Erectile Dysfunction: An Integrative Approach to Making It Work

Dr. Geo Espinosa, ND, LAc, IFMCP, CNS

The definition of erectile dysfunction (ED) is the inability to obtain or maintain an erection firm enough for sexual intercourse. Historically, admitting to having was considered taboo and downright embarrassing until the advent of sildenafil citrate (Viagra) in 1998. Sildenafil liberated men from the stigma of having ED, and it opened a conversation about a problem that has exist for centuries. Up to 10% of men younger than forty suffer from ED and upwards of 60% by age 69.1

The Physiology of an Erection

To learn how to treat erectile dysfunction, it is useful to understand how normal pelvic functioning works. Penile engorgement (tumescence) is a neurovascular event influenced by psychological and hormonal factors.

During sexual stimulation, sexual thoughts or nocturnal erections, the neurotransmitter nitric oxide (NO) is released from the endothelial cells and the parasympathetic nerve terminal causing relaxation of two cylinder-like muscles called the corpora carvenosum. Nitric oxide influences an increase in concentrations of cyclic guanosine monophosphate (cGMP), which after numerous pathways triggers smooth muscle relaxation, and simultaneous closing of small veins traps blood in the cavernosal muscles, keeping blood in the cavernosal tissues causing and maintain an erection.

Detumescence or a flaccid penis after ejaculation occurs from two events: a sympathetic effect during ejaculation inducing a breakdown of cGMP by the enzyme phosphodiesterase-5 and opening of the venous channels, thereby, expelling blood out of the carvenosum muscles, restoring flaccidity.2

The bottom line is that for penile erections to occur, there needs to be smooth and unobstructed transmission of nerve impulses and blood through the penile vessels.

 

What Are the Major Causes of ED?

ED is caused by vascular, hormonal, neurogenic, pharmacological, or psychogenic factors. Performance anxiety where the person fears failing in a sexual scenario is a common psychogenic cause for ED.3 Neurogenic causes are related to diseases like Alzheimer’s, Parkinson’s, stroke or spinal cord injuries. Radical removal of the prostate (also called prostatectomy) is the cause of nerve-related ED as nerve injury is possible despite advances in surgical methods.4

Testosterone (T) has an indirect influence on penile function. While the connection between T and erectile dysfunction is not linear, the master androgen is still significantly involved in penile function in adults. T supports the integrity of the corpus carvenosum and the vasculature that feeds the penis.

Nitric oxide (NO) is the key mediator for erectile function. NO is synthesized by the enzyme NO synthase (NOS), which is produced by endothelial cells (eNOS) and non-adrenergic/non-cholinergic (NANC) nerves (nNOS). Both eNOS and nNOS have been shown to be up-regulated by T.5

Lastly, T regulates the enzyme PDE5, which underlies the molecular mechanism that leads to the conclusion of an erection.6

Drug-Induced Erectile Dysfunction

Antidepressants, including selective serotonin reuptake inhibitors drugs and antihypertensives, are among the most common drug classes involved in the development of erectile dysfunction.7

Thiazides, followed by β blockers, are the most common groups of antihypertensive drugs that cause erectile dysfunction, whereas α blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers are the least likely of these drugs to cause erectile dysfunction.
8
Opioids are used for chronic pain or for recreational use, and there is currently an epidemic of opioid addiction in the United States. Opioids induce ED by inhibiting gonadotropin-releasing hormone (GnRH), which leads to a decrease in the production of luteinizing hormone (LH). Decreased levels of LH, in turn, inhibit production of testosterone, which – in both men and women – can cause depression and sexual dysfunction.9

 

Pharmaceutical Treatment for ED

The first line medical treatment for ED is phosphodiesterase inhibitors-5 (PDE-5) like sildenafil (Viagra; USA), tadanafil (Cialis; USA), verdenafil (Levitra; USA), udenafil (Zydena; South Korea), and mirodenafil (Mvix; South Korea).

These drugs facilitate erection by inhibiting the PDE5 enzyme, by blocking the degradation of cyclic guanosine monophosphate (cGMP) in the cavernous smooth muscles. This inhibition results in the prolonged activity of cGMP, which further decreases intracellular calcium concentrations, maintains smooth muscle relaxation and, hence, results in rigid penile erections.

Numerous placebo-controlled studies have shown that the number of erections and rates of penile rigidity, orgasmic function, and overall satisfaction improved with sildenafil than placebo.

The most common adverse events associated with all of the PDE-5 inhibitors10 are headaches in 16% of men; flushing in 10% of men; dyspepsia (7%); nasal congestion (4%), and visual disturbances/color sensitivity in about 3%. Tadalafil distinguishes itself from vardenafil and sildenafil by the relative lack of visual side effects. It does, however, have an additional possible adverse effect, which is back pain and/or myalgia.11

A clinical observation by the author is penile desensitization, where a numbing-like effect on the organ occurs. Patients would often say, “I feel like my penis is the detached from my body” or “I am getting an erection, but I am not enjoying it.”

Also, delayed ejaculation is another complained clinically observed in men using PDE-5 inhibitors where the man is unable to reach orgasm. This is a frustrating scenario for men that can lead to less sexual desire.

 

Metabolic Syndrome

Persons with metabolic syndrome can be identified by a distinct pattern of abdominal obesity (waist circumference >40 inches in men), atherogenic dyslipidemia (triglycerides ≥150 mg per 100 ml, HDL <40 mg per 100 ml, small LDL particles and normal or slightly elevated LDL), hypertension (≥130/85 mm Hg), insulin resistance (fasting blood glucose ≥10 0 mg per 100 ml), and elevated levels of prothrombotic and proinflammatory markers. Metabolic syndrome and insulin resistance are closely linked to ED. In one recently conducted study of 120 men with ED and no evidence of diabetes, 40% of patients fulfilled strict criteria for metabolic syndrome, and 73% were insulin resistant.12

 

Strong Cardiovascular-Penile Connection

There is a significant correlation between ED and cardiovascular disease (CDV).

In a meta-analysis of 12 prospective cohort studies, strong evidence showed that erectile dysfunction is indeed significantly and independently associated with an increased risk of not only CVD but also coronary heart disease, stroke, and all-cause mortality.13

 

Diagnosis

The main goals of assessment of erectile dysfunction are the following:

  1. Establish whether the patient truly has erectile dysfunction;
  2. Identify the cause of the disorder;
  3. Evaluate risk factors and potentially life-threatening comorbid disorders associated with erectile dysfunction.

The diagnosis of erectile dysfunction requires a comprehensive sexual and medical history that include a validated questionnaire, the Sexual Health Inventory for Men (SHIM), and asking if they experience a rigid erection at night, in the morning, or during masturbatory approaches. The presence of rigid morning or night erections, or rigid erections at any sexual thought suggests a mainly psychogenic cause. Conversely, erectile dysfunction with a gradual onset, progressive course, or long duration suggests a predominantly organic cause.

Laboratory testing should include the following:

  • Fasting blood glucose
  • Hemoglobin A1c
  • Total and Free Testosterone
  • Luteinizing hormone (LH)
  • DHEA -S
  • Prolactin
  • Lipid profile
  • C-Reactive Protein
  • Endothelin-1

 

Natural Treatment

The role of the practitioner providing a naturopathic treatment plan is to first identify the cause of the individual’s ED. If the cause is psychogenic (i.e. performance anxiety, depression, relationship problems), referral to a psychotherapist should be considered. Organic causes like metabolic syndrome, insulin resistance, or diabetes type II can be properly treated with lifestyle medicine and other numerous nutritional prescriptions beyond the scope of this article to discuss.

Hormonal causes should be treated with natural, lifestyle methods to help increase testosterone levels before prescribing supplemental, exogenous testosterone therapy. If DHEA-S levels are low, supplement with 50mg of DHEA.

 

Lifestyle Measures

A sedentary lifestyle, smoking, alcohol or drug misuse, sleep disorders, obesity, and metabolic syndromes have all been associated with erectile dysfunction.14

Intensive lifestyle changes that include a Mediterranean type diet, circuit-type resistance training, with 15- to 60-second rest between sessions has shown to improve erectile score in a randomized trial. Men in the intervention group had a significant decrease in glucose, insulin, low‐density lipoprotein cholesterol, triglycerides, and blood pressure, and a substantial increase in HDL cholesterol.15

 

Botanical and Natural Support for ED

Adaptogens are nontoxic agents that increase resistance to stressors and prevent fatigue. There are well-documented adverse effects of stress on libido and sexual function to suggest that adaptogens might have a role in counteracting stress-induced sexual dysfunction. In my clinical experience, adaptogens are the primary botanical approach in treating ED.

Panax or Asian ginseng ( also known as Korean or Chinese ginseng) is considered a “heating” or stimulating herb in Chinese traditional medicine, though the degree to which it is energizing vs. calming (as a result of counteracting the harmful effects of stress) appears to have been lost in translation as Asian ginseng moved from traditional Chinese medicine to being a Western commodity, according to Dr. Eric Yarnell in the book, Integrative Sexual Health.(16)

A meta-analysis of seven clinical trials using steamed, dried roots of four-year-old Asian ginseng roots (known as red ginseng or hóng shēn) in men with ED of various types found that overall red ginseng was effective compared to placebo. Doses ranged from 1,000 mg daily to 600 mg tid.16

Withania somnifera (ashwagandha) root, a member of the Solanaceae family, also has a long history of use and would be considered an adaptogen. As its Latin binomial suggests (somnifera coming from the Latin word for sleep), it is more clearly a calming or relaxing agent. It has a strong history of use as a sexual tonic, particularly for men, despite the fact that in a randomized, single-blind trial, crude root powder 2 g tid was not superior to placebo at improving psychogenic ED in 86 men, The short duration of this trial of 60 days, was probably a major limiting factor as adaptogens typically take more than three months to start to have noticeable effects.17 A good dose ranges from 500mg two times a day to 2 grams three times a day for at least three months.

Rhodiola rosea, like ginseng, is another popular research-supported adaptogen used for centuries to increase physical endurance and longevity, as well as to manage fatigue, depression, and impotence.  A multitude of published clinical studies supports Rhodiola’s well-known and established benefits to energy levels, stress management, immune function, and cellular health, as well as its role as a potent antioxidant. Given the strong connection between stress and increased sexual dissatisfaction, supplementation with this botanical becomes all the more important.

In one study, Rhodiola was given to 56 young physicians on night call, when there is typically a significant decrease in physical and mental performance. At the conclusion of the study, the researchers found a statistically significant reduction of stress-induced fatigue after just two weeks of supplementation with Rhodiola. No side effects of rhodiola were reported.18

Another well-designed study evaluated the one-time use of the same Rhodiola in 161 male military cadets undergoing sleep deprivation and stress. The results showed that rhodiola was more effective than placebo in fighting the effects of fatigue.19

The dose for Rhodiola is 500mg once to two times a day.

Epimedium or Horny goat weed and icarrin, a flavonoid found in it, have been repeatedly shown in preclinical trials to act as phosphodiesterase-5 inhibitors with similar mechanisms of action to the pharmaceuticals sildenafil, tadalafil, and vardenafil.20

Epimedium should be considered a long-term tonic medicine for men with erectile dysfunction and low libido. It takes one to three months to start to take effect and gets stronger with long-term use in most cases. A typical dose would be 1-2 g three times daily.

L-citrulline (L-Cit) is known to increase nitric oxide (NO) production via the increase of L-arginine (L-Arg) concentration in the blood and improve endothelial dysfunction in cardiovascular diseases. A small study of 24 patients reported improvement in the erection hardness score in the L-citrulline group compared to the placebo arm. All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied.21 The dosage for L-citrulline is 750 mg, once to two times a day.

Resveratrol is a natural antioxidant with benefits for a variety of age-related challenges, including circulatory and sexual health concerns. Studies indicate that resveratrol supplementation may help to ward off atherosclerotic changes associated with imbalanced cholesterol while enhancing nitric oxide circulation, erection quality, blood testosterone levels, and sperm count and motility. The result is safe support for superior erectile function and endothelial health.22

Pomegranate. The analysis shows that pomegranate is abundant in the antioxidant anthocyanin, a flavonoid that enhances erection-stimulating nitric oxide bioavailability while promoting arterial health and optimal penile blood flow. As a result, controlled trials have revealed that supplementation with pomegranate may be able to facilitate firm erections and enhanced sexual performance in men with both cardiovascular and erectile function concerns—two challenges that often present simultaneously.23 The dosage for pomegranate extract is 300 mg once or twice a day.

Dehydroepiandrosterone (DHEA). In a randomized clinical trial, men in the DHEA arm experienced significant improvement compared to placebo participants whose results were unchanged or worse. There was no change in testosterone or the serum biomarker PSA. Mean prostate size decreased slightly in the DHEA arm and increased in placebo.24  The dosage for DHEA is 50 to 100 mg once a day.

 

Dr. Geo Espinosa is a naturopathic doctor, licensed acupuncturist and certified functional medicine practitioner recognized as an authority in holistic urology and men’s health. He is faculty and holistic clinician in Urology at New York University Langone Medical Center and faculty at the Institute for Functional Medicine (IFM). As an avid researcher and writer, Dr. Geo has authored numerous scientific papers and books including co-editing the Integrative Sexual Health book, Oxford University Press, and author of the best selling prostate cancer book: Thrive, Don’t Only Survive. Dr. Geo is the Chief Medical Officer (CMO) and formulator at XY Wellness, LLC and lectures internationally on the application of science-based holistic treatments in urological clinics. In his free time, he enjoys writing on his popular blog, DrGeo.com, spending time with his wife and three kids and practicing the Israeli martial art Krav Maga.

 

References

1.    Lewis RW, et al. Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med. 2010; 7: 1598-1607.

2.    Shamloul R, Ghanem H. Erectile Dyfunction. The Lancet. 2013: 381 (9861):153 – 165.

3.    Carson C, Dean J, Wylie M.  Management of erectile dysfunction in clinical practice. Springer Medical Publishing, New York (2006)

4.    Mulhall JP. Penile rehabilitation following radical prostatectomy. Curr Opin Urol. 2008; 18: 613-620

5.    Park KH, et al. Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int. 1999;83: 327-333

6.    Traish AM, et al. Effects of medical or surgical castration on erectile function in an animal model. J Androl. 2003;24:381-387

7.    Aversa A, et al. Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users. Int J Impot Res. 2008;20: 566-573

8.    Thomas A, et al. Urologic complications of nonurologic medications. Urol Clin North Am. 2003;30:123-131

9.    Ajo R et al. Erectile dysfunction in patients with chronic pain treated with opioids. Med Clin (Barc). 2017 Jul 21;149(2):49-54.

10.    Morales A, et al. Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res. 1998;10(2):69-73; discussion 73-4.

11.    Padma-Nathan H. Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction. Am J Cardiol. 2003;92(9A):19M-25M.

12.    Bansal C, et al. Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med. 2005; 2: 96–103.

15.    Dong JY, et al. Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J Am Coll Cardiol. 2011;58:1378-1385

16.    Gatti A, et al. Metabolic syndrome and erectile dysfunction among obese non-diabetic subjects. J Endocrin Investigation. June 2009;32(6):542-545.

17.    Esposito K, et al. Effects of intensive lifestyle changes on erectile dysfunction in men. J Sex Med. 2009 Jan;6(1):243-50.

18.    Bartlik B, Espinosa G, Mindes J (eds.). Integrative Sexual Health. Oxford University Press. 2018.

19.    Mamidi P, Thakar AB. Efficacy of ashwagandha (Withania somnifera Dunal Linn) in the management of psychogenic erectile dysfunction. Ayu. 2011; 32(3):322-8.

20.    Darbinyan V, et al. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000;7:365-371.

21.    Shevtsov VA, et al. A randomized trial of two different doses of a SHR-5 rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003;10:95-105.

22.    Chiu JH, et al. Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway. Int J Impot Res. 2006;18:335-342.

23.    Cormio L, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011;77 (1):119 -22

24.    Fukuhara S et al. Vardenafil and resveratrol synergistically enhance the nitric oxide/cyclic guanosine monophosphate pathway in corpus cavernosal smooth muscle cells and its therapeutic potential for erectile dysfunction in the streptozotocin-induced diabetic rat: preliminary findings. J Sex Med. 2011 Apr;8(4):1061-71.

25.    Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. Int J Impot Res. 2007 Nov-Dec;19(6):564-7.

26.    Reiter WJ, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. 1999 Mar;53(3):590-4; discussion 594-5.