Is There a Male Equivalent to PCOS? (a.k.a. The Detrimental Effects of Hyperinsulinemia on Men's Health)

 

Insulin has gotten a bad reputation in the low carb and keto communities. But insulin isn’t a bad thing. Too much insulin, too often, is a bad thing. If you ask people whose homes are threatened by wildfires whether lots of rain would be a good thing, you’ll probably get a very different answer than if you ask people whose homes have just been destroyed by hurricane floods. Water is not a problem; too much or too little water is a problem, and it’s the same with insulin.

So I’m not trying to demonize insulin. I wrote an 8-part blog series detailing the gnarly and nefarious effects of chronically elevated insulin (soon to be 9 or 10 parts -- new posts coming soon!), but the operative phrase there is chronically elevated. In and of itself, insulin isn’t a problem. (Just ask a type 1 diabetic.) The bad stuff happens only when insulin is too high, too often. Now that that’s out of the way, on with the show!

We know for certain that PCOS (polycystic ovarian syndrome)—which is “is the most common endocrinopathy of reproductive aged women affecting 6-10% of the population,”—is driven primarily by chronic hyperinsulinemia. (Incidence may be as high as 18% among certain cohorts when different diagnostic criteria are used, putting the number of women affected worldwide at around 10 million.)

“Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism and metabolic disturbances.” (De Leo et al., 2004)

In fact, the causal link (not just an association!) between hyperinsulinema and PCOS is so well-known (and so powerful) that metformin—best known as a diabetes drug—is among the frontline pharmaceutical interventions for PCOS. Keep this in mind as you read about the men’s issues here.

Facial hair, acne, oily skin, mood swings, weight gain, menstrual irregularities, and infertility are not the only signs and symptoms of PCOS. These signs & symptoms are driven by the underlying hormonal disturbances, which include: elevated insulin, increased adrenal androgen synthesis (more testosterone and/or DHEA), decreased sex hormone binding globulin (SHBG), increased luteinizing hormone (LH), and decreased follicle stimulating hormone (FSH). And while the stereotypical PCOS patient is overweight or obese, as many as 50% of women with PCOS are not overweight or obese. (Remember, chronic hyperinsulinemia leads to obesity in some people, but not all. There are millions of people walking around with a “normal” body weight, but sky-high insulin levels.)

Since men produce all of these hormones as well, could there be a male equivalent of PCOS?

You bet your bald spot there is!

Let’s take a look at three different areas where chronic hyperinsulinemia has adverse effects on men:

• Early onset androgenetic alopecia (a.k.a. male-pattern baldness)
• Erectile dysfunction
• Benign prostatic hypertrophy (BPH) – enlargement of the prostate gland 

Early-onset Androgenetic Alopecia

(Male-Pattern Baldness)

Why do so many men lose their hair? Maybe it’s genetic, but when it happens to young men, maybe there’s more to the story.

In young men, early onset androgenetic alopecia (AGA), may be an indication of insulin resistance not revealed by other signs and symptoms. A meta-analysis of hormonal profiles in young men with early-onset AGA showed that compared to men without alopecia, young men with the condition had higher fasting insulin, HOMA-IR, and triglycerides, with slightly higher BMI, and lower HDL-C—all indicating that the men with AGA were affected more strongly by insulin. The study authors wrote, “Early-onset AGA might represent a phenotypic sign of the male PCOS-equivalent.”

In a case-control study of 57 men ages 19-30 presenting with AGA and 32 controls (no hair loss), mean fasting insulin levels were only slightly higher in the cases than the controls. However, compared with the controls, the AGA cases had significantly higher mean levels of testosterone, DHEA-sulfate and LH, with decreased mean levels of FSH and SHBG—precisely some of the same observations made in women with PCOS. The conclusion couldn’t have said it better: “Men with early AGA could be considered as male phenotypic equivalents of women with PCOS. They can be at risk of developing the same complications associated with PCOS, including obesity, metabolic syndrome, IR, cardiovascular diseases, and infertility.”

How’s that for a reality check upside the head of thinning hair? One place where they missed the mark a little, though, is that they could change the arrow of causality: yes, men with AGA might be at greater risk for metabolic syndrome and IR, but it might be more educational to say that men with insulin resistance and metabolic syndrome are at greater risk for early baldness.

But how does this work? Is the connection between insulin resistance and early onset AGA merely a correlation, or is there a plausible mechanism by which we could establish causation?

According to one of my favorite papers on hyperinsulinemia, written by well-known “Paleo diet” authority Loren Cordain, PhD, along with Drs. Michael and Mary Dan Eades, of Protein Power fame:

“Male balding clearly has a genetic component. However, it is well established that male pattern balding also is an androgen-dependent trait that occurs from elevated androgenesis after puberty. Consequently, any environmental factor or factors that would elevate serum androgen levels would promote increased balding, particularly in genetically susceptible individuals. High-glycemic-load carbohydrates, by inducing hyperinsulinemia, along with a concomitant elevation of serum androgens and reduction in SHBG represent a likely environmental agent that may in part underlie the promotion of male vertex balding.”

So yeah, there is a genetic component, but chronic hyperinsulinemia probably increases the chances that a young guy will lose his hair, compared to a guy with the same genetic risk who is not hyperinsulinemic.

Other researchers have proposed a mechanism more specific to hair follicles, themselves, rather than a downstream effect of altered androgen hormone levels:

“IR plays a pathogenetic role in the miniaturization of hair follicles. Vasoactive substances associated with endothelial dysfunction in IR lead to microcirculatory disturbance, perifollicular vasoconstriction, and proliferation of smooth muscle cells in the vascular wall. This condition leads to microvascular insufficiency, local-tissue hypoxia, and progressive miniaturization of hair follicles.” (Bakry et al., 2014)

Another case/control study comparing cohorts of young men with early-onset AGA and unaffected controls showed that the men with AGA were significantly higher than the controls with regard to fasting glucose, insulin, HOMA-IR, triglycerides, blood pressure, and more. Unfortunately, these were not weight-matched controls. The waist circumference, body weight and BMI were all higher in the men with alopecia. We can’t say whether that may have confounded the findings, but we could also just as easily hypothesize that the elevated insulin metrics in the affected men were driving the higher body weight and waist circumference.

In case you needed any more evidence that there’s at the very least a correlation between male pattern baldness and insulin resistance, another study found HOMA-IR to be significantly higher in cases of men with early onset AGA than in controls. For a breath of fresh air, the authors of this one recognized the implications of this: they recommend that young men with AGA be screened for insulin resistance and cardiovascular disease, writing, “Epidemiological studies have associated androgenetic alopecia (AGA) with severe young-age coronary artery disease and hypertension, and linked it to insulin resistance.” Of course, it would be wiser to simply make fasting insulin a standard part of routine bloodwork, right along with fasting glucose, which would then provide the HOMA-IR as well. Men shouldn’t have to wait until they lose their hair before they’re told they’re at risk for the very serious complications of metabolic syndrome.

Erectile Dysfunction

Okay. We just said that young men with early onset male-pattern baldness are at increased risk for coronary artery disease and hypertension, and they should be screened for cardiovascular disease (CVD). With that in mind, did you know that erectile dysfunction (ED) is a cardiovascular problem? And did you know that cardiovascular disease is an insulin problem?

Remember what Dr. Joseph Kraft wrote, in his epic work, Diabetes Epidemic and You, which was the inspiration for my big series on insulin:

“Individuals with normal fasting blood glucose may indeed be quite comfortable that they are nondiabetic—that is until they have their first heart attack. […] Those with cardiovascular disease not identified with diabetes are simply undiagnosed.” (Emphasis added.)

 If you have chronically high insulin, make no mistake: you are cooking your blood vessels. There’s a reason CVD is the number one cause of death in people with type 2 diabetes. The blood vessels take a serious beating from chronically high blood glucose and insulin. Either one can damage blood vessels all by itself; up against them both, together, your blood vessels don’t stand a chance. (Cardiovascular disease has almost nothing to do with cholesterol and everything to do with insulin and glucose.)  

Long-term poor blood glucose management and chronically elevated insulin can result in rampant glycation not just of the blood, itself (as measured via hemoglobin A1c), but of the blood vessels, as well. In this scenario, rather than nice, watery, fluid blood flowing through smooth and accommodating vessels that are able to dilate and contract as necessary (like a rubber garden hose), it’s more like pumping thick, sticky molasses through a fragile, brittle glass tube. The logical outcome of this is damage to the microscopic blood vessels in the eyes and the kidneys, which are well-known consequences of chronic hyperglycemia among type-2 diabetics.

But this type of impaired circulation can also affect blood flow to the male genitalia. In fact, physicians informed on these issues will confirm that ED may be the first sign of insulin resistance and endothelial dysfunction, particularly among younger men, whose cardiovascular health would not ordinarily be suspected of being in the shitter compromised. Erectile dysfunction and cardiovascular disease are different manifestations of the same underlying pathology. ED can be considered an early marker for CVD. Moreover, insulin resistance is associated with reduced nitric oxide synthesis and release, which could further impair blood flow to the penis. (Nitric oxide is a “vasodilator” – it helps blood vessels dilate so they can accommodate increased blood flow. In the vessels that supply blood to the penis: no dilation, no erection.)

A systematic review looking at the association between erectile dysfunction and cardiovascular disease concluded, “ED and CVD should be regarded as two different manifestations of the same systemic disorder.” (And we all know what the underlying systemic disorder is.)

I’m a woman, so I can only guess here, but I imagine that for young men (and maybe not-so-young men), fear of impotence would be a way more powerful motivator for dietary and lifestyle changes than fear of a heart attack twenty years down the line.

For a young man with no other signs and symptoms of metabolic derangement, ED could be the canary in the coalmine—an early warning sign that something is awry long before severe cardiovascular disease or type 2 diabetes have taken hold. One study found that in men under 40, compared to men without ED, those with ED had significantly higher HOMA-IR and systolic blood pressure, and significantly lower flow-mediated dilation (a measure of blood vessel function). The researchers wrote, “Subclinical endothelial dysfunction and insulin resistance may be the underlying pathogenesis of ED in young patients without well-known etiology.” And as we’ve covered, what’s likely driving the endothelial dysfunction is the insulin resistance.

If the man/men in your life experience ED that has no obvious cause (such as depression, chronic stress, or physical trauma), or you are a man experiencing unexplained ED, an insulin test might be warranted. Wanna save your hard-on? Make a hard change in your diet.

The incidence of various cardiovascular risk factors in 283 young ED patients (ages 18-45, with ED history at least 6 months). Insulin resistance is the most prevalent risk factor for ED in this study population.

(Source: Chen et al., 2013)

Metformin for ED

I said we’d come back to metformin! It’s pretty interesting that a diabetes drug has been shown to improve erectile function among insulin resistant men with ED who are not diagnosed diabetics. Why would a diabetes drug have any influence on erectile function if there was no connection to insulin or blood glucose? In a randomized, double-blind trial, compared to placebo, metformin led to significant improvements in HOMA-IR and erectile function. These two things are not unrelated. Better insulin management = better sexy time. 

Benign Prostatic Hypertrophy/Hyperplasia (BPH)

  

BPH is yet another insulin-driven condition, but most men and even their physicians are unaware of the connection. Men are told, “You’re just getting older. This is normal.” It may be common, but that doesn’t mean it’s normal.

Remember: insulin stimulates tissue growth. And researchers are waking up to the fact that one of the tissues insulin stimulates the growth is the prostate gland. Unfortunately, this finding—which is all over the medical literature—has not yet trickled down to the offices of many primary care physicians. This is bad news, because primary care docs (GPs, family physicians) are the ones most likely to encounter men complaining of the associated signs and symptoms (e.g., frequent or urgent need to urinate—particularly at night, or waking up to urinate; straining during urination, or inability to completely empty the bladder).

Among men with BPH, fasting insulin levels were positively correlated with annual increase in growth rate of the prostate gland: the higher the insulin, the faster the growth. Prostate growth was faster in men with type-2 diabetes, hypertension, and obesity, and growth rate was negatively correlated with HDL—all signs of hyperinsulinemia. In another study that compared 90 BPH patients and 90 controls, insulin, IGF-1 and estradiol levels were higher in the cases compared to the controls. (Insulin may upregulate the aromatase enzyme, enhancing the conversion of testosterone to estrogen/estradiol in men.) IGF binding protein 3 (IGFBP-3), which binds to IGF-1 and reduces its activity, was decreased in the cases compared to the controls. The study authors went so far as to say that insulin (and the IGFBP-3/PSA ratio) “predicts the prostate size in patients with BPH.” Again, the higher the insulin, the larger the prostate.    

Diabetes Drugs for BPH

As we saw with erectile dysfunction, metformin has a therapeutic role in BPH. In rats with prostate enlargement induced by hyperinsulinemia (which is telling in itself—they gave rats insulin for the express purpose of enlarging their prostates!), treatment with pioglitazone (brand name Actos) reduced insulin levels and prostate weight. In another study, metformin substantially inhibited the proliferation of cultured human prostate epithelial cells. (Yes, these were a rat study and an in vitro study, but they still give us some insights.) Again, the fact that drugs primarily used for diabetes are effective for things as seemingly unrelated as PCOS, erectile dysfunction, and BPH, suggests these three conditions share a common origin: chronic hyperinsulinemia.

Fin

We need to wake up and smell the Viagra!

It’s time to realize that type 2 diabetes and obesity are merely the tip of a much, much bigger iceberg of modern health issues rooted in chronically high insulin. And maybe it’s time for a new acronym: MIRS—male insulin resistance syndrome.

So if you’re a dude dealing with any of these issues, or a dude you love is dealing with them, do (or advise him to do) what men love to do anyway: eat a steak! (No potato.)

Disclaimer: Amy Berger, MS, CNS, NTP, is not a physician and Tuit Nutrition, LLC, is not a medical practice. The information contained on this site is not intended to diagnose, treat, cure, or prevent any medical condition and is not to be used as a substitute for the care and guidance of a physician. Links in this post and all others may direct you to amazon.com, where I will receive a small amount of the purchase price of any items you buy through my affiliate links.