Andy Cohen TRT: The Evidence Base Behind That Protocol

What Andy Cohen Has Said About TRT

Andy Cohen mentioned testosterone replacement therapy on the Daddy Issues podcast and in related press coverage in 2023, describing it as part of his broader approach to maintaining energy and wellbeing in his mid-fifties. He characterized the experience positively, noting changes in energy and mood. These statements are direct and on-record. No inference is required to confirm he uses TRT. The clinical question worth examining is what protocol the evidence actually supports for a man in his demographic, and why physicians prescribe it the way they do.

The Public Record

Cohen did not specify a particular dose, formulation, or prescribing physician in his public statements. That matters for this article. What follows is not a reconstruction of his personal chart. It is an examination of the evidence base that any board-certified endocrinologist or urologist would draw on when designing a TRT protocol for a symptomatic man in his mid-fifties with confirmed low testosterone.

Why Celebrities Discussing TRT Matters Clinically

When public figures disclose hormone therapy use, search volume for that therapy spikes and patient inquiries to clinicians increase. A 2021 analysis in JAMA Internal Medicine found that celebrity health disclosures significantly alter patient behavior and screening rates. That pattern means the quality of publicly available clinical information about TRT has real consequences for how men pursue or avoid evaluation.

Diagnosing Hypogonadism: What the Guidelines Require

Before any TRT prescription is written, guidelines require a confirmed biochemical diagnosis. The Endocrine Society's 2018 clinical practice guideline on testosterone therapy in men states that treatment should be offered only to men with "symptoms and signs consistent with androgen deficiency and consistently low testosterone concentrations" [1]. Symptoms include reduced libido, fatigue, depressed mood, decreased muscle mass, and increased adiposity.

The Two-Reading Rule

Two separate morning total testosterone measurements below 300 ng/dL on different days are required for diagnosis, not one borderline result. Morning draws matter because testosterone follows a diurnal rhythm, peaking between 7 and 10 a.m. A single afternoon draw can produce a falsely low reading in a eugonadal man.

Free vs. Total Testosterone

Total testosterone is the standard screening measure. Free testosterone becomes relevant when sex hormone-binding globulin (SHBG) is elevated, which occurs with aging, obesity, and certain medications. The Endocrine Society guideline recommends free testosterone measurement by equilibrium dialysis when total testosterone is in the 300 to 400 ng/dL range but symptoms are present [1]. Calculated free testosterone using the Vermeulen equation is an acceptable alternative when dialysis assays are unavailable.

LH and FSH Testing

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) differentiate primary from secondary hypogonadism. Elevated LH with low testosterone indicates primary testicular failure. Low or normal LH with low testosterone suggests a hypothalamic or pituitary cause, which requires MRI of the pituitary fossa before TRT is started. This distinction changes both the workup and the treatment plan.

The Testosterone Trials: The Strongest Evidence Base for TRT in Older Men

The Testosterone Trials (TTrials) represent the most rigorous placebo-controlled evaluation of TRT in older men to date. Published across multiple papers in the New England Journal of Medicine and JAMA between 2016 and 2018, the TTrials enrolled 788 men aged 65 and older with total testosterone below 275 ng/dL and at least one symptom domain [2].

Sexual Function Results

The sexual function trial, published in the New England Journal of Medicine in 2016 (N=470), showed that testosterone gel (targeting levels of 500 to 1000 ng/dL) produced statistically significant improvements in sexual desire and erectile function compared with placebo at 12 months (P<0.001) [2]. The Patient-Reported Outcomes Measurement Information System (PROMIS) sexual desire score improved by 0.58 points more in the testosterone group. Effect sizes were moderate but consistent.

Physical Function and Body Composition

The physical function trial found a 1.6 kg greater increase in lean body mass in testosterone-treated men versus placebo at 12 months, measured by dual-energy X-ray absorptiometry (DEXA) [3]. Leg press strength increased by 7.0 kg more in the testosterone group. The clinical relevance of these changes for daily function remains debated; the trial was not powered to detect falls or fracture reduction.

Bone Density

The bone trial (N=211) found that testosterone increased volumetric trabecular bone mineral density at the spine by 7.5% versus placebo at 12 months, a statistically significant difference (P<0.001) [4]. This is the most consistent benefit of TRT across age groups, which is why bone density monitoring appears in most prescribing guidelines for men on long-term therapy.

Mood and Depressive Symptoms

The TTrials depressive symptoms sub-trial showed a modest but significant improvement on the Patient Health Questionnaire-9 (PHQ-9) in men with baseline PHQ-9 scores of 5 or higher [5]. The mean improvement was 1.7 points greater in the testosterone group. For men with mild-to-moderate depressive symptoms and confirmed hypogonadism, this suggests TRT may contribute to mood improvement. TRT is not, however, a replacement for formal psychiatric evaluation or antidepressant therapy in men with major depression.

Formulations: What Gets Prescribed and Why

Several FDA-approved formulations deliver testosterone. Each has a distinct pharmacokinetic profile, and the choice depends on patient preference, vascular access, SHBG levels, and monitoring convenience [6].

Intramuscular Testosterone Cypionate and Enanthate

Testosterone cypionate and testosterone enanthate are the most commonly prescribed injectable formulations in the United States. Standard dosing is 100 to 200 mg intramuscularly every 1 to 2 weeks. The pharmacokinetic issue with biweekly dosing is peak-to-trough variability: testosterone levels may reach 800 to 1,100 ng/dL at day 3 to 4 post-injection, then fall to 300 to 400 ng/dL just before the next injection. Some men report energy and mood fluctuations that track this curve. Weekly subcutaneous injections of 50 to 100 mg cypionate produce a flatter concentration-time curve and have become popular in men's health clinics for that reason.

Transdermal Gels and Patches

Testosterone gel (AndroGel 1% and 1.62%, Testim, Vogelxo) delivers testosterone transdermally, producing relatively stable daily levels. The TTrials used a gel formulation targeting 500 to 1,000 ng/dL. Skin transfer to female partners or children is a documented safety concern and requires application to covered areas with hand-washing after use. The FDA label for testosterone gels carries a boxed warning for secondary exposure [6].

Testosterone Pellets

Subcutaneous pellet implantation (Testopel) delivers testosterone over 3 to 6 months via slow dissolution. Pellets are placed under local anesthesia in the buttock or hip. Dosing is typically 150 to 450 mg per insertion, adjusted to body weight and prior response. Because dose adjustment after insertion is not possible, over- and under-dosing occurs more frequently than with injectable or topical formulations. Some clinicians prefer pellets for patients with adherence challenges.

Oral and Buccal Options

Testosterone undecanoate (Jatenzo, FDA-approved 2019) is an oral capsule dosed twice daily with food containing at least 15 grams of fat for adequate absorption. It avoids first-pass hepatic metabolism via the lymphatic route. Blood pressure elevation has been reported; the FDA label notes a mean systolic blood pressure increase of approximately 4 to 5 mmHg in clinical trials [6].

Cardiovascular Safety: What the Evidence Currently Shows

Cardiovascular safety was the central controversy in TRT research after an early NEJM trial (Basaria et al., 2010, N=209) was stopped because of an excess of cardiovascular events in frail older men [7]. That finding generated a decade of conflicting observational data.

The TRAVERSE Trial

The definitive cardiovascular safety trial is TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE), published in the New England Journal of Medicine in 2023. TRAVERSE enrolled 5,204 men aged 45 to 80 with hypogonadism and pre-existing or high risk of cardiovascular disease, randomized to testosterone gel 1.62% or placebo [8]. The primary endpoint, a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, occurred in 7.0% of the testosterone group and 7.3% of the placebo group (hazard ratio 0.96, 95% CI 0.78 to 1.17), meeting the non-inferiority margin. The Endocrine Society and the FDA both updated their guidance following this publication: TRT does not appear to increase major adverse cardiovascular events in men with confirmed hypogonadism who meet trial entry criteria.

Atrial Fibrillation Signal

TRAVERSE did identify a higher incidence of atrial fibrillation in the testosterone arm (3.5% vs. 2.4%, P=0.02) [8]. This signal was exploratory and not a pre-specified endpoint, but clinicians now discuss it with patients who have a prior history of atrial fibrillation or significant structural heart disease before starting TRT.

Hematocrit and Polycythemia

Testosterone stimulates erythropoiesis. Hematocrit above 54% is a known risk factor for thromboembolic events and is listed as a contraindication in the FDA label. The TRAVERSE trial reported a higher rate of hematocrit elevation in the testosterone arm. Current practice requires a baseline hematocrit, repeat measurement at 3 and 6 months, then annually. If hematocrit exceeds 54%, dose reduction or temporary discontinuation is indicated [6].

Monitoring Protocol: What a Well-Run TRT Practice Does

A responsible TRT monitoring framework includes the following assessments at defined intervals. This framework reflects current Endocrine Society and American Urological Association guidance, synthesized into a single clinical reference.

Baseline Workup

Before initiating therapy, a clinician should obtain: two morning total testosterone levels, LH and FSH, complete blood count (CBC) with hematocrit, prostate-specific antigen (PSA) in men over 40, lipid panel, and a digital rectal exam or discussion of prostate health history. Untreated obstructive sleep apnea should be addressed before TRT is started, because testosterone worsens sleep apnea in some men.

3-Month Visit

At 3 months: serum total testosterone (trough for injectables, anytime for gels), hematocrit, PSA. Testosterone levels should target the mid-normal range, 400 to 700 ng/dL by most guidelines. Levels above 1,000 ng/dL on a stable dose indicate the need for dose reduction.

12-Month Visit and Beyond

Annual visits should include testosterone level, hematocrit, PSA, and a discussion of fertility intentions. TRT suppresses the hypothalamic-pituitary-gonadal axis, reducing intratesticular testosterone and causing azoospermia in many men. Men who want to preserve fertility should consider alternatives such as clomiphene citrate (off-label) or human chorionic gonadotropin (hCG), which stimulates endogenous testosterone production while maintaining spermatogenesis.

What TRT Does Not Do: Correcting Common Misconceptions

TRT is not anabolic steroid use. The doses used in replacement therapy target physiological testosterone levels, not supraphysiological ones. The distinction matters medically and legally. Anabolic steroid abuse involves doses 10 to 100 times higher than replacement doses and carries documented risks of cardiomyopathy, hepatotoxicity, and severe hypogonadism on cessation.

TRT also does not reliably cause prostate cancer. The Endocrine Society's 2018 guideline states: "We suggest against treating men with testosterone if they have been treated for prostate cancer" but notes that the historical fear of TRT-causing prostate cancer in men without the disease "is not supported by the available evidence" [1]. The prostate saturation model, developed by Abraham Morgentaler, MD, explains why testosterone at physiological levels does not drive prostate cancer growth the way supraphysiological levels might.

TRT will not resolve fatigue, depression, or sexual dysfunction caused by factors other than testosterone deficiency. Non-hormonal causes, including sleep disorders, hypothyroidism, elevated prolactin, iron deficiency anemia, and medication side effects, must be excluded before attributing symptoms to low testosterone.

Age-Related Testosterone Decline: Normal Physiology vs. Pathology

Total testosterone declines at approximately 1 to 2% per year after age 30 in most men [9]. By age 70, roughly 20 to 30% of men have total testosterone levels below 300 ng/dL. This decline is driven by decreased Leydig cell mass, reduced LH pulse amplitude, and increased SHBG with aging. The question of whether to treat asymptomatic age-related decline remains contested. The Endocrine Society guideline does not recommend TRT for men with low testosterone who lack symptoms, a position supported by the American Urological Association [1].

For men like Andy Cohen, who are in their mid-fifties, have publicly described symptoms consistent with hypogonadism, and have chosen to work with a physician on TRT, the clinical framework is clear. Confirm the diagnosis biochemically, rule out secondary causes, select a formulation matched to lifestyle and pharmacokinetics, target mid-normal testosterone levels, and monitor hematocrit, PSA, and cardiovascular markers at defined intervals.

The TRAVERSE trial's 5,204-patient dataset now gives clinicians a solid cardiovascular safety basis for offering TRT to appropriately selected men [8]. Mid-normal testosterone targets, regular monitoring, and attention to the atrial fibrillation signal from TRAVERSE represent the current standard of care. Men considering TRT should obtain two morning testosterone draws before any prescription is written.