As early as the 1960s doctors noted a phenomenon of “diabetes in bearded women.” They observed a clustering of blood sugar abnormalities or overt type 2 diabetes hirsutism and virilization in women. Originally found primarily in postmenopausal women this phenomenon was called Achard-Thiers syndrome (after the physicians who identified it). It has become much more common among younger women in recent decades and the similar clustering of symptoms is now known as PCOS (polycystic ovarian syndrome). It is also acknowledged now that chronically elevated insulin is the primary driving factor behind the condition. Oddly though the presence of ovarian cysts is not required for a PCOS diagnosis so the name is a bit of a misnomer. With this in mind might there be a male metabolic/hormonal equivalent to PCOS?
Other than hyperinsulinemia hormonal abnormalities seen in PCOS include elevated gonadotropin-releasing hormone and luteinizing hormone (LH) reduced follicle-stimulating hormone (FSH) reduced sex hormone binding globulin (SHBG) and increased bioavailable androgens. Indeed a similar pattern has been observed in males and it comes with its own set of signs and symptoms. The parallels are so striking that researchers have come to consider it a “male polycystic ovarian syndrome equivalent.”
The clinical manifestation of this may vary between younger and older men. In younger men early onset androgenetic alopecia (AGA a.k.a. male pattern baldness) is a clue particularly in those who exhibit few to no other signs of hyperinsulinemia. 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 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.”
Erectile dysfunction may be another sign of this “male PCOS.” When erectile dysfunction (ED) has no obvious cause (such as depression chronic stress or physical trauma) insulin resistance should be suspected. ED is a cardiovascular problem. It results from impaired blood vessel endothelial function not from lack of desire. Researchers have noted that ED may be the first clinical sign of insulin resistance in young men—that is for a young man with no other signs and symptoms of metabolic derangement ED could be the canary in the coal mine a very 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. The researchers stated that “Subclinical endothelial dysfunction and insulin resistance may be the underlying pathogenesis of ED in young patients without well-known etiology.” And it is likely the insulin resistance driving the endothelial dysfunction.
It is telling that metformin—the well-known diabetes drug—improves 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. It is not a logical leap to suggest that the former likely played a role in the latter.
Benign Prostatic Hyperplasia/Hypertrophy (BPH)
BPH is yet another insulin-driven condition but most men and even their physicians are unaware of the connection. Men are simply told “You’re just getting older. This is normal.” It may be common but that doesn’t mean it’s normal.
Insulin is a cellular growth promoter. It is increasingly recognized that signaling from insulin promotes prostatic growth; unfortunately this finding which is robust in the medical literature has not yet trickled down to the offices of many primary care physicians who are the professionals most likely to encounter patients complaining of the associated signs and symptoms (such as 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 increased in the cases compared to the controls. (Insulin may upregulate the aromatase enzyme enhancing the conversion of testosterone to estrogen 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.” The higher the insulin the larger the prostate.
As with erectile dysfunction animal and cell culture studies suggest that drugs typically marketed for diabetes may be beneficial for men with BPH. In rats with prostate enlargement induced by hyperinsulinemia (which is telling in itself!) treatment with pioglitazone reduced insulin levels and prostate weight. In another study metformin substantially inhibited the proliferation of cultured human prostate epithelial cells. As is the case with PCOS for which metformin is frequently prescribed that drugs primarily used for diabetes are effective for BPH underscores the common origin of the three conditions: hyperinsulinemia.
It is 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.