It has long been known that polycystic ovarian syndrome (PCOS) is driven largely by chronically elevated insulin (hyperinsulinemia). PCOS is the most common endocrine abnormality among reproductive age women, affecting as much as 10% of the population (1). But if insulin is primarily a “blood sugar hormone,” why would chronic hyperinsulinemia affect female fertility? Why would it contribute to irregular or absent menstrual periods, facial hair, acne, and other signs and symptoms of PCOS?
The answer is that insulin is not just a blood sugar hormone. In fact, insulin has such surprising and far-reaching effects throughout the whole body that lowering blood sugar might actually be one of the least notable things this hormone does.
In a past KetoDiet post exploring chronic hyperinsulinemia, I mentioned that high insulin plays a driving role in such diverse issues as hypertension, skin tags, gout, and migraines. A quick flip through a biochemistry or endocrinology textbook shows that hormones don’t exist in a vacuum. They interact with and influence each other in complex ways, with multiple control mechanisms and feedback loops, so that changing the levels of one inevitably causes changes in the levels of others, too.
If hyperinsulinemia produces multiple hormonal abnormalities in women leading to PCOS, might it also produce hormonal abnormalities in men? Is there a male equivalent to PCOS?
Insulin Isn’t the Enemy; Chronically High Insulin Is
Insulin has gotten a very negative reputation in the keto community. But by itself, insulin isn’t a bad thing. Insulin is an essential hormone that performs numerous critical functions.
Insulin is only a problem when there’s too much of it in the bloodstream too often. Just like water, or even oxygen, it’s possible to get too much of a good thing. Insulin isn’t the enemy. For example, if you want to put on healthy muscle mass, you need insulin. But you don’t need a flood of it circulating in your body all the time. Keeping it pulsatile—that is, rising now and then for short periods of time—is sufficient for this purpose. What we want to avoid are prolonged periods of sustained high insulin.
Association Versus Causation
In medical research, the phrase “associated with” is often used when researchers are wary of using the term “causes.” It’s not always straightforward to establish cause and effect between two things with absolute certainty, so when things tend to occur together, it’s more scientifically responsible to say those things are “associated,” rather than declaring that one or more of them causes the others. However, in the case of PCOS, researchers believe that chronic hyperinsulinemia is a causative factor:
“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.” (2)
In fact, this causal link between hyperinsulinemia and PCOS is so well-known and so powerful that metformin — which is best known as a diabetes drug — is among the frontline pharmaceutical interventions for PCOS. As we’ll see soon, metformin and other diabetes drugs are also now being used for certain men’s health issues for the same reason — these issues stem from chronically elevated insulin.
The signs and symptoms of PCOS are driven by the underlying hormonal disturbances, which, apart from elevated insulin, include increased adrenal androgen synthesis (higher levels of testosterone and/or DHEA), decreased sex hormone binding globulin, increased luteinizing hormone (LH), and decreased follicle stimulating hormone (FSH). All of these features have also been observed in men, leading researchers to believe that yes, there is indeed a male hormonal equivalent of PCOS, and it has interesting repercussions for men of all ages (3).
And while many women with PCOS are overweight or obese, as many as 50% of PCOS patients are not (4). So it stands to reason that men with the male equivalent of PCOS won’t all be overweight, nor will they be diabetic, as defined by high blood sugar level. In PCOS and the male equivalent — just as in so many other chronic conditions — high blood glucose isn’t the driving factor; it’s high insulin.
Let’s look at three men’s health issues that seem to be coming from chronic hyperinsulinemia:
- Androgenetic alopecia (a.k.a. “male pattern baldness”)
- Erectile dysfunction
- Benign prostate hypertrophy (enlargement of the prostate gland)
Male-Pattern Baldness: Does Insulin Affect Hair Loss in Men?
Why do so many men lose their hair? Is it solely genetic? If someone comes from a long line of men who lost their hair, are they destined to lose theirs, too? If so, what would the evolutionary advantage to this be?
After all, many genetic conditions that have persisted throughout the ages are believed to have conferred a survival advantage in the distant past. For example, the sickle-shaped red blood cells produced by the genes responsible for sickle cell anemia also offer some degree of protection against malaria, so it makes sense that even though there’s a drawback to these genes in the modern age, in the past, it offered a distinct advantage. If there is an evolutionary advantage to men losing their hair, it hasn’t been identified yet. What has been identified, however, is a role for chronic hyperinsulinemia in contributing to male pattern baldness.
At first glance, you might think of male balding as an aesthetic issue and not a health problem. And no one could blame you for thinking it’s solely about appearance, rather than an underlying health issue. But looking at the role of insulin here tells us that for men losing their hair, things are more than “skin deep.”
The role of chronically elevated insulin as a contributor to male pattern baldness seems especially pronounced in young men. In fact, some researchers believe that in some men, hair loss might be the only warning sign of hyperinsulinemia.
An analysis of hormonal profiles in young men with early-onset androgenetic alopecia (AGA) (5) showed that compared to men without alopecia, young men with the condition had higher fasting insulin, HOMA-IR (a measurement of insulin resistance), and triglycerides, with slightly higher BMI, and lower HDL. All of these indicate 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 young men (age 19-30) presenting with AGA and 32 controls (men without AGA), mean fasting insulin levels were only slightly higher in the men with AGA than in those without it. However, compared with the controls, the men with AGA had significantly higher mean levels of testosterone, DHEA-sulfate and luteinizing hormone, with decreased mean levels of FSH and SHBG — precisely some of the same observations seen in women with PCOS.
The study 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 [insulin resistance], cardiovascular diseases, and infertility.”(6)
It seems early male pattern baldness is more of a metabolic issue than a cosmetic one. The conclusion could have been written differently, though, with the arrow of causality pointing in the other direction: rather than saying men with AGA are at greater risk for metabolic syndrome and IR, 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 an “association,” or is there a plausible mechanism by which causation can be established?
According to a paper written (7) by well-known Paleo diet authority Loren Cordain, PhD, along with low-carb advocates Drs. Michael and Mary Dan Eades, authors of Protein Power:
“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 it seems there is a genetic component to male balding. Obviously, not all men with hyperinsulinemia lose their hair, and not all men who are balding are hyperinsulinemic. Among young men with a genetic propensity for alopecia, chronic hyperinsulinemia simply increases the chances that they’ll lose their hair, compared to men of the same age who also have this genetic propensity but who are not hyperinsulinemic. The oft-uttered phrase regarding modern non-communicable health issues seems apropos here: “Genetics loads the gun, but diet and lifestyle pull the trigger.”
Other researchers have proposed a mechanism more specific to hair follicles, themselves, rather than a downstream effect of altered androgen hormone levels. The contend that insulin resistance “plays a pathogenetic role in the miniaturization of hair follicles.”(8) They go on to say that hyperinsulinemia causes alterations in blood vessel function that result in adverse effects on local circulation affecting the hair follicles, leading to a shrinking of follicles and eventual hair loss.
Another case/control study comparing groups of young men with early-onset AGA (9) and unaffected controls showed that compared to the men without hair loss, the men with AGA had higher fasting glucose, insulin, HOMA-IR, triglycerides, and blood pressure, all of which are suggestive of chronic hyperinsulinemia (10).
Unfortunately, the two groups were not matched for weight. Waist circumference, body weight, and BMI were all higher in the men with alopecia. This might have confounded the findings in that the higher weights could have been a contributing factor, but it could just as easily be true that higher insulin in the affected men was driving the higher body weight and waist circumference. That is, higher insulin may have been responsible for the higher weight, larger waist circumference, and the alopecia.
In case you needed another bit of evidence that there’s at the very least a correlation between male pattern baldness and insulin resistance, another study found that HOMA-IR was significantly higher in cases of men with early onset AGA than in men without alopecia (11).
For a nice change of pace, the authors of this one recognized the important implications: 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 — including cardiovascular disease.
As just discussed, researchers believe young men with early onset male pattern baldness are at increased risk for coronary artery disease and hypertension, and suggest they should be screened for cardiovascular disease (CVD). With this in mind, it’s crucial to note that erectile dysfunction (ED) doesn’t result from lack of sexual desire. It’s not a libido problem, it’s a cardiovascular problem. And cardiovascular problems are largely insulin problems. CVD is not driven by high cholesterol or dietary saturated fat! (12)
Chronically high insulin — even when blood glucose is normal — is very damaging to the blood vessels. When combined with high blood glucose levels, it’s the perfect storm. Damage to the microscopic blood vessels in the eyes and the kidneys leads to the retinopathy and nephropathy that are well known consequences of poorly managed type 2 diabetes. But it’s not just those tiny blood vessels that suffer. The larger ones — major arteries — take a beating, too. In fact, cardiovascular disease is the number one cause of death in people with type 2 diabetes (13).
Impaired circulation also affects blood flow to the male genitalia. In fact, physicians informed on the hyperinsulinemic basis of blood vessel disfunction posit that ED may be the first sign of insulin resistance and endothelial dysfunction (14). This is especially true among younger men, who would not otherwise be suspected of having poor cardiovascular health. Make no mistake: erectile dysfunction and cardiovascular disease are different manifestations of the same underlying pathology (15). ED can be considered an early warning indicator of CVD.
Additionally, insulin resistance has been shown to reduce the synthesis and release of a compound called nitric oxide. 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 and no increased blood flow means 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.” (15) And signs point to that systemic disorder being chronic hyperinsulinemia.
For a young man with no other signs and symptoms of metabolic derangement, erectile dysfunction 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 developed. 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. The researchers wrote, “Subclinical endothelial dysfunction and insulin resistance may be the underlying pathogenesis of ED in young patients without well-known etiology.” (16) In other words, for young men dealing with ED that has no known cause, insulin resistance should be suspected.
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, a fasting insulin test might be warranted.
The incidence of various cardiovascular risk factors in 283 young ED patients (ages 18-45, with ED history at least 6 months). Insulin resistance (IR) is the most prevalent risk factor for ED in this study population. (17)
Metformin for Erectile Dysfunction: Why a Diabetes Drug?
It’s noteworthy that metformin — mainly a diabetes drug — has been shown to improve erectile function among insulin resistant men with ED who are not diagnosed diabetics (18). 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! Based on the research we’ve explored here, it makes sense that better insulin management leads to better erectile function.
Benign Prostate Hypertrophy/Hyperplasia (BPH)
BPH is likely another condition with a surprising foundation in chronic hyperinsulinemia, but most men and even their physicians are unaware of this connection. Men are told, “You’re just getting older. This is normal.” It may be common, but that doesn’t mean it’s normal.
Insulin is a growth-promoting hormone. It stimulates growth of adipose tissue (fat cells), muscle tissue, and even the aforementioned skin tags and ovarian cysts. Another tissue insulin promotes growth of is the prostate gland (19). This finding, which is well documented in the scientific literature, has not yet made its way to the offices of many primary care physicians.
This is unfortunate, because these doctors are the ones most likely to encounter men complaining of the associated signs and symptoms, which include frequent or urgent need to urinate, waking up during the night to urinate, pain or straining during urination, or inability to completely empty the bladder.
One study showed that 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 (20). Prostate growth was faster in men with type-2 diabetes, hypertension, and obesity, all signs of hyperinsulinemia. In another study that compared 90 BPH patients and 90 men without the condition, levels of insulin and two other hormones, IGF-1 and estradiol, were higher in the cases compared to the controls. (Insulin may upregulate an enzyme called aromatase, which converts testosterone to estrogen/estradiol.) The researchers found that insulin and the related hormonal imbalances predicted the prostate size in patients with BPH: the higher the insulin, the larger the prostate (22).
Diabetes Drugs for BPH
As shown for 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 the diabetes drug pioglitazone reduced insulin levels and prostate weight (23).
In a study looking at cultured human prostate cells in vitro, metformin substantially inhibited the proliferation of human prostate epithelial cells (24). Since these were a rat study and an in vitro study, we can’t be sure the same effects would be seen in human males, but the findings can still provide 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.
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