Testicular Germ Cell Cancer: Rising Risks and The Role of Muscle Building Supplements


Testicular germ cell cancer (TGCC) represents the most prevalent cancer type among men aged 14-44. The incidence of TGCC has notably increased from 3.73 per 100,000 in 1975 to 6.31 per 100,000 in 2017. While genetic predispositions, such as a family history of testicular cancer or conditions like cryptorchidism, significantly elevate the risk, these factors alone do not account for the rising rates. Increasing evidence suggests that environmental exposures, particularly during adolescence, may contribute to this rise through mechanisms involving hormone disruption and genetic susceptibility alterations.

The burgeoning use of dietary supplements for muscle building, driven by both athletic performance aspirations and societal pressures for an idealized muscular physique, is a growing public health concern. A study found that 87.5% of elite athletes, who train in various sports at state-based institutes, consume dietary supplements. The global dietary supplement industry was valued at $123.28 billion in 2019 and continues to expand. The intersection of this industry with potential health risks, including TGCC, necessitates a thorough examination of muscle building supplements (MBS) and their components.

Health Risks of Muscle Building Supplements

While short-term outcomes of MBS use have been widely studied, the long-term health risks, including carcinogenic potential, are less understood. Notably, about 20% of TGCC patients were reported to be using performance-enhancing substances at the time of their diagnosis. A case-control study involving TGCC patients from Connecticut and Massachusetts identified MBS use as a significant risk factor, particularly for those who began using these supplements before age 25.

Classifying dietary supplements specifically for muscle building poses challenges due to the multipurpose nature of many products, which often include ingredients for energy enhancement, muscle building, and weight loss. Multi-ingredient pre-workout supplements (MIPS) have gained popularity and frequently contain banned substances.

The FDA defines dietary supplements as products taken orally containing dietary ingredients. However, the distinction between anabolic androgenic steroids (AAS) and MBS is blurred, especially since some MBS are adulterated with AAS. Studies have focused on products ingested orally, yet the inclusion of substances like androstenedione, which is not a dietary ingredient but an anabolic steroid, complicates the categorization. Androstenedione, initially considered a dietary supplement, was reclassified as an anabolic steroid in 2004. This reclassification highlights the evolving nature of supplement regulation and the potential for contaminants within MBS.

Regulatory Challenges and Contaminants

The FDA does not regulate dietary supplements for safety before they hit the market, creating a significant gap in oversight. The vast and rapidly growing industry makes it impractical to test a substantial proportion of available products. Harmful ingredients found in MBS range from impurities and prohormones to banned substances and pharmaceuticals. Some supplements are intentionally tainted with compounds not listed on the label to enhance their effects, while others contain environmental contaminants like bisphenol A (BPA) and lead.

A critical review of commonly used supplements among NCAA male athletes revealed that products such as protein, creatine, amino acids, energy boosters, diuretics, and weight loss supplements are prevalent. While pure creatine is generally regarded as safe, and no definitive studies link protein supplementation to carcinogenic effects, other ingredients and contaminants pose significant risks. Androstenedione, categorized as a schedule III-controlled substance, has shown potential for testicular atrophy and carcinogenic effects.

Potential Risks from MBS Ingredients

Various ingredients and contaminants in MBS have been identified as potential risks for carcinogenic effects, hormone disruption, or testicular damage. For instance, lorcaserin and phenolphthalein, found in weight loss and bodybuilding supplements, carry carcinogenic warnings from the FDA. Environmental contaminants like BPA, lead, cadmium, and arsenic have been detected in protein powders and other supplements, with BPA specifically linked to testicular tumorigenesis in mice. Heavy metals like cadmium and lead are known endocrine disruptors and have shown to cause testicular injury and hormonal imbalances in animal studies.

Prohormones and anabolic steroids, including nandrolone and stanozolol, have been found in MBS, with studies indicating their role in enhancing testicular Leydig cell proliferation and increasing tumor development risk. The International Agency for Research on Cancer (IARC) lists these substances as probable carcinogens concerning hormone-related cancers.

Selective androgen receptor modulators (SARMs) are another class of compounds found in bodybuilding products, designed to have anabolic effects in specific tissues like muscle and bone. However, the FDA has raised concerns about their safety, including the potential for heart attacks, strokes, and liver damage.

Environmental Contaminants in Supplements

The lack of pre-market regulation by the FDA means that much of the data on environmental contaminants in supplements comes from private entities like Labdoor, Consumerlabs, and The Clean Label Project. Heavy metals, including cadmium and lead, have been frequently detected in MBS. Cadmium, an endocrine disruptor, can cause testicular injury at low exposure levels, though direct links to TGCC in humans are not well-established. Lead, classified by the IARC as a probable carcinogen, has been linked to hormonal effects and testicular damage.

The presence of contaminants like BPA, lead, cadmium, and arsenic in MBS raises significant concerns about their potential health impacts. The combined use of MBS and anabolic steroids further complicates the risk assessment, as many MBS are adulterated with these substances, which have known carcinogenic potential.

Investigating the Risks and Future Research

The association between MBS use and TGCC warrants further investigation through population-based studies to confirm the observed correlations. Future research should account for the variability in supplement use, including changes in brands, types, and dosages. Detailed assessments of multiple substance use, especially at younger ages, are crucial to understanding the risks.

Toxicological studies on the health effects of MBS ingredients and contaminants are necessary to elucidate their potential risks. Such studies will aid in monitoring and regulating MBS ingredients, minimizing exposure to carcinogenic compounds.

Public Health Implications

The increasing use of MBS among athletes and adolescents poses a significant public health concern. These supplements often contain harmful ingredients, including those with carcinogenic potential. Chemical exposures from MBS can disrupt hormone pathways, potentially contributing to testicular cancers.

Enhanced regulatory oversight by the FDA, including regular testing of products, is essential to address the issues of adulteration and contamination in the supplement industry. Educating the public, particularly teenagers, about the risks associated with MBS use and making these products less accessible to younger individuals can help mitigate the potential health impacts.

In conclusion, the rise in TGCC incidence and the widespread use of MBS necessitate comprehensive research and regulatory measures to protect public health. Understanding the intricate relationships between genetic factors, environmental exposures, and supplement use is crucial in developing effective prevention and intervention strategies for testicular cancer.

AspectDetailNumerical DataAdditional NotesReferences
PrevalenceTesticular Cancer (TC)1% of male neoplasmsMost common among young males, prevalence increasing globally[1, 2, 3]
Common TumorSolid Malignant TumorHigh cure ratesTC common in young age, long-term effects of disease and treatment[4, 5]
Survival Rate5-year survival rate>95%Due to cisplatin-derived chemotherapy introduced in the 1970s[6]
Age FactorDiagnosis before age 40Additional 40-50 years lifespan post-treatmentEarly detection crucial[7]
Long-term EffectsDelayed repercussionsSubsequent malignant neoplasms, cardiovascular ailments, pulmonary, kidney, nervous toxicities, reduced fertility, hypogonadism, psychosocial problemsFrequency and duration vary by treatment type and severity[6, 7]
Early ManifestationsMass/enlargement in testesNot recommended for regular screening in asymptomatic individualsTesticular self-examinations advocated by American Cancer Society and American Urological Association[6, 8]
SymptomsDiscomfort, piercing sensation, twinge in abdomen/scrotum, heaviness, rigidity, gynecomastia, lumbagoSymptoms indicating possible metastasisDyspnea, hemoptysis, lumps in cervical region[9, 10, 11]
MetastasisInfrequent to other organsMainly pulmonary systemSymptoms if metastasized: dyspnea, hemoptysis, cervical lumps[5, 11]
SyndromeTesticular Dysgenesis Syndrome (TDS)Cryptorchidism, hypospadias, suboptimal semen qualityLinked to TC[5, 11]
Risk FactorsCryptorchidism, inguinal hernias, Klinefelter syndrome, mumps orchitis, early male characteristics, cannabis consumptionMultifactorial causesPhysical activity reduces risk; sedentary lifestyle increases risk[12, 13, 14, 15, 16]
HistopathologyGerm Cell Tumors (GCTs)>95% of casesNon-seminoma more prevalent in third decade; seminoma in fourth decade[17, 18, 19]
DiagnosisBlood examinations, histopathological scrutinyRadical inguinal orchiectomyEnsures localized tumor management and comprehensive assessment[2, 20]
EpidemiologyCommon in Western and Northern Europe8.7 and 7.2 per 100,000 malesHigh cure rates due to early detection and multi-modal therapy[21, 22, 23, 24]
Ethnicity CorrelationSignificant disparityHigher in white individualsLower in black individuals in the US and southern England[17]
Prenatal CausesEnvironmental exposures, pregnancy hormone levelsBirth cohort effectsImpacts germ cell maturation, leading to CIS and TC[25, 26, 27, 28]
Inherited SusceptibilityFamilial studiesMale siblings: 8-fold risk, Fathers/sons: 4-fold riskRecessive inheritance with 43% penetrance in homozygous individuals[29, 30, 31, 32, 33]
Prenatal and Perinatal FactorsGenetic vs. environmental exposureLow birth weight as a risk indicatorPotential link to maternal smoking and DES exposure[44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60]
Postnatal FactorsEarly puberty, subfertilityEnvironmental elements during pubertyPotential risk factors: milk consumption, EDCs, cadmium, mercury, cobalt exposure[64, 65, 66, 67, 68, 69, 70]
CryptorchidismSignificant risk factor2-8 fold increased risk of TCEarly surgical intervention suggested for prevention[62, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86]
SubfertilityCorrelation with TCShared susceptibility and risk factorsGenetic predispositions, environmental estrogens, EES exposure[87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97]
BiomarkersAFP, HCG, LDH, HMGA1/2, PLAP, NANOG, OCT3/4, SALL4, SOX proteins, MicroRNA-371a-3p, CDK10Used for diagnosis, prognosis, and surveillanceSpecificity and sensitivity vary; ongoing research to enhance detection and prognosis[98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125]
TreatmentRadical inguinal orchiectomy, testis-sparing surgery, chemotherapy, RPLND, radiation therapyBased on histology, stage, prognosisCisplatin-derived chemotherapy; ongoing trials for surgery efficacy in early metastatic seminoma[126, 127, 128, 129, 130, 131, 132, 133]

reference link :

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834066/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10953835/


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