Peter Attia MD260 ‒ Men’s Sexual Health: why it matters, what can go wrong, and how to fix it
CHAPTERS
- 0:00 – 5:21
Career Path and the Anatomy of Male Sexual Health
Peter Attia introduces the topic and Mohit Khera describes his path from healthcare analyst to urology and a fellowship in male reproductive medicine. He then explains how the penis combines urinary, reproductive and sexual systems.
- •Khera trained in urology with a fellowship in male reproductive medicine and surgery, and has been on Baylor faculty since 2007
- •Sexual medicine covers erectile dysfunction, premature ejaculation, Peyronie's disease and hypogonadism, often paired with infertility
- •The penis involves the bladder/prostate/urethra, the ejaculatory ducts and seminal vesicles, and the corpora cavernosa responsible for erections
- •He treats these systems as interrelated rather than separate problems
- 5:21 – 10:08
Prevalence of Sexual Dysfunction and Suffering in Silence
Khera lays out how common ED, premature ejaculation and Peyronie's disease are, and how many men never seek help. He cites a survey in which embarrassment and clinicians not asking kept men silent.
- •52% of men over 40 have some degree of ED, roughly 40% at 40, 50% at 50, and so on
- •Roughly 30% of men have some premature ejaculation, and 7 to 9% have Peyronie's disease
- •About a third of men with ED have depression and 37% have anxiety because of it
- •In a survey of 1,500 men only 51% told their doctor and 44% told their partner
- •He frames health as a triad of mental, physical and sexual health
- 10:08 – 13:39
Defining and Diagnosing ED: Organic vs Psychogenic Causes
Khera explains how ED is defined with simple questions and a validated questionnaire. He introduces the VENT mnemonic for causes, and how psychogenic ED is distinguished and treated.
- •Two yes/no questions: can you get an erection sufficient for penetration and maintain it until orgasm
- •The VENT mnemonic covers vascular, endocrine, neurologic and trauma causes, plus medications
- •Erections with masturbation or in the morning point toward psychogenic ED
- •Psychogenic ED is treated with sex therapy and daily Cialis, and a first failure can start a vicious cycle of anxiety and avoidance
- •Penile ultrasound showing normal findings can itself be therapeutic
- 13:39 – 18:51
How PDE5 Inhibitors Work and the History of Viagra
Khera explains the nitric oxide and cyclic GMP pathway and how phosphodiesterase inhibitors preserve erections. The conversation covers differences among the drugs, cost, and the story of how Viagra emerged from a failed blood pressure trial.
- •PDE5 inhibitors block the enzyme that breaks down cyclic GMP
- •Cross-reactivity with other phosphodiesterases explains side effects such as back pain with Cialis and visual changes with Viagra
- •Avanafil has the least cross-reactivity but is not yet generic and is expensive
- •Viagra began as a cardiovascular drug and its erection effect was noticed in the trial
- •Addyi and Vyleesi for women have not had the impact Viagra had in men, and HRT may be the strongest agent for women
- 18:51 – 30:47
Venous Leak, Aging, and the Case for Daily Cialis
Khera describes venous leak as the root of age-related ED and ways to overcome it. He argues for daily low-dose Cialis for tissue health and for BPH and endothelial benefits, and discusses generic costs and the refractory period.
- •Muscle atrophy and fibrosis with age let blood in but not stay in, and low testosterone may contribute
- •Use it or lose it: nocturnal erections and sexual activity keep penile tissue oxygenated
- •Daily 5 mg Cialis acts like about 8 mg continuously, is FDA approved for BPH, and may improve endothelial function
- •Generic Cialis can cost about $17 for 90 pills, and he has not seen generics be less effective
- •The refractory period lengthens with age, partly linked to prolactin and the greater difficulty of getting erections
- 30:47 – 36:08
Lifestyle, Cardiovascular Disease, and ED as a Warning Sign
Peter Attia raises how improving insulin resistance can improve erections, and Khera ties lifestyle to sexual function. He explains that organic ED is a sentinel for cardiovascular disease, likely through endothelial dysfunction.
- •Khera stresses four pillars: diet, exercise, sleep and stress reduction
- •ED and cardiovascular disease share nearly identical risk factors
- •Studies cited show about 15% of men with new ED had a cardiovascular event within seven years, and half of men with an event had ED earlier
- •Endothelial dysfunction is the prevailing common link
- •A trial of obese men found diet and exercise improved IIEF scores by about three points without drugs
- 36:08 – 38:50
Penile Ultrasound Diagnostics
Khera describes injecting a vasodilator and using ultrasound to measure blood flow into and out of the penis. The measurements distinguish arterial insufficiency from venous leak and guide management.
- •Peak systolic velocity below about 25-30 indicates arterial insufficiency
- •End-diastolic velocity above 5 indicates venous leak, usually the first problem
- •Both sides are measured, and the corpora are fenestrated so medication reaches both
- •Ultrasound can also show plaque in the tunica albuginea
- •Low peak systolic velocity in a young man worries him as a marker of cardiovascular risk
- 38:50 – 51:56
Peyronie's Disease and Penile Fracture
The discussion turns to curvature caused by plaque in the tunica albuginea. Khera covers its likely causes, the active and quiescent phases, and medical, device and surgical treatments, as well as penile fracture.
- •Plaque tends to form dorsally; curvature over 60 degrees prohibits intercourse
- •Collagenase injection (Xiaflex) was the first FDA-approved treatment in 2015, and vitamin E and colchicine are not recommended
- •The 15/40/45 rule: 15% improve, 40% stay the same, 45% worsen in the first year, so surgery waits for the quiescent phase
- •Traction devices such as RestoreX are off-label and may reduce curvature and add length
- •Penile fracture is a sudden pop with swelling and needs immediate surgical care
- 51:56 – 59:40
ED Treatment Options: Injections and Penile Prosthesis
Khera walks through treatment options beyond pills, including intracavernosal injections and the penile prosthesis, with details on surgical safety and infection prevention.
- •Trimix injections are titrated in the office, and too much can cause priapism
- •Treatment is now guided by shared decision-making rather than a strict first, second, third line
- •The penile prosthesis, invented at Baylor in 1973, uses cylinders, a scrotal pump and a reservoir
- •Surgeons should perform at least 50 to 60 implants a year, with an infection rate near 1 to 2%
- •Khera uses vancomycin, gentamicin, antifungal and Irrasept irrigation, since an infection is a disaster
- 59:40 – 1:05:40
Priapism: Causes and Emergency Management
Khera defines priapism and explains why a prolonged erection is an emergency. He describes how it is treated and its link to Peyronie's and implants.
- •Priapism lasts more than six hours, and patients should seek care after four
- •After about 36 hours the chance of recovery is very low, and fibrosis makes later implants harder
- •Causes include excess injection and drugs such as trazodone and cocaine
- •Treatment escalates from phenylephrine to aspiration and irrigation to a T shunt
- •Repeated Trimix injections are a risk factor for Peyronie's, so patients alternate sides
- 1:05:40 – 1:11:33
Shockwave Therapy, Stem Cells, and PRP for ED
Khera reviews emerging regenerative treatments for ED and why caution is needed. He explains the science of low-intensity shockwave, the commercial hype, and the lack of placebo-controlled evidence for stem cells and PRP.
- •Low-intensity shockwave induces angiogenesis and stem cell recruitment; true Class 3 devices may help mild to moderate ED
- •Cheap pneumatic devices are sold at $500 to $1,000 a session and the ED population is vulnerable with a high placebo response
- •Society and AUA positions from 2018 call shockwave investigational
- •His stem cell study had no placebo group and showed about a four-point IIEF gain that tapered after six to nine months
- •PRP has little science behind it, though a Miami trial of PRP with shockwave is due
- •Khera is most optimistic about shockwave; Attia summarizes the ED takeaways
- 1:11:33 – 1:26:35
Premature Ejaculation and Retrograde Ejaculation
The discussion shifts to ejaculatory dysfunction, starting with how premature ejaculation is defined and why most men do not seek treatment. Khera covers causes, treatment algorithm, and retrograde ejaculation.
- •Lifelong versus acquired PE determines the workup, and PE requires short latency, loss of control and bother
- •Causes include penile sensitivity, neurotransmitters, genetics and psychology
- •First-line options are lidocaine spray and sex therapy, with SSRIs as an option
- •Second-line options are tramadol, which carries a high addiction risk, and alpha blockers
- •Retrograde ejaculation from alpha blockers is harmless except for fertility
- 1:26:35 – 1:31:53
Anorgasmia, Delayed Ejaculation, and Treating ED First
Khera discusses delayed ejaculation and how ejaculatory latency is measured. He covers the role of SSRIs and 5-alpha reductase inhibitors, and why ED should be treated first when combined with PE.
- •Average intravaginal ejaculatory latency is about six to seven minutes, measured best with a partner's stopwatch
- •SSRIs such as Paxil prolong latency in a dose-dependent way and are a common cause of delayed orgasm
- •There are no FDA-approved treatments for delayed orgasm, and testosterone is one off-label option
- •5-alpha reductase inhibitors may impair orgasm by lowering DHT
- •When ED and PE coexist, treating the ED first can improve the PE
- 1:31:53 – 1:47:14
Hormone Axis, Free Testosterone, and Who Needs Treatment
Khera explains the hypothalamic-pituitary-testicular axis and why free testosterone and SHBG matter more than total T. He and Attia discuss symptoms-based decisions and the risks of starting therapy in younger men.
- •GnRH drives LH and FSH, acting on Leydig and Sertoli cells, with feedback from testosterone and estrogen
- •Testosterone is bound mainly to albumin and SHBG, and free T best correlates with symptoms
- •Healthy aging does not greatly lower total T, but SHBG rises and free T falls
- •Symptoms such as low energy, low libido, ED, fat gain and poor sleep guide treatment rather than numbers alone
- •Starting testosterone suppresses the endogenous axis, and young men starting in T clinics may become infertile
- 1:47:14 – 2:00:03
Raising Testosterone Endogenously and Preserving Fertility
Khera reviews clomiphene, enclomiphene and hCG, their drawbacks and supply problems, and their role in Klinefelter's and fertility. He describes protocols to protect or reverse spermatogenesis and the nasal testosterone Natesto.
- •Clomid can raise T but about 40% of men lose libido and erections because it blocks central estrogen
- •hCG can no longer be compounded, so Clomid shortages and expensive hCG followed
- •Klinefelter's affects about 1 in 500 and men with already high LH and FSH cannot use Clomid or hCG
- •Low-dose hCG (500 units) alongside testosterone helps protect intratesticular testosterone and fertility, while 3,000 units plus FSH is a reversal protocol
- •Natesto nasal testosterone did not significantly suppress spermatogenesis in a Miami study
- 2:00:03 – 2:11:03
Exogenous Testosterone Options: Injections, Orals, Pellets, Gels
Khera compares formulations for men committed to long-term therapy. He favors twice-weekly subcutaneous injections for physiologic levels and low cost, and discusses the autoinjector, oral undecanoate, pellets, and why he dislikes topicals.
- •Subcutaneous cypionate or enanthate Sunday and Thursday costs about $25 a month, and large biweekly doses cause erythrocytosis
- •Xyosted autoinjector costs about $150 cash but avoids drawing doses
- •Oral testosterone undecanoate requires food, is dosed twice daily, and has three FDA-approved options
- •Pellets peak quickly but decline after three to four months and require 72 hours without exercise
- •Gels have 20% non-absorbers, variable penetrance, transference risk and one-year attrition of about 80%
- 2:11:03 – 2:18:30
Androgen Receptor Sensitivity and DHT
Khera explains why the 300 ng/dL cutoff is arbitrary and how androgen receptor sensitivity, including CAG repeats, varies. The conversation turns to DHT, 5-alpha reductase isoenzymes, and why he avoids 5-ARIs for BPH.
- •Different tissues respond at different testosterone levels, so aiming for the upper quartile covers more symptoms
- •CAG repeat length reflects receptor sensitivity, but no CLIA-certified clinical assay is available
- •DHT is the most potent androgen and matters for sexual function, prostate growth and hair
- •Finasteride acts mainly on type 2 and dutasteride on types 1 and 2, enzymes found throughout the body
- •For BPH he uses alfuzosin or daily Cialis instead of 5-ARIs
- 2:18:30 – 2:26:42
Post-Finasteride Syndrome
Khera says he believes a subset of finasteride users develop lasting sexual, neurologic and psychological symptoms. He and Attia debate the evidence, including suicide data, study design limits and possible epigenetic mechanisms.
- •Khera believes post-finasteride syndrome is real in a subset of patients but acknowledges he is in the minority
- •He proposes 5-alpha reductase blockade also reduces conversion of progesterone to allopregnanolone, a neurosteroid tied to mood and cognition
- •In his study of 25 men, two died by suicide, and Attia pushes back on confounding and the need for randomized or better-matched designs
- •Several countries added suicidal ideation warnings to package inserts
- •Persistence after stopping suggests epigenetic mechanisms such as DNA methylation, but this is unknown
- 2:26:42 – 2:38:30
Testosterone and Prostate Cancer
Attia raises prostate cancer as the most common concern about testosterone therapy. Khera reviews the history, AUA guidance, bipolar androgen therapy trials, his lab work on an inverted U, and the prostate saturation model.
- •The fear dates to 1941 and one patient, while the 2018 AUA guideline strongly says patients should be told there is no association
- •Bipolar androgen therapy halved PSA and radiographic disease in some metastatic patients, and the TRANSFORMER trial showed similar survival to enzalutamide with better quality of life
- •His cell and mouse work showed an inverted U where castrate and normal levels were less promoting than low levels
- •Most urologists surveyed treat men after prostatectomy or radiation with testosterone
- •The saturation model suggests PSA rises when T goes from low levels to about 250 ng/dL and then plateaus
- 2:38:30 – 2:42:02
Testosterone in Breast Cancer and Finding a Specialist
Attia asks about testosterone as an adjunct for estrogen-sensitive breast cancer, and Khera notes limited experience. They close with how to find qualified providers through the Sexual Medicine Society of North America.
- •Khera uses non-hormonal options like Addyi for sexual function in women with breast cancer history
- •Studies he has seen gave testosterone without an aromatase inhibitor and found it protective, but he has little experience
- •The Sexual Medicine Society of North America has about 1,200 members, around 400 to 450 of them urologists
- •The society's website helps people locate providers, and Khera can do telemedicine only within Texas
