274 - Performance-enhancing drugs and hormones—risks, rewards, & broader implications for the public
Peter Attia MDKey Moments
A deep dive into performance-enhancing drugs, growth hormone, testosterone, androgens, and SARMs, outlining risks, rewards, and implications.
Key Insights
Growth Hormone (GH) is often perceived as an anti-aging elixir, but its effectiveness outside of medical deficiencies is limited, and its use can lead to side effects like insulin resistance and increased risk of tumor propagation.
The bodybuilding community extensively uses performance-enhancing drugs (PEDs), including anabolic steroids, GH, and insulin, at supraphysiological doses to achieve extreme physiques, often prioritizing muscle growth over long-term health.
Underground labs and compounding pharmacies are major sources of these drugs, lacking stringent quality control and posing significant health risks due to non-sterile manufacturing and unknown purity.
Testosterone Replacement Therapy (TRT) is generally justified for primary hypogonadism, but optimizing dosing frequency (e.g., twice weekly injections) can reduce side effects, such as excessive estrogen conversion and hematopoiesis.
Estrogen is crucial for men's cardiovascular, neurological, and bone health; arbitrarily suppressing it with aromatase inhibitors based on reference ranges is an outdated and potentially harmful practice.
Selective Androgen Receptor Modulators (SARMs) and peptides offer more targeted anabolic effects with fewer androgenic side effects than traditional steroids, but their long-term safety and efficacy are still under investigation.
DEREK'S FORAY INTO BODYBUILDING AND PHARMACOLOGY
Derek, a fitness educator and entrepreneur, developed an intense interest in hormones and pharmacology during high school after getting into weightlifting. Motivated by the desire to understand the extreme physiques of bodybuilders, he delved into forums and early scientific literature. This led to personal experimentation with anabolic steroids, which, while achieving significant muscle mass (up to 260+ pounds), also resulted in severe side effects like sleep apnea and androgen-induced hair loss. His early experiences highlighted the lack of scientific understanding and reliance on anecdotal 'bro rules' within the bodybuilding community regarding drug use and side effect management.
GROWTH HORMONE: MYTHS, MECHANISMS, AND MEDICAL USES
Growth hormone (GH) is often touted as a 'fountain of youth,' with proponents suggesting its use to combat age-related decline. However, its primary physiological role is in childhood growth and development. In adulthood, GH’s importance diminishes, and exogenous use to boost height or as an anti-aging agent beyond treating deficiencies is largely unproven and potentially risky. GH primarily mobilizes free fatty acids, making it lipolytic, and its effect on muscle growth is modest and often conflated with fluid retention. IGF-1, produced in the liver in response to GH, serves as the most reliable proxy for measuring GH activity, as GH itself is pulsatile.
GH RISKS, REJUVENATION, AND ADMINISTRATION
The use of GH carries significant risks, particularly when administered chronically or at supraphysiological doses. While it's used medically for burn victims to aid tissue repair, its application in orthopedic injuries is largely anecdotal. Chronic use can lead to insulin resistance, potentially inducing diabetes, and may propagate existing tumors due to its growth-promoting properties. The idea of GH as a longevity elixir is often driven by financial incentives, lacking robust evidence. Some individuals use GH to improve body composition and sleep quality, but high doses can cause lethargy. Interestingly, the pituitary often recovers its ability to produce GH after cessation, unlike the testes' response to exogenous testosterone.
THE EVOLVING LANDSCAPE OF BODYBUILDING PHYSIQUES AND DRUG USE
The dramatic increase in muscle mass seen in bodybuilders from the 1970s to today is primarily attributed to advanced drug use, followed by nutrition and training. Early bodybuilders used relatively conservative doses of testosterone, but contemporary athletes employ supraphysiological amounts of anabolic steroids, often combined with GH and insulin. This 'polypharmacy' can lead to profound physiological changes, including significant organ growth, particularly of the heart, which is evident in autopsies of bodybuilders who died young. The 'GH gut' or distended abdomen seen in some bodybuilders is hypothesized to be a multifactorial issue, stemming from excessive food intake and gastrointestinal issues, rather than solely organomegaly.
TESTOSTERONE AND ANDROGEN PHYSIOLOGY
The body's complex hypothalamic-pituitary-gonadal (HPG) axis regulates testosterone production. The hypothalamus releases GnRH, stimulating the pituitary to produce LH and FSH, which act on the testes to produce testosterone and support spermatogenesis. Testosterone's fate involves conversion to DHT (a potent androgen) via 5-alpha reductase and estradiol (estrogen) via aromatase, both critical for various bodily functions. DHT is essential for male sexual differentiation and maturation, while estradiol plays a vital role in cardiovascular, neurological, and bone health. Maintaining a balance between these hormones is crucial, and arbitrary suppression of estrogen can lead to detrimental health outcomes.
TESTOSTERONE REPLACEMENT THERAPY (TRT) AND OPTIMIZATION
TRT is most justified for primary hypogonadism, where the testes fail to respond to pituitary signals. For individuals with low testosterone due to lifestyle factors (e.g., poor sleep, high glucocorticoids), addressing these underlying issues is paramount. For those requiring TRT, a starting dose of 80-120mg per week of testosterone cypionate is common. Optimizing injection frequency to twice weekly or even daily is crucial to maintain stable hormone levels, minimize side effects like excess estrogen conversion, and reduce hematopoiesis. This approach better mimics natural physiological pulsatility compared to less frequent, higher-dose injections, which can cause significant hormonal spikes and troughs.
AROMATASE INHIBITORS: RECONSIDERING ESTROGEN SUPPRESSION
Historically, there was a misconception that minimizing estrogen in men on TRT was beneficial, leading to widespread use of aromatase inhibitors (AIs). However, research indicates that estrogen is vital for male health, including mood, libido, bone density, and cardioprotection. Aggressive estrogen suppression can be detrimental, causing neurotoxicity and negatively impacting overall well-being. A balanced approach that allows for adequate estrogen levels, typically achieved through optimized testosterone dosing, is generally preferred. Some synthetic anabolic steroids can also compete for aromatase, lowering estrogen naturally without the need for AIs.
HAIR LOSS AND 5-ALPHA REDUCTASE INHIBITORS
Derek’s experience with androgen-induced hair loss led him to use 5-alpha reductase inhibitors (5-ARIs) like finasteride and dutasteride, which reduce DHT production. While effective for hair loss, these drugs have potential side effects, including sexual dysfunction and mood changes, with reversibility debated. The choice to use 5-ARIs needs careful consideration, weighing the cosmetic benefits against the risks to endocrine function. There's ongoing research into topical anti-androgens that aim to provide localized benefits without systemic side effects, offering a potentially safer alternative for hair loss management.
THE DIVERSITY OF ANABOLIC STEROIDS AND SARMs
Beyond testosterone, a wide array of synthetic anabolic steroids exists, often derived from testosterone or DHT, designed to maximize anabolic effects while minimizing androgenic properties. Examples include Dianabol, Boldenone, Primobolan, and Oxandrolone. These compounds are extensively used by bodybuilders, often in combinations tailored to specific goals (e.g., bulking vs. cutting). Selective Androgen Receptor Modulators (SARMs) represent a newer class of compounds, designed to selectively bind to androgen receptors in target tissues, offering more anabolic activity with fewer androgenic side effects than traditional steroids, though their long-term impacts are not fully understood.
CLOMID AND HCG: FERTILITY MAINTENANCE AND HPG AXIS MANIPULATION
Human Chorionic Gonadotropin (HCG) mimics LH, stimulating testicular testosterone production and preserving testicular function during exogenous testosterone use, crucial for maintaining fertility. Clomid, a Selective Estrogen Receptor Modulator (SERM), blocks estrogen receptors in the hypothalamus, tricking the brain into increasing LH and FSH production, thus boosting natural testosterone synthesis. While effective for fertility and testosterone elevation, Clomid can have mood-related side effects and its mechanism of action (central estrogen inhibition) may not be as physiologically optimal as direct testosterone replacement or HCG. The choice between these depends on individual goals, particularly fertility.
PEPTIDES: BPC-157
BPC-157, a peptide naturally found in the gut, is known for its angiogenic (blood vessel growth-promoting) properties and is often used anecdotally for injury recovery. While it shows promise in healing minor injuries, particularly those with low blood flow, concerns exist regarding its potential to promote cancer growth due to its pro-angiogenic effects. Its efficacy and optimal administration method (local vs. systemic injection) are not definitively established, and robust scientific studies are lacking, making its widespread proactive use a potential risk without clear benefit.
Mentioned in This Episode
●Supplements
●Products
●Tools
●Companies
●Organizations
●Concepts
●People Referenced
Common Questions
Derek's interest began in high school when he started lifting weights and noticed the extreme physiques of bodybuilders. He then experienced hair loss from recreational androgen use, prompting him to research anti-androgens and 5-alpha reductase inhibitors, which led to a broad understanding of pharma.
Topics
Mentioned in this video
A GHRP peptide with significant impact on hunger, considered by Derek as one of the 'worst' for appetite stimulation. Used by bodybuilders to force food intake.
A PP delta agonist, initially showed good results for lipid management and acts as an 'exercise mimetic', but was cancelled after rodent studies showed it caused cancer at every dose.
A famous and influential bodybuilder who died in his 40s with a 660-gram heart, illustrating the cardiac risks of extreme bodybuilding.
An experimental topical anti-androgen used by Derek for hair loss, not FDA approved but with new alternatives emerging with better safety data.
A refined DHT derivative, considered a pure protein accretion compound with less burdensome androgenic profile, often skewing towards anabolic activity.
A GHRP peptide, grouped with GHRP-6, known for its impactful effects on hunger.
A company that had LGD-4033 (ligandrol) in a phase two trial for hip fracture patients under the code name VK5211.
A testosterone derivative, commonly used in bodybuilding and historically for horses, but never had human use.
Still used to interact with SHBG, noted as one of the most potent drugs for this purpose.
A 30-year-old German social media influencer and fitness model who died suddenly, raising questions about health monitoring and potential contributing factors like the COVID-19 vaccine.
A type of heparin injection, used by Peter Attia for DVT prevention during flights until an adverse injection experience.
A well-known SARM that has not achieved FDA approval but is used by women bodybuilders to bridge between natural and steroid use without virilization.
Informal and unregulated facilities that produce and distribute anabolic steroids, often with questionable sterility and quality control.
A genetic condition characterized by uncontrolled eating, used as an analogy to describe the appetite-stimulating effects of some GHRPs.
A bodybuilder who has publicly discussed his drug use, with his accounts varying over time.
A topical treatment for hair loss, generally considered safer and more predictable than oral minoxidil.
Drugs like Arimidex used to reduce estrogen conversion from testosterone, often used preventative in bodybuilding but with potential negative health consequences.
The university where Derek pursued an undergraduate business degree.
A peptide produced endogenously in the gut, noted for angiogenic properties useful for injury healing, but with concerns about cancer cell proliferation if used proactively.
Derek's hometown, where he was born and raised.
An orally bioavailable GHRP (peptide) known for significantly increasing hunger and IGF-1 levels. Used off-label for GH deficient children.
A GHRH peptide, often combined with a DAC (drug affinity complex) to extend its half-life.
A former high-level IFBB Pro bodybuilder, noted for reversing gut distension by reducing food intake, suggesting food volume's role in the condition.
An early synthetic testosterone derivative, known as 'the breakfast of champions' and for its water-retentive properties.
Compounds designed to be tissue-specific, aiming for pure anabolic activity with minimal androgenic effects, but with a lower ceiling for muscle gain.
Discussed as a 'fountain of youth elixir' used by pro athletes, but also noted for being cost-prohibitive. Derek used it in his bodybuilding past.
An anabolic steroid used by bodybuilders, noted for water retention and its historical prescription for muscle wasting.
A compounded form of methylprednisolone which, when administered from a contaminated batch, caused a fungal meningitis outbreak killing hundreds.
A bodybuilder mentioned as having used thousands of milligrams of drugs, exemplifying extreme drug use.
A 'mass monster' IFBB Pro bodybuilder who died with an 860-gram heart, further exemplifying the extreme organ enlargement seen in the sport.
A compound developed by Kintor, noted as a promising topical anti-androgen for hair loss with good safety data.
A commonly used SARM, also known as VK5211, currently in phase two trials for hip fracture patients.
A blood test for cancer screening, mentioned by Peter Attia in the context of his patient's cancer screening before using simorelin.
A drug used for hair growth, noted for its effectiveness but potential side effects and unpredictable dosing.
An anabolic steroid with aggressive dosing known for virilization, discussed in the context of historical protocols.
A lab mentioned for using an enzyme-based system prone to overestimating estradiol levels.
A more selective stereoisomer of Clomid, aimed at acting as a pure estrogen receptor antagonist in the hypothalamus with fewer side effects, but not FDA approved.
A refined anabolic steroid, highly prized among athletes for its anabolic properties without significant androgenic side effects, and ability to lower SHBG.
Compounds like Clomid and Tamoxifen that interact tissue-specifically with estrogen receptors, serving as the conceptual basis for SARMs.
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