The TRT Blog - Testosterone Replacement Therapy

Testosterone Replacement Therapy Laws in the US

A brief summary of the laws governing TRT in the United States

Controlled Substances Act (CSA): The CSA is a federal law that regulates the manufacture, distribution, and dispensing of controlled substances, including testosterone. Testosterone is classified as a Schedule III controlled substance under the CSA, which means that it has a moderate to low potential for abuse and dependence.

Food, Drug, and Cosmetic Act (FDCA): The FDCA is a federal law that regulates the safety and effectiveness of drugs and medical devices. Testosterone replacement therapy products are subject to regulation by the FDA under the FDCA.

Drug Enforcement Administration (DEA) Regulations: The DEA is responsible for enforcing the CSA and has established regulations governing the registration, prescribing, and dispensing of controlled substances, including testosterone.

State Medical Boards: State medical boards regulate the practice of medicine within their respective states, including the prescribing and administration of testosterone replacement therapy. State medical boards can discipline or revoke the licenses of healthcare providers who violate state laws or regulations related to testosterone replacement therapy.

An Abbreviated History of TRT

A timeline of testosterone replacement therapy milestones

1849: Arnold Adolph Berthold, a German physiologist, conducts experiments on roosters and observes that removing their testes causes changes in their physical characteristics.

1889: Charles-Édouard Brown-Séquard, a French physician, injects himself with a concoction made from the testicles of dogs and guinea pigs, claiming that it improved his physical and mental health.

1935: The chemical structure of testosterone is first identified by Ernst Laqueur, a Dutch biochemist.

1937: The first clinical trial of testosterone replacement therapy is conducted by Paul Heinrich Emmett and Enrest Laqueur in Amsterdam. They administer testosterone to a patient with low testosterone levels and report improvements in his physical and mental health.

1944: The first synthetic form of testosterone, testosterone propionate, is developed.

1953: A study published in the Journal of the American Medical Association (JAMA) reports that testosterone replacement therapy can improve muscle mass and strength in men with low testosterone levels.

1960s: Testosterone replacement therapy becomes more widely available and is prescribed to men with low testosterone levels.

1970s-1980s: The use of testosterone replacement therapy declines due to concerns about the risk of prostate cancer and cardiovascular disease.

1990s: The development of newer forms of testosterone, such as testosterone enanthate and testosterone cypionate, leads to a renewed interest in testosterone replacement therapy.

2000s: Testosterone replacement therapy becomes more popular, with sales of testosterone increasing rapidly.

2010s: Studies suggest that testosterone replacement therapy may increase the risk of cardiovascular disease and prostate cancer in some men, leading to increased scrutiny of the safety and efficacy of testosterone replacement therapy.

2015: The FDA issues a safety alert warning that testosterone replacement therapy may increase the risk of heart attack, stroke, and death in some men, leading to increased regulation of testosterone replacement therapy.

Today, testosterone replacement therapy continues to be a popular treatment option for men with low testosterone levels. However, it is important for individuals to work with a qualified healthcare provider to determine the appropriate form and dosage of testosterone for their individual needs and to monitor for potential side effects.

The Half Lives of Different Forms of Testosterone

The following table lists the half-life of the most popular forms of testosterone used in testosterone replacement therapy from longest to shortest.

Form of Testosterone	Half-Life
Testosterone cypionate	8 days
Testosterone enanthate	4.5 days
Testosterone undecanoate	20 days
Testosterone propionate	2 days
Testosterone gel (transdermal)	2-4 hours
Testosterone patches (transdermal)	24 hours
Testosterone pellets (implanted subcutaneously)	3-6 months
Buccal testosterone	10-12 hours
Nasal testosterone	2 hours

How long does it take to reach peak testosterone levels with TRT?

The table below shows how long it would take for testosterone to reach peak levels in the bloodstream for each type of testosterone. After the peak, testosterone levels will gradually decline until the next administration.

Form of Testosterone	Time to Reach Peak Levels
Testosterone cypionate	2-3 days
Testosterone enanthate	2-4 days
Testosterone undecanoate	7-14 days
Testosterone propionate	1-2 days
Testosterone gel (transdermal)	2-6 hours
Testosterone patches (transdermal)	24 hours
Testosterone pellets (implanted subcutaneously)	1-2 weeks
Buccal testosterone	30 minutes
Nasal testosterone	30 minutes

How often do you take testosterone for TRT?

The table below shows how frequently each form of testosterone is typically administered.

Form of Testosterone	Typical Administration Frequency
Testosterone cypionate	Every 7-10 days
Testosterone enanthate	Every 7-10 days
Testosterone undecanoate	Every 10-14 weeks
Testosterone propionate	Every 2-3 days
Testosterone gel (transdermal)	Daily
Testosterone patches (transdermal)	Daily
Testosterone pellets (implanted subcutaneously)	Every 3-6 months
Buccal testosterone	Twice daily
Nasal testosterone	Twice daily

I personally split up dosage of testosterone enanthate into two shots per week because it provides me with more stable testosterone levels and reduces side effects.

TRT Man

Why are testosterone enanthate and testosterone cypionate taken at the same frequencies when they have very different half-lives?

Testosterone enanthate has a half-life of approximately 4-5 days, while testosterone cypionate has a half-life of approximately 8 days. This means that it takes longer for testosterone cypionate to be eliminated from the body compared to testosterone enanthate. However, both forms of testosterone have a similar duration of action, which is why they are both typically administered every 7-10 days in testosterone replacement therapy.

In this context, "duration of action" refers to the length of time that a drug remains active in the body after administration. For testosterone replacement therapy, the duration of action refers to the length of time that the testosterone levels remain within the therapeutic range after a dose of testosterone is administered.

The duration of action of a drug can depend on many factors, not just the half-life of the drug. While testosterone enanthate and testosterone cypionate have different half-lives, they have a similar duration of action because they both have a similar pharmacokinetic profile.

While testosterone cypionate has a longer half-life than testosterone enanthate, the duration of action is not solely determined by the half-life. Other factors, such as the rate of absorption and metabolism, can also impact the duration of action. Additionally, the frequency of administration can be adjusted to achieve the desired duration of action.

Ultimately, the appropriate form of testosterone and the frequency of administration should be determined by a healthcare provider based on the individual's specific needs and medical history.

Natural Aromatase Inhibitors for TRT

Anti-Estrogen Options Without a Prescription

Aromatase inhibitors are a group of compounds that inhibit the enzyme aromatase, which is responsible for converting androgenic hormones, such as testosterone, into estrogen. In men, excessive estrogen levels can lead to a variety of health issues, including gynecomastia, decreased libido, and prostate problems.

Natural, over-the-counter aromatase inhibitors:

Nettle:

Nettle is a perennial plant that is commonly used in traditional medicine. Nettle leaves and root contain compounds that inhibit aromatase, including lignans and flavonoids. A study on rats showed that nettle root extract decreased aromatase activity and estrogen levels (1). Another study on humans showed that nettle leaf extract decreased SHBG (sex hormone-binding globulin) levels, which in turn increased free testosterone levels (2).

Grape seed extract:

Grape seed extract is a potent antioxidant and anti-inflammatory agent that also has aromatase-inhibiting properties. A study on rats showed that grape seed extract decreased aromatase activity and estrogen levels (3). Another study on humans showed that grape seed extract decreased SHBG levels and increased free testosterone levels (4).

Alpinia purpurata:

Alpinia purpurata, also known as red ginger, is a tropical plant that is traditionally used to treat a variety of ailments. A study on rats showed that Alpinia purpurata extract decreased aromatase activity and estrogen levels (5).

Coccothrinax Sarg.:

Coccothrinax Sarg. is a species of palm tree that is native to the Caribbean. A study on rats showed that Coccothrinax Sarg. extract decreased aromatase activity and estrogen levels (6).

Agaricus bisporus:

Agaricus bisporus, also known as the white button mushroom, is a common edible mushroom that has been shown to have anti-cancer and anti-inflammatory properties. A study on rats showed that Agaricus bisporus extract decreased aromatase activity and estrogen levels (7).

Cyperus:

Cyperus is a genus of plants that is commonly used in traditional medicine. A study on rats showed that Cyperus extract decreased aromatase activity and estrogen levels (8).

Flavonoids:

Flavonoids are a group of compounds that are found in many fruits and vegetables. Some flavonoids, such as apigenin, chrysin, 7-hydroxyflavone, isolicoflavonol, and eriodictyol, have been shown to have aromatase-inhibiting properties. A study on rats showed that apigenin and chrysin decreased aromatase activity and estrogen levels (9). Another study on rats showed that 7-hydroxyflavone and isolicoflavonol decreased aromatase activity and estrogen levels (10). A study on human cells showed that eriodictyol inhibited aromatase activity (11).

Differences between estriol, estrone, and estradiol in men:

Estriol, estrone, and estradiol are three different types of estrogen. Estriol is the weakest and least potent of the three estrogens, and it is primarily produced during pregnancy. Estrone is the second weakest estrogen and is produced in small amounts in men and postmenopausal women. Estradiol is the most potent estrogen and is the primary estrogen produced in premenopausal women.

In men, estradiol is primarily produced by the conversion of testosterone by the enzyme aromatase. High levels of estradiol in men can lead to a variety of health issues, including gynecomastia, decreased libido, and prostate problems. Therefore, inhibiting aromatase and reducing estradiol levels in men can have beneficial effects on their health.

Natural, over-the-counter aromatase inhibitors can be a safe and effective way for men to reduce estrogen levels and improve their hormonal balance. Compounds such as nettle, grape seed extract, Alpinia purpurata, Coccothrinax Sarg., Agaricus bisporus, Cyperus, and flavonoids have been shown to inhibit aromatase activity and reduce estrogen levels. It is important to note that while these compounds are generally safe, they should be used under the guidance of a healthcare professional to ensure proper dosing and to avoid any potential interactions with other medications.

In addition to the references below, I found this Pub Med review of an article first published in Anticancer Agents Med Chem. 2008 Aug; 8(6): 646–682 called Natural Products as Aromatase Inhibitors to be most helpful.

References:

Nahata A, Dixit VK. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone-induced prostatic hyperplasia in rats. Andrologia. 2012;44 Suppl 1:396-409.

Safarinejad MR. Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study. J Herb Pharmacother. 2005;5(4):1-11.

Sun Z, Huang Y, Cao Y, et al. Grape seed proanthocyanidin extract regulates aromatase activity and expression in human adipose stromal cells and adipose tissue in vitro and in vivo. Endocrinology. 2014;155(11):4234-4242.

Singh RB, Mengi SA, Xu YJ, et al. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med. 2009;26(5):526-531.

Kim J, Han SH, Lee JH, et al. Alpinia purpurata ethanol extract suppresses estrogen biosynthesis through the modulation of estrogen-related receptor alpha in MCF-7 cells. BMC Complement Altern Med. 2016;16:467.

Kim J, Jeong D, Kang S, et al. Coccothrinax Sarg. ethanol extract inhibits estrogen biosynthesis in human ovarian granulosa cells by suppressing aromatase activity and mRNA expression. BMC Complement Altern Med. 2017;17(1):353.

Kamat SG, Saxena N, Rai AK. Evaluation of anti-aromatase activity of phytoconstituents from white button mushroom (Agaricus bisporus). Int J Med Mushrooms. 2014;16(2):119-127.

Li J, Li S, Guan H, et al. Cyperus rotundus extract inhibits aromatase activity in mammalian cells. J Ethnopharmacol. 2011;137(2):1023-1027.

Wang Y, Lee KW, Chan FL, et al. The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells. Toxicol Sci. 2006;92(1):71-77.

Lee YJ, Lee YM, Lee CK, Jung JC, Han SB, Hong JT. Therapeutic applications of compounds in the Magnolia family. Pharmacol Ther. 2011;130(2):157-176.

Kim Y. W., Zhao F., Qi H., et al. Flavonoids inhibit aromatase expression and activity in mouse trophoblast cells. Biol Reprod. 2011;84(3): 579–586.

10 TRT Side Effects to Talk to Your Doctor About

While TRT can be an effective treatment for men with low testosterone, there are several potential side effects and risks that your doctor may not have fully explained to you. Here are ten things you should know about testosterone replacement therapy:

High hematocrit levels: Testosterone can stimulate the production of red blood cells, which can lead to an increase in hematocrit levels. High hematocrit levels can increase the risk of blood clots, stroke, and heart attack. Regular monitoring of hematocrit levels is necessary during TRT. I am a regular at the local blood donation centers because it helps me keep my hematocrit levels low. Win-Win!

Hair loss: TRT can lead to an increased risk of hair loss in men who are genetically predisposed to male pattern baldness. If you are concerned about hair loss, talk to your doctor about alternative treatments or medications that can help. Speaking of...

Side effects of medications for hair loss: Medications commonly used to treat hair loss, such as finasteride, can have sexual side effects such as decreased libido, gynecomastia and erectile dysfunction.

Gynecomastia: TRT can lead to an imbalance of hormones that can cause the development of breast tissue in men. This condition, known as gynecomastia, can be treated with medications or surgery if it becomes a concern.

Side effects of medications for gynecomastia: Medications commonly used to treat gynecomastia, such as tamoxifen, can have side effects such as hot flashes and mood changes.

Testicular shrinkage: TRT can lead to testicular shrinkage due to a decrease in natural testosterone production. This is typically a temporary side effect and may be reversed by discontinuing TRT.

Infertility: TRT can suppress the production of sperm in the testicles, which can lead to infertility. If you are interested in preserving fertility, talk to your doctor about options such as sperm banking before starting TRT.

Increased risk of prostate cancer: TRT has been associated with an increased risk of prostate cancer, particularly in men over the age of 65. Regular prostate exams and monitoring are necessary during TRT.

Skin irritation: TRT can lead to skin irritation at the application site of topical testosterone gels or patches.

Cardiovascular risks: TRT has been associated with an increased risk of cardiovascular events such as heart attack and stroke, particularly in men with pre-existing cardiovascular disease. Your doctor should carefully evaluate your cardiovascular risk factors before prescribing TRT.

HGH Vs Testosterone for Male Hormone Replacement Therapy

Two of the most commonly prescribed hormones for male HRT are human growth hormone (HGH) and testosterone. In this article, we will discuss the differences between HGH and testosterone therapy, compare their risks and side effects, and explore whether taking both may be beneficial for some individuals.

Human Growth Hormone Therapy

HGH is a hormone produced by the pituitary gland that stimulates cell reproduction, growth, and regeneration. HGH therapy involves the administration of synthetic HGH to help counteract the decline in natural production due to aging. Some potential benefits of HGH therapy include increased muscle mass, improved bone density, reduced body fat, and enhanced energy levels.

Testosterone Replacement Therapy

Testosterone is a vital male hormone responsible for maintaining muscle mass, bone density, and sexual function. As men age, testosterone levels gradually decline, leading to various health issues, including reduced muscle mass, increased body fat, decreased libido, and erectile dysfunction. Testosterone replacement therapy (TRT) involves the administration of synthetic testosterone to help restore optimal hormone levels and alleviate these symptoms.

Which is Better?

The choice between HGH therapy and testosterone replacement therapy depends on an individual's specific needs and health concerns. While both treatments can improve muscle mass, bone density, and overall well-being, they work through different mechanisms and target different aspects of hormonal health.

HGH therapy may be more appropriate for individuals with growth hormone deficiency, while TRT is generally prescribed for men with low testosterone levels. It's essential to consult a healthcare professional to determine the most appropriate course of treatment based on your unique needs and hormone levels.

Risks and Side Effects

Both HGH therapy and TRT carry potential risks and side effects, and it's crucial to weigh these factors against the potential benefits of treatment.

HGH therapy can lead to side effects such as joint pain, swelling, carpal tunnel syndrome, and increased risk of diabetes. In some cases, HGH therapy has also been associated with an increased risk of certain cancers.

TRT, on the other hand, can cause side effects like acne, breast enlargement, reduced sperm production, and an increased risk of blood clots. There is also some concern about the potential link between TRT and prostate cancer, although more research is needed to establish a definitive connection.

Should I Take Both?

In some cases, combining HGH therapy with TRT may provide synergistic benefits for men experiencing hormonal imbalances. However, this approach should only be considered under the guidance and supervision of a qualified healthcare professional. Combining these treatments can increase the risk of side effects and may not be suitable for everyone.

When it comes to human growth hormone therapy vs. testosterone for male hormone replacement therapy, the decision depends on individual needs, hormone levels, and overall health. Both treatments can offer significant benefits for those experiencing hormonal imbalances, but it's crucial to work closely with a healthcare professional to determine the most appropriate course of action. By carefully weighing the potential risks and benefits, you can make an informed decision about the best approach to addressing your hormonal health concerns.

What Causes Low-T? Why Do I Have Low Testosterone?

In this article, we will explore the potential causes of low testosterone, ranging from genetic factors to environmental influences and lifestyle choices.

Age

Testosterone levels naturally decline as men age. Studies have shown that testosterone levels decrease by approximately 1% per year after the age of 30. This gradual decline is a normal part of the aging process and may be responsible for some of the symptoms associated with "male menopause" or andropause.

Genetic Factors

Some men may have a genetic predisposition to low testosterone levels. For example, Klinefelter Syndrome, a genetic disorder affecting approximately 1 in 500-1,000 men, is characterized by the presence of an extra X chromosome and can result in low testosterone production.

Environmental Factors

Exposure to certain environmental toxins, such as pesticides and heavy metals, can disrupt hormone production and contribute to low testosterone levels. A study published in the journal Human Reproduction Update found that exposure to endocrine-disrupting chemicals (EDCs) could adversely affect male reproductive health, including reduced testosterone levels.

Drug Abuse

The abuse of certain drugs, such as opioids and anabolic steroids, can negatively impact testosterone production. Long-term opioid use has been shown to suppress the hypothalamic-pituitary-gonadal axis, leading to decreased testosterone levels. Similarly, anabolic steroid abuse can suppress the body's natural testosterone production, resulting in low testosterone levels once steroid use is discontinued.

Estrogen

Elevated estrogen levels can suppress testosterone production in men. Aromatase, an enzyme responsible for converting testosterone into estrogen, can be overactive in some individuals, leading to an imbalance in hormone levels. Certain medications, such as aromatase inhibitors, can help address this issue by reducing estrogen production and supporting healthy testosterone levels.

Diet

A poor diet, particularly one high in processed foods and low in essential nutrients, can negatively impact testosterone levels. Research has shown that diets rich in healthy fats, such as monounsaturated and polyunsaturated fats found in olive oil, nuts, and fish, can support optimal testosterone production. Additionally, ensuring adequate intake of key nutrients, such as zinc and vitamin D, is essential for maintaining healthy testosterone levels.

Weight

Carrying excess body weight, particularly in the form of visceral fat, can negatively affect testosterone levels. A study published in the journal Clinical Endocrinology found that obese men had significantly lower testosterone levels compared to their non-obese counterparts. Losing weight through a combination of healthy diet and regular exercise can help improve hormone balance and support optimal testosterone production.

Low testosterone levels can result from a variety of factors, including age, genetics, environmental exposure, drug abuse, estrogen levels, diet, and weight. Understanding these potential causes can help individuals make informed decisions about how to address their low testosterone levels and improve overall hormonal health. If you suspect you have low testosterone, it is essential to consult a healthcare professional for a proper evaluation and guidance on the most appropriate course of action.

A Testosterone Pellet Patient’s Review

I've tried it all: Gels, shots and pills. The gel was terrible. The pills will destroy your liver. The shots were OK for the first five years, but the weekly (or bi-weekly if you want to avoid the peaks and valleys) testosterone shots got old after awhile. Switching between shoulders, thighs and gluts each week felt like doing The Macarena and I still felt like a pin cushion.

That left only the pellets and, I gotta say, I was very disappointed. Had I opted for the name-brand Testopel version, things may have gone better. The ones I got from the Trader Joe's compounding pharamcy were not good at all.

The biggest problem with pellets is if it's not working for you, you'll still have to wait for them to dissolve to get another type of testosterone. That means 3-6 months of waiting. I lost muscle, got depressed and was super lethargic for a couple of months. My review of testosterone pellet therapy? It sucked.

Back to injections for me! "Heeeey Macarena!"

Sprinting to Boost Testosterone

Research has shown that short, intense workouts like sprinting can significantly impact muscle mass and hormone production, particularly when compared to long-distance running. Here we explore the science behind sprinting and testosterone production, providing you with valuable insights on how to optimize your workouts for maximum hormonal benefits.
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What to Do About High Red Blood Cell Count while on TRT

Testosterone replacement therapy can increase hemoglobin and hematocrit production beyond normal/safe levels, a condition known clinically as polycythemia. If you are on TRT it is important to be regularly tested for this condition, as it may increase the risk of thrombosis and stroke.

Hemoglobin is an iron-containing biomolecule that can bind oxygen, and is responsible for the red color of blood cells. Hematocrit levels refer to the percentage of blood volume occupied by red blood cells. The test I get is a red blood cell (RBC) count, which measures the number of red blood cells per volume of blood and includes readings for both hemoglobin and hematocrit.

How to Lower RBC while on TRT

If your RBC test results come back abnormally high, treatment options given by the doctor might involve lowering your testosterone dosage or discontinuing your hormone therapy. Personally, neither of these is an acceptable option so I opt for a third: Donating Blood. The doctor could theoretically prescribe a therapeutic phlebotomy (draining some of your blood, which would be destroyed instead of donated). However, it is not a widely adopted practice and is unlikely to be prescribed. Besides that, I'd rather my blood be donated to someone in need.

Can You Donate Blood if You Take Testosterone?
The Red Cross form you fill out will ask if you take any injectable drugs, and may even specifically mention testosterone, but the fine print says "Without a prescription" so you can answer "No" to that question. As long as you are taking doctor prescribed testosterone for hormone replacement (Not 500mg + every week like a bodybuilder) it should be OK to donate because there is only a normal amount of testosterone in the blood stream.

I donate blood to the Red Cross about once every three or four months. If they have the facilities at the donation center I'll even opt for a Double Red Blood Cell Donation, and it feels much like I'd imagine an oil change might feel to a sentient vehicle.

Click Here to find a Red Cross blood donation opportunity near you.