Who Needs Testosterone, and Who's Not Getting It I Signal Episode 4

Episode Overview

• Physicians Dr. Jordan Feigenbaum and Dr. Austin Baraki examine the clinical reality of testosterone replacement therapy (TRT), exploring who genuinely needs treatment, who is being sold inappropriate prescriptions, and why the medical system simultaneously overtreats and undertreats men.
• The narrative progresses from proper diagnostic workups and the history of the "Low T" pharmaceutical market to randomized controlled trial data showing how men with "low-normal" testosterone actually respond to treatment.
• The discussion concludes with an evidence-based breakdown of real-world dosing protocols, high discontinuation rates, and the physiological risks and nuances concerning fertility, cardiovascular health, prostate cancer, and elevated blood counts.
• This episode is essential for men considering TRT, patients currently navigating wellness clinics, and clinicians seeking to separate evidence-based endocrinology from commercial optimization pitches (both hosts disclose financial ties to Barbell Medicine, which sells coaching, training programs, a testosterone course, and their co-authored book on testosterone, Signal).

Key Concepts

• Testosterone as a Biological Output, Not an Input: Lowered testosterone is frequently a downstream readout of broader health issues rather than an isolated disease. In secondary testosterone deficiency—the most common modern pattern—the testes are functional, but the brain/pituitary reduces signaling (LH and FSH) due to reversible upstream factors like visceral adiposity (obesity), obstructive sleep apnea, opioid use, or prior anabolic steroid use. Primary deficiency occurs when the testes themselves fail due to genetics, structural issues, or chemotherapy.
• Total vs. Free Testosterone and the SHBG Trap: Total testosterone measures both biologically active (free) hormone and inactive hormone bound to Steroid Hormone Binding Globulin (SHBG). Because obesity, insulin resistance, and metabolic syndrome suppress SHBG, a patient's total testosterone can appear artificially low (e.g., 240 ng/dL) while their usable free testosterone remains completely normal.
• The Paradox of Simultaneous Overtreatment and Undertreatment: While US testosterone prescriptions have at least quadrupled over the last 20 years—driving overall population testosterone averages up over the last decade—treatment is severely misdirected. The Hypogonadism in Males (HIM) study found that while nearly 40% of middle-aged men in primary care had total levels below 300 ng/dL, requiring matching clinical symptoms drops true deficiency prevalence to 2% to 6%. Yet 25% of men prescribed TRT had no baseline blood test in the prior year, 19.5% of tested recipients did not meet clinical criteria, and only 3% in a VA study received a full recommended workup. Conversely, only 1 in 10 genuinely deficient men in the HIM study received treatment, leaving high-risk groups (such as patients with HIV/AIDS, chronic inflammatory diseases, or chronic opioid use, who can present with total levels of literally 0) largely ignored.
• Efficacy in "Low-Normal" Men (The Sydney Crossover Trial): Raising testosterone in symptomatic men without organic pathology does not reliably resolve their complaints. In a 6-week randomized, double-blind, placebo-controlled crossover study of 45 men over age 40 with symptoms like fatigue and low libido and baseline levels averaging ~310 ng/dL, topical testosterone raised levels to ~510 ng/dL. Despite >90% statistical power, there was no difference between testosterone and placebo across 21 of 22 quality-of-life measures (the single positive measure was dismissed as statistical noise), and the 26 of 42 men who chose to continue the gel that turned out to be testosterone represented neither a statistically nor clinically significant preference. Dr. Feigenbaum caveats that this 6-week trial in 45 men does not negate TRT's life-changing efficacy in genuinely hypogonadal patients, and the final preference phase was the study's weakest powered element.
• Market Forces and High Discontinuation Rates: Commercial promotion heavily shaped TRT demand, peaking at a $1.6 billion market in 2014 after AbbVie spent $75 million in 2012 and $65 million in 2013 marketing AndroGel (despite the FDA warning AbbVie in 2000 that marketing for "age-related low testosterone" was misleading). Following 2013 observational signals of heart risk, an FDA safety warning for heart attack and stroke, and over 25,000 federal lawsuits starting in 2014, direct-to-consumer ads vanished and prescriptions fell by over half between 2013 and 2016. Today, 70% of men who start TRT quit within one year; while studies do not capture the exact reasons, Dr. Feigenbaum speculates it stems from a lack of perceived benefit relative to financial cost and injection inconvenience.
• Fertility Suppression via Negative Feedback: Exogenous testosterone suppresses pituitary production of FSH and LH, shutting down testicular sperm production and acting as a contraceptive. While recovery after stopping typically takes 6 to 12 months, a small subset never fully recovers. Alarmingly, a survey of urologists revealed that 25% incorrectly believed testosterone therapy improves male fertility.
• Cardiovascular Safety and the TRAVERSE Trial Caveats: Following an early-halted 2010 trial showing increased cardiac events and a 2017 study suggesting increased non-calcified coronary plaque, the 2023 NEJM TRAVERSE trial randomized over 5,000 hypogonadal men (aged 45 to 80 with heart disease or high risk) to topical gel or placebo for an average of 2 years. Major cardiac events were equal (~7% in both groups), though testosterone caused slightly higher, statistically significant rates of atrial fibrillation and pulmonary embolism. Both hosts heavily caveat that because TRAVERSE lasted only 2 years and only raised average testosterone to ~375 ng/dL at one year, it cannot guarantee long-term safety for younger wellness-clinic patients injecting to reach 900 ng/dL (in a real-world study of >9,000 men on TRT, average levels landed around 800 ng/dL).
• Prostate Cancer and the Saturation Model: The belief that testosterone fuels prostate cancer dates to a 1941 castration study. To explain why modern trials (the Testosterone Trials and TRAVERSE) show identical prostate cancer rates between TRT and placebo, the Saturation Model hypothesizes that prostate androgen receptors fully saturate at very low hormone levels, meaning further increases do not stimulate tissue growth or PSA. Dr. Baraki hedges that this model is an interesting hypothesis rather than a universally accepted "slam dunk." Notably, a 2026 retrospective study of >900 men on active surveillance for prostate cancer found low baseline testosterone carried a 61% higher likelihood of progressing to aggressive, high-grade disease, and a study of 850 post-prostatectomy men showed lower cancer recurrence among those given TRT.
• Erythrocytosis (Thick Blood) and Estrogen Management: Testosterone stimulates renal erythropoietin (EPO) production, causing up to 20% of men on injectable TRT to develop erythrocytosis (elevated hematocrit). Clinicians intervene at a hematocrit cutoff of 54%, though Dr. Baraki notes this threshold is a clinical weakness extrapolated from blood disorders like polycythemia vera rather than direct evidence linking TRT-induced erythrocytosis to clots. Additionally, routine co-prescription of aromatase inhibitors to block estrogen conversion causes bone loss, joint pain, worsened body composition, and low libido.
• Future Pharmacology (GLP-1s and TRT): Discussing obese men with secondary deficiency, Dr. Feigenbaum explicitly speculates ("taking a trip down speculation lane") that combining tirzepatide (a GLP-1 receptor agonist) with TRT could produce additive or synergistic benefits, though Dr. Baraki emphasizes that clinicians must currently advise patients without any randomized controlled trial data testing this combination.

Quotes

• At 0:00:41 - "And they felt exactly the same. The energy, the libido, the mood, it was no better on the testosterone than on the placebo." - Dr. Jordan Feigenbaum explaining the results of the Sydney crossover trial on men over 40 with low-normal testosterone (~310 ng/dL).
• At 0:03:02 - "The current medical system gets it wrong in both directions: men who are genuinely testosterone deficient who don't get treatment, and men who get a prescription without a full workup behind it, so inappropriate prescription." - Dr. Jordan Feigenbaum framing the core paradox of modern testosterone management.
• At 0:05:27 - "There is no scenario where somebody presents for this sort of a concern and the only lab test that I get on them is just a testosterone level." - Dr. Austin Baraki emphasizing that non-specific symptoms like fatigue require evaluating thyroid function, iron/anemia, sleep apnea, and metabolic health.
• At 0:10:28 - "A quarter of men starting testosterone replacement therapy had no testosterone level drawn in the year before the prescription, and 50% won't have any labs afterwards in the following year, which is pretty interesting." - Dr. Jordan Feigenbaum citing real-world prescribing data showing widespread lack of baseline testing and follow-up monitoring.
• At 0:16:00 - "We can make the testosterone number whatever we want it to be. And we could make the number look pretty, we could make the number go really high—that would not be wise, but we could—and that might help some of the things, but it might not help all of the things, and it might make some of the things that we're ignoring worse." - Dr. Austin Baraki explaining why masking upstream health problems with exogenous hormones can harm patients.
• At 0:26:46 - "Both of us hold the opinion that it is both overtreated and undertreated. It is essentially like misdirected." - Dr. Austin Baraki summarizing how commercial clinics overprescribe while primary care misses true deficiency in vulnerable populations.
• At 0:42:20 - "We're not here to like debunk the idea that testosterone can help people, right? It's that when it is appropriately used and dosed properly in people who are, you know, clinically deficient, certainly can be life-changing. I've seen it many, many times with folks." - Dr. Austin Baraki clarifying that criticism of wellness-clinic overprescribing does not invalidate legitimate medical TRT.
• At 0:45:07 - "Of individuals who start on testosterone replacement therapy, 70% will stop using it within a year." - Dr. Jordan Feigenbaum highlighting the massive real-world drop-off rate among men who initiate therapy.
• At 0:46:09 - "A guy who's sitting at 1,200 isn't being really treated, he's being juiced. And the 'we'll optimize you to 900' thing is mostly a sales pitch based on the assumption that higher is better, which isn't necessarily true." - Dr. Jordan Feigenbaum contrasting evidence-based mid-range targets (450–600 ng/dL) with commercial clinic dosing.
• At 0:46:38 - "You shoot up to like 1,400 in the first few days, you're supratherapeutic, you feel amazing, and then it craters down into the basement by the end of two weeks, where you're genuinely deficient, feeling worse than when you started. It's a roller coaster, and you're basically microdosing a breakup with yourself every two weeks." - Dr. Jordan Feigenbaum critiquing outdated medical protocols that administer 200 mg injections once every two weeks.
• At 0:47:45 - "So when some guy tells you that testosterone changed his life or that it did nothing for him, honestly, neither one tells you much by itself. Not unless you know his dose, you know why he started, and you've seen his labs. Otherwise, all you're hearing is a story." - Dr. Jordan Feigenbaum explaining why personal anecdotes about TRT are useless without clinical context.
• At 0:58:36 - "You ask the same question to urologists in a survey: a quarter of them incorrectly believed that testosterone therapy would improve fertility." - Dr. Jordan Feigenbaum pointing out a major knowledge gap among specialists regarding exogenous testosterone's contraceptive effect.
• At 1:04:01 - "So this is a safety result for guys who are getting gently topped up, which is hard to apply and subsequently give the all-clear to some 35-year-old injecting himself up to 900 because he went to a wellness clinic, because that guy wasn't even in the study." - Dr. Jordan Feigenbaum explaining the external validity limits of the 2023 TRAVERSE cardiovascular trial.
• At 1:23:17 - "Testosterone is an output. It's a readout of what the rest of your body's doing, and if we can fix the inputs, the output is going to look a whole lot better." - Dr. Jordan Feigenbaum distilling the foundational philosophy for addressing low-normal hormone levels.
• At 1:26:34 - "So the problem isn't too much or too little; the problem is aim." - Dr. Jordan Feigenbaum concluding the episode's thesis on how to reform testosterone prescribing.

Takeaways

• Require both symptoms and proper morning labs before considering TRT: Never accept a prescription based on a single afternoon blood draw or non-specific fatigue alone; ensure a full medical history, physical exam, and evaluation of SHBG, free testosterone, LH/FSH, thyroid function, iron/anemia, and sleep quality.
• Treat upstream reversible causes first in secondary deficiency: As demonstrated by the case study of "Mark" (who reversed his 240 ng/dL afternoon level and tapered off TRT by treating his 60-events-per-hour sleep apnea with a CPAP for 6 weeks, lifting weights 3 days a week, and losing visceral fat), fix sleep, diet, alcohol intake, and body composition before committing to exogenous hormones.
• Target the middle of the reference range, not supraphysiologic peaks: When on TRT, follow clinical guidelines by aiming for mid-cycle blood levels around 450 to 600 ng/dL (e.g., 550 ng/dL halfway between doses) rather than falling for clinic sales pitches to "optimize" levels to 900 or 1,200 ng/dL.
• Split injectable doses to once or twice weekly: Avoid the outdated protocol of injecting 200 mg once every two weeks; use 1 to 2 smaller injections per week to prevent supratherapeutic spikes (~1,400 ng/dL) and end-of-cycle crashes.
• Approach TRT as a monitored 3-to-9-month trial: Because study timelines on symptom resolution are imperfect and individual responses vary, evaluate whether your specific symptoms actually improve over 3 to 9 months rather than viewing initiation as an automatic lifelong sentence.
• Avoid TRT monotherapy if you want children: Because exogenous testosterone shuts down LH, FSH, and sperm production for 6 to 12+ months, men desiring active or near-term fertility should avoid standalone TRT and discuss alternatives like hCG (to directly stimulate the testes) or off-label clomiphene with their physician.
• Monitor hematocrit and manage levels above 54%: Commit to follow-up blood work (which 50% of patients currently skip); if hematocrit reaches the 54% threshold, work with your doctor to investigate secondary causes like untreated sleep apnea or adjust your protocol to smaller, more frequent doses.
• Do not take aromatase inhibitors routinely with TRT: Avoid crushing estradiol with aromatase inhibitors unless medically indicated, as estrogen deficiency drives bone loss, joint pain, poor body composition, and low libido.
• Screen for absolute contraindications and baseline PSA: Before starting TRT, verify a baseline PSA (investigating levels >3 to 4 or rapid PSA velocity) and rule out hard stops, including newly diagnosed/active prostate or male breast cancer, polycythemia/blood cancers, active fertility goals, and acute/unstable hospitalizations like active heart failure or sepsis.