#260 ‒ Men's Sexual Health: why it matters, what can go wrong, and how to fix it | Mohit Khera, M.D., M.B.A., M.P.H.

Episode Summary

Executive Summary: Peter Atiyah interviews urologist Dr. Mohit Kara on male sexual health, covering erectile dysfunction, Peyronie’s disease, ejaculation disorders, testosterone physiology and replacement, and the controversial role of finasteride. The discussion emphasizes that sexual dysfunction is common, often underreported, frequently linked to cardiovascular/metabolic health, and increasingly treatable through lifestyle, medications, devices, and selected procedures.

Main Topics: Erectile dysfunction: prevalence, diagnosis, and causes (Priority: 5/5): ED is framed as a common, age-associated but not age-caused condition, diagnosed with validated questionnaires and simple functional questions. Causes include vascular, endocrine, neurologic, trauma, medications, and psychogenic factors. ED treatment ladder and emerging therapies (Priority: 5/5): The conversation reviews PDE5 inhibitors, daily tadalafil, injections, penile prostheses, shockwave therapy, stem cells, and PRP, with strong emphasis on evidence quality, cost, and patient selection. Peyronie’s disease and penile trauma (Priority: 4/5): Peyronie’s is presented as a common, under-discussed curvature disorder often linked to microtrauma and impaired healing, with treatments ranging from collagenase and traction to surgery and prosthesis in severe cases. Priapism and penile emergencies (Priority: 4/5): The episode explains priapism as a time-sensitive emergency, its causes, and stepwise management including phenylephrine, aspiration/irrigation, shunting, and sometimes early prosthesis to avoid fibrosis. Premature ejaculation, delayed orgasm, and retrograde ejaculation (Priority: 4/5): The discussion distinguishes lifelong vs acquired premature ejaculation, outlines diagnostic criteria, and reviews therapies such as topical anesthetics, SSRIs, tramadol, alpha blockers, and sex therapy. Delayed orgasm and retrograde ejaculation are also covered. Testosterone physiology, testing, and replacement options (Priority: 5/5): The episode explains the HPG axis, SHBG/free testosterone, androgen receptor sensitivity, and multiple TRT modalities including injections, gels, pellets, oral undecanoate, and intranasal testosterone, with fertility implications. DHT, finasteride, and post-finasteride syndrome (Priority: 4/5): Dr. Kara argues DHT is important for sexual function and warns that 5-alpha reductase inhibitors may cause persistent sexual and neuropsychiatric symptoms in a subset of men, despite controversy.

Key Arguments: ED is common and should be treated as a medical issue, not a shameful private problem; many men and clinicians avoid discussing it, which delays care. ED and cardiovascular disease share major risk factors and endothelial dysfunction may be the common biological link; ED can be an early warning sign of vascular disease. Daily tadalafil is presented as both a treatment and a tissue-preserving strategy that may help maintain cavernosal smooth muscle health. Lifestyle changes—diet, exercise, sleep, stress reduction, smoking cessation, and weight loss—can meaningfully improve erectile function and sometimes reduce medication needs. PDE5 inhibitors work by preserving cyclic GMP and improving blood inflow; side effects differ by agent due to phosphodiesterase cross-reactivity. Shockwave therapy may help mild-to-moderate ED, but the evidence is still evolving and many commercial offerings outpace the science. Stem cells and PRP are promising but remain insufficiently validated; placebo-controlled trials are still needed before broad adoption. Peyronie’s disease is often trauma-related and may worsen if treated too early surgically; traction and collagenase can help selected patients. Priapism requires urgent treatment because prolonged ischemia can permanently damage erectile tissue; after long durations, prosthesis may be the best salvage option. Premature ejaculation should be classified as lifelong or acquired, and treatment differs; ED should be treated first when both ED and PE coexist. Free testosterone and symptoms matter more than total testosterone alone; SHBG can mask low bioavailable androgen despite a “normal” total T. TRT should be individualized by symptoms, fertility goals, and formulation tradeoffs; injections are often favored for cost and physiologic control, while gels have absorption and transfer problems. Testosterone is not supported by current evidence as a cause of prostate cancer, and in some advanced prostate cancer settings high-dose testosterone may have therapeutic roles. Finasteride may cause persistent sexual and neuropsychiatric adverse effects in a subset of men, potentially via neurosteroid disruption and epigenetic mechanisms.

Data Points: Men over 40 with some degree of ED: 52% - Cited as the prevalence estimate from the original 1994 study Age-prevalence heuristic for ED: 40% at 40, 50% at 50, 60% at 60, 70% at 70 - Used as an easy way to remember how ED prevalence rises with age Men in the U.S. with ED: ~30 million - Derived from the prevalence estimate Women in the U.S. with sexual dysfunction: 43% - Mentioned for comparison with male sexual dysfunction Men with premature ejaculation/ejaculatory dysfunction: 30% - Estimated prevalence discussed in the episode Men with Peyronie’s disease: 7% to 9% - Prevalence estimate cited repeatedly Men with ED who experience depression: 33% - Attributed to the quality-of-life burden of ED Men with ED who experience anxiety: 37% - Attributed to the quality-of-life burden of ED Men with sexual dysfunction who wanted treatment but didn’t know where to go: 50% - From a survey of 1,500 men aged 18 to 80 Men who told their doctor about sexual dysfunction: 51% - Survey result illustrating underreporting Men who told their partner/wife about sexual dysfunction: 44% - Survey result illustrating underreporting Peak systolic velocity threshold for arterial insufficiency: <25 to 30 mm/s - Penile Doppler ultrasound criterion after induced erection End diastolic velocity threshold for venous leak: >5 mm/s - Penile Doppler ultrasound criterion after induced erection Peyronie’s curvature threshold affecting intercourse: >60 degrees - Curvature level described as prohibitive for intercourse Peyronie’s natural history in active phase: 15% improve, 40% stay the same, 45% worsen - The “15-40-45 rule” during the first ~12 months Average intravaginal ejaculatory latency time: 6 to 7 minutes - Described as the typical average based on stopwatch measurement Lifelong premature ejaculation threshold: <2 minutes - Current guideline-based definition discussed Delayed orgasm threshold: >15 to 20 minutes - Practical clinical threshold mentioned Men with ED who develop cardiovascular events within 7 years: 15% - Prospective data cited as evidence ED can be a sentinel sign of CVD Diet/exercise effect on IIEF score: +3 points - Mediterranean diet and exercise in obese men improved erectile function without medication Daily tadalafil conversion factor: 5 mg daily ≈ 8 mg in system - Speaker stated a 1.6x conversion for daily dosing Intratesticular testosterone decline with exogenous testosterone: 94% decline in 3 weeks - Coviella study cited to show suppression of intratesticular T HCG dose used to preserve intratesticular testosterone: 250-500 IU - Dose range cited as preventing significant decline in intratesticular testosterone TRT dose used in fertility-preservation protocol: 50 mg testosterone cypionate twice weekly - Speaker’s physiologic dosing approach HCG dose used with TRT for fertility protection: 500 IU every other day - Protocol described to mitigate suppression of spermatogenesis Klinefelter syndrome prevalence: 1 in 500 - Used to emphasize how common the condition is Stem cell pilot study size: 30 patients - Non-placebo-controlled ED stem cell study described Stem cell yield from adipose processing: 37 to 50 million cells - Yield from the machine after processing fat Stem cell durability: 6 to 9 months - Benefit described as temporary and tapering Shockwave therapy protocol: 2,500 shocks per session - Delivered across six penile zones over 25-30 minutes Shockwave treatment frequency: 1 to 2 times per week for 3 to 6 weeks - Typical low-intensity shockwave regimen described Penile prosthesis infection rate: <2% (closer to 1%) - Modern infection risk estimate given by the speaker Priapism emergency threshold: >4 hours - Patients should seek urgent care if erection persists beyond this point Priapism tissue recovery threshold: ~36 hours - Chance of recovery described as extremely low after this duration TRT saturation model threshold: ~250 ng/dL - Point at which PSA/testosterone response is said to saturate TRAVERSE trial size: 6,000 patients - Large randomized trial of testosterone and cardiovascular outcomes Testosterone conversion to estradiol: ~0.3% - Approximate aromatization rate mentioned Testosterone conversion to DHT: 6% to 8% - Approximate 5-alpha reduction rate mentioned Normal total testosterone threshold used clinically: 300 ng/dL - Speaker criticized this as an oversimplified cutoff Normal testosterone level in erectile function discussion: ~200 ng/dL - Below this, nocturnal erections begin to decline Finasteride post-syndrome study sample: 25 men with symptoms, 25 controls - Small study used to explore gene expression differences Suicide rate in that finasteride cohort: 2 of 25 men - Reported among symptomatic men in the speaker’s study Oral testosterone undecanoate dosing: BID - Jatenzo/Tlando/Kyzatrex discussed as twice-daily oral options Intranasal testosterone dosing: 11 mg per nostril, 3 times daily - Natesto regimen described as fertility-sparing

Pivotal Quotes: "The problem is that this population, I call it suffer in silence." — Dr. Mohit Kara: On why sexual dysfunction is underreported and undertreated "ED is the sentinel sign of cardiovascular disease." — Dr. Mohit Kara: On the link between erectile dysfunction and endothelial/cardiovascular health "If you have a man and you drop to 50 milligrams twice a week, the erythrocytosis rate goes down. It’s more physiologic." — Dr. Mohit Kara: On why smaller, more frequent testosterone injections are preferred

Implications: Listeners should treat sexual dysfunction as a medical signal, not just a quality-of-life issue. Earlier evaluation can uncover cardiovascular, endocrine, fertility, or medication-related problems, while evidence-based treatment choices matter because many commercial therapies outpace the science.