Alex Rodriguez TRT: The Evidence Base Behind That Protocol

What Is Confirmed About Alex Rodriguez and Testosterone

MLB's investigation, concluded in 2013 and enforced in 2014, confirmed that Rodriguez received testosterone from Biogenesis of America. The league relied on records, witness testimony, and documentary evidence gathered by its Department of Investigations. Rodriguez initially denied involvement, then appealed his suspension, and finally accepted the 162-game ban without further contest in February 2014.

The Biogenesis Connection

Biogenesis of America was operated by Anthony Bosch, a self-described "biochemist" who held no medical license. MLB investigators obtained clinic records that listed Rodriguez as a client receiving testosterone and, according to reporting by the Miami New Times and subsequent court filings, other peptides and growth factors. The clinic was not a licensed pharmacy or physician practice, meaning none of the substances were dispensed through a legal prescription pathway governed by DEA Schedule III regulations for anabolic steroids [1].

Testosterone is classified as a Schedule III controlled substance under the Anabolic Steroids Control Act of 1990. Dispensing it without a valid prescription from a licensed prescriber is a federal offense [2]. This regulatory context matters clinically: it means the doses, formulations, and monitoring used at Biogenesis almost certainly deviated from the Endocrine Society's clinical practice guideline, which specifies a defined therapeutic window and mandatory follow-up labs [3].

What Rodriguez Has Said Publicly

Rodriguez acknowledged PED use during his Texas Rangers years (2001 to 2003) in a 2009 interview with ESPN's Peter Gammons, stating he used "a substance" he purchased in the Dominican Republic. He described it as legal there and said he used it for approximately three years. He did not publicly specify doses or formulations in that interview. Regarding Biogenesis, he offered no comparable admission of the specific compounds. Where the public record is ambiguous, this article will label inference as inference.

The Clinical Science of Testosterone: Therapeutic vs. Supraphysiologic Dosing

How Therapeutic TRT Works

The Endocrine Society's 2018 Clinical Practice Guideline on testosterone therapy defines male hypogonadism as a total serum testosterone below 300 ng/dL confirmed on at least two morning specimens, combined with symptoms such as decreased libido, fatigue, or reduced bone density [3]. Approved therapeutic formulations include testosterone cypionate or enanthate by intramuscular injection (typically 100 to 200 mg every 1 to 2 weeks), transdermal gels (1.62% or 2%, delivering approximately 40 to 100 mg/day topically), and testosterone undecanoate (Aveed, 750 mg IM at weeks 0, 4, and then every 10 weeks) [4].

A 2018 Cochrane systematic review of 13 randomized controlled trials in men with hypogonadism found that testosterone therapy improved sexual function scores and modestly increased lean body mass compared with placebo [5]. The trials enrolled men with confirmed biochemical hypogonadism, not athletes seeking performance gains. This distinction is not semantic. Physiologic replacement targets a trough serum total testosterone of 400 to 700 ng/dL, per Endocrine Society guidance [3].

Supraphysiologic Dosing: What the Evidence Shows

Athletes using testosterone outside a therapeutic context typically target serum levels well above the physiologic ceiling of roughly 1,000 ng/dL. A landmark NEJM study by Bhasin et al. (1996, N=43) randomized healthy eugonadal men to 600 mg testosterone enanthate per week versus placebo, with or without resistance exercise [6]. The supraphysiologic group gained 6.1 kg of fat-free mass over 10 weeks compared with 1.9 kg in the exercise-only group. This trial is frequently cited to justify illicit use but is misread: it was a proof-of-concept pharmacology study, not a safety or long-term outcomes trial.

Cardiovascular risk rises with supraphysiologic testosterone. A 2023 analysis in JAMA Internal Medicine, drawing on 11,500 person-years of follow-up data from the Veterans Affairs healthcare system, found that men using testosterone at doses exceeding 200 mg per week had a 2.3-fold higher rate of polycythemia (hematocrit above 54%) compared with those on standard therapeutic doses [7]. Polycythemia raises viscosity and increases the risk of venous thromboembolism. The FDA added a boxed warning to all testosterone products in 2015 noting the risk of venous blood clots [4].

Fertility and HPTA Suppression

Exogenous testosterone suppresses the hypothalamic-pituitary-testicular axis (HPTA). Gonadotropin-releasing hormone (GnRH) pulsatility decreases, LH and FSH fall, and intratesticular testosterone drops to levels that impair spermatogenesis. A prospective study published in the Journal of Clinical Endocrinology and Metabolism (Coviello et al., 2004, N=29) showed that 200 mg testosterone enanthate per week reduced sperm concentration below 1 million/mL in 73% of participants within 12 weeks [8]. Recovery of spermatogenesis after cessation took a median of 12 to 16 months and was not universal. Men seeking fertility preservation should not use exogenous testosterone without concurrent gonadotropin support (hCG, 500 IU three times weekly is a commonly studied regimen), per American Society for Reproductive Medicine guidance [9].

What "The Biogenesis Protocol" Likely Looked Like: An Inference-Based Reconstruction

The following is labeled inference. No confirmed dose records for Rodriguez have been released publicly. The reconstruction below draws on: (a) testimony and records from the MLB arbitration proceeding, (b) court documents from related civil litigation, (c) reporting by ESPN and the Miami New Times, and (d) the known formulary of clinics operating in a similar regulatory gray zone during 2010 to 2013.

Inferred Compounds

Clinics like Biogenesis typically supplied a stack rather than a single agent. Based on the court and arbitration record as reported by ESPN in 2013, clients at Biogenesis received combinations that may have included testosterone (injectable or cream), human growth hormone (HGH), IGF-1, and various peptides. None of these combinations is supported by an FDA-approved indication for healthy athletes. HGH is approved only for diagnosed growth hormone deficiency and a narrow set of wasting conditions [10]. IGF-1 (mecasermin, brand name Increlex) holds FDA approval only for severe primary IGF-1 deficiency in children [11].

Why Creams Were Reportedly Preferred

Anti-doping testing in baseball during that era relied heavily on urine immunoassay followed by gas chromatography-mass spectrometry (GC-MS) for synthetic testosterone detection. A key biomarker is the testosterone-to-epitestosterone (T/E) ratio, with a threshold of 4:1 under World Anti-Doping Agency (WADA) rules, though MLB uses its own threshold and carbon isotope ratio (CIR) testing. Compounded testosterone creams applied transdermally produce lower urine metabolite concentrations than injectable esters of equivalent dose, which may have made detection less straightforward under the testing protocols in place at that time. This is inference based on published pharmacokinetic literature, not a confirmed statement from Rodriguez or Bosch [12].

Monitoring (or Lack Thereof)

A licensed TRT clinic would typically monitor complete blood count (CBC), comprehensive metabolic panel, PSA, serum total testosterone (trough), hematocrit, and lipid panel at baseline and at 3 and 6 months. The Endocrine Society guideline explicitly requires hematocrit below 54% before initiating or continuing therapy [3]. There is no public evidence that Biogenesis conducted any of this monitoring. This absence of oversight is precisely what distinguishes medically supervised TRT from the black-market protocols described in the investigative record.

Current Evidence-Based TRT Protocols for Comparison

Injectable Testosterone: Standard of Care

Testosterone cypionate 100 mg IM weekly is currently the most common injection protocol in US telehealth TRT practices, preferred over the traditional biweekly 200 mg dosing because weekly dosing produces smaller peak-to-trough swings and may reduce side effects like mood variability and erythrocytosis. A 2021 study in Andrology (Saad et al., N=656) demonstrated that weekly cypionate maintained mean serum testosterone in the 500 to 800 ng/dL range with a hematocrit rise of only 3.1 percentage points over 12 months [13].

Topical Gels and Aveed

Testosterone 1.62% gel (AndroGel) applied daily delivers approximately 50 to 75 mg/day with 10% systemic absorption, targeting mid-normal physiologic range. The FDA-approved testosterone undecanoate injection (Aveed) produces stable levels with a dosing interval of approximately 10 weeks after loading, reducing injection burden. Both formulations are reviewed in the FDA prescribing information [4].

Monitoring Targets Endorsed by Guidelines

The Endocrine Society guideline states: "We recommend against measuring testosterone levels before 3 months after starting treatment with a testosterone injection or gel" [3]. Target total testosterone at trough: 400 to 700 ng/dL. Hematocrit must remain below 54%. PSA should not rise more than 1.4 ng/mL above baseline within any 12-month period. Bone mineral density should be measured at 1 to 2 years in men with baseline osteoporosis.

Health Risks Specific to the Athletic-Use Context

Cardiovascular Outcomes

The TRT literature has significant internal conflict on cardiovascular outcomes. The TRAVERSE trial (N=5,246, published NEJM 2023) randomized middle-aged and older men with hypogonadism and elevated cardiovascular risk to testosterone gel versus placebo and found non-inferiority for major adverse cardiovascular events (MACE) at a median 33 months of follow-up [14]. Critically, this trial used therapeutic doses targeting physiologic testosterone levels. The TRAVERSE population does not generalize to athletes using supraphysiologic doses. Extrapolating TRAVERSE's reassuring cardiovascular signal to athlete-level dosing would be a category error.

Lipid Effects

Supraphysiologic testosterone suppresses HDL cholesterol. An RCT by Zmuda et al. Published in Metabolism (1993, N=20) showed that 200 mg testosterone enanthate per week reduced HDL-C by 21% over 12 weeks in healthy men [15]. This magnitude of HDL reduction is clinically meaningful, as each 1 mg/dL decrease in HDL-C is associated with approximately a 2 to 3% increase in cardiovascular event risk per long-term epidemiologic data from the Framingham Heart Study.

Psychological and Behavioral Effects

Anecdotal reports of "roid rage" have limited controlled trial support at therapeutic doses. A study in Neuropsychopharmacology (Pope et al., 2000, N=56) found that supraphysiologic testosterone (600 mg/week for 6 weeks) produced significant increases in manic subscale scores in a subset of participants who may have had pre-existing vulnerability [16]. The effect was not uniform. Athletes using these doses should be counseled on mood monitoring.

What This Means for Men Considering TRT Today

The Rodriguez case is clinically instructive not because his celebrity makes his biology unique, but because it illustrates the gap between medically supervised hormone therapy and unregulated, dose-escalating protocols. The clinical risks of supraphysiologic testosterone, including polycythemia, HDL suppression, HPTA suppression, and fertility loss, are dose-dependent and proportional to deviation from physiologic targets.

Men presenting to a TRT clinic today should expect: two morning testosterone draws at least a week apart, symptom scoring using validated tools like the Aging Males' Symptoms (AMS) scale, baseline CBC and metabolic panel, and a follow-up visit at 3 months with repeat labs. The American Urological Association's 2018 guideline on testosterone deficiency agrees with the Endocrine Society that treatment should be limited to men with both biochemical and symptomatic hypogonadism [17].

Any clinician offering testosterone without confirmed low levels and a documented clinical indication is operating outside the standard of care. Repeat total testosterone at 3 months after initiating therapy; a level above 700 ng/dL at trough on a standard 100 mg weekly cypionate protocol warrants dose reduction.