Advice on low dose daily testosterone

[madman]

FIGURE 1 | Percent change in mean gonadotropin levels (LH & FSH), from baseline through 6 months of testosterone treatment. Nasal testosterone (blue), dosed t.i.d., adapted from (15), n = 33. Topical testosterone (orange), dosed daily, adapted from (9), n = 123. IM injectable - 100 mg testosterone enanthate, (red), adapted from (10), n = 10. All changes from baseline were statistically significant. Nasal testosterone—FSH p = 0.03, all others p < 0.001. Standard error calculated using delta method.

 

[camygod]

Topical gel formulations achieve a sustained mid-normal T level with a once-daily application (8). While the topical gel results in less fluctuation of T levels between dosing intervals when compared to IM T, the sustained T levels result in inhibition of HPG axis activity (9). The inhibition of HPG axis activity is evidenced by the nearly full suppression of gonadotropin levels following treatment with either IM injectable testosterone (10) or topical gel administration (9).

Nasal administration of T (4.5% testosterone nasal gel, Natesto) allows for rapid absorption through the nasal mucosa such that serum T levels reach a peak concentration in ∼40 min. Once in the circulation, the T is quickly metabolized, with a return to near baseline T levels in 3–6 h (11). Therefore, multiple administrations of nasal T throughout the day (three times daily) maintain normal mean serum T levels over 24 h. The fluctuations in T levels potentially minimize the duration of exposure to exogenous T that is suppressive to the HPG axis, compared to other available T therapies.


Endocrine systems are regulated dynamically in response to positive or negative stimuli within a homeostatic environment. Modalities of T therapy evolved to extend the dosing interval and maintain sustained “steady-state” T levels. Long-acting TTh can inhibit the HPG axis, which in turn suppresses pituitary LH and FSH secretion, reducing circulating levels of LH and FSH and endogenous T production

Short-acting T therapy, consisting of several doses of T with a shorter half-life throughout the day, minimizes inhibition of the HPG axis and reduces the impairment of spermatogenesis.

makes sense then

 

[Wolverine]

14mg /daily Test Cyp here. Been on that dose forever and doing great. I’m typically in the high 800’s - to low900s on that dose and feel great. E2 of 36 at last bloodwork. I highly recommend daily shots to be very one on TRT-

Indy

Indy: What is your SHBG level? I'm doing twice a week at 50mg each, but thinking on going to 3 times a week. My SHBG is always around 20. HCT a little high in the low 50s. Tx

 

[Indy57]

Indy: What is your SHBG level? I'm doing twice a week at 50mg each, but thinking on going to 3 times a week. My SHBG is always around 20. HCT a little high in the low 50s. Tx

My SHBG is 30. 8 on my last bloodwork. HCT is holding steady a between 47 and 48 at 14mg per day.
Indy

 

[Bigben]

FIGURE 1 | Percent change in mean gonadotropin levels (LH & FSH), from baseline through 6 months of testosterone treatment. Nasal testosterone (blue), dosed t.i.d., adapted from (15), n = 33. Topical testosterone (orange), dosed daily, adapted from (9), n = 123. IM injectable - 100 mg testosterone enanthate, (red), adapted from (10), n = 10. All changes from baseline were statistically significant. Nasal testosterone—FSH p = 0.03, all others p < 0.001. Standard error calculated using delta method.
View attachment 12490

This is great. Would you think using testosterone suspension could be just a bit more than nasal and less than gel supression?

 

[Bigben]

This is great. Would you think using testosterone suspension could be just a bit more than nasal and less than gel supression?

Also, can anyone explain this? I know there is no half life with the crystals in suspension but what does this really show?

 

[Bigben]

Also, can anyone explain this? I know there is no half life with the crystals in suspension but what does this really show?

J Vet Pharmacol Ther. 2011 Mar 2. doi: 10.1111/j.1365-2885.2011.01277.x. [Epub ahead of print]

An interlaboratory study of the pharmacokinetics of testosterone following intramuscular administration to Thoroughbred horses.

Moeller BC, Sams RA, Guinjab J, Szabo N, Colahan P, Stanley SD.

Source

K.L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California at Davis, Davis, CA, USA Florida Racing Laboratory, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Gainesville, FL, USA.

Abstract

Moeller, B. C., Sams, R. A., Guinjab, J., Szabo, N., Colahan, P., Stanley, S. D.

An interlaboratory study of the pharmacokinetics of testosterone following intramuscular administration to Thoroughbred horses. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01277.x.

Testosterone is an anabolic androgenic steroid (AAS) that is endogenously produced by both male and female horses that also has the potential for abuse when administered exogenously to race horses. To recommend appropriate withdrawal guidelines so that veterinarians can discontinue therapeutic use prior to competition, the pharmacokinetics and elimination of testosterone were investigated. An aqueous testosterone suspension was administered intramuscularly in the neck of Thoroughbred horses (n?=?20). The disposition of testosterone from this formulation was characterized by an initial, rapid absorption phase followed by a much more variable secondary absorption phase. The median terminal half-life was 39?h. A second focus of this study was to compare the testosterone concentrations determined by two different laboratories using a percentage similarity model with a coefficient of variation of 16.5% showing good agreement between the two laboratories results. Based on the results of this study, a withdrawal period of 30?days for aqueous testosterone administered IM is recommended.

© 2011 Blackwell Publishing Ltd.

 

[Cataceous]

... Would you think using testosterone suspension could be just a bit more than nasal and less than gel supression?

We've speculated about this. The equine study suggests that the pharmacokinetics of testosterone suspension are complicated and prolonged, which makes it less of a candidate for keeping the HPTA active. Ester-less testosterone in oil (TNE) is perhaps a little more promising, but nobody has turned up any studies, so we still don't know if the half-life is short enough.

 

[madman]

This is great. Would you think using testosterone suspension could be just a bit more than nasal and less than gel supression?

Regarding aqueous testosterone suspension, although there would be rapid absorption of the aqueous vehicle, the crystals of T depending on the particle size (human/veterinary grade) may very well behave like small implants which would be more slowly absorbed from the tissues although it is much faster acting than an esterified T such as (propionate).

With T base (oil/no ester) it would most likely be absorbed/degraded more quickly.




*Pulsatile secretion of a hormone refers to the intermittent secretion of the hormone in a burst-like or episodic manner rather than constantly, with the frequency varying from minutes to hours, determined in part by the half-life of the hormone.


*T levels in a healthy male follow a diurnal variation and circadian rhythm, with levels highest early in the morning and subsequently declining as the day progresses, as a direct result of pulsatile LH secretion (3).


*A sustained steady-state level of T, however, differs from the normal circadian physiology of a healthy individual.


*The 24-hour pharmacokinetic profile of testosterone for patients on TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur on average every 2 hours. A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h). The nadir (trough) between doses correlates well with pre-treatment endogenous levels at diagnosis.


*The unique, pulsatile, pharmacokinetic profile is believed to have limited impact on the HPG axis with significant trough time preserving luteinizing hormone (LH), follicle-stimulating hormone (FSH), endogenous testosterone production, and sperm counts, while also limiting excess RBC production, estradiol, DHT and PSA in clinical trials.



*In between NATESTO® doses, all patients in the phase 3 study maintained their natural testosterone at the same levels they had prior to entry into the study, indicating that NATESTO® does not suppress natural testosterone production. Based on the data, Acerus believes that the mechanism of action of NATESTO® is unique whereby the peaks in testosterone generated by NATESTO® dosing provide efficacy and improvement of symptoms, while the time between doses (4-8 hours) allows for the maintenance of testicular testosterone production and sperm production.




Even then keep in mind that Natesto is dosed 2-3 times daily which results in 2-3 discrete peaks (achieved max TT level is around 800 ng/dL) which are well below supra-physiological.

 

[madman]

Although TS is unesterified the crystals of T may very well behave like small implants being more slowly absorbed from the tissues which would have an impact on the half-life.

Depending on the source the half-life given was 2 – 4 hours and some studies (animal) stating 24-39 hours.

Daily injections let alone multiple would most likely result in the shutdown HPG axis.


Andronaq (testosterone suspension)

Description:

Testosterone suspension is an injectable preparation containing testosterone (no ester), usually in a water base.


History:

Testosterone suspension is one of the oldest anabolic/androgenic steroids, dating all the way back to the 1930’s. Used generically to describe any injectable form of free testosterone, testosterone suspension predates the development of slow-acting (depot) injections of esterified testosterone by several years. Even after the development of esterified derivates, testosterone suspension remained on The U.S. and other select drug markets. For example, testosterone propionate and testosterone enanthate were both commercially available by the 1950s, yet testosterone suspension remained a regularly produced item in the U.S. for decades more. Previous American trade names for the drug have include Sterotate (Ulmer), Andronaq (Central), Aquaspension Testosterone (Pitman-Moore), Injectable Aqueous Testosterone (Arlington-Funk), Virosterone (Endo), and Testosterone Aqueous (National Drug). A full accounting of the former generic manufacturers and brand names for this drug would be too numerous to list.


Structural Characteristics:

Testosterone suspension contains (free) testosterone in a water-based suspension, although oils are sometimes also used as carriers. Without esterification, testosterone has a short half-life in the body. Testosterone suspension may require a minimum of 2-3 injections per week to maintain consistent hormone elevations. When calculating dose, especially when moving from one testosterone preparation to another, it is also important to remember that testosterone suspension contains more active testosterone per milligram than its esterified derivatives. For example, when the weight of the ester is taken into account, 100 mg of testosterone enanthate actually only provides 72 mg of raw testosterone.


*Testosterone suspension contains undissolved testosterone particles, which form a short-acting repository in the muscle following injection. Depending on the size of the particles and other agents present, injections of testosterone suspension may result in local irritation, pain, and redness. Veterinary testosterone suspensions may use large particles that require a needle as large as 21 gauge for injection, for example, and can be very uncomfortable to use. Modern testosterone suspension preparations made for human use often contain microcrystalline steroid particles. These crystals are highly refined and are too small to see with the naked eye. This design provides significantly more patient comfort than less refined products and is generally well tolerated.





Injectable Aqueous Suspensions of Sex Hormones and How Depot Injectables Work

Introduction

Depot injectable sex steroids are administered by intramuscular injection (into the muscle) or subcutaneous injection (into fat) and are formulated in two main ways: 1) as oil solutions, and 2) as crystalline aqueous suspensions. What most transfeminine people are familiar with when it comes to injectable steroid preparations are oil solutions. This is how most common preparations like injectable estradiol valerate (Delestrogen, Progynon-Depot), estradiol cypionate (Depo-Estradiol), testosterone esters, progesterone, and hydroxyprogesterone caproate are formulated. However, injectable aqueous suspensions of sex steroids also exist and are used medically. The most major and well-known formulations include depot medroxyprogesterone acetate (Depo-Provera) and combined injectable contraceptives containing estradiol cypionate/medroxyprogesterone acetate (Cyclofem, Lunelle). Additionally, there exist more obscure preparations of aqueous suspensions such as estradiol benzoate (Agofollin Depot) and progesterone (Agolutin Depot) among others which are marketed in addition to the more common oil solutions of these steroids. These preparations may remain commercially available, including online from sites like EU Aibolit (Reddit). Many transfeminine people are unaware of what aqueous suspensions are or their medical availability. It is notable in this regard that aqueous suspensions are very different from oil solutions in their properties but can have much longer durations in comparison. This is potential of therapeutic value especially in the case of otherwise shorter-acting injectables like progesterone. The purpose of this article is to shed light on injectable aqueous suspensions, describe how injectable oil solutions and aqueous suspensions work to achieve their depot effect and how they are different, and discuss how relevant aqueous suspensions can be obtained for medical use.


How Depot Injectables Work

Sex steroids are typically lipophilic (fat-soluble or “lipid-loving”) and hydrophobic (water-insoluble or “water-hating”). In other words, they dissolve in and are “attracted to” lipids (e.g., fats), and they are poorly solubility in and repelled by water. From chemistry, this is because sex steroids are very non-polar, whereas water is a quite polar molecule. As a result of their lipophilicity, sex steroids readily form clear homogenous solutions when mixed into oil—that is, they form oil solutions. In contrast, because sex steroids are hydrophobic, they do not easily form solutions when mixed into the water—that is, they do not easily form aqueous solutions (like, e.g., salt and water). Instead of aqueous solutions, solid “clumps” or crystal particles of sex steroids can be mixed into and thereby suspended in water—that is, aqueous suspensions of sex steroid crystals can be made. Depot injectables are formulated as oil solutions or aqueous suspensions and these preparations have very different properties.


Injectable Oil Solutions

When an oil solution of a sex steroid is administered by intramuscular or subcutaneous injection, the solution is trapped within the tissue compartment it is injected into and remains there. As the tissue fluid is a water mixture, the oil solution stays together inside the tissue compartment and does not easily separate or distribute. This is because the lipophilic fats and sex steroids within the solution are attracted to each other and are repelled by water. Instead of rapidly dissolving, the fats and sex steroids at the edges of the oil solution are very slowly absorbed into the surrounding water. Once they have escaped the oil depot into the surrounding tissue fluid, they can be distributed into the bloodstream and then into other tissues to exert their biological effects. Eventually, the whole oil solution will be absorbed.

Oftentimes sex steroids that are used by intramuscular or subcutaneous injection are esterified with one or more lipophilic hydrocarbon esters. These esters include fatty acids like propanoic acid (propionate), pentanoic acid (valerate), hexanoic acid (caproate), heptanoic acid (enanthate), decanoic acid (decanoate or decylate), and undecanoic acid (undecylate or undecanoate) as well as cyclic compounds like benzoic acid (benzoate), cyclopentyl propanoic acid (cypionate), and phenylpropanoic acid (phenylpropionate), among many others. Examples of these sex steroid esters include the well-known estradiol valerate, estradiol cypionate, estradiol benzoate, hydroxyprogesterone caproate, and numerous others. The attachment of a lipophilic ester (e.g., valeric acid) to a sex steroid (e.g., estradiol) will increase the lipophilicity of the sex steroid compared to merely injecting the unesterified sex steroid in an oil solution. The longer the carbon atom chain in the case of the simple fatty acid esters (e.g., propionate, valerate, enanthate, undecylate), the more lipophilic the resulting esterified sex steroid will be. As a result, the injected sex steroid ester will escape the oil tissue depot more slowly, lengthening the amount of time it takes for the sex steroid ester to be absorbed and therefore its duration in the body. The tables here and here show the lengthening duration of estradiol with longer or bulkier and more lipophilic esters. Whereas an intramuscular injection of estradiol or progesterone in an oil solution has a duration of only around 2 days, an intramuscular injection of an oil solution of estradiol undecylate, an ester of estradiol with a long fatty acid chain, has a duration measured in months. And an intramuscular injection of an oil solution of hydroxyprogesterone caproate, an ester of a derivative of progesterone that has a medium-length fatty acid chain, has a duration measured in weeks.

Most sex steroid esters themselves are biologically inactive. Once they have left the oil tissue depot, they are rapidly cleaved by esterase enzymes into free unesterified steroid (e.g., estradiol, testosterone) and the previously connected ester moiety (e.g., valeric acid). Hence, most sex steroid esters are prodrugs and are otherwise identical to their parent sex steroids in their biological actions. In the case of esters of estradiol and testosterone, this means that they are bioidentical just like the unesterified steroids. Certain synthetic progesterone derivatives like hydroxyprogesterone caproate and medroxyprogesterone acetate are however not prodrugs and are not meaningfully cleaved into the unesterified parent compound. Instead, they have intrinsic hormonal activity of their own and act without bioactivation.


Injectable Aqueous Suspensions

Aqueous suspensions of sex steroids also form an injection-site depot and achieve a long-lasting depot effect when administered by subcutaneous or intramuscular injection. However, they work in a completely different way than oil solutions. Aqueous suspensions of sex steroids consist of tiny crystal particles of pure sex steroids that are suspended in water. These sex steroid particles are highly lipophilic and hydrophobic. When injected, the hydrophilic water vehicle is rapidly mixed into the fluid of the tissue compartment and absorbed by the body. But the hydrophobic sex steroid crystals are not, and instead float about in the fluid of the tissue compartment. As with oil solutions, the sex steroids at the edges of the crystals very slowly dissolve off the surface of the crystals into the surrounding water and are then distributed into the circulation and tissues. Eventually, the crystal will be fully absorbed into the body, but only after a long period of time. Since the rate of absorption is dependent on lipophilicity and hydrophobicity, lipophilic esters lengthen the durations of aqueous suspensions of sex steroids by intramuscular or subcutaneous injection similarly to the case of oil solutions of sex steroids.

In the case of aqueous suspensions, the duration of the sex steroid is additionally highly dependent on particle size. These particle sizes have ranged from nanocrystalline to microcrystalline to macrocrystalline in their range. Almost always however it is microcrystalline particle sizes that have been used in injectable aqueous suspensions of sex steroids. (The present author has seen macrocrystalline preparations described a few times, specifically in research on combined injectable contraceptives (Garza-Flores, Del, & Perez-Palacios, 1992; Newton, d’Arcangues, & Hall, 1994; Sang, 1994), and is fairly sure that no such preparations have ever been marketed. On the other hand, nanocrystalline aqueous suspensions have been used with depot antipsychotics (Spanarello & Ferla, 2014; Correll et al., 2021).) Typically, there is a given particle size range for the formulation, such as 0.01 to 0.1 mm in diameter. The larger the particle sizes, the slower the absorption into the body, and the longer the duration of the preparation; the smaller the particle sizes, the faster the absorption, and the shorter the duration. When microcrystalline aqueous suspensions of sex steroids are manufactured nowadays, the particle sizes are defined and carefully controlled. Particle sizes influence the duration of injectable aqueous suspensions because they result in different surface areas from which sex steroid ester can escape particles. A single large particle has a smaller total surface area and hence dissolution rate than the same particle divided up into many smaller particles.

Particle sizes are manipulated during manufacturing via micronization—the process of decreasing the diameter of larger particles, such as via milling or grinding. Whereas more micronization improves the absorption and bioavailability of estradiol and progesterone with oral administration by increasing the surface area available for absorption into the body (Wiki; Wiki), less micronization decreases the rate of absorption of crystalline aqueous suspensions via depot injection and thereby extends the durations of these preparations by decreasing the total surface area for absorption.

There is a notable similarity of injectable aqueous suspensions of sex steroids to implantable sex steroid pellets, for instance of estradiol, testosterone, and progesterone (Wiki; Wiki; Wiki). Pellet implants are basically just pure crystalline sex steroids compressed into the shape of a small cylinder (Photo; Photo). They are inserted into subcutaneous fat in the body through a small incision using a large needle-like instrument called a trocar (Diagram). Once implanted, pellets slowly dissolve and absorb into the body over time, eventually disappearing completely. As they are nothing but pure crystalline hormones, there is no need for them to be removed or retrieved later on. In other words, implantation of a pellet is in a way the same thing as a subcutaneous injection of an aqueous suspension of sex steroid crystals—a single pellet is just one massive crystal instead of many tiny crystals suspended in water. And with very large crystals comes a very long duration—typically 6 months or more for each subcutaneous pellet of estradiol or testosterone (Kuhl, 2005; Wiki; Wiki). However, though injectable aqueous suspensions are typically much less prolonged than pellet implants, they have the advantages over pellets of being less expensive and not requiring a surgical incision. Due to the similarity between aqueous suspensions and pellet implants, aqueous suspensions have been described and marketed as “micropellets” in the past.

 

[Bigben]

We've speculated about this. The equine study suggests that the pharmacokinetics of testosterone suspension are complicated and prolonged, which makes it less of a candidate for keeping the HPTA active. Ester-less testosterone in oil (TNE) is perhaps a little more promising, but nobody has turned up any studies, so we still don't know if the half-life is short enough.

Thanks for responding. Yeah makes sense. I tried tne and became sex mad. But only tried it for a week. May give it another go. I've tried everything and mostly go by load size. On 10 suspension they are the biggest. So I figure less suppression. Started the suspension again yesterday. Another thing I notice on suspension is my skin is tighter under my jaw. In my 50s here. No test does this. I wonder if it upps gh.

 

[JA Battle]

Thanks for responding. Yeah makes sense. I tried tne and became sex mad. But only tried it for a week. May give it another go. I've tried everything and mostly go by load size. On 10 suspension they are the biggest. So I figure less suppression. Started the suspension again yesterday. Another thing I notice on suspension is my skin is tighter under my jaw. In my 50s here. No test does this. I wonder if it upps gh.

was this 10mg of TNE and in what carrier oil? Did you run anything else during this time?

 

[Bigben]

was this 10mg of TNE and in what carrier oil? Did you run anything else during this time?

I don't remember the oil. No only test at the time. No hcg either or ai

 

[tropicaldaze1950]

Madman is on top of it, as usual. I agree with everything he's stated so far. I'm just jumping in to say that as a member of the community that does daily shots, don't do it unless you need to. Every 3.5 works great for many guys, so there's no reason to not try that first. I moved to daily shots to help keep my E2 under control with less AI. Unless you have a very specific reason to do daily shots (and at this point, it's fair to say you don't yet), I wouldn't do it. Think about diagnosing any mechanical malfunction... a good mechanic/electrician/repairman/etc. always starts with the most common issues and only elevates it if needed. I would follow the same course.

What about if someone hyperexcretes or is a hypermetabolizer? Don't know if I fit in either category but low dose daily or EOD might compensate for those biochemical defects, IMO.

 

[tropicaldaze1950]

i have heard and im not saying its fact or true that its the ester with the tesosterone that can cause more of the shut down and issues and low dose of pure base on its own wont do this i havent tried it so dont quote me but the person who was claiming this did not seem a idiot so take it for whats it worth also if you are hypogonadal i guess it wont help any way its worth a try i want to experiment with test base but a number of facotrs have prevented me this last year

We're talking injecting pure testosterone sans an ester. Will a pharmacy,such as Empower or Hallandale, compound this? I'll be consulting with my urologist next week and I'd like to discuss with him.

 

[tropicaldaze1950]

Absorption time matters if you want to simulate Natesto with fast peaks and fast valleys. This reduces suppression or testosterone production in the body. If all of your testosterone comes from TRT, you would not care of that - you are already suppressed.

TNE (unmodified testosterone suspension) is not in current use, probably because it is absorbed too fast, requiring too many injections to maintain testosterone levels. Also, its absorption will depend on the size of the testosterone crystals in the suspension, which is hard to control, making it unreliable. Last, testo crystal suspensions in water cause local reactions lasting for days, which are less frequent with oil solutions: Wikipedia - testosterone phenylacetate water suspension

I could not find a contemporary pharmacokinetic study for TNE in humans. Probably these were done in the early years of discovering testosterone and then TNE was replaced by the esters in oil because of the above arguments. Everywhere, there is cited the same dumb statement that "unmodified testosterone has a half-life of only 10 minutes and would have to be injected very frequently". However this is surely talking about the half-life in blood. When the suspension is injected in the muscle, it forms a water depot and it is not released instantly into circulation. By the way, the half-life of testosterone propionate in blood is also about 10 minutes because it is converted to pure testosterone very fast. The prolonged half-life of the propionate is actually due to
the oil depot in the muscle from which it is slowly released with the oil.

Thanks for responding. Yeah makes sense. I tried tne and became sex mad. But only tried it for a week. May give it another go. I've tried everything and mostly go by load size. On 10 suspension they are the biggest. So I figure less suppression. Started the suspension again yesterday. Another thing I notice on suspension is my skin is tighter under my jaw. In my 50s here. No test does this. I wonder if it upps gh.ou

You had TNE compounded or did you homebrew? This has me fascinated. Didn't know about this form of testosterone.

 

[tropicaldaze1950]

Although TS is unesterified the crystals of T may very well behave like small implants being more slowly absorbed from the tissues which would have an impact on the half-life.

Depending on the source the half-life given was 2 – 4 hours and some studies (animal) stating 24-39 hours.

Daily injections let alone multiple would most likely result in the shutdown HPG axis.


Andronaq (testosterone suspension)

Description:

Testosterone suspension is an injectable preparation containing testosterone (no ester), usually in a water base.


History:

Testosterone suspension is one of the oldest anabolic/androgenic steroids, dating all the way back to the 1930’s. Used generically to describe any injectable form of free testosterone, testosterone suspension predates the development of slow-acting (depot) injections of esterified testosterone by several years. Even after the development of esterified derivates, testosterone suspension remained on The U.S. and other select drug markets. For example, testosterone propionate and testosterone enanthate were both commercially available by the 1950s, yet testosterone suspension remained a regularly produced item in the U.S. for decades more. Previous American trade names for the drug have include Sterotate (Ulmer), Andronaq (Central), Aquaspension Testosterone (Pitman-Moore), Injectable Aqueous Testosterone (Arlington-Funk), Virosterone (Endo), and Testosterone Aqueous (National Drug). A full accounting of the former generic manufacturers and brand names for this drug would be too numerous to list.


Structural Characteristics:

Testosterone suspension contains (free) testosterone in a water-based suspension, although oils are sometimes also used as carriers. Without esterification, testosterone has a short half-life in the body. Testosterone suspension may require a minimum of 2-3 injections per week to maintain consistent hormone elevations. When calculating dose, especially when moving from one testosterone preparation to another, it is also important to remember that testosterone suspension contains more active testosterone per milligram than its esterified derivatives. For example, when the weight of the ester is taken into account, 100 mg of testosterone enanthate actually only provides 72 mg of raw testosterone.


*Testosterone suspension contains undissolved testosterone particles, which form a short-acting repository in the muscle following injection. Depending on the size of the particles and other agents present, injections of testosterone suspension may result in local irritation, pain, and redness. Veterinary testosterone suspensions may use large particles that require a needle as large as 21 gauge for injection, for example, and can be very uncomfortable to use. Modern testosterone suspension preparations made for human use often contain microcrystalline steroid particles. These crystals are highly refined and are too small to see with the naked eye. This design provides significantly more patient comfort than less refined products and is generally well tolerated.





Injectable Aqueous Suspensions of Sex Hormones and How Depot Injectables Work

Introduction

Depot injectable sex steroids are administered by intramuscular injection (into the muscle) or subcutaneous injection (into fat) and are formulated in two main ways: 1) as oil solutions, and 2) as crystalline aqueous suspensions. What most transfeminine people are familiar with when it comes to injectable steroid preparations are oil solutions. This is how most common preparations like injectable estradiol valerate (Delestrogen, Progynon-Depot), estradiol cypionate (Depo-Estradiol), testosterone esters, progesterone, and hydroxyprogesterone caproate are formulated. However, injectable aqueous suspensions of sex steroids also exist and are used medically. The most major and well-known formulations include depot medroxyprogesterone acetate (Depo-Provera) and combined injectable contraceptives containing estradiol cypionate/medroxyprogesterone acetate (Cyclofem, Lunelle). Additionally, there exist more obscure preparations of aqueous suspensions such as estradiol benzoate (Agofollin Depot) and progesterone (Agolutin Depot) among others which are marketed in addition to the more common oil solutions of these steroids. These preparations may remain commercially available, including online from sites like EU Aibolit (Reddit). Many transfeminine people are unaware of what aqueous suspensions are or their medical availability. It is notable in this regard that aqueous suspensions are very different from oil solutions in their properties but can have much longer durations in comparison. This is potential of therapeutic value especially in the case of otherwise shorter-acting injectables like progesterone. The purpose of this article is to shed light on injectable aqueous suspensions, describe how injectable oil solutions and aqueous suspensions work to achieve their depot effect and how they are different, and discuss how relevant aqueous suspensions can be obtained for medical use.


How Depot Injectables Work

Sex steroids are typically lipophilic (fat-soluble or “lipid-loving”) and hydrophobic (water-insoluble or “water-hating”). In other words, they dissolve in and are “attracted to” lipids (e.g., fats), and they are poorly solubility in and repelled by water. From chemistry, this is because sex steroids are very non-polar, whereas water is a quite polar molecule. As a result of their lipophilicity, sex steroids readily form clear homogenous solutions when mixed into oil—that is, they form oil solutions. In contrast, because sex steroids are hydrophobic, they do not easily form solutions when mixed into the water—that is, they do not easily form aqueous solutions (like, e.g., salt and water). Instead of aqueous solutions, solid “clumps” or crystal particles of sex steroids can be mixed into and thereby suspended in water—that is, aqueous suspensions of sex steroid crystals can be made. Depot injectables are formulated as oil solutions or aqueous suspensions and these preparations have very different properties.


Injectable Oil Solutions

When an oil solution of a sex steroid is administered by intramuscular or subcutaneous injection, the solution is trapped within the tissue compartment it is injected into and remains there. As the tissue fluid is a water mixture, the oil solution stays together inside the tissue compartment and does not easily separate or distribute. This is because the lipophilic fats and sex steroids within the solution are attracted to each other and are repelled by water. Instead of rapidly dissolving, the fats and sex steroids at the edges of the oil solution are very slowly absorbed into the surrounding water. Once they have escaped the oil depot into the surrounding tissue fluid, they can be distributed into the bloodstream and then into other tissues to exert their biological effects. Eventually, the whole oil solution will be absorbed.

Oftentimes sex steroids that are used by intramuscular or subcutaneous injection are esterified with one or more lipophilic hydrocarbon esters. These esters include fatty acids like propanoic acid (propionate), pentanoic acid (valerate), hexanoic acid (caproate), heptanoic acid (enanthate), decanoic acid (decanoate or decylate), and undecanoic acid (undecylate or undecanoate) as well as cyclic compounds like benzoic acid (benzoate), cyclopentyl propanoic acid (cypionate), and phenylpropanoic acid (phenylpropionate), among many others. Examples of these sex steroid esters include the well-known estradiol valerate, estradiol cypionate, estradiol benzoate, hydroxyprogesterone caproate, and numerous others. The attachment of a lipophilic ester (e.g., valeric acid) to a sex steroid (e.g., estradiol) will increase the lipophilicity of the sex steroid compared to merely injecting the unesterified sex steroid in an oil solution. The longer the carbon atom chain in the case of the simple fatty acid esters (e.g., propionate, valerate, enanthate, undecylate), the more lipophilic the resulting esterified sex steroid will be. As a result, the injected sex steroid ester will escape the oil tissue depot more slowly, lengthening the amount of time it takes for the sex steroid ester to be absorbed and therefore its duration in the body. The tables here and here show the lengthening duration of estradiol with longer or bulkier and more lipophilic esters. Whereas an intramuscular injection of estradiol or progesterone in an oil solution has a duration of only around 2 days, an intramuscular injection of an oil solution of estradiol undecylate, an ester of estradiol with a long fatty acid chain, has a duration measured in months. And an intramuscular injection of an oil solution of hydroxyprogesterone caproate, an ester of a derivative of progesterone that has a medium-length fatty acid chain, has a duration measured in weeks.

Most sex steroid esters themselves are biologically inactive. Once they have left the oil tissue depot, they are rapidly cleaved by esterase enzymes into free unesterified steroid (e.g., estradiol, testosterone) and the previously connected ester moiety (e.g., valeric acid). Hence, most sex steroid esters are prodrugs and are otherwise identical to their parent sex steroids in their biological actions. In the case of esters of estradiol and testosterone, this means that they are bioidentical just like the unesterified steroids. Certain synthetic progesterone derivatives like hydroxyprogesterone caproate and medroxyprogesterone acetate are however not prodrugs and are not meaningfully cleaved into the unesterified parent compound. Instead, they have intrinsic hormonal activity of their own and act without bioactivation.


Injectable Aqueous Suspensions

Aqueous suspensions of sex steroids also form an injection-site depot and achieve a long-lasting depot effect when administered by subcutaneous or intramuscular injection. However, they work in a completely different way than oil solutions. Aqueous suspensions of sex steroids consist of tiny crystal particles of pure sex steroids that are suspended in water. These sex steroid particles are highly lipophilic and hydrophobic. When injected, the hydrophilic water vehicle is rapidly mixed into the fluid of the tissue compartment and absorbed by the body. But the hydrophobic sex steroid crystals are not, and instead float about in the fluid of the tissue compartment. As with oil solutions, the sex steroids at the edges of the crystals very slowly dissolve off the surface of the crystals into the surrounding water and are then distributed into the circulation and tissues. Eventually, the crystal will be fully absorbed into the body, but only after a long period of time. Since the rate of absorption is dependent on lipophilicity and hydrophobicity, lipophilic esters lengthen the durations of aqueous suspensions of sex steroids by intramuscular or subcutaneous injection similarly to the case of oil solutions of sex steroids.

In the case of aqueous suspensions, the duration of the sex steroid is additionally highly dependent on particle size. These particle sizes have ranged from nanocrystalline to microcrystalline to macrocrystalline in their range. Almost always however it is microcrystalline particle sizes that have been used in injectable aqueous suspensions of sex steroids. (The present author has seen macrocrystalline preparations described a few times, specifically in research on combined injectable contraceptives (Garza-Flores, Del, & Perez-Palacios, 1992; Newton, d’Arcangues, & Hall, 1994; Sang, 1994), and is fairly sure that no such preparations have ever been marketed. On the other hand, nanocrystalline aqueous suspensions have been used with depot antipsychotics (Spanarello & Ferla, 2014; Correll et al., 2021).) Typically, there is a given particle size range for the formulation, such as 0.01 to 0.1 mm in diameter. The larger the particle sizes, the slower the absorption into the body, and the longer the duration of the preparation; the smaller the particle sizes, the faster the absorption, and the shorter the duration. When microcrystalline aqueous suspensions of sex steroids are manufactured nowadays, the particle sizes are defined and carefully controlled. Particle sizes influence the duration of injectable aqueous suspensions because they result in different surface areas from which sex steroid ester can escape particles. A single large particle has a smaller total surface area and hence dissolution rate than the same particle divided up into many smaller particles.

Particle sizes are manipulated during manufacturing via micronization—the process of decreasing the diameter of larger particles, such as via milling or grinding. Whereas more micronization improves the absorption and bioavailability of estradiol and progesterone with oral administration by increasing the surface area available for absorption into the body (Wiki; Wiki), less micronization decreases the rate of absorption of crystalline aqueous suspensions via depot injection and thereby extends the durations of these preparations by decreasing the total surface area for absorption.

There is a notable similarity of injectable aqueous suspensions of sex steroids to implantable sex steroid pellets, for instance of estradiol, testosterone, and progesterone (Wiki; Wiki; Wiki). Pellet implants are basically just pure crystalline sex steroids compressed into the shape of a small cylinder (Photo; Photo). They are inserted into subcutaneous fat in the body through a small incision using a large needle-like instrument called a trocar (Diagram). Once implanted, pellets slowly dissolve and absorb into the body over time, eventually disappearing completely. As they are nothing but pure crystalline hormones, there is no need for them to be removed or retrieved later on. In other words, implantation of a pellet is in a way the same thing as a subcutaneous injection of an aqueous suspension of sex steroid crystals—a single pellet is just one massive crystal instead of many tiny crystals suspended in water. And with very large crystals comes a very long duration—typically 6 months or more for each subcutaneous pellet of estradiol or testosterone (Kuhl, 2005; Wiki; Wiki). However, though injectable aqueous suspensions are typically much less prolonged than pellet implants, they have the advantages over pellets of being less expensive and not requiring a surgical incision. Due to the similarity between aqueous suspensions and pellet implants, aqueous suspensions have been described and marketed as “micropellets” in the past.

Thank you for this trove of information, madman.

Thanks for responding. Yeah makes sense. I tried tne and became sex mad. But only tried it for a week. May give it another go. I've tried everything and mostly go by load size. On 10 suspension they are the biggest. So I figure less suppression. Started the suspension again yesterday. Another thing I notice on suspension is my skin is tighter under my jaw. In my 50s here. No test does this. I wonder if it upps gh.

What was your dosage? Since it was only for a week, daily, E3.5D or EOD? Thanks.

 

[Cataceous]

What about if someone hyperexcretes or is a hypermetabolizer? Don't know if I fit in either category but low dose daily or EOD might compensate for those biochemical defects, IMO.

It's important to distinguish between fast metabolism and fast absorption. Fast metabolism has essentially nothing to do with the apparent half-life of an injected testosterone ester, in which the ester is slowly released from the depot over time. Someone with unusually fast metabolism of testosterone would notice that his total testosterone is proportionally lower at all times compared to someone with normal metabolism who is otherwise identical. The rates of decline of serum testosterone will be the same for the two if they are absorbing the testosterone ester at the same rate. For example, in five days the normal metabolizer sees his serum testosterone drop from 1,000 ng/dL to 500 ng/dL. Meanwhile, in five days the fast metabolizer sees his testosterone drop from 500 ng/dL to 250 ng/dL.

On the other hand, someone who absorbs much faster than usual will see a shorter apparent half-life in his serum testosterone. For example, his levels on testosterone cypionate might drop by half in two days, compared to the more typical five days. The fast absorber is the one who clearly benefits from a higher injection frequency if he needs more stable serum testosterone.

 

[tropicaldaze1950]

It's important to distinguish between fast metabolism and fast absorption. Fast metabolism has essentially nothing to do with the apparent half-life of an injected testosterone ester, in which the ester is slowly released from the depot over time. Someone with unusually fast metabolism of testosterone would notice that his total testosterone is proportionally lower at all times compared to someone with normal metabolism who is otherwise identical. The rates of decline of serum testosterone will be the same for the two if they are absorbing the testosterone ester at the same rate. For example, in five days the normal metabolizer sees his serum testosterone drop from 1,000 ng/dL to 500 ng/dL. Meanwhile, in five days the fast metabolizer sees his testosterone drop from 500 ng/dL to 250 ng/dL.

On the other hand, someone who absorbs much faster than usual will see a shorter apparent half-life in his serum testosterone. For example, his levels on testosterone cypionate might drop by half in two days, compared to the more typical five days. The fast absorber is the one who clearly benefits from a higher injection frequency if he needs more stable serum testosterone.

Thank you. Never established why my response to testosterone injections has been fair to poor. Your experiments with peptides intrigues me, as does using TNE instead of Test E. Much to discuss with my urologist after I do labs and see what things look like. Been off testosterone for several months because of significant weight gain. Lost 10 pounds in the months off of shots.

 

[SSHSSA74]

Have you ever taken a break from TRY

I'm injecting the equivalent of 43 mg testosterone cypionate a week. It's the best I've felt overall on TRT, and I've been on as much as 100 mg per week. I inject daily, and peak testosterone is probably close to 700 ng/dL, at least mid to upper 600s. The actual protocol is 3.2 mg T enanthate and 2.4 mg T propionate injected daily subcutaneously.

I'll put in a plug for starting with a higher injection frequency: The data you gather can be useful in making predictions later on. Starting with at least EOD injections means that after things settle down you will likely have a pretty constant total serum testosterone. If you measure this along with SHBG and ideally albumin too then the dose-response relationship lets you estimate in advance the results of other protocols. The more data points you collect, the better your estimates.

I'm injecting the equivalent of 43 mg testosterone cypionate a week. It's the best I've felt overall on TRT, and I've been on as much as 100 mg per week. I inject daily, and peak testosterone is probably close to 700 ng/dL, at least mid to upper 600s. The actual protocol is 3.2 mg T enanthate and 2.4 mg T propionate injected daily subcutaneously.

I'll put in a plug for starting with a higher injection frequency: The data you gather can be useful in making predictions later on. Starting with at least EOD injections means that after things settle down you will likely have a pretty constant total serum testosterone. If you measure this along with SHBG and ideally albumin too then the dose-response relationship lets you estimate in advance the results of other protocols. The more data points you collect, the better your estimates.

I'm injecting the equivalent of 43 mg testosterone cypionate a week. It's the best I've felt overall on TRT, and I've been on as much as 100 mg per week. I inject daily, and peak testosterone is probably close to 700 ng/dL, at least mid to upper 600s. The actual protocol is 3.2 mg T enanthate and 2.4 mg T propionate injected daily subcutaneously.

I'll put in a plug for starting with a higher injection frequency: The data you gather can be useful in making predictions later on. Starting with at least EOD injections means that after things settle down you will likely have a pretty constant total serum testosterone. If you measure this along with SHBG and ideally albumin too then the dose-response relationship lets you estimate in advance the results of other protocols. The more data points you collect, the better your estimates.

Have you even taken a break from TRT, If so, how long and did you find it helpful when you restarted? And do you take hCG?