Estrogen causes the most urinary tract symptoms for men

Lower urinary tract symptoms (LUTS) in men have often been blamed on increased androgens, particularly dihydrotestosterone (DHT).  A study just published in The Journal of Sexual Medicine provides more evidence for what I have noticed clinically for a long time: elevated estrogen causes more urinary tract symptoms than DHT and other androgens. The authors first observe:

“In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity.”

They conducted their investigation by testing the relative effects of estrogens, aromatase expression (aromatase converts testosterone to estrogen) and androgens (male hormones) on male genitourinary tract tissues, including cells from the bladder, prostate and urethra. What did the data show?

“Our data indicate for the first time that estrogen-more than androgen-receptors up-regulate RhoA/ROCK signaling [increases urinary tract symptoms]. Since an altered estrogen/androgen ratio characterizes conditions, such as aging, obesity and metabolic syndrome, often associated to LUTS, we speculate that a relative hyperestrogenism may induce bladder overactivity through the up-regulation of RhoA/ROCK pathway.”

This is part of the reason why I always measure free-fraction (bioactive) estrogen as part of a hormone profile for men. All too often men are given supplemental testosterone with no consideration for how much of it is being turned into estrogen by aromatase activity—with a potential increase in LUTS, not to mention cardiovascular, prostate cancer and depression risk factors.

Bicycle riding and erectile dysfunction

The standard bicycle seat can deliver a significant insult to the nerve and blood vessel supply to the male genitalia. There have been numerous studies investigating the relationship between bicycle riding and erectile dysfunction. The authors of a paper published a while back in The Journal of Sexual Medicine that reviewed the science set out to:

“…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.

Incorrect testosterone supplementation can increase cardiovascular risk

New England Journal of MedicineAn important paper just published in The New England Journal of Medicine is a reminder that supplementing any hormone to levels above the normal physiological range can backfire. The authors intent was to investigate the safety and efficacy of testosterone treatment in older men with mobility limitations.

“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.

Eat a Mediterranean diet for better sex

Journal of Sexual MedicineTwo papers recently published in the Journal of Sexual Medicine document the benefit of the low glycemic Mediterranean diet for sexual function in both women and men. The authors of Adherence to Mediterranean Diet and Sexual Function in Women with Type 2 Diabetes evaluated how well they stuck to the diet and correlated it with sexual function…

“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 dietwomen 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.

Diet induced weight loss can rapidly improve sexual function for men

International Journal of ObesityReaders of these posts know about the profound impact of insulin resistance on glandular and metabolic function; as the authors of this study just published in the International Journal of Obesity note…

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.

Low testosterone is associated with abdominal aneurysm

Journal of Clinical Endocrinology & MetabolismHere’s one more paper for now in the ‘series’ on erectile dysfunction, testosterone, cardiovascular disease and insulin resistance, this one published recently in the Journal of Clinical Endocrinology & Metabolism.

“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….

Low testosterone is associated with insulin resistance

European Journal of EndocrinologyA study published recently in the European Journal of Endocrinology links to the previous post on erectile dysfunction as a predictor of death with cardiovascular disease. The authors mention the well-known fact that:

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?

Erectile dysfunction predicts death with CVD

CirculationA study just published in the journal Circulation reports a result that is not too surprisingly if we consider the underlying biology of erectile dysfunction. The authors begin with this in mind:

“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 importance of testing cytokines: prostate cancer

There are many studies that demonstrate the importance of testing cytokines (‘messenger molecules’ of the immune system) for prostate cancer. One  paper published some time ago in the Journal of Clinical Oncology examined whether the cytokines IL-6 Soluble Receptor and TGF-Beta can predict if clinically localized prostate cancer will progress or not. The authors demonstrated that measuring IL6SR and TGF-β1…

“…improved the ability to predict biochemical progression by a prognostically substantial margin.”

In other words, this helps determine who needs a more aggressive intervention and who doesn’t.

The authors of a paper published in the journal Clinical Cancer Research investigated how cytokines before and after surgery correspond to prostate cancer progression:

“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.”

The ProstateAnother study demonstrating that cytokines greatly increase the accuracy of predicting the potential for prostate cancer recurrence was published in the journal The Prostate. The authors  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:

“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.”

Restless Leg Syndrome and Erectile Dysfunction

SleepThose of you interested in how brain function is significant for virtually all aspects of health will like this study just published in the medical journal Sleep. It’s also another example of the importance of healthy dopamine signalling. The investigators note that Dopaminergic hypofunction in the central nervous system may contribute to restless legs syndrome (RLS) and erectile dysfunction (ED). We therefore examined whether men with RLS have higher prevalences of ED.” After analyzing the data on a group of 23,119 men they conclude: Men with RLS had a higher likelihood of concurrent ED, and the magnitude of the observed association was increased with a higher frequency of RLS symptoms. These results suggest that ED and RLS share common determinants.” The take home message here is that dopamine function can play a role in both Restless Leg Syndrome and Erectile Dysfunction. This can be helped with a functional medicine approach to restoring dopamine regulation.

Sleep MedicineCoincidentally, 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.”