in addition to ideal cognitive function since they facilitate/promote synaptic plasticity, neurogenesis and ensure proper glutamate regulation (essential for synaptic transmission), cerebral blood flow, cholinergic flow and maintenance of your cerebral white matter. In other words, you're essentially a few picograms of estrogen less away from becoming a total vegetable. So whether or not you like it, AIs are going to leave you with ADHD-like symptoms (bad short term memory, lack of focus and motivation etc), mood disorders which may affect your sexual performance and even your gut health (if you suffer with gastroenterological issues like IBS) since the gut-brain axis is quite closely linked.​

​

- Then again, steroidal AIs like Exemestane are a safer bet than non-steroidal ones since they tend to mimic androgenic behaviour which allows them to compensate for the inhibition of estrogens and minimize its adverse effects to some extent. ​

The potential side effects of Exemestane as I mentioned earlier have the potential to be worse than those of Triazoles should you mess up your dosage and end up with an estrogen crash that spans a week and might even take longer to fully recover from. ​

My advice is to put AIs on the backburner if it's affecting your cognitive function and mood. Specially if it's taxing to your academic performance. ​

​

I would also suggest taking nootropics and mood stabilizers to counteract the adverse effects of AIs on cognitive function and mood. I'll admit that I barely know anything about neuroendocrinology and that there are other, more qualified users you can look up to. There are countless threads on this forum that will help you maximize your neurological health as you steer through you growthmaxxing journey. I suggest you look those up.​

Conclusion

There is no definitive AI that will help you breeze through your growthmaxxing journey. What may work for you may not work for someone else and vice versa. The answers to "which AI should I use?" are "all", "none" and "it depends". There are tradeoffs associated with the use of all AIs that you must take into consideration before planning your approach. You need to test out different drugs at different doses and devise an optimal regimen through trial and error.

While this entire thread must have read like a propaganda piece warning you all against the use of AIs, the fact is that this is just the reality of the subject matter. AIs, while manageable are not as safe as most of us like to think they are and biohacking may sound good in theory but it isn't all that practical. Not all of us are blessed with good genetics and there is a cost for those who wish to ascend the limitations that were imposed onto them by nature.

The point of this thread is not just to inform the newcomers but also to ignite a discussion that will allow exchange of valuable information on a topic that isn't discussed in detail very often. Ask whatever you want, I'll try to answer what I can.

TL;DR- There is no summary. Read the whole damn thing (or at least the second half of the thread) you lazy halfwits.



P.S. Although I have been a long time lurker on this forum, this is my first thread. So pardon the atrocious formatting and my overly-rigid style of writing, it'll improve with time.​

Dnr, there is no dilemma. My estrogen has been single digits since 17 and 1 month. Are you even a looksmaxxer if your estrogen isn’t single digit? (Assuming growth plates are still open)

 

[sb23]

Preface

So I've been scouring the forum for opinions and personal experiences of users on AIs as of late and I found it quite surprising that despite its significance in growthmaxxing, the topic of AIs seems to be one that hasn't been discussed extensively (in detail) on this forum. That hopefully changes with this thread though. All my concerns regarding AIs (based on what I have learnt so far) will be duly addressed in this thread. To whomever this may be of interest, do yourself a favor and read this to the end.

For the newbies to understand the gish gallop that I will be momentarily spitting, we need to cover fundamentals of this topic first. You may skip the following part if you are well acquainted with AIs.

*Skip to the next purple highlight if you know what AIs are and how they work*​

​

What is aromatization?​

To understand Aromatase inhibitors, you must first understand the process of aromatization. Aromatization is the process in which certain androgens when in excess amounts, are converted into estrogens which are easier for the body to metabolize. These androgens are called aromatizing androgens (there are non-aromatizing ones too but that's a topic for another thread). Testosterone and androstenedione are two examples of aromatizing androgens that are fairly abundant in the average male human body. This process of aromatization is irreversible and it's a reaction that's catalyzed by an enzyme called Aromatase. ​

​

It's also important to know the function of SHBGs (Sex Hormone-Binding Globulins) here. These biological superstructures bind with sex-hormones and regulate the amount of free androgens and estrogens in your tissues that can be used by your body's cells. ​

By facilitating the downregulation of SHBGs you can increase the concentration of androgens and estrogens in your tissues that can be then used by your body's cells to perform various functions. ​

​

Now back to aromatization, it's worth noting that mobile aromatizing androgens are aromatized into estrogens wherever the enzyme aromatase is in abundance and these locations in your body can be your gonads, your brain, your bones, your adipose tissues and even the goddamn endothelial walls of your vascular surfaces. ​

As I mentioned earlier, aromatization is simply your body's way of disposing unused androgens since androgens are more taxing on your organs and harder to metabolize than estrogens. It's crucial for you to understand that the abundance of mobile/unused aromatizing androgens in your tissues, is directly proportional to the rate of aromatization. Your objective should be to enable your body to utilize the mobile androgens in your tissues. That way you're not just hindering unnecessary aromatization but also using the free androgens in your tissues to your advantage. Taking effective measures to desensitize and upregulate the amount of androgen receptors in order to allow your body to utilize the free/unused androgens in your tissues would effectively reduce aromatization to some extent by causing a reduction in the concentration of serum androgens with the formation of more hormone-receptor complexes. ​

​

It goes without saying that androgens in slightly higher than average amounts are ideal and estrogens in higher concentrations are not. That's not to say that you need to avoid estrogens like the plague. All hormones including estrogens are ESSENTIAL for the ideal functioning of your body and I'll be talking more about this later my post while addressing the adverse effects of estrogen deficiency.​

​

The burning question is, what steps must one take to ensure that their serum estrogen levels are ideally minimal? Enter...​

​

Aromatase Inhibitors!​

Aromatase inhibitors are a class of compounds which bind with the enzyme aromatase and prevent it from binding with its substrate androgen, thus inhibiting the process of aromatization.​

​

​

​

To understand how AIs go about inhibiting the action of aromatase, you need to know what enzymes and inhibitors are and how they work. ​

​

So enzymes like aromatase are basically biological catalysts which provide their substrates with the necessary activation energy to make or break bonds in order to trigger a chemical reaction. Structurally, they almost entirely consist of proteins, each with their own distinct primary structure which refers to the number or sequence of amino acids in a polypeptide chain. All amino acids being structurally and compositionally different tend to form a variety (potentially near-infinite variations) of bonds and each bond causes the polypeptide chain to fold differently. This folding of proteins gives rise to three-dimensional super structures called tertiary proteins and this is the form in which proteins can function as enzymes (since this folding of peptide chains gives rise to indentations of specific shape in the protein structure which are its active and allosteric sites).​

Since tertiary proteins come in near-infinite variations, every biological compound in the world has an enzyme that complements its shape and can bind with it like lock and key. The chemical compound that complements the shape of an enzyme is its substrate. This makes each enzyme highly specific in nature considering they can only bind with substrates that complement their shape (like lock and key). Substrates bind with enzymes on their active sites and it's these zones in an enzyme that make it highly specific in its action. Androstenedione and testosterone for example are the substrates of the enzyme aromatase.​

​

​

Then there are zones in the protein structure of an enzyme other than its active site which are called allosteric sites. This is where substances besides the enzyme's complementing substrate can attach themselves to, in order to inhibit the activity of enzyme. The binding of substances to the allosteric sites of enzymes induces structural changes into the enzyme's active sites which prevents the formation of enzyme-substrate complexes. No enzyme-substrate complexes equals no chemical reaction.​

​

There are competitive enzyme inhibitors and then there are non-competitive enzyme inhibitors. The inhibitors that bind to the enzyme's active sites are competitive inhibitors and they compete with an enzyme's substrate to bind with with its active site. The greater the abundance of substrates will be, the more ineffective a competitive inhibitor will be and vice versa. Non-competitive inhibitors on the other hand are the ones that bind with an enzyme's allosteric site regardless of the substrate concentration. ​

​

​

Inhibitors, regardless of their mode of action can be either reversible or irreversible. Reversible inhibitors are homeostatically controlled and can bind and unbind with an enzyme without disturbing its structure or composition. Irreversible inhibitors on the other hand are disruptive and can cause permanent changes to the protein structure of an enzyme denaturing in the process. There is no intrinsic negative feedback loop to counteract the action of irreversible inhibitors and the factors that offset the reduction of functional enzymes in blood plasma and tissues are all extraneous. Irreversible inhibitors can disrupt serum substrate levels in unoptimized dosages because the process of restoration of functional enzymes takes a while.​

​

*The devil is in the details*​

Now if we talk about inhibitors of the enzyme aromatase, there are both irreversible and reversible varieties. Amongst the three most researched selective inhibitors of aromatase, Exemestane (Aromasin) is an irreversible inhibitor, whereas Letrozole (Femara) and Anastrozole (Arimidex) are reversible. Exemestane forms permanent (covalent) bonds with the aromatase enzyme irreparably disrupting its specific shape in doing so. Aanastrozole and Letrozole on the other hand inhibit the synthesis of estrogen via reversible competition.​

These three inhibitors can be further classified into two categories, steroidal and non-steroidal. Exemestane (Aromasin) is a steroidal inhibitor as opposed to Letrozole (Femara) and Anastrozole (Arimidex) which are non-steroidal inhibitors.​

​

View attachment 3021991​

​

​

I might be boring some of you to death with all the obvious nonsense that I've been spitting up until this point but I want you all to hang in there for a moment, I promise I'm going somewhere this. I now present to you a number of problems and benefits associated with the use of each of the aforementioned AIs.​

1. Drug properties (Selectiveness/bioavailability/dosage/half-life/pharmacokinetic profile)​

​

- Exemestane being a non-competitive aromatase inhibitor is markedly more selective in its action than both Letrozole and Anastrozole since the latter two inhibit estrogen by actively competing with its substrate androgens to bind with the active site of aromatase.​

The rule of thumb is, the more selective a drug, the lower its chances of interacting with other drugs and vice versa.​

​

- Being a steroidal inhibitor, Exemestane has its tradeoffs. It is poorly soluble in water (or aqueous mediums in general like all molecular compound that are lipid in nature) and that significantly affects its bioavailability which is extremely low (at about 5%) compared to its non-steroidal (Letrozole and Anastrozole) counterparts. Cyclodextrin are a class of hydrophilic sugar molecules and their complexation enhances solubility and oral bioavailability of poorly soluble drugs. While I don't know if such a variant of Exemestane is commercially available but scientists have previously tried to introduce cyclodextrin complexes in powdered and tablet Exemestane to improve its aqueous solubility.​

​

- One standard Aromasin tablet contains about 25 mg of Exemestane to compensate for its poor bioavailability. Each Fermara tablet contains 2.5 mg of Letrozole whereas Arimidex contains only 1 mg of Anastrozole per tablet.​

​

It's imperative to note that these clinically administered doses are optimized for female breast cancer patients only. Their hormonal profile is drastically different even from that of the average female let alone the average male or worse a male on different PEDs and supplementation. You need to get your bloodwork done frequently and adjust your dosage in accordance to your hormonal profile. I strongly recommend you to do your own research on the subject matter and also seek professional advice from reputable endocrinologists before devising your drug regimen.​

​

- At clinically administered doses, the plasma half-lives of Anastrozole (1 mg once daily), Letrozole (2.5 mg once daily), and Exemestane (25 mg once daily) are between 41-48h, 2-4 days, and 24-27 h, respectively. Letrozole is the most potent AI with the longest half life but is also the least selective amongst the three inhibitors. Triazoles are better at estrogen inhibition than Exemestane in because their inhibitory activity is vast and constant throughout their half-lives. Exemestane tends to have a lasting effect but it is more selective and reserved in its action than Triazoles.​

​

- Letrozole and Anastrozole have a better pharmacokinetic profile than Exemestane because they are unlikely to cause a long-lasting estrogen crash. An oral dose of Exemestane is rapidly absorbed and reaches peak plasma concentrations within 2 hours of administration. After 4 hours, the plasma concentration falls to undetectable levels yet the inhibitory activity persists still for at least 5-7 days despite a plasma half-life of only 27 hours.​

This long-lasting inhibitory effect is due to the irreversible aromatase inhibition caused my Exemestane. A new process of enzyme biosynthesis is required to restore estrogen production, leading to a persistent inhibitory effect even after clearance of the drug from plasma and tissues.​

​

2. Toxicity profile (lipid profile/renal and hepatic stress/estrogen crash and rebound)​

​

- Since both Anastrozole and Letrozole belong to the same class of compounds, called Triazoles their toxicity profiles are similar. Letrozole and Anastrozole had no impact on serum LDL and Triglycerides concentrations in clinically administered doses but the HDL levels were noticeably reduced. Since HDL is considered good cholesterol given that its responsible for the disposal of LDL which is considered bad cholesterol, a reduction in serum HDL may increase the risk of thrombosis (blood clotting) and other cardiovascular morbidities. A low fat (low cholesterol in particular) diet on Anastrozole and Letrozole is essential for those who are already at a high risk for cardiovascular diseases.​

THE USE OF TRIAZOLES IS COMPLETELY OUT OF QUESTION FOR THOSE WHO ALREADY SUFFER WITH CARDIOVASCULAR DISEASES (you'll be paving your way to an early grave). ​

​

Exemestane on the other hand has negligible impact on lipid profiles and might reduce Triglycerides and HDL concentrations by 5-7% at most depending on your lifestyle. The reduction of Triglycerides is somewhat beneficial and Exemestane may even improve your lipid profile to a marginal extent.​

All AIs will affect total blood cholesterol levels since estrogen plays a minor role in cholesterol disposal but it will be negligible with Exemestane unless the dosage is unoptimized.​

​

- Liver injury is sometimes attributed to Letrozole (rare <1% of occurrences) but it is usually mild, self-limited and typically a transient, asymptomatic elevation in serum enzymes. The impact of Anastrozole and Exemestane on renal and hepatic health is neutral and any complications associated with the usage of the aforementioned drugs isn't commonly reported.​

​

- Although all AIs can cause your serum estrogen levels to crash, Exemestane in particular can have lasting effects on your serum estrogen levels if it is administered in unoptimal doses. An estrogen crash caused by the administration of Triazoles will usually resolve as soon as the inhibitory effects of the drug fade, it will however be offset by a homeostatic response from your body which will cause your serum estrogen levels to skyrocket temporarily.​

While this pattern of crash and rebound may not be of significant concern in the short-term, if you miss Letrozole and Anastrozole dosages or administer them in unoptimal doses habitually, this can become a serious problem.​

​

3. Other health concerns and side effects (musculoskeletal effects/androgenic effects/neurological and psychological effects)​

- AIs (even the more selective third generation varieties be it Exemestane or Triazoles) are quite notorious for the syndromous effects they tend to have on the musculoskeletal system. Aromatase inhibitor–induced musculoskeletal symptoms (AIMSS) is the term for it.​

​

This is because estrogens play a significant role in the growth and maturation of bone as well as in the regulation of bone turnover in adulthood. It's quite ironic that the supposed female sex hormone has such a significant hand in facilitating the development of dimorphic skeletal traits.​

Estrogens play an elaborate role in the formation of osteoblast cells. Its inhibition or deficiency in young skeletons results in decreased osteoblast formation. While the formation of osteoblasts decreases, the formation of osteoclasts is unbothered and since osteoblasts and osteoclasts have antagonistic roles, the reduction in the number of osteoblasts causes osteoclasts to go about their function without osteoblasts to counteract them. This results in bone resorption. These responses inevitably lead to decreased bone mass, disturbed architecture and reduced bone strength. Basically, your bones go from having timber-like consistency to that of bamboo if you're not mindful of your doses or abusing AIs religiously.​

​

Heightmaxxing by nature is a double edged sword. You're trading your bone health and integrity for a few inches of longitudinal growth. And it's worth noting that the issues caused by changes that occur in your bones (or the changes that were supposed to occur in your bones during your developmental years but didn't occur) due to hormonal intervention, may very well persist over the long-term. ​

​

And it's not just the bones that are affected negatively by estrogen inhibition but also your joints and muscles since the bones and soft tissues in your body connect together to form a kinetic chain. Approximately 47-50% of AI users experience joint stiffness and muscle atrophy besides a perception of heightened pain which results from increases sensitivity of nerves in the region.​

​

It's essential to religiously engage in strength training and stretching while taking a balanced diet with loads of supplements while on AIs to manage the adverse musculoskeletal effects of estrogen inhibition.​

​

However it's also worth mentioning that in several clinical studies, incidences of bone morbidity were reported to be noticeably greater with the use of non-steroidal AIs like Letrozole and Anastrozole (Triazoles basically) than steroidal ones like Exemestane. This has to do with with the steroidal structure of Exemestane which boasts relatively greater osteoprotective effects. That leads us to our next point.​

​

- Exemestane isn't transported in the body in its original form. It is metabolized into another steroidal molecule called 17-Hydroexemestane. This variant of Exemestane is structurally not dissimilar enough from its template molecule to keep it from binding with aromatase. ​

However, 17-hydroexemestane is even more steroidal (read: potent) than basic Exemestane and that allows it to function as an active metabolite which is capable of binding with certain androgenic receptors in your body and promote mild androgenic effects which can compensate for the osteodegenerative effects that result from estrogen inhibition to some extent. ​

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The ability of Exemestane to mimic androgenic behaviour makes it a superior option for those suffering with or concerned about with bone-related issues than non-steroidal aromatase inhibitors. However Exemestane also tends to have osteodegenerative effects in higher doses and it can be even more problematic than Triazoles should that happen habitually because its inhibitory effects are lasting. ​

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- Estrogens like androgens are hormones with anti-oxidative properties which helps with neurological protection in addition to ideal cognitive function since they facilitate/promote synaptic plasticity, neurogenesis and ensure proper glutamate regulation (essential for synaptic transmission), cerebral blood flow, cholinergic flow and maintenance of your cerebral white matter. In other words, you're essentially a few picograms of estrogen less away from becoming a total vegetable. So whether or not you like it, AIs are going to leave you with ADHD-like symptoms (bad short term memory, lack of focus and motivation etc), mood disorders which may affect your sexual performance and even your gut health (if you suffer with gastroenterological issues like IBS) since the gut-brain axis is quite closely linked.​

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- Then again, steroidal AIs like Exemestane are a safer bet than non-steroidal ones since they tend to mimic androgenic behaviour which allows them to compensate for the inhibition of estrogens and minimize its adverse effects to some extent. ​

The potential side effects of Exemestane as I mentioned earlier have the potential to be worse than those of Triazoles should you mess up your dosage and end up with an estrogen crash that spans a week and might even take longer to fully recover from. ​

My advice is to put AIs on the backburner if it's affecting your cognitive function and mood. Specially if it's taxing to your academic performance. ​

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I would also suggest taking nootropics and mood stabilizers to counteract the adverse effects of AIs on cognitive function and mood. I'll admit that I barely know anything about neuroendocrinology and that there are other, more qualified users you can look up to. There are countless threads on this forum that will help you maximize your neurological health as you steer through you growthmaxxing journey. I suggest you look those up.​

Conclusion

There is no definitive AI that will help you breeze through your growthmaxxing journey. What may work for you may not work for someone else and vice versa. The answers to "which AI should I use?" are "all", "none" and "it depends". There are tradeoffs associated with the use of all AIs that you must take into consideration before planning your approach. You need to test out different drugs at different doses and devise an optimal regimen through trial and error.

While this entire thread must have read like a propaganda piece warning you all against the use of AIs, the fact is that this is just the reality of the subject matter. AIs, while manageable are not as safe as most of us like to think they are and biohacking may sound good in theory but it isn't all that practical. Not all of us are blessed with good genetics and there is a cost for those who wish to ascend the limitations that were imposed onto them by nature.

The point of this thread is not just to inform the newcomers but also to ignite a discussion that will allow exchange of valuable information on a topic that isn't discussed in detail very often. Ask whatever you want, I'll try to answer what I can.

TL;DR- There is no summary. Read the whole damn thing (or at least the second half of the thread) you lazy halfwits.



P.S. Although I have been a long time lurker on this forum, this is my first thread. So pardon the atrocious formatting and my overly-rigid style of writing, it'll improve with time.​

Actually really good thread. I was kinda pissed when taking letro and anastrazol because I thought it spiked ldl, turns out it doesn’t??? Hdl is for the most part negligible. This is a huge relief though, I thought I was trading time off my life for this. This thread honestly made my day .

 

[sb23]

All this "pubertymaxing" shit is complete fucking C O P E
And @PubertyMaxxer is proof of that

When did he start his protocol?

 

[ItsyBitsyJayhawk]

Dnr, there is no dilemma. My estrogen has been single digits since 17 and 1 month. Are you even a looksmaxxer if your estrogen isn’t single digit? (Assuming growth plates are still open)

Single digit estrogen=below average to shit bone mass density
You need estrogen to build and maintain bones.

 

[sb23]

You need estrogen to build and maintain bones.

True to some extent but men mostly rely on androgens to maintain bone health. If I were a woman, your point would hold more gravity.

 

[ItsyBitsyJayhawk]

True to some extent but men mostly rely on androgens to maintain bone health. If I were a woman, your point would hold more gravity.

You need both. Androgens proliferate bone mass, estrogens preserve it. Women have lower bone mass density than men because they have minimal androgens but their bone mass is still consistent because they have estrogens. Men have more bone mass than women owing to androgens but the male body is able to preserve that mass not because of their greater androgen supplu but because of a small but consistent supply of estrogens. If you were to take even androgenic AIs like Aromatase in excess, you will still experience the negative sides of the drug irrespective of how high your androgen levels are. I'm speaking from both first-hand and second-hand experiences.

 

[sixfootfive]

Why even bother to heightmaxx if "it doesn't matter after 5'11"