Side Effects, Trade-offs, and Virility's Paradox

It used to be that getting older meant slowing down. A little less pep, a little less zip, a little less zest. So it goes.

For men, this was partly about testosterone. After 40 or so, our bodies produce less and less testosterone, the hormone that helps give men energy and vigor and sex drive. Lower testosterone was just part of growing older.

But that was then! Nowadays, “Low T” is a bonafide medical condition - easily treated with a shot at your local neighborhood men’s health clinic.

Today, what used to be a secret sauce of bodybuilders or cheating athletes is now downright normal. Millions of men worldwide take testosterone therapy - and not just those over 40. Check out Reddit or TikTok...It is a WHOLE THING.

In this episode of Drug Story, we look at how TRT went mainstream, and how part of ordinary aging somehow became a disease.

Sources for this episode

[1] Male Hypogonadism (2024) STAT Pearls:Male hypogonadism is defined as inadequate testosterone production or impaired spermatogenesis, diagnosed via symptoms and low morning testosterone levels.

[2] Brown-Séquard: An improbable genius who transformed medicine (2011) The Journal of Clinical Investigation: Charles-Edouard Brown-Séquard, a pioneering 19th-century scientist who rose from a difficult childhood in Mauritius is said to be the founder of modern endocrinology and neurology.

[3] The life and legacy of Brown-Séquard (2017) Brain: Charles-Edouard Brown-Séquard’s insights helped show how nerves control blood vessels and laid the foundation for modern endocrinology by identifying internal secretions and early hormone therapy.

[4] The “Elixir of Life” (1889) J.G. Cupples Co: In a self-report, Charles-Édouard Brown-Séquard covers his controversial self-experiments where he injected animal testicle extracts in pursuit of rejuvenation.

[5] The effect produced on man by subcutaneous injections of a liquid obtained from the testicles of animal (1889) Lancet: In a 1889 Lancet article, Brown-Séquard describes his pioneering experiments with subcutaneous injections of animal testicular extracts to combat the physical and mental decline associated with aging.

[6] A Brief History of Testosterone (2001) Journal of Urology: Hormone therapy became widely used to treat age and disease-related hormone decline, before risks were fully understood.

[7] History of Testosterone and Therapeutic Potential (2020) Sexual Medicine Reviews: Testosterone was isolated in 1935 by the Organon group, with independent synthesis by Adolf Butenandt and Leopold Ruzicka.

[8] Adolf Butenandt—Nobel Prize for Chemistry (2012) Mayo Clinic Proceedings: Adolf Butenandt isolated key sex hormones, contributing to foundational methods for steroid chemistry and earning the 1939 Nobel Prize in Chemistry.

[9] Monkey business: reflections on testosterone (2012) BMJ: Testosterone is widely believed to drive masculinity, aggression, and performance, but strong evidence in humans is limited and inconsistent.

[10] The male hormone (1945) Harcourt, Brace and Company: The Male Hormone was an influential book that shaped public and medical perceptions of testosterone as central to masculinity and male health.

[11] Endocrines: The Use of Testosterone (1940) The New England Journal of Medicine: Dr. Joseph C. Aub’s NEJM article discusses testosterone as proven therapy for hypogonadism, with experimental applications for women and other conditions.

[12] History of Doping in Sport (2001) International Sports Studies: Testosterone and anabolic steroids became central substances in performance enhancement, prompting regulatory responses and anti-doping frameworks in international sport.

[13] New 'Breakfast of Champions': A Recipe for Victory or Disaster? (1988) The New York Times: Anabolic steroid use, including testosterone derivatives, was widespread in elite athletics despite known health risks and weak enforcement.

[14] FTC Sues Drug Companies for Unlawfully Conspiring to Delay the Sale of Generic AndroGel Until 2015 (2009) Federal Trade Commission: Pharmaceutical companies used patent litigation and settlement agreements to delay generic testosterone gel competition and maintain market exclusivity.

[15] Androgen deficiency in males (2010) Expert Review of Endocrinology & Metabolism: Clinical definitions of androgen deficiency rely on serum testosterone thresholds combined with symptoms, with variability across populations.

[16] The male menopause—does it exist? (2000) BMJ: Age-related testosterone decline occurs gradually and inconsistently and does not parallel the hormonal cessation observed in female menopause.

[17] Evolution of Guidelines for Testosterone Replacement Therapy (2019) Journal of Clinical Medicine: Article examines how definitions, diagnoses, treatments, and follow-up recommendations for testosterone replacement therapy have evolved across major societies (ISSAM, Endocrine Society, ISSM, AUA).

[18] The Hazards of Male Menopause (1997) Science: Medicalization of age-related testosterone decline outpaced clinical evidence, raising concerns about overtreatment and long-term risk.

[19] Selling That New-Man Feeling (2013) The New York Times: Direct-to-consumer advertising reframed testosterone therapy as a solution for fatigue, low mood, and diminished masculinity in aging men.

[20] Prevalence of hypogonadism in males aged at least 45 years: the HIM study (2008) The International Journal of Clinical Practice: A study established low measured testosterone levels prevalent among men over 45, particularly in those with obesity, diabetes, and chronic illness.

[21] Testosterone Aids Older Men's Brains, UCSF Study Says (2002) Science Daily: Testosterone supplementation was associated with short-term improvements in certain cognitive measures in older men.

[22] Association Between Direct-to-Consumer Advertising and Testosterone Testing and Initiation in the United States, 2009–2013 (2017) JAMA: A study finds increased exposure to testosterone advertising correlated with higher rates of testosterone testing and treatment initiation.

[23] 2013 All-Star Large Pharma Marketing Team of the Year: AndroGel (2013) Medical Marketing and Media: AndroGel’s marketing strategy successfully expanded testosterone therapy into a high-revenue lifestyle pharmaceutical category.

[24] The marketing of testosterone treatments for age-related low testosterone or 'Low T' (2018) Current Opinion in Endocrinology & Diabetes and Obesity: Discusses how pharmaceutical companies promoted testosterone for off-label, age-related use without strong supporting evidence.

[25] “Manopause?! Aging, Insecurity and the $2 Billion Testosterone Industry” (2014) TIME: Highlights how clinics like Low T Centers exploit aging men’s fears and market testosterone as a cure-all for aging.

[26] “More Men Are Seeking Out Testosterone Tests. Are They Getting Duped?” (2022) The New York Times: Reports on rising interest in testosterone testing and treatment, often marketed through online platforms targeting fatigue and low sex drive.

[27] FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use (2025) U.S. Food & Drug Administration: Testosterone products were required to update labeling to reflect increased risks of heart attack and stroke and to limit use to clinically verified hypogonadism.

[28] The Virility Paradox (2018) Simon & Schuster: Testosterone has a wide influence on human behavior, health, culture, and society, shaping traits from strength and drive to aggression and selfishness.

[29] The Testosterone Myth (2018) WIRED: Article explores the widespread but unfounded belief that testosterone can reverse aging and restore vitality.

[30] Effects of Testosterone Treatment in Older Men (2016) New England Journal of Medicine: In men 65 and older with low testosterone, raising levels of testosterone improved sexual desire and activity and had modest effects on mood and physical function, but did not improve vitality or walking distance.

[31] Promoting “Low T: A Medical Writer’s Perspective (2013) JAMA Internal Medicine: A former ghost writer for the Low T campaign reveals how they got their message out in "educational" materials and articles.