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June 24 2022
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In a recent article we explored the connection between chronically elevated insulin—a.k.a. metabolic syndrome—and benign prostate hypertrophy (BPH). We noted that BPH is included among the issues believed to have roots in what researchers call “a male polycystic ovarian syndrome equivalent.” And if chronic hyperinsulinemia is the underlying cause of PCOS, then the same hormonal state may be driving the conditions believed to result from this “male phenotypic equivalent.” This time, let’s take a closer look at erectile dysfunction and see if it, too, may result from insulin resistance.
Contrary to its public perception as something that does little more than regulate blood sugar, insulin has numerous other roles completely unrelated to this. Insulin can be considered an anabolic hormone. Its effect on stimulating tissue growth can be seen in the enlargement of the prostate gland, development of skin tags, and the growth of fat tissue—as many patients and doctors alike know only too well from personal experience! Chronic hyperinsulinemia is also a major player in cardiovascular disease (CVD) owing to numerous influences it has on endothelial function, nitric oxide production, and sympathetic nervous system stimulation. Perhaps this is why the phrases “metabolic syndrome” and “cardiovascular disease” have been blended into the catch-all, cardiometabolic disease.
Turning toward erectile dysfunction (ED), if other potential causes have been ruled out (such as depression, low testosterone, or physical trauma to the area), then the starting point in looking for an association between ED and elevated insulin is recognizing that ED is driven in part by vascular disease and impaired endothelial function. Erectile dysfunction and cardiovascular disease are different manifestations of the same underlying pathology. Researchers have suggested ED could even be “an early marker of symptomatic CVD.”
This may be especially relevant when working with younger male patients. Compared to older men, younger men may be less often suspected of having compromised cardiovascular health, especially if they have no other signs or symptoms. It’s been noted, however, that ED could actually be the first sign of insulin resistance and endothelial dysfunction in young men. If so, what seems like a troubling yet benign sexual issue should be taken far more seriously so that dietary and lifestyle measures can be implemented to reverse insulin resistance long before this underlying metabolic dysfunction progresses to full-blown cardiovascular disease or type 2 diabetes.
One study showed that in men under 40, those with ED had significantly higher HOMA-IR and significantly lower flow-mediated dilation (FMD) compared to men without ED. The authors wrote, “Subclinical endothelial dysfunction and insulin resistance may be the underlying pathogenesis of ED in young patients without well-known etiology.” And it’s likely not “endothelial dysfunction and insulin resistance,” but rather, endothelial dysfunction resulting from the insulin resistance.
In a separate study of men ages 28-39 with ED, insulin resistance (IR) was independently associated with presence and severity of ED: IR was found in 68% of patients with severe ED, 62% of those with moderate ED, and 51% and 40% of those with mild-to-moderate and mild ED, respectively. With regard to individual factors that may contribute to ED, subjects with IR had lower FMD, lower testosterone, and lower sex hormone binding globulin (SHBG) compared to subjects with ED who did not have insulin resistance. Among these relatively young subjects, IR was the most common risk factor for ED, with a prevalence of over 50%. Insulin resistance was more prevalent than any other common cardiovascular risk factor, including body mass index (BMI), smoking, alcohol intake, triglycerides, hypertension, C-reactive protein, total cholesterol, and even the presence of type 2 diabetes (T2D). This last point is crucial, because T2D is a well-established risk factor for CVD, yet there are millions of people who are not diagnosed with diabetes (owing to normal blood glucose) but whose insulin level may be chronically elevated.
A systematic review in the American Journal of Men’s Health noted, “There is strong consensus that men with ED should be considered at high risk of CVD.” And if they’re at high risk of CVD, then it would be wise to evaluate them for insulin resistance/metabolic syndrome because this condition reliably improves from simply dietary changes. The review authors explained that “the pathophysiological linkage between ED and CVD […] may permit physicians, including urologists, to perform opportunistic screening and initiate secondary prophylaxis with regard to cardiovascular risk factors, particularly in young, nondiabetic men with ED.” Emphasis on “nondiabetic.” Again, glucose measurements may be normal, and this is why it’s critical for medical professionals to understand the pathological implications of chronically elevated insulin regardless of a patient’s glucose levels.
It’s worth noting here that insulin resistance was determined via the QUICKI formula (quantitative insulin-sensitivity check index), which is based on fasting glucose and insulin. This is certainly a better measure of insulin sensitivity than fasting glucose or HbA1c by themselves, but it doesn’t account for the potentially numerous patients whose fasting levels of glucose and/or insulin are normal but whose levels rise sharply after meals and stay pathologically elevated for longer than normal.
It is telling that drugs typically used for treating T2D are being tested for use in men with ED. Adding metformin to the treatment regimen of men with ED and IR (but who were non-diabetic) who were already taking sildenafil with lackluster results was shown to improve erectile function compared to placebo. Multiple other drug classes are also being studied for potential use in ED, such as SGLT2 inhibitors, incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors), sulfonylureas, and thiazolidinediones. Considering the difficulty of securing research funds, if such funds are being spent on this pursuit, that’s a pretty clear indication that researchers are well aware of the potential links between insulin sensitivity and erectile function. Now it’s time to make the men affected by this condition aware as well. The sooner they know there may be an explanation for the issue, the sooner they can start taking action to resolve it.
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