#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.
Dr. Mohit Khera, a professor of urology at Baylor College of Medicine and expert in male sexual health, discusses erectile dysfunction, Peyronie's disease, premature ejaculation, and anorgasmia. He also provides a comprehensive overview of testosterone physiology, replacement therapy, and its controversial role in prostate cancer and post-finasteride syndrome.
Deep Dive Analysis
21 Topic Outline
Mohit Khera's Background and Urology Specialization
Anatomy of Male Genitalia and Interconnected Systems
Prevalence and Impact of Male Sexual Dysfunction
Erectile Dysfunction (ED): Definition, Diagnosis, and Psychogenic Causes
Mechanism and History of PDE5 Inhibitors (Viagra, Cialis)
Aging, Comorbidities, and ED Pathophysiology (Venous Leak)
Lifestyle, Endothelial Dysfunction, and ED-Cardiovascular Link
Diagnostic Penile Ultrasound for ED and Peyronie's
Peyronie's Disease: Causes, Prevalence, and Treatment Options
Penile Fractures and Urgent Surgical Intervention
Penile Traction Devices for Curvature and Enlargement
ED Treatment Progression: Injections, Penile Prosthesis, Priapism
Investigational ED Treatments: Shockwave, Stem Cells, PRP
Premature Ejaculation: Types, Causes, and Treatment Approaches
Delayed Ejaculation and Anorgasmia: Causes and Management
Physiology of Testosterone, DHT, Estrogen, and SHBG
Endogenous Testosterone Enhancement (Clomid, HCG)
Exogenous Testosterone Replacement Therapy (TRT) Options
Post-Finasteride Syndrome: Symptoms, Mechanisms, and Controversy
Testosterone and Prostate Cancer: Shifting Paradigms
Testosterone's Role in Breast Cancer and Provider Resources
7 Key Concepts
Erectile Dysfunction (ED)
Defined as the inability to get or maintain an erection sufficient for penetration or until orgasm. It affects a significant percentage of men, increasing with age, and can be categorized as psychogenic (often in younger men) or organic (due to vascular, endocrine, neurologic, or trauma issues).
Venous Leak (Veno-occlusive Dysfunction)
A common cause of organic ED where the penile smooth muscle atrophies and fibroses with age, preventing sufficient pressure on the subtunical veins to trap blood, leading to an inability to maintain an erection despite adequate inflow.
Endothelial Dysfunction
A condition where the inner lining of blood vessels (endothelium) doesn't function properly, impairing vasodilation. It is considered a common link between erectile dysfunction and cardiovascular disease, as both share similar risk factors.
Peyronie's Disease
A condition characterized by the formation of plaque in the tunica albuginea (the casing of the penis), often due to trauma during intercourse, leading to an abnormal curvature of the penis when erect. It has an active phase with pain and a quiescent phase where the curvature stabilizes.
Priapism
A prolonged erection lasting greater than six hours, which is a medical emergency. If not treated promptly, it can lead to necrosis and permanent damage to the penile tissue due to lack of oxygen and clotting of blood.
Post-Finasteride Syndrome (PFS)
A controversial condition where individuals who have taken finasteride experience persistent, irreversible sexual, neurologic, and psychological symptoms even after discontinuing the drug. It is hypothesized to involve the blocking of neurosteroid conversions beyond just DHT.
Prostate Saturation Model
A concept suggesting that prostate growth and PSA levels do not increase linearly with rising testosterone levels. Instead, the prostate's androgen receptors become saturated at a certain testosterone level (around 250 ng/dL), after which further increases in testosterone do not lead to additional growth or PSA elevation.
11 Questions Answered
ED affects 52% of men over the age of 40 to some degree, with prevalence increasing with age (e.g., 40% at 40, 50% at 50, 60% at 60).
ED is diagnosed using validated questionnaires like the IIEF, or by asking two simple questions: 'Are you able to get an erection sufficient for penetration?' and 'Are you able to maintain that erection until orgasm?' Answering 'no' to either indicates ED.
ED is a strong predictor of cardiovascular disease; studies show that men who develop ED have a 15% chance of a heart attack or stroke within seven years, making it a 'sentinel sign' of CVD, primarily linked by endothelial dysfunction.
These medications block phosphodiesterase, an enzyme that breaks down cyclic GMP. By inhibiting this enzyme, they increase cyclic GMP levels, which causes the dilation of penile blood vessels and allows more blood flow to sustain an erection.
Yes, daily Cialis has been shown to cause hypertrophy of cavernosal smooth muscle, keeping penile tissue healthy, and may also improve systemic endothelial dysfunction, acting as a preventative measure against ED progression.
Peyronie's disease is a curvature of the penis caused by plaque formation in the tunica albuginea, often due to trauma. Treatments include collagenase injections (Zyaflex) to break down plaque, surgical options like plication or grafting, and off-label use of penile traction devices.
Priapism is a prolonged erection lasting more than six hours. If an erection lasts longer than four hours, immediate medical attention in an emergency room is necessary to prevent permanent damage to penile tissue.
PE can be lifelong or acquired, often linked to increased glandular sensitivity, neurobiological factors (serotonin levels), genetics, or psychological stress. Treatments include lidocaine sprays, SSRIs (daily or on-demand), sex therapy techniques (start-stop, squeeze), and off-label use of tramadol or alpha-blockers.
Exogenous testosterone therapy typically suppresses endogenous testosterone production, leading to decreased spermatogenesis and potential infertility. While some methods like HCG or Clomid can help preserve or restore fertility, direct testosterone injections usually impair it.
Current guidelines and research indicate there is no association between testosterone therapy and an increased risk of prostate cancer. Emerging evidence even suggests that maintaining eugonadal testosterone levels may be protective against prostate cancer, and high-dose testosterone is being investigated as a therapy for metastatic prostate cancer.
PFS is a condition where men who have taken finasteride experience persistent, irreversible sexual, neurological, and psychological symptoms even after stopping the drug. It is believed to be linked to the drug's effect on neurosteroid conversions beyond just DHT, potentially leading to epigenetic changes.
35 Actionable Insights
1. ED Signals Cardiovascular Risk
View erectile dysfunction (ED) as a potential early warning sign of cardiovascular disease, prompting a comprehensive cardiovascular health assessment, as risk factors for both conditions are nearly identical.
2. Prioritize Lifestyle for Sexual Health
Implement lifestyle modifications, including diet, exercise, adequate sleep, and stress reduction, as these have a significant positive impact on erectile function and overall quality of life.
3. Avoid Finasteride and Dutasteride
Refrain from using finasteride or dutasteride due to concerns about ‘post-finasteride syndrome,’ which can cause irreversible sexual and neurological symptoms, and an increased risk of suicidal ideation.
4. Testosterone Therapy: Symptom-Driven
When considering testosterone replacement therapy (TRT), prioritize addressing symptoms like low energy, libido, ED, increased fat, decreased muscle, depression, or poor sleep, rather than focusing solely on blood test numbers.
5. Avoid Unnecessary Testosterone Therapy
Do not start testosterone replacement therapy (TRT) if you are asymptomatic, as it can suppress your body’s natural production and may lead to lifelong dependence without current need.
6. Daily Cialis for Penile Health
Consider taking 5mg daily Cialis as a preventative measure or when mild ED symptoms appear, as it can promote hypertrophy of cavernosal smooth muscle, keep penile tissue healthy, and improve endothelial function.
7. Address Sexual Dysfunction Openly
Do not suffer in silence; seek care for sexual dysfunction due to its significant impact on quality of life. Patients should feel empowered to discuss sexual health, and clinicians should proactively ask about it.
8. Priapism: Seek Emergency Care
If an erection lasts longer than four hours (priapism), seek immediate medical attention at the emergency room to prevent potential permanent damage to penile tissue.
9. Penile Fracture: Immediate Medical Attention
If you experience a ‘sudden pop’ and significant swelling in the penile shaft during sexual activity, seek immediate medical attention for a potential penile fracture.
10. Treat ED Before Premature Ejaculation
When a patient presents with both erectile dysfunction (ED) and premature ejaculation (PE), prioritize treating the ED first, as improving erection maintenance can often resolve or improve PE.
11. Injectable Testosterone: Preferred Method
For testosterone replacement, consider subcutaneous injections (e.g., 50mg cypionate twice a week) as a preferred method due to its effectiveness, lower cost, and more physiological levels compared to other forms.
12. Protect Spermatogenesis with HCG
If taking exogenous testosterone, consider co-administering 500 units of HCG every other day to help protect endogenous testicular function and spermatogenesis.
13. Fertility Preservation on Testosterone
For men on testosterone therapy who wish to preserve or restore fertility, consider HCG (1500-3000 units three times a week) or Clomid; for recovery from long-term suppression, HCG with recombinant FSH may be used.
14. BPH: Alpha Blocker or Cialis
For benign prostatic hyperplasia (BPH), consider alpha blockers (e.g., alfuzosin for lower retrograde ejaculation risk) or daily Cialis as medical treatment options, avoiding 5-alpha reductase inhibitors.
15. Peyronie’s: Use Traction Devices
For Peyronie’s disease, use penile traction devices (e.g., Restorex) for 30 minutes, twice daily for three months, to potentially increase length, girth, and straighten curvature (also off-label for general enlargement).
16. Maintain Regular Erections
Engage in regular sexual activity and ensure nocturnal erections to maintain penile muscle health and oxygenation, preventing atrophy and supporting erectile function.
17. Identify Psychogenic ED
If you experience ED but can achieve erections with masturbation or morning erections, it suggests psychogenic ED, which is treated with sex therapy and/or daily Cialis, rather than solely organic treatments.
18. Intranasal Testosterone for Fertility
Consider intranasal testosterone (Natesto, 11mg three times daily) as an option that may not significantly suppress spermatogenesis, offering a potential advantage for fertility-conscious men.
19. Oral Testosterone Undecanoate Considerations
Oral testosterone undecanoate (e.g., Jotenzo, Talando, Keisotrex) is an option that avoids hepatotoxicity, but requires twice-daily dosing with meals (preferably fatty meals for older formulations) for proper absorption.
20. Testosterone Pellets: Manage Expectations
If considering testosterone pellets, be aware of the sharp decline in levels after 3-4 months, potentially requiring shorter intervals, and plan for 72 hours of no exercise post-insertion.
21. Avoid Topical Testosterone for Men
Avoid topical testosterone gels for men due to variable absorption, difficulty achieving desired levels, the burden of daily application, and the risk of transference to others.
22. Cialis Benefits for BPH
For men with BPH, daily Cialis (5mg) is an FDA-approved treatment that can also improve erections, offering an alternative to Flomax which can cause retrograde ejaculation.
23. Cialis for Endothelial Health
Daily Cialis (5mg) may improve systemic endothelial dysfunction, with benefits potentially persisting even after cessation, suggesting a broader cardiovascular health benefit.
24. Peyronie’s: Active Phase Management
During the active phase of Peyronie’s disease (first 12 months), focus on anti-inflammatories and potentially traction devices to prevent progression, as surgical options are typically reserved for the quiescent (stable) phase.
25. Vary ED Injection Sites
If using penile injections for ED, vary the injection site (e.g., opposite sides every other day) to mitigate trauma and reduce the risk of Peyronie’s disease.
26. Shockwave Therapy: Use Caution
Low-intensity shockwave therapy (LIST) for mild to moderate ED shows promise by promoting neo-angiogenesis and stem cell recruitment, but use with caution as it’s still considered investigational and many commercial devices may be ineffective.
27. Stem Cells/PRP: Investigational Therapies
Stem cell and PRP therapies for ED are largely investigational, with limited or no placebo-controlled trial data and no FDA approval, so approach with caution and awareness of the lack of proven efficacy.
28. Premature Ejaculation: First-Line Treatments
For premature ejaculation (PE), first-line treatments include lidocaine spray (applied 10 minutes prior, wiped off), on-demand SSRIs (taken 6-8 hours prior), and sex therapy techniques like start-stop or squeeze.
29. Premature Ejaculation: Second-Line Options
Second-line therapies for premature ejaculation (PE) include tramadol (use with caution due to addiction risk) and alpha blockers like Flomax.
30. SSRIs and Delayed Ejaculation
If experiencing anorgasmia or delayed ejaculation while on SSRIs, discuss with your doctor reducing the SSRI dose, as ejaculatory latency can be sensitive to dosage.
31. Testosterone Therapy: Monitor PSA
If starting testosterone therapy after radiation for prostate cancer, expect an initial rise in PSA until testosterone levels reach saturation (around 250 ng/dL), and discuss this with your oncologist and patient to manage expectations.
32. Seek Sexual Medicine Specialist
If seeking specialized care for male sexual health, find a provider through the Sexual Medicine Society of North America website, which lists qualified professionals.
33. Diagnose ED with SEP2/SEP3
Use the simple SEP2 and SEP3 questions (ability to get and maintain an erection for penetration/orgasm) to self-diagnose or discuss with a doctor if you have erectile dysfunction (ED).
34. Self-Diagnose Premature Ejaculation
Self-diagnose premature ejaculation (PE) if you experience a decreased ejaculatory time (e.g., <2 minutes for lifelong PE, or 50% reduction for acquired PE), a sense of loss of control, and are bothered by the condition.
35. Penile Band for Venous Leak
If experiencing venous leak, a penile band (or manual pressure at the base) can be used to compress veins and prevent blood outflow, improving erection rigidity.
7 Key Quotes
52% of men over the age of 40 suffer from erectile dysfunction, to some degree.
Mohit Khera
The problem is that this population, I call it suffer in silence.
Mohit Khera
When you take Viagra, you are not curing your ED. You're just covering it that night while the disease continues to progress.
Mohit Khera
It is the sentinel sign of cardiovascular disease.
Mohit Khera
I don't know about five or 10 years from now, but today I'm not going to put you on it because the reality is if I do put you on it, it will suppress your endogenous access and you may need to be on it for life and you don't need it today. You have no symptoms.
Mohit Khera
I think finasteride is a very bad drug. And I think it has very detrimental effects.
Mohit Khera
The higher the testosterone, the greater the PSA. We were taught it was linear. And the higher the testosterone, the greater the growth. That is not true. At some point, it saturates.
Mohit Khera
5 Protocols
Penile Prosthesis Implantation (Infection Mitigation)
Mohit Khera- Administer prophylactic antibiotics (e.g., vancomycin and gentamicin, with vanc given an hour before surgery).
- Administer antifungal medication (as 10% of infections can be fungal).
- Use IriSept (chlorhexidine) intraoperatively.
- Ensure short operative time.
- Limit movement in the operating room, tape gloves, and limit personnel at the surgical table.
Peyronie's Disease Traction Device Use (Restorex)
Mohit Khera- Apply the device around the glans (head) and base of the flaccid penis.
- Extend the traction as far as comfortable.
- Bend the penis in the opposite direction of its natural curve.
- Hold for 30 minutes, at least twice a day.
- Continue this regimen for three months.
Premature Ejaculation Treatment (Sex Therapy Techniques)
Mohit Khera- Utilize the 'start-stop' technique to learn to prolong ejaculation.
- Utilize the 'squeeze' technique to learn to prolong ejaculation.
Reversal of Spermatogenesis Suppression from Testosterone Therapy
Mohit Khera- Stop exogenous testosterone therapy.
- Administer HCG 3,000 units, three times a week.
- Administer recombinant FSH (Gonol F) 75 units, three times a week.
- Continue this regimen for 3 to 7 months to potentially recover spermatogenesis.
Testosterone Replacement Therapy (Subcutaneous Injectable)
Mohit Khera- Inject testosterone cypionate (for younger patients) or enanthate (for older patients) subcutaneously.
- Use a 5/8 inch, 1 CC syringe with a 25 gauge needle.
- Pinch the fat on the belly for injection.
- Inject twice a week (e.g., Sunday and Thursday) at a dose of 50 mg to achieve more physiologic levels and reduce erythrocytosis.