Tetrahydrogestrinone (THG)

July 23, 2023

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Tetrahydrogestrinone (THG), colloquially known as “The Clear,” is a synthetic and orally active anabolic-androgenic steroid (AAS). Unlike other anabolic steroids, which are typically pharmaceuticals intended for veterinary or human use, THG had neither been approved nor marketed for any clinical indication. This compound is considered a designer drug closely related to the banned anabolic steroid trenbolone and gestrinone.

THG was developed by Patrick Arnold and was used by several high-profile athletes such as Marion Jones, Barry Bonds, and Dwain Chambers. The revelation of the use of THG by these top athletes in 2003 highlighted the ethical issue confronting sports. THG is widely recognized as the first designer steroid in the sports world.

The discovery of THG confirms the existence of a network of clandestine laboratories involved in the production of prohibited steroids. Tetrahydrogestrinone was a newly discovered chemical compound that had not been synthesized, recorded, or sold by any pharmaceutical company or recognized laboratory before its discovery.

THG is essentially an oral version of the anabolic steroid Nandrolone. It has several benefits, including increased lean muscle mass and strength. In contrast to other anabolic steroids, THG also forms strong bonds with the glucocorticoid receptor. This effect may cause additional weight loss, but it is also likely to cause additional side effects such as immunosuppression that are not seen with most other steroids.

Despite its performance-enhancing effects, the use of THG carries significant risks. The effects and risks of THG use are not well understood because its synthesis is often done secretly. Known side effects include liver damage, cardiovascular issues, and changes in mood and behavior.

Several athletes have been found using THG and have faced bans from their respective sports. The discovery of THG highlights the ongoing need for vigilance and innovation in the fight against doping in sports.

Creation of THG

Patrick Arnold is a significant figure in the history of Tetrahydrogestrinone (THG). An American organic chemist and amateur bodybuilder, Arnold is known for his contributions to the world of performance-enhancing drugs. He is often referred to as the “father of prohormones” due to his role in introducing several designer drugs and compounds to the market.

One of Arnold’s most notorious creations is THG. He developed this synthetic anabolic steroid with the specific intention of evading detection from drug testers. This characteristic made THG a popular choice among athletes seeking a performance edge.

Arnold’s expertise in chemistry and his understanding of the athletic world’s demands allowed him to create a compound that could enhance performance without being detected in standard drug tests. The discovery of THG and its subsequent classification as a banned substance marked a significant turning point in the fight against doping in sports.

Structure and Synthesis of THG

Structure of THG

Tetrahydrogestrinone (THG) is a synthetic anabolic-androgenic steroid (AAS) that shares a common structural feature with all steroids: a central complex of four hexagonal carbon rings. The uniqueness of each steroid, including THG, lies in the molecular groups attached to the periphery of this central ring complex.

A comparison of the testosterone-binding domain bound to testosterone and THG reveals the unique structure of this designer steroid. THG was infamously dubbed the “undetectable” anabolic steroid due to its unique structure that allowed it to evade standard doping tests.

Synthesis of THG

The synthesis of THG is not widely documented due to its status as a designer steroid. It was developed by Patrick Arnold, a chemist known for creating performance-enhancing substances. The specific process of synthesizing THG is not publicly available, likely due to its illegal status and the ethical implications of its production and use.

Biological Activity of THG

THG binds to the androgen receptor (AR), activating AR-mediated signaling. This activation promotes myogenesis in mesenchymal multipotent cells, leading to muscle development. Thus, THG exhibits both anabolic (muscle-building) and androgenic (masculinizing) activities in vivo. This dual action makes it an attractive, albeit illegal and dangerous, substance for athletes seeking to enhance their performance.

THG in the Doping Scandal

THG gained notoriety in the 2003 BALCO doping scandal, where it was used by high-profile athletes such as Marion Jones, Barry Bonds, and Dwain Chambers. Its unique structure allowed it to go undetected in standard drug tests, leading to its nickname, “The Clear.”

Pharmacodynamics

Tetrahydrogestrinone (THG) is a highly potent drug that acts as an agonist of the androgen and progesterone receptors. This means that it binds to these receptors and activates them, leading to a variety of physiological effects.

One of the key characteristics of THG is its potency. Studies have shown that it is approximately 10 times more potent than comparison drugs such as Nandrolone or Trenbolone. This high level of potency means that even small doses of THG can have significant effects on the body.

Unlike many other steroids, THG does not have any estrogenic activity. This means that it does not lead to the development of typically female characteristics, such as breast tissue growth, which can be a side effect of some other performance-enhancing drugs.

The pharmacodynamics of THG involves its binding to the androgen receptor with a similar affinity to dihydrotestosterone, a naturally occurring hormone in the body. This binding stimulates the growth of muscle tissue, making THG a powerful tool for athletes looking to increase their strength and muscle mass.

It is important to note that the use of THG is not without risks. The drug has been linked to several health issues, including liver damage, cardiovascular problems, and changes in mood and behavior. Further to that, the use of THG is banned in most sports, and athletes found to be using the drug can face severe penalties, including suspension and loss of titles.

How THG Works

Tetrahydrogestrinone (THG) operates in a unique way that makes it a potent performance-enhancing drug. The mechanism of action of THG involves reaching the nucleus of a cell and binding to the androgen receptor at the ligand binding pocket.

Androgen receptors are proteins that respond to androgens, which are hormones that play a crucial role in male traits and reproductive activity. When THG binds to these receptors, it activates anabolic and androgenic functions.

Anabolic functions refer to the process of metabolism that builds larger molecules from smaller ones, such as the synthesis of muscle tissue. Androgenic functions, on the other hand, are responsible for developing and maintaining male characteristics.

By activating these functions, THG can enhance athletic performance by promoting muscle growth and increasing strength. But understand this too, the use of THG also comes with significant health risks, including liver damage, cardiovascular issues, and changes in mood and behavior.

Effects and Usage

Tetrahydrogestrinone (THG), also known as “The Clear,” is a synthetic and orally active anabolic-androgenic steroid (AAS) that was never marketed for medical use. It was developed by Dr. Patrick Arnold, an American organic chemist known for introducing various substances into the dietary supplement market.

THG was identified as a novel steroid used illicitly to improve athletic performance. Its structure is closely related to gestrinone, a 19-nor progestin, and resembles that of Trenbolone. Since THG was never marketed, information on its hormonal properties is not widely known.

THG has a unique quality of binding strongly with the glucocorticoid receptor, unlike other anabolic steroids. This effect may cause additional weight loss, but it is also likely to cause additional side effects such as immunosuppression that are not seen with most other steroids.

Apart from the aforementioned side effects, the use of AAS like THG may lead to withdrawal symptoms after these drugs have been discontinued. These symptoms are very similar to those observed in subjects with age-related testosterone decline, including increased fat storage and loss of muscle mass.

Effects of Tetrahydrogestrinone (THG)

Tetrahydrogestrinone (THG) is a potent and effective steroid known for its performance-enhancing properties. Its structure is closely related to gestrinone, a 19-nor progestin, and resembles that of Trenbolone. The effects of THG are not fully understood due to its illicit nature and the lack of comprehensive studies on its hormonal properties.

Performance Enhancement

The primary reason athletes use THG is its ability to enhance athletic performance. It is known to increase lean muscle mass and strength. This makes it a popular choice among athletes looking for a competitive edge, despite the severe penalties for its use.

Binding Affinity

THG has a high affinity for binding to the glucocorticoid receptor, unlike most other anabolic steroids. This effect may cause additional weight loss, but it is also likely to cause additional side effects such as immunosuppression that are not seen with most other steroids.

Androgenic and Anabolic Effects

THG was classified as a controlled substance by the U.S. Congress due to reports of abuse by elite athletes, although there is limited evidence supporting its anabolic/androgenic activity. Additional research is necessary to ascertain its binding to the androgen receptor (AR) and its potential androgenic and anabolic effects in vivo.

Side Effects

The use of THG is associated with several side effects, including liver damage, cardiovascular issues, and changes in mood and behavior. Its binding to the glucocorticoid receptor may also lead to immunosuppression.

Designer Steroids

THG is considered a designer steroid, along with Desoxymethyltestosterone and Norbolethone. These steroids have appeared either in confiscated powders or urine samples of elite athletes in recent years.

THG as a Performance-Enhancing Drug

As a powerful steroid, THG offers several benefits that make it an attractive option for those looking to enhance their athletic performance. One of the primary effects of THG is its ability to increase lean muscle mass. By promoting the growth of muscle tissue, THG can help athletes build strength and power, which can be crucial in sports that require explosive movements or sustained effort.

In addition to increasing muscle mass, THG also enhances strength. This can be particularly beneficial in sports such as weightlifting, where the ability to lift heavy weights is a key determinant of success.

Another significant benefit of THG is its ability to speed up recovery. Intense physical activity can cause muscle damage, leading to soreness and a decrease in performance. By enhancing recovery, THG allows athletes to train harder and more frequently, leading to improved performance over time.

Finally, THG reduces catabolism, the process by which the body breaks down muscle tissue for energy. By inhibiting this process, THG helps to preserve muscle mass, making it an effective tool for athletes looking to maintain their strength and physique.

Despite these benefits, it is important to note that the use of THG is not without risks. The drug has been linked to several health issues, including liver damage, cardiovascular problems, and changes in mood and behavior. The use of THG is banned in most sports, and athletes found to be using the drug can face severe penalties, including suspension and loss of titles.

Dosage of THG

THG is a powerhouse when it comes to activating the androgen and progesterone receptors, leaving comparison drugs like Nandrolone or Trenbolone in the dust with its mind-blowing potency, approximately 10 times stronger.

But do note, It has no estrogenic activity. The effective dose for men is typically between 2-5 mg/day. It is not recommended for women due to its potent effects and potential side effects. The half-life and detection time of THG are currently unknown. It is important to note that the use of THG is illegal and it has been involved in several doping scandals, such as the BALCO scandal, where it was one of the most common compounds used for doping.

The BALCO Scandal and THG

The BALCO Scandal and THG are closely intertwined. The Bay Area Laboratory Co-operative (BALCO) was an American company led by Victor Conte. Patrick Arnold, a key figure in the development of THG, provided Conte with several doping compounds, including THG. These compounds were then distributed to athletes, primarily in the US and Europe.

Physical Side Effects

Infertility

One of the most significant side effects of prolonged THG use is infertility. This can affect both men and women who use the drug. The steroid can disrupt the body’s natural hormone balance, leading to fertility issues.

Acne and Hirsutism

THG use can also lead to other steroid side effects such as acne and hirsutism. Hirsutism is a condition characterized by unwanted, male-pattern hair growth in women.

Increased Lean Muscle Mass and Strength

While these are often the desired effects of THG use, they can also be considered side effects. Increased lean muscle mass and strength can lead to an unnatural and potentially unhealthy body composition if not managed correctly.

Psychological Side Effects

Mood and Behavior Changes

As with many steroids, THG can cause changes in mood and behavior. This can include increased aggression, mood swings, and other behavioral changes. These psychological side effects can have a significant impact on a user’s quality of life and relationships.

Other Potential Side Effects

While the above side effects are some of the most commonly reported, it is important to note that the side effects of THG can vary widely between individuals. Factors such as dosage, duration of use, and individual health and genetic factors can all influence the side effects a user may experience.

Detection Methods for THG

Tetrahydrogestrinone (THG) is a designer steroid that was specifically designed to avoid detection in standard drug tests. But since the discovery, advancements in drug testing technology have made it possible to detect THG in athletes’ samples.

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

One of the primary methods for detecting THG is through Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). This technique allows for the detection of THG in low concentrations in urine, with a limit of detection (LOD) ranging from 0.5 to 5 ng/mL. The process involves reversed-phase liquid chromatography in combination with gradient elution. The mobile phases consist of aqueous solutions of formic acid (0.1%) or ammonium acetate in combination with acetonitrile or methanol.

Future Detection Methods

While LC-MS/MS is currently the most reliable method for detecting THG, research is ongoing to develop more efficient and accurate detection methods. As our understanding of THG and its metabolic processes improves, so too will our ability to detect its presence in athletes’ samples.

Challenges in THG Detection

Despite advancements in detection methods, THG remains a challenging substance to detect. Its chemical structure allows it to evade many standard drug tests, and its potency means that only small amounts are needed to enhance performance. As a designer steroid, THG is not naturally produced by the body, making it difficult to establish baseline levels for comparison.

The Importance of THG Detection

The detection of THG is crucial in maintaining the integrity of competitive sports. By ensuring that athletes are not using performance-enhancing substances like THG, sports organizations can ensure a level playing field and protect the health and safety of their athletes.

Usage by Athletes

Several high-profile athletes have been linked to the use of Tetrahydrogestrinone (THG), highlighting the extent to which this potent performance-enhancing drug has infiltrated the world of professional sports.

Marion Jones, a former world champion track and field athlete, is one of the most notable figures associated with THG. In 2007, Jones admitted to using THG before the 2000 Sydney Olympics, where she had won three gold medals. Following her admission, Jones resigned from her athletic career and was subsequently stripped of her Olympic medals.

Barry Bonds, a former professional baseball player, was also implicated in the use of THG. Bonds were linked to the Bay Area Laboratory Co-operative (BALCO), the company that distributed THG to athletes. Despite Bonds’ denial of knowingly using performance-enhancing drugs, his connection to BALCO and THG has cast a shadow over his career achievements.

Dwain Chambers, a British sprinter, is another athlete who has admitted to using THG. Chambers tested positive for the drug in 2003 and was subsequently banned from athletics for two years. His case serves as a stark reminder of the severe penalties athletes face if they are found to be using performance-enhancing drugs.

Unnamed Athletes: The U.S. Anti-Doping Agency announced in October 2003 that THG, which had been undetectable in tests, was used by several athletes. source
General Ban: The use of performance-enhancing drugs, including THG, is prohibited within the sport of athletics. Athletes found to have used such banned substances may receive a competition ban for a length of time which reflects the severity of the infraction. source

Legal Status of Using THG

The use of Tetrahydrogestrinone (THG) is not only banned in sports but is also illegal. Being caught with THG can lead to serious legal consequences. While specific laws and penalties can vary by country and state, they often include:

Arrest: Possession of THG can lead to immediate arrest.
Jail Time: Depending on the jurisdiction and the amount of the substance found in possession, jail time can be a potential consequence.
Criminal Record: Being charged with possession or distribution of THG can result in a permanent criminal record, which can affect future employment opportunities and personal rights.
Financial Penalties: Courts often impose hefty fines on those found guilty of possessing or distributing illegal substances like THG.
Probation: In some cases, individuals may be placed on probation, requiring regular check-ins with a probation officer and adherence to specific rules and regulations.
Community Service: Courts may also mandate community service as part of the penalty for THG possession or distribution.

These consequences can have long-lasting effects on an individual’s personal and professional life. The risks associated with using THG far outweigh any potential performance benefits. Please note that this information is a general overview and legal consequences can vary greatly depending on specific circumstances and jurisdictions. Always consult with a legal professional for advice about specific situations. source

Tetrahydrogestrinone (THG), is not only illegal but also considered a controlled substance by the U.S. Congress. The discovery of its use among elite athletes led to this classification, despite the lack of conclusive evidence of its anabolic/androgenic activity.

The penalties for using THG can be severe, both legally and professionally. Athletes caught using this substance can face suspensions, fines, and even lifetime bans from their respective sports. The reputational damage can be significant, affecting sponsorship deals and future career opportunities.

Alternatives to Tetrahydrogestrinone (THG)

While Tetrahydrogestrinone (THG) is known for its performance-enhancing properties, it is illegal and carries significant health risks. It is crucial to consider safer, legal alternatives for those seeking to enhance their athletic performance.

Legal Performance Enhancers

There are several legal substances that athletes can use to improve their performance. These include dietary supplements, such as protein powders and creatine, which can help increase muscle mass and strength. It is important to note that these substances should be used responsibly and in conjunction with a balanced diet and regular exercise.

Natural Methods

Natural methods of enhancing performance, such as proper nutrition, adequate sleep, and regular training, are not only legal but also beneficial for overall health. These methods can help improve endurance, strength, and speed without the risks associated with illegal substances like THG.

Medical Alternatives

In some cases, individuals may be prescribed legal medications to improve their athletic performance. These are typically used to treat specific medical conditions and should only be used under the supervision of a healthcare professional.

The Risks of Alternatives

While alternatives to THG are generally safer, they are not without risks. Dietary supplements, for example, are not regulated in the same way as prescription medications, which means their quality can vary. Overuse of these supplements can lead to health problems. It is important to use these substances responsibly and under the guidance of a healthcare professional.

Future Implications

THG and Muscle Accretion: THG is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats. This suggests potential implications for its use in muscle-building and recovery. Source
Designer Steroids and THG: Designer steroids such as THG have appeared in confiscated powders or urine samples of elite athletes in recent years. The future implications of this are significant, as it suggests an ongoing trend of illicit steroid use in professional sports. Source
Legal Consequences of THG Use: The legal consequences of THG use are severe, with athletes found using the substance facing bans from their respective sports. The future implications of this are significant, as it could deter athletes from using THG and other similar substances. Source

The future implications of Tetrahydrogestrinone (THG) are multifaceted, encompassing areas such as illicit use, health implications, research and development, regulatory challenges, and public awareness and education.

Continued Illicit Use

Despite being banned by sports authorities worldwide, THG continues to be used illicitly to enhance athletic performance. Its potent androgenic and progestin properties make it an attractive option for those seeking an unfair advantage in competitive sports. The future may see continued attempts to use THG or similar substances, leading to ongoing challenges in detection and enforcement.

Health Implications

The health implications of THG use are not fully known due to its status as a designer steroid. It is known to have potential adverse side effects, including liver damage, cardiovascular issues, and changes in mood and behavior. Future research may uncover more about the long-term health impacts of THG use.

Research and Development

As a potent androgenic steroid, THG has been found to stimulate androgen receptor-mediated, myogenic differentiation in multipotent mesenchymal cells and promote muscle accretion in male rats. This suggests potential areas for future research and development. While its use in sports is illegal, these properties could potentially be harnessed for medical or therapeutic uses under controlled conditions.

Regulatory Challenges

The development and use of THG highlight the challenges faced by regulatory bodies in detecting and controlling the use of designer steroids. As technology advances, so too do the methods used to create and detect these substances. Future efforts will likely need to focus on improving detection methods and regulatory measures to prevent the use of such substances.

Public Awareness and Education

The high-profile cases of athletes using THG underscore the need for public awareness and education about the risks and consequences of using banned substances. Future initiatives may focus on prevention through education, informing athletes and the public about the dangers of THG and similar substances.

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