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Testosterone, Hormones and General Men's Health / Lab test sales
« on: May 01, 2021, 01:06:40 pm »
There are a couple sales going on at the moment, so it's a good time of year to purchase your requisitions.

Nelson has a 20% off sale at Discounted Labs good through May 15: Link. This service uses Quest labs.

Life Extension Foundation is having its annual sale at the moment. Some really great deals, such as a Male Basic Hormone panel for $56 which includes DHEA-S, E2, T, fT, and PSA. It's unclear how much longer the sale will continue, so don't delay. Link. This service uses LabCorp. Requisitions are good for six months and can be renewed for another six months upon request.

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I get a few requests for more details about my protocol, so I’m putting them here for easy reference. This protocol represents an attempt to fix some of the problems created by regular TRT, those which stem from the suppression of other important hormones. The protocol is not a casual undertaking. It is demanding and may take several months to yield consistent results. At this point there’s too little data to say if those results are likely to be as good for others as they have been for me.

• Testosterone. This is a blend of testosterone propionate and a longer ester, such as enanthate or cypionate. It is injected daily—upon waking—to give realistic levels and diurnal variation. Ideally the ester ratio is tuned to provide the appropriate variation, with trough testosterone about 40% below the peak. For me, getting half the testosterone from each ester gives the appropriate result. In the case of cypionate the ester ratio is 0.837 / 0.70 = 1.2 parts cypionate to 1 part propionate by weight. For example, 120 mg of cypionate and 100 mg of propionate would be mixed in a separate vial. The dose size is adjusted to yield appropriate peak free testosterone. If better information is unavailable then "appropriate" is assumed to be what's average for young men. This corresponds to about 15 ng/dL for the Vermeulen calculation and 23 ng/dL for Tru-T. With normal SHBG, at around 30 nMol/L, total peak testosterone ends up around 600-800 ng/dL. Troughs are around 400-500. My current daily dose contains 3.2 mg enanthate and 2.4 mg propionate.

• Progesterone. This often ends up low under TRT and should be supplemented if that's the case. In the absence of better information I target mid-range serum levels for morning tests after nighttime dosing. Progesterone can be injected or applied topically. I currently inject 0.6 mg each day at bedtime.

• GnRH/LH/FSH. GnRH is injected in the form of gonadorelin to stimulate the pituitary to produce LH and FSH. Men naturally generate a pulse of GnRH every two hours or so. Without an infusion pump we can't easily mimic this dosing. The alternative is to inject a number of times each day. I don't know what the minimum number of daily doses is for this to work. There is some evidence that single larger doses may still stimulate LH and FSH. But this is less natural and may or may not provide acceptable subjective results. In any case, I chose six daily injections because that's the maximum I thought I could reasonably tolerate. I found that a larger bedtime dose interferes with sleep. Therefore I inject 20 mcg five times during the day, and 5 mcg at bedtime. Pulsed doses in the literature range from 5-30 mcg. It's been mentioned that some guys may be able to obtain gonadorelin as a nasal spray. With an appropriate dose size this delivery method could make it more practical to take multiple daily doses.

• Enclomiphene. Estrogens are suppressive at the pituitary. Under TRT estradiol is high enough to mute the pituitary's response to GnRH, reducing LH and FSH output. To avoid this a SERM is used. Initially I used 12.5 mg enclomiphene daily. I also tried using 12.5 mg every other day for a period, but have since gone back to daily. I still have reservations about using this drug long-term, as its effects are not fully understood. It's possible that in some men it actually causes imbalances in estrogenic activity, potentially explaining the mixed subjective results seen in monotherapy.

• Kisspeptin. Unfortunately, kisspeptin may not be prescribed in the U.S. and a pharmaceutical grade product is not available. Any use thereof is purely experimental and at one's own risk. The research on kisspeptin lags that on GnRH, so dosing is pure guesswork. Let's say that a plausible dose is 5-10 mcg taken with each 20 mcg dose of GnRH. Note that in theory this could yield pulses of both endogenous and exogenous GnRH. It's a good idea to delay introduction of kisspeptin relative to GnRH so that its independent effects can be discerned.

• Selegiline. I hadn't considered this drug as part of the "official" protocol, but I think it must be mentioned as a potentially useful tool for the aging male. Loss of dopaminergic activity harms us in various ways—including reducing libido—and selegiline can counteract this. Objectively I know it lowers my prolactin. Subjectively I believe it contributes to better mood and libido. My preferred dose is 2.5 mg daily. I'd advise younger guys to steer clear of it unless prolactin is a problem.

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In trying to visualize the process of testosterone injection and consumption, I created the analogy below, which involves the flow of fluid driven by gravity instead of concentrations and binding affinities.



To start with, the pitcher represents injections. You pour some fluid into the upper tank, which is like giving yourself an injection of a fixed amount of a testosterone ester. The tank represents the accumulation of the current injection and the remaining portions of all previous injections.

The hole in the upper tank represents the steady flow—absorption—of testosterone from the injected depots. The flow rate is directly proportional to the outlet size—that is, the higher the fluid level the faster the outflow rate. The outlet size incorporates the various things that affect testosterone ester absorption, including ester size, carrier oil, injection location and activity level.

The lower tank represents total testosterone in the body. The hole in the lower tank represents use and elimination of testosterone in the body. The outflow rate is proportional to the hole size, which represents factors such as testosterone metabolism in the liver and elsewhere, along with different levels of SHBG. Higher SHBG means a smaller hole size, lower SHBG means a larger hole size. An important point is that the lower tank's hole is much larger than the upper tank's hole. This reflects the differing time constants for absorption of testosterone—on the order of days—and utilization of testosterone in circulation—on the order of minutes.

There's one clear weak point in the intuitive nature of this model: we are used to tanks that empty completely when there's a hole in the bottom. This is because in physical tanks the outflow rate is not always directly proportional to fluid height, which is a stipulation of this model. Requiring proportionality means that these tanks can never empty all the way, so in the absence of inputs the tank levels drop at an exponential rate, not emptying until infinite time has elapsed.

This model illustrates some interesting features, which I'll discuss in more detail later. Among these is that injections are controlling the flow rate of testosterone through the body, with inflow and outflow matching at steady state. This may suggest that at constant dose rates, differing SHBG values lead to differing amounts of total testosterone, while free testosterone stays fairly constant.

Comments? Questions?

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A tip of the hat to "Marco N Cognito" over at ExcelMale for posting about this.

Tailor Made Compounding now offers enclomiphene and will ship it to most states. I called to confirm this and it appears legitimate, with FDA inspections, etc. If you can persuade your doctor to give you a prescription then you are good to go—though I did not find out about pricing. Unfortunately for patients of Defy Medical, it appears as though they will not be prescribing it just yet.

For those who are unaware, enclomiphene is the non-estrogenic component of Clomid/clomiphene. There's been a thus-far unsuccessful attempt to have this drug approved for hypogonadism under the name Androxal. Anyone taking or considering taking Clomid should think about enclomiphene as a potentially better option. Some of the unwanted side effects of Clomid are attributable to the zuclomiphene component. In addition, enclomiphene has a short half-life, around ten hours, meaning it's relatively easy to change protocols or stop taking it. Zuclomiphene has a very long half-life, maybe as much as a month, and therefore takes a long time to get out of your system.

5
Maybe just a bad heart, but doesn't seem worth the risks anyway...

Quote
A billionaire diamond trader has died during a penis enlargement operation at a posh Parisian clinic, it was reported.

Ehud Arye Laniado died at the age of 65 in the clinic of an unnamed plastic surgeon on the Avenue des Champs-Elysees in the French capital Paris.

According to local media, complications during surgery proved fatal for the Belgian-Israeli dual national and he suffered a heart attack when a substance was injected into his penis.
https://www.foxnews.com/health/billionaire-diamond-trader-dies-during-penis-enhancement-procedure-reports-say

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It's being reported on ExcelMale that Dr. Crisler has died, cause not yet disclosed. If true this is very sad, and quite a coincidence that we learn of it a year to the day after we lost PeakT.

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I posed this question in a thread on ExcelMale, but would like to have a devoted topic here. Negating the question: Couldn't there be one level of estradiol that's best for vascular health, a different level for sexual function, another for prostate health, etc.? Ideally the levels wouldn't differ greatly, but how close do they have to be? The thread on Rouzier's videos got me thinking about this issue. Basically Rouzier is saying estradiol is totally beneficial, and even supplementation to levels over 100 pg/mL is a good thing. For simplicity just say his position is that supraphysiological estradiol is good for longevity. But this is in contrast to clinical and anecdotal evidence showing that sexual function degrades in some men at higher levels of estradiol. So this already contradicts the notion that a particular level of estradiol is best for everything.

Thoughts?

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In recent years I've had six sensitive (LC-MS/MS) estradiol tests performed by LabCorp. Two of these have come back with results that were half of the correct levels. The first time it happened the doctor and I assumed that the standard immunoassay test was incorrectly high. But later tests revealed that in fact it was the sensitive test that had been incorrectly low. Because of this experience, when a recent sensitive estradiol test result came back at 15 pg/mL, much lower than expected, I had the test performed again with both methodologies. This time the sensitive and non-sensitive results agreed, with values of 31 and 35 pg/mL respectively.

These experiences jibe with statements made by LEF when they were defending their continued use of immunoassay testing in standard panels: the LC-MS/MS test is complicated and easy to mess up.

Counterarguments? It's just one guy and two tests. I sincerely hope they are not screwing up a third of these tests for everyone. The sensitive test is still important to verify the immunoassay result, which can be falsely elevated by other molecules, such as C-reactive protein.

Recommendation? Get both tests if you can afford it. A substantial disparity between them is usually grounds for concern.

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The forum was being attacked by some persistent spambots, so we had to take pretty aggressive action to stop them from creating new accounts. Legitimate users who had trouble registering Wednesday or Thursday should try again.

10
Overall the results are pretty unimpressive.

Quote
More than 25,800 people were randomly assigned to one of four groups: one received 2,000 IU of vitamin D a day and a placebo, another took 1g of omega-3 fatty acids a day with a placebo, a third took both 2,000 IU of vitamin D and 1g of omega-3 a day, and the last group received two daily placebos. All volunteers took their assigned nutrients for approximately five years, and researchers logged everything from cancer diagnoses to major heart events including heart attack and stroke, as well as deaths from cancer and heart disease.

Quote
The people taking omega-3 fatty acids did not have a lower rate of heart events compared to the people taking placebo.

Quote
When they looked at the effects of vitamin D, they also found little difference among those taking the nutrient and those taking placebo when it came to overall heart disease and cancer measures.

They do try a little positive spin:

Quote
While they don’t appear to do much overall in this study, fish oil seems to help specific groups of people and the researchers believe that vitamin D may simply take longer to have an effect on cancer rates and deaths.
https://www.yahoo.com/news/fish-oil-vitamin-d-supplements-200048557.html

Detailed summary: https://www.vitalstudy.org/findings.html

Quote
Key findings

Vitamin D supplementation
• Did not reduce risk of cancer
• Did not reduce risk of major cardiovascular events (heart attack, stroke, or cardiovascular death considered together)
• Appeared to reduce risk of cancer-related death

Omega-3 fatty acid supplementation
• Did not reduce risk of cancer
• Did not reduce risk of major cardiovascular events in the overall study population, but did reduce risk of these events by 19% in people with low fish intake
• Reduced risk of heart attack by 28%, when heart attack was considered separately from other cardiovascular events; the benefit appeared strongest in African Americans

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Quote
For the first time, scientists have discovered a confirmed genetic link to erectile dysfunction.

Researchers pinpointed a stretch of DNA where variations made it more difficult for men to perform as expected.

The finger of suspicion points to a gene called SIM1 which could be a target for new impotence treatments.
...
Besides having a potential influence on men’s erections, SIM1 is thought to play a role in brain development.

The scientists carried out the study by analysing the complete genomes, or genetic codes, of more than 36,000 American and 222,000 British men.

A search was made for genetic differences that occurred more often in men with a history of erectile dysfunction.

Variations in the SIM1 locus, the region of DNA containing the SIM1 gene, was associated with a 26 per cent increased risk of impotence.
Link.

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A man developed red-tinted vision after taking too much sildenafil citrate. "... the patient had ingested far more than the recommended 50 mg dose."

Quote
The latest case report is the first study to show that color vision problems caused by retinal damage can result from a high dose of sildenafil citrate, and that excessive use of the drug may lead to long-term, possibly irreversible, vision problems.

"People live by the philosophy that if a little bit is good, a lot is better,” Richard Rosen, lead author of the study and Director of Retina Services at NYEE, said in a statement. “This study shows how dangerous a large dose of a commonly used medication can be. People who depend on colored vision for their livelihood need to realize there could be a long-lasting impact of overindulging on this drug."
https://www.newsweek.com/man-took-so-many-erectile-dysfunction-drugs-his-vision-was-permanently-tinted-1150102

13
Here's another recent study sent our way by Nelson. It doesn't address the issue of causality, so low T could contribute to poor sleep, or vice versa, or both.

https://www.ncbi.nlm.nih.gov/m/pubmed/30225799/

Quote
CONCLUSIONS: Among men aged 16-80 in the United States, we found increasing age, impaired sleep and elevated BMI is associated with low testosterone. It is important, therefore, that evaluation and treatment of reduced serum testosterone should also include improving sleep duration in combination with weight management.

14
This link forwarded by Nelson hits close to home, as a good friend of mine suffered a severe spinal cord injury, leaving him unable to indulge in his passion for bicycle riding. He's a couple years post-injury now, but I'm wondering if testosterone therapy in some form could still be of use, at least making it easier for him to hand-cycle.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032131

Quote
Abstract

Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone.

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Testosterone, Hormones and General Men's Health / Prostate cancer and TRT
« on: September 17, 2018, 06:04:34 pm »
More evidence against the premise that TRT fuels prostate cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025358/

Quote
Purpose

Both testosterone deficiency (TD) and prostate cancer (CaP) have increasing prevalence with age. However, because of the relationship between CaP and androgen receptor activation, testosterone therapy (TT) among patients with known CaP has been approached with caution.
...
Conclusions

In the absence of randomized placebo controlled trials, our study supports the hypothesis that TT may be oncologically safe in hypogonadal men following definitive treatment or active surveillance for CaP.

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