“…summarize accumulating data on the safety of bicycle riding based on medical evidence categorized by levels of evidence, including case reports, observational studies, case control studies, mechanistic studies, and population-based epidemiologic investigations. The secondary aim was to address the concerns of bicyclists and propose measures to minimize the risk of ED associated with bicycle riding.”

The mass of data revealed a clear picture and yielded specific recommendations:

“Bicycle riding more than 3 hours per week was an independent relative risk for moderate to severe ED. Therefore, bicycle riders should take precautionary measures to minimize the risk of ED associated with bicycle riding: change the bicycle saddle with a protruding nose to a noseless seat, change the posture to a more upright/reclining position, change the material of the saddle (GEL), and tilt the saddle/seat downwards.”

The authors note in their conclusion:

“Straddling bicycle saddles with a nose extension is associated with suprasystolic perineal compression pressures, temporarily occluding penile perfusion and potentially inducing endothelial injury and vasculogenic ED.”

In a subsequent paper published in the same journal this year the authors revisit the problem and begin by noting:

“For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications.”

They conducted a comprehensive review of the scientific literature and found that further studies had firmly established the risk of cycling-related sexual dysfunction and extended it to females:

“There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists.”

The authors of a review published earlier in European Urology caution practitioners to be aware of this widespread phenomenon. They report that a range of problems have been documented:

“The most common bicycling associated urogenital problems are nerve entrapment syndromes presenting as genitalia numbness, which is reported in 50–91% of the cyclists, followed by erectile dysfunction reported in 13–24%. Other less common symptoms include priapism, penile thrombosis, infertility, hematuria, torsion of spermatic cord, prostatitis, perineal nodular induration and elevated serum PSA, which are reported only sporadically.”

They conclude by exhorting practitioners to be alert:

“Urologists should be aware that bicycling is a potential and not an infrequent cause of a variety of urological and andrological disorders caused by overuse injuries affecting the genitourinary system.”

Perhaps this could contribute, at least to some degree, occurrences of ‘cyclist road rage’. Are there any remedies or recommendations for cyclists to follow? Another study in The Journal of Sexual Medicine investigated the condition in police officers:

“The average bicycle police officer spends 24 hours a week on his bicycle and previous studies have shown riding a bicycle with a traditional (nosed) saddle has been associated with urogenital paresthesia and sexual dysfunction.”

The officers manifested the typical problems, but also demonstrated some improvement when using a ‘no-nose saddle’:

“(i) With few exceptions, bicycle police officers were able to effectively use no-nose saddles in their police work. (ii) Use of no-nose saddles reduced most perineal pressure. (iii) Penile health improved after 6 month using no-nose saddles as measured by biothesiometry and IIEF. There was no improvement in Rigiscan® [nocturnal erection] measure after 6 months of using no nose saddles, suggesting that a longer recovery time may be needed.”

It only makes anatomical sense that insult to the nerves and blood vessels that supply the genitalia could cause sexual dysfunction in both males and females.

“Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter or a free serum testosterone level of less than 50 pg per milliliter were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months.”

Things turned out so poorly that…

“The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.”

As the data came in a worrisome picture clearly emerged:

“…the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group…The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period.”

There is an extremely important practical message here buried in the data for anyone interested in hormone replacement/supplementation and the practitioners caring for them. The authors made a supplementary appendix available with more detailed data. It showed what we always see when hormones are applied transdermally (through the skin by gel, cream or patch): in time they accumulate to levels of elevated beyond the range of what is physiologically normal (when we properly measure the bioactive free-fraction hormones). Higher than normal hormone levels cause problems, including symptoms similar to hormone deficiency due to receptor desensitization. This applies to any hormone. Deep in the supplemental appendix we find that the free testosterone went as high as 82 pg/mL during gel supplementation. The functional (physiological) range we use for males age 51-60 is 36-65 pg/mL, for males over 70 years it’s 15-45 pg/mL.

Another important point: the protocol for this study did not even include how much testosterone was being converted into estrogen by aromatase activity. Elevated estrogen is a serious risk factor for men. For hormone supplementation to be effective and safe we must properly assess all aspects of production, accumulation, receptor function, metabolism and elimination.

“The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function.”

What did the data show?

“Diabetic women with the highest scores (of adherence to the diet) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles…The proportion of sexually active women showed a significant increase…of adherence to Mediterranean diet…women with the highest score of adherence had a lower prevalence of sexual dysfunction…These associations remained significant after adjustment for many potential confounders.”

The authors of Adherence to Mediterranean Diet and Erectile Dysfunction in Men with Type 2 Diabetes conducted a similar investigation for men. This time the International Index of Erectile Function-5 was used as a metric for sexual function. Here’s what the data showed:

“The proportion of sexually active men showed a significant increase…of adherence to Mediterranean diet. Moreover, men with the highest score of adherence were more likely to have a lower prevalence of global ED and severe ED as compared with low adherers.”

No surprise, right? Low glycemic vegetables and fruits, lots of olive oil, nuts, a little wine, etc: the Mediterranean Diet.

“Abdominal obesity and type 2 diabetes mellitus are associated with erectile and urinary dysfunction in men.”

The investigators set out to determine the extent to which weight loss would impact overall sexual function and lower urinary tract symptoms by measuring the effects of an 8 week low-calorie diet using meal replacements* on insulin sensitivity, testosterone, erectile function, sexual desire, prostate symptoms, abdominal obesity and waist circumference. What did their data show?

“Weight loss of ~10% was significantly associated with increased insulin sensitivity, plasma testosterone levels, IIEF-5 (erectile function) and SDI (sexual desire) scores, as well as reduced WC (waist circumference) and IPSS (prostate) scores, in diabetic as well as nondiabetic men.”

They further observed that…

“The degree of weight loss was significantly associated with improvements in plasma testosterone levels, erectile function and LUTS. Reduction in LUTS was significantly associated with increased plasma testosterone, erectile function and sexual desire.”

Hence their clear-cut conclusion:

“Diet-induced weight loss significantly and rapidly improves sexual function, and reduces LUTS, in obese middle-aged men with or without diabetes.”

This is a compelling illustration of the link between insulin resistance and male sexual function.

* Although effective in this study (at 800 calories per day) there are better meal replacement products available for weight loss than this one loaded with fructose, milk protein, and low grade minerals and fish oil.

“The objective of the study was to examine whether male sex hormones are independently associated with AAA or increased abdominal aortic diameter.”

AAA (abdominal aortic aneurysm) is a swelling of the aorta in the abdomen; a rupture means sudden death. They measured abdominal aortic diameter, total testosterone, SHBG (sex hormone binding globulin), and LH (luteinizing hormone). Free testosterone was calculated. This is what they found:

“Lower free testosterone and higher LH levels are independently associated with AAA in older men. Impaired gonadal function may be involved in arterial dilatation as well as occlusive vascular disease in older men.”

Add the previous two posts to this and connect the dots. Low testosterone, erectile dysfunction with cardiovascular disease, death from cardiovascular disease, aortic aneurysm (blood vessel damage), and insulin resistance are all connected. So what do you do?

Obviously life style factors and individually determined supplementation for healthy blood sugar and insulin are important. What about testosterone? Standard testosterone supplementation suppresses endogenous production after a brief ‘honeymoon’ period. This is why in my practice I always measure both free (biologically active) testosterone and free LH when evaluating male hormone function. (LH is produced by the pituitary gland. In men it stimulates the testicles to produce testosterone. When they are not responding adequately LH goes up, indicating that the problem is ‘hypogonadia‘, usually due to background inflammation. Supplementary testosterone suppresses LH and dulls the receptors over time. There is a better way….

“Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease.”

They set out to investigate a link between insulin resistance and low testosterone, even in the absence of overweight. What did their data show?

“In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range.”

Do you see the connections between erectile dysfunction, cardiovascular disease, insulin resistance and low testosterone that are emerging here?

“Although erectile dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis, it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease. We evaluated whether ED is predictive of mortality and cardiovascular outcomes…”

After crunching the numbers on a study cohort of 1549 patients over more than two years, this is there clear-cut conclusion:

“ED is a potent predictor of all-cause death and the composite of cardiovascular death, myocardial infarction, stroke, and heart failure in men with cardiovascular disease.”

They also noted this about the medications used in their trial, Altace and Micardis…

“The study medications did not influence the course or development of ED.”

There is a lot more to the functional approach to ED than ACE inhibitors and angiotensin receptor antagonists. See the next two posts.

The cytokines IL-6 Soluble Receptor and TGF-Beta whether clinically localized prostate cancer will progress or not.

The is paper published some time ago in the Journal of Clinical Oncology demonstrated that measuring IL6SR and TGF-β1 “improved the ability to predict biochemical progression by a prognostically substantial margin.” In other words, who might need a more aggressive intervention, and who doesn’t?

Cytokines before and after surgery correspond to prostate cancer progression

The authors of this paper published in the journal Clinical Cancer Research note that “We have shown that preoperative plasma levels of transforming growth factor-β1 (TGF-β1), interleukin 6 (IL)-6, and its receptor (IL-6sR) are associated with prostate cancer progression and metastasis. The objectives of this study were to…examine the association of …these markers after surgery with disease progression in a large consecutive cohort of patients.” Their conclusion: “For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-β1 and IL-6sR are associated with metastases…and disease progression. After prostate removal, postoperative TGF-β1 level increases in value over preoperative levels for the prediction of disease progression.”

Another study demonstrating cytokines greatly increase the accuracy of predicting the potential for prostate cancer recurrence

The investigators who conducted this study that was published in the journal The Prostate set out to test “the ability of several pre-operative blood-based biomarkers to enhance the accuracy of standard post-operative features for the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP).” They measured the cytokines IL-6, ILsR and TGF-β and concluded that “Pre-operative plasma biomarkers improved the accuracy of established post-operative prognostic factors of BCR by a significant margin. Incorporation of these biomarkers into standard predictive models may allow more accurate identification of patients who are likely to fail RP thereby allowing more efficient delivery of adjuvant therapy.”

Coincidentally, a related paper has also just been published in the journal Sleep Medicine examining the role of dopaminergic dysfunction and treatment in Restless Leg Syndrome. Here the authors conclude their observations by stating: “Since dopaminergic treatment can reverse delayed facilitation in RLS, we hypothesized that cortical plasticity related to dopaminergic systems may play a crucial role in RLS pathophysiology.”