First post. Can’t get E2 under control, starting to worry

[jmbb]

profit motive

This is almost universally the answer for seemingly poor decisions

 

[Charliebizz]

We have the studies showing that lower thyroid function is associated with greater longevity, but you are understandably skeptical, because disease states that produce higher thyroid hormone levels may cause damage independently from thyroid hormone itself.

It may be useful then to consider experimental models in animals to demonstrate the effects of higher levels of thyroid hormones in otherwise healthy animals. From the attached paper:

THs are known to accelerate basal metabolism and increase oxygen consumption, thus leading to increased reactive oxygen species (ROS) production and oxidative stress 22,23. Additionally, THs are able to unsaturate membrane phospholipids, leading to membrane damage and mitochondria lipid peroxidation 24,25. Such pro-oxidant effects are tissue-dependent, with liver and heart more subject to oxidative stress than spleen and glycolytic muscle fibers 26. However, THs can also affect the cell antioxidant status, directly (iodine compounds act as free radical scavengers able to reduce oxidative damage in vitro) 27,28 or indirectly, by stimulating or inhibiting the activity of antioxidant enzymes 29,30 and free radical scavengers 31. Such an ambivalence in producing and counteracting oxidative stress has lead to controversial results about pro-oxidant or anti-oxidant activity by THs 31-38.

Recently, it has been demonstrated that binding of triiodothyronine (T3) to thyroid hormone receptor B (THRB) induces DNA damage and cell senescence. The mechanism of such a THRB mediated disruption of cell homeostasis is related to the activation of ataxia telangiectasia mutated (ATM)/adenosine monophosphate–activated protein kinase (PRKAA) signal transduction and nuclear respiratory factor 1 (NRF1), with consequent stimulation of mitochondrial respiration, increased production of ROS, and DNA damage ultimately leading to premature cell senescence 39. Studies in animal models seem to confirm this view. Indeed, several mice models of longevity, either naturally long-living or manipulated and genetic mutant strains, share some commons traits, among which low levels of THs. The naked mole rat (NMR), the longest-living rodent, shows very low levels of thyroxine (0.004 ± 0.001 mg/dl) 40. Moreover, it has been also shown that experimental hypothyroidism increased the lifespan of Wistar rats up to 28 months, while experimental hyperthyroidism reduced lifespan 41. Hypothyroidism was found associated with reduced ROS generation and oxidative damage, while hyperthyroidism was found associated with an increase in ROS production and a compensatory increase in anti-oxidant defense enzyme levels in several studies on murine models 29,42-44.

Ames and Snell dwarf mice represent an interesting model to investigate the impact of endocrine disorders on lifespan. They are naturally mutant mice characterized by pituitary hormone deficiencies (growth hormone -GH-, prolactin and TSH, and a consequent low level of circulating THs) resulting in small body size and delayed puberty. Ames and Snell dwarf mutant mice were found to live 40-70% longer than mice with normal thyroid hormone levels 45. It is worth noting that these mice not only live longer, but are also an example of successful aging, since they exhibit a less frequent development of age-related chronic diseases, including cataracts, kidney disease, and cancer with respect to wild type mice 45-48. Finally, long lasting administration of thyroxine was found to shorten dramatically their lifespan, though they still lived longer than wild type mice 45. In conclusion, the above described experimental studies clearly suggest that hypothyroid state may favor longevity by reducing metabolism rate, oxidative stress and cell senescence.

There's a mechanism for harm laid out by the experimental studies: running the metabolism too hot with excessive thyroid hormone increases oxidative stress, leads to premature cell senescence, and premature aging. While humans are not naked mole rats, wistar rats, or ames and snell dwarf mice, we see the same pattern in humans, where lower thyroid function is associated with longer lives. The picture that emerges here suggests a cavalier attitude toward thyroid optimization may cause harm to patients in the long run.

is that study solely based off TSH ? And not everyone with low normal thyroid hormones have issues. But doing a trial of thyroid hormone on a patient with clear symptoms but numbers in range, shouldn’t cause harm. Now if the patient is getting symptom resolution with out right hyper symptoms how can we prove that will effect longevity?

 

[Charliebizz]

This is exactly what I'm talking about. If you didn't look deeply into it, you probably just concluded the cypionate ester sucks and enanthate is better. The Internet is full of those anecdotes. But if you look more closely at those empower and pfizer cypionate formulas that you couldn't tolerate, there was more benzyl excipients in there than testosterone. THAT is what is missing from the empower and westward/hikma test E, and I believe that is the real cause for your different experiences.

but I also feel that much better on cream vs enanthate. So does that also boil down to excipients?

 

[FunkOdyssey]

but I also feel that much better on cream vs enanthate. So does that also boil down to excipients?

Probably the extra DHT or greater fluctuation of levels making the difference there I'd say.

 

[Charliebizz]

Probably the extra DHT or greater fluctuation of levels making the difference there I'd say.

I’ve seen a bunch of people who added dht derivatives to injections say they couldn’t replicate the feeling of being on the cream alone. Not sure I’m sold on the whole dht thing. Especially if dr Nichols is right with his take on dht.

 

[jmbb]

I’ve seen a bunch of people who added dht derivatives to injections say they couldn’t replicate the feeling of being on the cream alone. Not sure I’m sold on the whole dht thing. Especially if dr Nichols is right with his take on dht.

So many things it could be. Dht derivatives probably don't feel like endogenous dht the same way steroids are testosterone derivatives but have different effects. Plus the lack of excipients as a possibility. I believe Dr Serrano made the arguments that the esters themselves have a biological effect, and the cream being ester free could feel different in that sense. Plus the fluctuations, differences in metabolite conversion rates being topical vs injectable, etc...probably too many variables to nail down just one reason. But it's working for you! That's the important part.

 

[FunkOdyssey]

I’ve seen a bunch of people who added dht derivatives to injections say they couldn’t replicate the feeling of being on the cream alone. Not sure I’m sold on the whole dht thing. Especially if dr Nichols is right with his take on dht.

There are some tissues that are carefully regulating their local levels of DHT. Emphasis on SOME. It's silly to think high levels of DHT in serum universally have no effect. Take proviron for example. Look at all the subjective effects proviron has on men, both positive and negative. That's the power of DHT floating around in serum. Does it have effects? You bet it does! Serum DHT is anything but a meaningless number.

 

[Systemlord]

That's the power of DHT floating around in serum. Does it have effects? You bet it does!

This seems more like a conclusion. I do agree the lab value for DHT is anything but meaningless.

 

[Mastodont]

I had not heard of him prescribing ARBs, but that seems to be something a lot of the TRT docs are doing….especially telmisartan. I think a lot of them are doing it more for the longevity/ age management aspect, especially with the “older” set. I watched a podcast with Dr Andrew Winge and he and his guests (other docs) were all over being proactive with ARBs and Bystolic (beta blocker)…..don’t know enough about it to run my mouth too much, but I always thought the idea was to try to minimize drug use unless necessary..?

I'm not actually sure anymore, i recalled him talking about it on jay campbells pod a few years ago, but it actually was an episode with just Scott Howell, they have been on that show together around that time so that is why it got mixed.
Anyway, after one hour 15 minutes he talks using ace and arb, he calls losartan ACE by mistake as well. I hope @RobRoy would comment if he is using these when "optimal" levels result in BP elevation.

 

[Mastodont]

No HCG for me at the moment, I feel good for a shot or two but then its nothing but sides. I saw a guy on a youtube channel recently play an old Leo and Longevity clip (so take that with a grain of salt) where he said that after the testicles are shut down long enough that libido/erections/orgasms would be diminished no matter what. If that's true, that has to mean that some guys are naturally resistant to shutdown of the testes more than others and can maintain at least some intratesticular function without LH or HCG.

recently on another forum when the topic was raised there were quite a few guys on high end doses long term without hcg that reported poor orgasm quality...So you get sides from hcg? I get them as well, mood issues especially, then again i get shrinkage and would like to run hcg. There must be some local effects of ITT that affect things other than avoiding shrinkage.

 

[jmbb]

recently on another forum when the topic was raised there were quite a few guys on high end doses long term without hcg that reported poor orgasm quality...So you get sides from hcg? I get them as well, mood issues especially, then again i get shrinkage and would like to run hcg. There must be some local effects of ITT that affect things other than avoiding shrinkage.

Yeah mainly mood issues. It also just makes me feel "off" not necessarily sick but unwell. And for whatever reason it's like fertilizer for gyno. I had a small amount of gyno which I had removed but hcg used to make it grow like a weed. Brings back nipple sensitivity even after the surgery so I'm paranoid to use it in case it comes back, the procedure wasn't cheap.

 

[Seagal]

Slide title: harm of aromatase inhibition
Bullet points: blocking aromatase
However I agree with the renin–angiotensin system imbalance.
IMO the problem with most of these medical experts is that their expertise/focus does not include neurology/psychiatry.

 

[tropicaldaze1950]

Benzyl benzoate greatly speeds up the absorption of testosterone while it is present. However, the benzyl benzoate itself is absorbed quickly, and when it is gone from the solution, the rate of absorption for the remaining testosterone in the oil depot slows down. Consequently, you have a biphasic pattern of absorption with a BB formula: a fast spike in the beginning, followed by the slower, normal release pattern for the unadulterated ester.

Benzyl benzoate is rapidly hydrolyzed to benzyl alcohol in the body, so we want to consider the effects of benzyl alcohol. From the Encylopedia of Toxicology:

High doses of benzyl alcohol cause nausea, vomiting, diarrhea, CNS depression, and vertigo. Dilute solutions (1%) produce local anesthesia and slight irritation when instilled into the eye. Pure benzyl alcohol produces corneal necrosis. Following acute exposure lethargy, seizures, intraventricular hemorrhage, and neurological sequelae (cerebral palsy, developmental delay) have been seen in neonates with parenteral benzyl alcohol toxicity. Metabolic acidosis was a common finding with parenteral toxicity in neonates. Thrombocytopenia was a delayed feature of parenteral toxicity in neonates. Deaths associated with intravenous or endotracheal administration of benzyl alcohol-containing solutions in neonates were preceded by symptoms of respiratory distress progressing to gasping respirations, metabolic acidosis, CNS depression, hypotension, renal failure, and occasionally seizures and intracranial hemorrhage. Thrombocytopenia was a delayed feature of parenteral toxicity in neonates. Severe striated keratopathy, progressing to chronic edema of cornea, was noted following intraocular use of a sodium chloride solution containing 2% benzyl alcohol.

A typical dose of testosterone cypionate delivers more benzyl benzoate and benzyl alcohol than testosterone. For each 100 mg of testosterone, you get about 110 mg of these excipients.

I believe BB & BA are the reasons I never could tolerate Test P.(from Empower). Always would feel vaguely sick, like I'm coming down with a cold(scratchy throat, runny nose, malaise). Cottonseed oil in Test C produced the same symptoms. Test E; no problems.

 

[tropicaldaze1950]

Here is another solution....DELATESTRYL, which seems to be a very good option, testosterone enanthate with no BA/BB instead they use sesame oil with 5 mg chlorobutanol (chloral derivative) as a preservative. I knew a few lab guys and the all said that chlorobutanol is probably oneof the best preservative options for injectable oils. The biggest problem is it is much more expensive compared to BB.

That's Hikma's Test E; formerly Watson-Ward(or the other way around).

 

[FunkOdyssey]

I believe BB & BA are the reasons I never could tolerate Test P.(from Empower). Always would feel vaguely sick, like I'm coming down with a cold(scratchy throat, runny nose, malaise). Cottonseed oil in Test C produced the same symptoms. Test E; no problems.

I also suffered the same problems with a different ester and that was an important part of how I figured this all out for myself: nasty symptoms with cypionate and compounded propionate (both containing BB/BA), absence of symptoms with cream and BB/BA-free enanthate.

 

[jmbb]

I also suffered the same problems with a different ester and that was an important part of how I figured this all out for myself: nasty symptoms with cypionate and compounded propionate (both containing BB/BA), absence of symptoms with cream and BB/BA-free enanthate.

This whole discussion had me curious and I was able to find at least a few brands of sustanon as well that contain no BB, only BA.

 

[tropicaldaze1950]

That guy probably had good intentions to stop guys from needlessly crushing their E2 with poor T mill protocols, but overall his combative personality and that whole "anti-AI no matter what" crowd probably set back the overall TRT community by a good amount until the pendulum started swinging back to a more reasonable approach. Agreed, definitely not chemical castration.

When I have gone through the old daily injection reddit threads, one year old or more, and actually click on the usernames for a lot of the guys doing dailies to see if the protocol is still being used, it seems most revert back to 2x per week, MWF, or an EOD protocol. They are usually enthusiastic at first but end up saying they didn't see much difference over time.

There are always people that it works well for that don't suffer from injection fatigue, but going over the old threads, I got the opposite impression - it doesn't seem the majority that try daily injections are sticking with it a year or more later. You'll also find a lot of people saying they felt flat and like they lost the benefits of TRT - maybe this would be different for some with the blended prop Cataceous mentioned.

As many of the men on here know, I've been on many doses and dosing protocols over the past 10 years, as well as cream and a round of pellets. I also have bipolar illness, CPTSD, non-restorative sleep and now almost 2 years into caring for my wife who has Alzheimer's.

Been going to the same urologist for those 10 years. Highly knowledgeable, progressive. Keeps working with me, LOL. So, now, doing 20 mg daily IM Test E. No protocol or dose has been 'the one', so I made the decision to be serious about dailies for the next 12 weeks. A few weeks ago I posted that I was going to take a break for a few months, then decided to try 70 mg weekly. Started to feel flat and, living with depression, I didn't want to tough it out for 6 to 8 weeks. Only been doing daily for about 5 days. At the moment, BP has come down, pissed my brains out for a few days, losing about 2 pounds. Sleep is worse but might not have anything to do with the change in protocol. Libido/desire is there, sometimes strong. Erectile function I know will take 2 or 3 months or longer, IF there is to be any improvement.

1X weekly or 2X weekly would be so much easier(which I'd done) but when I tried 140 mg in one injection, experienced significant bloat and abdominal discomfort. Again, maybe if I had given it a few weeks or even used furosemide, I could have gotten past it. But, at the moment, daily is okay. I pre-load syringes. I'm just another work in progress.

 

[tropicaldaze1950]

I also suffered the same problems with a different ester and that was an important part of how I figured this all out for myself: nasty symptoms with cypionate and compounded propionate (both containing BB/BA), absence of symptoms with cream and BB/BA-free enanthate.

On T-Nation and Reddit, read many posts from guys experiencing various physical symptoms on Test C and I tell them it's either the oil and/or the preservative and that they should try Test E, particularly if they're under the care of a doctor. Yes, it is pricier. Even with using Good Rx, about $62 per 5mL vial. No competition. Hikma appears to have the market locked up. I've vented about this before. Even complained to the FDA. They're a joke. I was told there are other brands available. I looked. Couldn't find them. But, it's just easier to get Hikma and be done with it.

 

[BigTex]

I also suffered the same problems with a different ester and that was an important part of how I figured this all out for myself: nasty symptoms with cypionate and compounded propionate (both containing BB/BA), absence of symptoms with cream and BB/BA-free enanthate.

I completely understand. You know I have problem with different esters too. I get lots of side effects with cypionate, little with enanthate and very few with undecanoate. Never had a problem with BS/BB but would prefer both be sparingly used.

 

[BigTex]

I honestly think most of us posting agree much more than we disagree. Understandably it seems that many in our medical profession, most especially these T clinics make it easy on themselves by applying the cookie cutter T fix on every client that walks in their doors. Most likely this is why so many men come here unhappy and looking for answers.

I see quite a few good things on some of the UK sites, like this:

Gold Standard TRT - The Men's Health Clinic

In my professional opinion, Gold Standard TRT is daily subcutaneous injections of Testosterone Enanthate or Cypionate and HCG, this is something I discuss in detail in TRT Best Practice. The aim of Testosterone Replacement Therapy (TRT) is to restore your androgen levels to within normal...

themenshealthclinic.co.uk

Why a Cookie-Cutter Approach Doesn’t Work

It is recognised that there is variance of the peak and trough levels between individuals(6) and so the data cannot apply to everybody. We all have a unique genetic blue-print, no one person’s physiology is identical to that of another.

The primary aim of TRT is to achieve stable hormone levels within the body so that homeostasis is maintained. The above data demonstrates that the current recommendations regarding dose and injection frequency do not achieve this.

When choosing a testosterone, it’s important to understand how long it will typically take to achieve a ‘steady state’. This is when the rate of drug input is equal to the rate of drug output. Irrespective of your choice, it is impossible to achieve true stability, something I talk about in The Perfect TRT Protocol. It is recognised that it takes approximately 5 half-lives for this to occur.

Steady state according to the different esters available:

Testosterone Enanthate / Cypionate​

• 35-45 days

Sustanon​

• Propionate Ester – 17.5 days
• Phenylpropionate Ester – 22.5 days
• Isocaproate Ester – 45 days
• Decanoate Ester – 75 days

Nebido (Testosterone Undeconate)​

• 450 days

The aim of dosing is to build up the plasma concentration of testosterone so that it achieves an optimal level according to your genetics, physiology and utilisation. You cannot predetermine that number based on the current data. The current UK reference range of 12-29 nmol/l is very non-specific, doctors do not take age into consideration despite knowing there is an age-related decline in testosterone. This is an arbitrary discussion since we know there are health benefits in having a testosterone above 19nmol/l(7).