The Peter Attia Drive

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.

Mon Jun 26 2023

male sexual healtherectile dysfunctionpenile injuriestestosterone replacement therapyPeyronie's diseasepremature ejaculationpost-finasteride syndromeprostate cancerbreast cancer

Description

This episode covers various aspects of male sexual health, including erectile dysfunction, treatments for ED, penile injuries, testosterone replacement therapy, and the relationship between ED and cardiovascular disease. It also explores topics such as Peyronie's disease, premature ejaculation, and post-finasteride syndrome. The episode provides insights into diagnostic tests, treatment options, and the impact of lifestyle modifications on sexual function. Additionally, it discusses the use of stem cell therapy and shockwave therapy for ED. The episode concludes with discussions on testosterone replacement therapy for prostate cancer and breast cancer.

Insights

Erectile Dysfunction Treatment

Treatment options for erectile dysfunction include medications like Cialis, Viagra, and Levitra, as well as shockwave therapy and lifestyle modifications.

Penile Injuries and Treatments

Penile injuries can be treated with traction devices, collagenase injections, or surgical interventions like grafts or penile prosthesis.

Testosterone Replacement Therapy

Testosterone replacement therapy can be administered through injectables, oral options, or pellet implants. It is important to consider fertility preservation and individualized treatment plans.

Post-Finasteride Syndrome

Post-finasteride syndrome is a condition characterized by prolonged side effects after taking finasteride. More research and awareness are needed to understand and address this condition.

Prostate Cancer Treatment

Testosterone therapy may have potential benefits in the treatment of prostate cancer, but further research is needed to determine the optimal approach.

Chapters

Summary

Transcript

Introduction

00:11 - 06:46

The podcast focuses on translating the science of longevity into accessible content in health and wellness.
Dr. Mohit Karah, a professor of urology at Baylor College of Medicine, is the guest for this episode.

Male Sexual Health

06:27 - 23:53

The episode discusses various aspects of male sexual health, starting with erectile dysfunction and its diagnosis and connection to cardiovascular disease.
Different treatments for erectile dysfunction are explored, including drugs, shockwave therapy, stem cells, PRP, and lifestyle modifications.
Peroni's disease, causes and treatments for curvature of the penis, is discussed.
Topics such as penal fractures and penile enlargement treatments are covered.
The conversation moves on to discuss issues like prolonged erections (over four hours), premature ejaculation, and delayed orgasms (anoregasmia), including their causes and treatments.
Testosterone physiology is explained, along with measuring testosterone levels through blood panels and symptoms of low testosterone.
Testosterone replacement therapy options are discussed, including pellets, topical formulations, injectable formulations, oral formulations, and intranasal formulas.
The role of testosterone in patients with prostate cancer is also mentioned.
DHT (dihydrotestosterone) and finasteride are touched upon along with concerns about post-finasteride syndrome.

Erectile Dysfunction

11:57 - 17:59

Erectile dysfunction (ED) can be caused by various factors including vascular, endocrine, neurologic, trauma, medications, and psychogenic issues.
Psychogenic ED is more common in younger patients and is treated differently from organic ED.
Sex therapy can be effective for psychogenic ED, but many men prefer medication.
Daily Cialis at a low dose can help improve erections in young patients with psychogenic ED.
The fear of losing an erection can create a vicious cycle of anxiety and avoidance of sexual activity.
Peno ultrasound can be used to assess erectile function and provide therapeutic reassurance.
Cialis, Viagra, and Levitra work by inhibiting phosphodiesterase to increase cyclic GMP levels and maintain erections.
Different phosphodiesterases are present in different parts of the body, leading to potential side effects with these medications.
The newest medication Vanafil has less cross-reactivity with other phosphodiesterases but is more expensive than generic options like Cialis.

Viagra and Sexual Health

17:42 - 23:53

Viagra was initially developed as a blood pressure medication but failed in clinical trials.
Patients on the placebo were more willing to return samples, while those on Viagra kept it, leading to further investigation.
Viagra became a game changer in the field of sexual medicine for treating erectile dysfunction in men.
Other drugs for female sexual health like ADI and Vileesi had less impact compared to Viagra.
Estrogen replacement therapy (HRT) may have the greatest effect on women's sexual health when combined with other medications.
The main issue in erectile dysfunction is venous leak or vino-occlusive dysfunction caused by muscle atrophy and fibrosis as we age.
Increasing inflow with medications like Viagra or using a penile band can help overcome venous leak.
Aging and lower testosterone levels can contribute to venous leak and muscle atrophy in the penis.
Regular use of the penile muscle through erections and sexual activity can help prevent muscle atrophy.

Male Reproductive System and Sexual Dysfunctions

23:25 - 29:35

The male reproductive system consists of the corpora cavernosa responsible for erections and the urethra responsible for urinary functions.
Infertility can affect hypogonadism, and vice versa.
Medication for BPH can cause retrograde ejaculation, affecting fertility and sexual function.
52% of men over the age of 40 suffer from erectile dysfunction (ED), with conservative estimates suggesting around 30 million men in the US have this condition.
The IIEF questionnaire is used to assess ED severity, with mild, moderate, or severe classifications.
ED prevalence increases with age: 40% at 40, 50% at 50, 60% at 60, and 70% at 70.
43% of women in the US experience some degree of sexual dysfunction.
30% of men in the US have premature ejaculation or ejaculatory dysfunction.
7-9% of men in the US have Peyronie's disease.
Many individuals suffering from sexual dysfunctions remain silent about their condition, leading to negative impacts on mental health and relationships.
Approximately only half of those affected by sexual dysfunctions inform their doctor or partner due to embarrassment.
Clinicians often do not ask about sexual dysfunctions during appointments due to time constraints.

Physiology, Aging, and Cardiovascular Health

29:19 - 35:32

Physiology changes as we age, making it more difficult to get an erection and contributing to refractory time.
Evolution may have prioritized women's reproductive health over sexual health as they age.
Men's ability to reproduce may decrease with age due to genetic mutations in sperm, but overall health plays a significant role.
Lifestyle modifications such as diet, exercise, sleep, and stress reduction can improve erectile function.
There is a strong correlation between erectile dysfunction (ED) and cardiovascular disease.
ED can be a warning sign of future cardiovascular events.
The prevailing theory linking ED and cardiovascular disease is endothelial dysfunction.
Improving endothelial dysfunction can reverse cardiovascular disease and potentially improve ED.
Risk factors for cardiovascular disease like smoking, high blood pressure, obesity, and diabetes also contribute to ED.
A study showed that diet and exercise alone can lead to a meaningful improvement in erectile function.

Diagnostic Tests and Treatment Options

35:11 - 41:26

A three-point increase in endothelial function from diet and exercise alone can be considered a meaningful improvement for erectile dysfunction (ED).
Lifestyle modifications, such as diet and exercise, are important for improving ED.
Diagnostic ultrasound of the penis can help identify arterial insufficiency or venous leak as causes of ED.
Injection of trimex or alprosidil into the corpora can induce an erection for diagnostic purposes.
Peak systolic velocity less than 30 or endyostolic velocity greater than 5 indicate arterial insufficiency or venous leak, respectively.
Plaque in the corpora cavernosa can cause abnormal curvature of the penis, known as pronis disease.
Xiaflex or collagenase injection is an FDA-approved treatment for pronis disease that breaks down plaque and improves curvature.
Medical treatments like vitamin E and Colchicine are not effective for pronis disease; anti-inflammatories are indicated instead.
Pronis disease has an active phase and a quiescent phase, with about 15% of patients improving within the first year after injury.
Trauma during sexual activity is believed to be a common cause of pronis disease, resulting in plaque formation and curvature of the penis.
Medications like collagenase injections or surgical interventions like grafts or penile prosthesis can help treat pronis disease and restore straightness to the penis.

Penile Injuries and Treatment Options

40:59 - 47:07

Pinoff fracture is a sudden injury that requires immediate medical therapy.
Low testosterone levels may increase the risk of penile injuries and impair wound healing.
During the active phase of Peyronie's disease, 15% of patients get better, 40% stay the same, and 45% get worse.
Traction devices can be used off-label to treat Peyronie's disease and may improve curvature by 30-40% when used consistently for three months.
Traction devices can also be used to increase penis length and girth, with potential gains of up to one inch in length.
The use of traction devices should be done daily for at least 30 minutes, up to three months.
Using traction devices during the active phase of Peyronie's disease may help prevent further progression of the condition.

Insights

46:37 - 52:29

Success can be defined as reducing a score from 30 to zero or preventing it from increasing from 30 to 70 in the active phase.
Stretching devices are off-label but potentially worth it for treating damage, although they are expensive.
Ultrasound results help determine the location and severity of the problem in erectile dysfunction (ED).
If there is a venous leak, a band can be offered as a treatment option.
Low peaks of systolic velocity in young men may indicate cardiovascular risk.
Endo-pat 2000 was used to measure endothelial function and correlate it with cardiovascular disease.
Injections, such as trimex, into the penile tissue can be effective for ED but require careful dosing to avoid priapism.
Penile implants are an option for severe cases of ED.
Shared decision making is now used to offer patients all treatment options.

Treatment Options for Erectile Dysfunction

52:03 - 57:40

ED is a progressive disease, requiring higher and higher doses of medication.
Shared decision making allows patients to choose their preferred treatment option for ED.
Urethra suppositories are no longer used due to discomfort and side effects.
Penile prosthesis is a reliable and effective treatment option for ED.
The device consists of cylinders, a pump, and a reservoir that create an erection when activated.
Erection can be maintained even after ejaculation with the penile prosthesis.
Injection therapy wears off over time, but some men use it recreationally.
Penile implant surgery is relatively safe with low infection rates.
Surgeons should have experience performing at least 50-60 procedures per year.
Infection risk is mitigated by using prophylactic antibiotics and antibiotic-coated devices.
Strict protocols are followed in the operating room to minimize infection risk during surgery.
Infections may require removal of the implant, with salvage success rate around 86% if caught early.
Priapism (prolonged erection) lasting more than six hours may also be treated with a penile implant.

Priapism and Treatment Options

57:13 - 1:02:49

Priapism is a prolonged erection that lasts longer than six hours, and patients should seek medical attention if it lasts longer than four hours.
Patients with priapism may delay seeking care due to shame or the belief that the erection will go down on its own.
It is crucial to implant a penile prosthesis within three months of priapism onset to avoid fibrosis and scarring in the tissue.
If a shunt procedure is performed, it is necessary to wait for three weeks before implanting a penile prosthesis.
Ultrasound can be used to determine if there is a shunt present in the patient.
High flow priapism, typically caused by trauma, requires different treatment compared to low flow priapism.
Priapism can be caused by various factors, including medications like trazodone and excessive use of phosphodiesterase inhibitors.
If an erection lasts for more than four hours, patients should go to the emergency room where phenylephrine can be injected as an antidote.
Aspiration irrigation can be performed off the base of the penis using normal saline to remove sluggish blood and clots.
A T-Shunt procedure involves making an incision through the glands into the corpora under local anesthesia or in the operating room. This procedure carries a risk of erectile dysfunction.

Shockwave Therapy and Stem Cell Treatment

1:02:32 - 1:08:43

Physiology changes as we age, making it more difficult to get an erection and contributing to refractory time.
Evolution may have prioritized women's reproductive health over sexual health as they age.
Men's ability to reproduce may decrease with age due to genetic mutations in sperm, but overall health plays a significant role.
Lifestyle modifications such as diet, exercise, sleep, and stress reduction can improve erectile function.
There is a strong correlation between erectile dysfunction (ED) and cardiovascular disease.
ED can be a warning sign of future cardiovascular events.
The prevailing theory linking ED and cardiovascular disease is endothelial dysfunction.
Improving endothelial dysfunction can reverse cardiovascular disease and potentially improve ED.
Risk factors for cardiovascular disease like smoking, high blood pressure, obesity, and diabetes also contribute to ED.
A study showed that diet and exercise alone can lead to a meaningful improvement in erectile function.

Stem Cell Therapy and Testosterone Replacement

1:08:15 - 1:14:17

Stem cells can be used for erectile dysfunction (ED), but there is no FDA approval for this treatment in the United States.
Patients may need to go outside the country, such as Costa Rica or Panama, to receive stem cell therapy for ED.
A study conducted with adipose-derived stem cells showed some increase in erectile function, but the effect was not long-lasting.
There is a lack of placebo control trials for stem cell therapy for ED, so more research is needed to determine its efficacy.
Exosomes, which are secreted by stem cells, are being explored as an alternative to stem cell therapy for ED.
Platelet-rich plasma (PRP) therapy also shows potential benefits for ED, but there is limited scientific evidence available.
A study at the University of Miami is currently investigating the combination of PRP and shockwave therapy for ED.
It is important for men experiencing ED to seek help and not suffer in silence.
Daily phosphodiesterase inhibitors are a viable solution and should not be stigmatized or feared as dependency-inducing drugs.
Psychogenic factors should be ruled out before proceeding with pharmacologic therapies for ED.
Diagnostic tests such as arterial and venous assessments can help determine the cause of ED.

Treatment Options for Premature Ejaculation

1:14:00 - 1:20:04

Delayed orgasmia can be treated with testosterone, but using phosphodiesterase inhibitors may expose the delay rather than induce it.
When a patient presents with both erectile dysfunction (ED) and premature ejaculation (PE), it is important to treat the ED first.
Treating the ED can help prolong ejaculatory time by removing the worry of losing an erection.
Testosterone replacement therapy involves the hypothalamus, pituitary gland, testes, and adrenals in hormone generation.
LH and FSH are secreted by the pituitary gland and stimulate testosterone production in the testicles.
The size of a man's testicles is more indicative of fertility status than hormonal status.
Testosterone has a negative feedback on both the pituitary gland and hypothalamus, as does estrogen.
Testosterone can be converted into estrogen and dihydrotestosterone (DHT).
Some clinics use aromatase inhibitors and five alpha reductase to control these conversions.
FSH, LH, SHBG, free testosterone, bioavailable testosterone, and free endrogen index are all measurable factors related to testosterone levels.

Testosterone Replacement Therapy

1:19:37 - 1:25:32

There are online calculators that can estimate free testosterone levels based on albumin, SHBG, and total testosterone.
LCMS assay is the gold standard for measuring free testosterone, but it's expensive and hard to obtain.
Data on the distribution of free testosterone across different age groups is limited.
Total testosterone levels don't decline significantly with age in healthy males; comorbid conditions can lower testosterone levels.
SHBG levels tend to increase with age, leading to a decrease in free testosterone.
Genetics and comorbid conditions can influence SHBG levels.
Obesity can cause SHBG levels to decrease due to hyperinsulinemia.
The link between plasma concentration of free testosterone and its physiological effects in cells is not well understood.
Symptoms should be considered when deciding whether or not to treat low free testosterone levels.
Treatment decisions should be based on how the patient feels rather than solely relying on numerical values.

Testosterone Replacement Therapy Options

1:25:04 - 1:31:14

Low energy, low libido, erectile dysfunction, depression, poor sleep are common symptoms to ask about.
Recovery from workouts and bone fractures are important considerations.
Obesity and metabolic syndrome should be assessed.
Appendicular lean mass index is a factor to evaluate for testosterone treatment.
Testosterone may not be necessary for young patients who can improve muscle mass with training and protein intake.
Some men start testosterone therapy at a young age without being informed about potential infertility.
Historically, testosterone replacement has been done through Clomid (pill), HCG (injectable), or injectable testosterone cipionate or its derivatives. Pellets were also used but are less common now.
Clomid preserves testicular volume and spermatic function but may cause a decrease in desire for sex due to blocking estrogen receptors.
HCG is an injectable mimetic for LH that preserves testicular volume but its efficacy in preserving fertility is unclear compared to Clomid.
Injectable testosterone cipionate or its derivatives are the mainstay of testosterone replacement therapy.
Endogenous ways to raise testosterone include using Chlomiphene or HCG, although HCG is more expensive and delicate to handle.
Chlomiphene can cause a discrepancy effect where patients have increased testosterone levels but no desire for sex due to blocking estrogen receptors.

Treatment Options for Low Testosterone

1:30:59 - 1:37:04

There is a shortage of Clomid and HEG due to high demand.
The FDA may have restricted compounding HEG due to patent infringement.
Clomid is used for fertility treatment, but it needs to be taken every other day.
HCG can be used for fertility treatment, but it is expensive.
Klinefelter syndrome is a genetic abnormality that affects male infertility.
Patients with Klinefelter syndrome may have low testosterone levels.
Testosterone treatment may not be the first-line option for Klinefelter syndrome patients who want to have children.
Reversal procedures like micro testi can help restore fertility in patients who have taken testosterone for a long time.

Preserving Fertility and Testosterone Levels

1:36:49 - 1:43:03

Study by Koveela in 2005 showed a 94% decline in intra-testicular testosterone in three weeks with 200mg of testosterone IM every week
Different doses of HCG (250-1000 units) did not significantly decline intra-testicular testosterone
HCG can help protect against the decrease in spermogenesis, but it's not completely safe
HCG has some FSH properties and can improve sperm production when used for fertility
Recombinant FSH is more efficacious for maintaining sperm production, but it is extremely expensive
Intranasal testosterone (Nettesto) does not significantly suppress spermatogenesis and has rapid onset, but its bioavailability is lower than injection
Injectable testosterone (Cypionate or Nanthet) is affordable and commonly used, with Cypionate being more anabolic and suitable for younger patients

Testosterone Replacement Therapy Administration

1:43:45 - 1:48:26

Injectables are typically administered subcutaneously using a 25 gauge needle and a one cc syringe.
The recommended injection schedule is on Sundays and Thursdays, as the drugs peak in 24 hours.
Pinching the fat during injection can help reduce pain.
Patients can choose to inject in the belly or upper outer gluteal fold, but injecting in the fat results in higher blood levels of the drug.
Zai is an alternative to traditional injections that uses a pre-loaded, spring-loaded device with a tiny 27-gauge needle.
Zai costs $150 per month and eliminates the need for travel and drawing up doses.
Oral testosterone options have become popular due to their convenience, but they must be taken with a meal for proper absorption.
Taking oral testosterone at breakfast and lunch can provide more consistent blood levels throughout the day.
There are currently three FDA-approved oral testosterone options available, with varying dosages and titration protocols.
Pellet implants are effective but require more frequent administration due to a sharp decline in hormone levels after three months.

Insights

1:48:02 - 1:53:48

A technique called stacking is used for testosterone pellet insertion, where the pellets are stacked vertically like a column to prevent expulsion and trauma.
After inserting pellets, patients should avoid exercise for 72 hours and keep the bandage on for 48 hours.
The injectable form of testosterone therapy is favored over other forms due to its lower erythrocytosis rate, better physiologic level, and cost-effectiveness.
Topical testosterone is not recommended for men due to poor absorption rates, variable penetrance, and transference issues.
Gels have a high attrition rate and may not achieve desired testosterone levels compared to injectables.
Testosterone has different effects on various body parts at different levels, with erectile function typically starting to decline below 200 nanograms per deciliter.
The cutoffs for free testosterone levels vary among individuals based on the sensitivity of their antigen receptors.

Post-Finasteride Syndrome

1:53:31 - 2:00:10

There is a subset of patients who develop post-finasteride syndrome, characterized by prolonged side effects such as libido issues, psychological problems, depression, and suicidal ideations.
The official position of the American Urologic Association acknowledges that there are patients who experience prolonged side effects with finasteride.
Finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), but it also affects other steroids and their neurosteroids.
Blocking certain neurosteroids like alopregnanolone can lead to depression, anxiety, and cognitive issues.
There has been an increase in suicide rates among men with post-finasteride syndrome.
Less than 5% of men who take finasteride experience negative side effects that persist after stopping the drug.
Many men attribute these symptoms to normal aging when they occur later in life.
Regardless of whether one believes in post-finasteride syndrome or not, there is an increased risk of suicides in this population of men.
A study found that two out of twenty-five men taking finasteride for alopecia committed suicide during the trial period.
It would be important to isolate the group of men experiencing negative symptoms from those who do not for further analysis.
More attention needs to be given to this condition and warnings about its potential risks should be included in drug labeling.

Insights

2:00:00 - 2:06:50

SSRIs have a warning about increased suicide risk, but it's unclear if they actually cause it.
The lingering sexual side effects of certain drugs may be epigenetic.
Testosterone replacement therapy does not increase the risk of prostate cancer, and may even protect against it.
Exogenous testosterone therapy does not significantly increase the risk of cardiovascular disease.
High doses of testosterone have been used to treat metastatic prostate cancer with positive results.
Bipolar androgen therapy has shown promising results in treating castrate-resistant metastatic prostate cancer.

Treatment Options for Prostate Cancer

2:06:30 - 2:12:20

The Transformer Trial showed impressive results using enzalutamide versus bicalutamide in the treatment of metastatic prostate cancer.
Therapeutic use of testosterone is expected to increase, with studies suggesting potential benefits in men after radical prostatectomy.
In laboratory studies, higher doses of testosterone led to greater suppression of prostate cancer cell growth.
Castration and high doses of testosterone both resulted in a statistically significant decrease in prostate cancer growth compared to castration alone.
Chemical castration can have negative effects on metabolic health and quality of life for men with prostate cancer.
Treatment after radiation therapy with testosterone is controversial, but many urologists do prescribe it.
The risk-benefit ratio of testosterone therapy after prostate cancer surgery or radiation is unknown, so informed decision-making is necessary.
The saturation model suggests that there is a point at which increasing testosterone levels no longer significantly affect PSA levels.
Patients who have undergone endocrine deprivation therapy may experience a rise in PSA when starting testosterone replacement due to saturation levels.

Insights

2:12:00 - 2:17:40

Testosterone may be used as an adjunct therapy in estrogen-sensitive breast cancers.
Some studies suggest that testosterone replacement therapy is protective against breast cancer.
Aromatase inhibitors may not be necessary when using testosterone for breast cancer treatment.
There are doctors specializing in sexual health and men's health, with about 1,200 members in the Sexual Men's Society of North America.
Most of these doctors are in academic institutions.
The society's website can help people find providers in their area.