Podcast Summary: The Curbsiders Internal Medicine Podcast

Episode: REBOOT: #462 Male Hypogonadism Pearls with Dr. Bradley Anawalt
Date: January 26, 2026
Host(s): Matthew Watto, Paul Nelson Williams, Paul Wertz
Guest: Dr. Bradley Anawalt (Chief of Medicine, University of Washington Medical Center)

Overview

This episode dives deep into the evaluation and management of male hypogonadism (testosterone deficiency), featuring renowned endocrinologist Dr. Bradley Anawalt. The discussion covers clinical approaches to diagnosis, laboratory evaluation, risk assessment, patient counseling, and evidence-based treatment strategies. Dr. Anawalt emphasizes practical tips, pitfalls, and key updates relevant for primary care and internal medicine providers, while blending clinical pearls with humor and real-world anecdotes.

Key Discussion Points & Insights

1. The Patient Approach: Symptom Analysis and History Taking

• Common Patient Presentation: Middle-aged men presenting with decreased energy, fatigue, weight gain, and concerns about low testosterone ("low T").
• Chief Complaint to Key Clue: Dr. Anawalt stresses that declining libido is the most specific and useful symptom indicating possible hypogonadism, rather than non-specific complaints like fatigue or erectile dysfunction.
  • “Probably the most specific and important clue to new onset of hypogonadism or recent onset is a decline in libido.” (09:03 – Dr. Anawalt)
• Patient Goals: Before ordering tests, clarify what the patient is hoping to achieve. Many simply want to feel better, not always asking for a diagnosis.
• BMI and Risk Factors: Obesity, inactivity, and features like thick neck suggest additional contributors such as sleep apnea rather than isolated testosterone deficiency.
  • Dr. Anawalt recommends measuring waist circumference (target <40 inches) for visceral adiposity when BMI is high.

2. Clinical Pearl: How to Talk About Libido

• Plain Language: Avoid medical jargon; use “sex drive” instead of “libido.”
  • “I'll usually use the words ‘sex drive’ as opposed to libido... Are you as interested in it? Do you think about sex as often as you used to?” (14:25 – Dr. Anawalt)
• Context Matters: Ask for changes compared to two to three years ago, not to their 18-year-old self.
• Situational Assessment: Consider if differences exist with multiple partners or contexts.
• Clues from History: Congenital hypogonadism patients (e.g., Klinefelter’s) never report loss of libido—they never had normal function.

3. Initial Laboratory Workup

• When to Test: Obtain early morning (7–10am) fasting testosterone, as levels are highest and variation is least.
  • Skipping fasting can lower results by up to 50 ng/dL (18:00).
• Lab Selection: Use CDC-validated assays—look for reference ranges around 264–916 ng/dL.
• Suggested Labs:
  • Total testosterone (fasting, early AM)
  • FSH and LH: Assists in identifying primary vs. secondary hypogonadism (22:30)
  • Hematocrit (baseline, screens for anemia and high pre-test risk for sleep apnea)
  • TSH and thyroid studies as needed for fatigue evaluation
• Rationale: Low marginal cost for FSH/LH, can shortcut future diagnostic steps and help patient counseling.

4. Test Interpretation & Diagnosis

• Total vs. Free Testosterone:
  • In overweight/diabetic men, free T may remain normal while total T appears low due to decreased SHBG.
  • Only use laboratories that report SHBG with free testosterone, signaling reliable calculated measurement.
    • “If you get back a total testosterone and a free testosterone and no shbg, you should be suspicious that they're doing a direct measurement... and they're worthless.” (35:22)
  • Avoid direct platform (analog) free testosterone methods—prone to false lows.
• Repeat Testing: Confirm low results; treat only persistently and concordantly low total and free testosterone on reliable assays.

5. Diagnosing Primary vs. Secondary Hypogonadism

• Primary (testicular failure)
  • Low testosterone
  • Elevated FSH and LH
  • Most common over age 65 (age-related, acquired; also Klinefelter’s)
• Secondary (pituitary/hypothalamic dysfunction)
  • Low testosterone
  • Low or “inappropriately normal” FSH/LH
  • Often due to obesity, stress, drugs, or brain lesions

“If you find that the patient has a low testosterone and a high FSH and lh, those men don't get better. They don't get better with weight loss. Their labs stay the same, and they have probably real primary hypogonadism that's related to either to aging or ... undiagnosed Klinefelter's syndrome.” (50:56 – Dr. Anawalt)

6. Importance of Lifestyle Counseling

• Lifestyle trumps pills for most: Majority of borderline low-T men are eugonadal. Emphasize weight loss, physical activity, treating sleep apnea for optimization.
• Weight reduction data: In high-risk men (WW/Weight Watchers study), sexual function improved with any weight loss—regardless of testosterone supplementation (27:26).
• Markers for Progress: Focus on waist size before/after, rather than weight.

7. Treatment Decisions and Risks

When to Treat

• Treat when: Persistently and concordantly low labs and classic symptoms (marked loss of libido), or very low T with clear cause (Klinefelter, tumor, pituitary disease, etc.)
• Do NOT treat: Mild, non-specific symptoms or lab values alone.
  • “The patients who get the most benefit from testosterone therapy will have a low total and a low free [testosterone].” (45:23)

Testosterone Options

• IM (intramuscular) testosterone (cypionate/enanthate)
  • Preferred for cost, fewer secondary exposure risks
  • Peaks/valleys more significant—higher risk for erythrocytosis
• Transdermal gels
  • Lower peaks; less risk of increased hematocrit but risk of transfer to partners/kids
• Dosing: Not start low/go slow (unless frail/severe LUTS); titrate to mid-normal range (69:35)

Risks, Benefits, and Monitoring

• Risks: New RCT evidence (Traverse, T4DM, TEAM studies) shows no increased risk of major CVD or prostate cancer, but a signal for increased pulmonary embolism and mild PSA elevation in some.
• PEARL: Don’t start testosterone if baseline hematocrit >50%; reassess for sleep apnea if high.
• Monitor:
  • Testosterone (target: mid-normal)
  • Hematocrit (for polycythemia; lower dose or stop if >54%)
  • PSA (age 50–70, life expectancy >10 years)
  • Interval: annually or after dosage change; nadir levels for IM, 4–6 hours post-application for gel

8. Special Cases

Young Men with Primary Hypogonadism

• Case: 30-year-old, low T, high FSH/LH, small testes
• Likely Klinefelter’s: Confirm with karyotype (expensive, not always essential if high clinical probability, but useful for fertility counseling)
  • Discussed assisted reproduction (ICSI) and implications.
• Testicular shrinkage with treatment: Reversible if stopped, but can be a source of distress for some.

Fertility Concerns (Secondary Hypogonadism)

• Do NOT give testosterone replacement—it suppresses sperm production.
• Alternatives:
  • hCG injections: Replaces LH, restarts testosterone/sperm production
  • +/- FSH if infertility persists
  • Clomiphene: Selective estrogen receptor modulator—useful in young, healthy men with intact hypothalamic-pituitary axis but less effective in older/true central hypogonadism; not Dr. Anawalt’s first choice due to lack of long-term safety and risk of DVT/CRVO.

9. Imaging and Further Workup

• Indications for pituitary MRI (63:56):
  1. Severely low T, especially in men <50 years
  2. Low/undetectable FSH/LH in context of low T
  3. Elevated prolactin
  4. Young patients with no other explanation
  5. Symptoms/referral for pituitary disease
• If older (>50), mild T-lowering, no symptoms, and no abnormal prolactin/gonadotropins: MRI rarely yields, can often avoid.

10. Practical Pearls & Monitoring

• Orchidometer: For $20, a valuable tool to diagnose Klinefelter’s; testicle <15 mL is concerning.
• Testicular atrophy: Expected, but reversible after discontinuing therapy.
• Stopping testosterone:
  • Irreversible cases (Klinefelter’s, pituitary tumor): lifelong therapy
  • Potentially reversible (obesity, sleep apnea, drugs): Remove underlying cause first; avoid unnecessary long-term suppression

Notable Quotes & Memorable Moments

• “If you've never had testosterone, you won't know what it is to experience loss of libido.” (09:03 – Dr. Anawalt)
• “You don't want to check a test result if you don't want to manage the outcome of the result.” (09:03 – Dr. Anawalt)
• “Are you comparing yourself to yourself at 18, or is it just the past couple years that you've had the change?” (18:13 – Dr. Watto)
• “Your clinical assessment is absolutely vital to making the diagnosis ... and libido is your most specific symptom.” (89:06 – Dr. Anawalt)
• “If Sertoli has a low hematocrit on top of everything else, that also is a predictor that he's going to have a more significant benefit [from testosterone].” (66:01 – Dr. Anawalt)
• "You want to use an accurate testosterone assay, particularly in the setting where you have a patient you think is eugonadal and has a borderline value." (89:06 – Dr. Anawalt)

Timestamps for Important Segments

• 08:25 - Case 1: Approach to the symptomatic patient
• 09:03 - Key symptom: libido loss
• 14:25 - How to ask about sex drive
• 18:00 - Fasting & morning testing tricks
• 22:30 - Laboratory test selection (Testosterone, FSH, LH, hematocrit, TSH)
• 27:26 - Weight loss, sexual function study
• 35:22 - Free testosterone measurement pitfalls
• 47:53 - Case 2: Older patient, interpreting discordant total/free testosterone
• 50:56 - Aging, Klinefelter's, missed diagnoses
• 54:32 - Treatment risks, benefits, and RCT data
• 66:01 - Predictors of benefit (e.g., low hematocrit)
• 70:47 - Case 3: Young man, Klinefelter’s, fertility, and diagnosis
• 78:36 - Secondary hypogonadism, HCG, Clomiphene
• 82:02 - Monitoring strategies (testosterone, hematocrit)
• 85:54 - Stopping therapy, reversible vs. irreversible causes
• 89:06 - Dr. Anawalt’s top 5 take-home points

Dr. Anawalt’s Top 5 Take-Home Points (89:06)

1. Clinical assessment is crucial for diagnosis—focus on libido.
2. Libido loss is the most specific symptom—ask about it directly.
3. Always consider other etiologies for vague symptoms—especially depression.
4. Physical exam: Measure testes (orchidometer). Klinefelter’s is more common than realized.
5. Use accurate labs—especially in borderline or equivocal cases.

This summary is designed to provide clear, actionable insights from the Curbsiders’ episode on male hypogonadism. For primary care physicians and learners, these pearls offer a practical, evidence-informed approach to evaluating and managing “low T” effectively and responsibly.