A study just published in The Journal of Sexual Medicine documents the persistent sexual side effects of finasteride (Propecia, Proscar), a medication commonly used for both male pattern baldness and prostate hyperplasia, that too often are not discussed when prescribed. The authors observe:

“Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.””

They set out to…

“…characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL,”…

…by investigating the new onset of sexual side effects lasting for at least 3 months despite discontinuing finasteride. What did their data show?

“Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm…The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date.”

The authors admonished practitioners in their conclusion to offer patients the courtesy of full disclosure:

“Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.”

This report follows a study published earlier this year on persistent sexual side effects from finasteride and another 5α-reductase inhibitor (5α-RI), dutasteride, when used to treat urinary tract symptoms caused by prostate enlargement. They also stated:

“Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship…We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.”

Clinicians reading this will know that 5α-reductase inhibitors block the conversion of testosterone to dihydrotestosterone (DHT). DHT is 10 times stronger in conferring androgen stimulation on tissues—the loss of male hormone effects is more precipitous with smaller reductions of DHT. It is important to note that the hormone measurements were not done for these patients. Other factors, and other hormones, including estrogen and insulin, also affect the prostate. In the functional approach to MPHL and prostate hyperplasia the bioactive free fractions of testosterone, DHT and estrogen, along with other analytes are always measured to determine (1) if DHT is actually too high (not always the case), and (2) if a natural or synthetic 5α-reductase inhibitor is used, to make sure that DHT is not reduced too much (by follow-up tests). Excessive reduction of testosterone receptor stimulation is a risk not only for sexual side effects but also depression, cardiovascular disease, sarcopenia (loss of muscle mass), osteoporosis and other ailments.

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More evidence of the importance of testosterone in preventing heart disease for men is offered in a study just published in the journal Heart in which the authors set out to…

“…examine the effect of serum testosterone levels on survival in a consecutive series of men with confirmed coronary disease and calculate the prevalence of testosterone deficiency.”

They followed 930 men with coronary disease for an average of seven years and correlating all-cause mortality and vascular mortality with testosterone deficiency. What did the data show?

“The overall prevalence of biochemical testosterone deficiency in the coronary disease cohort using bio-available testosterone (bio-T) was 20.9%, using total testosterone was 16.9% and using either was 24%. Excess mortality was noted in the androgen-deficient group compared with normal (41 (21%) vs 88 (12%). The only parameters found to influence time to all-cause and vascular mortality in multivariate analyses were the presence of left ventricular dysfunction, aspirin therapy, β-blocker therapy and low serum bio-T.”

Notice that the bio-available testosterone (free fraction or unbound testosterone, the small percentage that is actually ‘working’) was more revealing than the total testosterone. This is most conveniently measured in a saliva specimen. Clinicians and patients should bear in mind the authors’ conclusion:

“In patients with coronary disease testosterone deficiency is common and impacts significantly negatively on survival.“

Important: testosterone replacement by gel, cream or patch (transdermal) can easily accumulate to abnormally high (supraphysiologic) levels which ‘back-fires’ by causing testosterone receptor desensitization and pituitary suppression. This may be missed if the correct testosterone test (the bio-active, free fraction portion) is not done.

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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.

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An 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.

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There is an evidence-based middle ground between the dogmas of those who assert that cholesterol is the main cause of cardiovascular disease and those who insist that its contribution is trivial. An interesting paper just published in the Journal of Clinical Lipidology illustrates an important mechanism by which cholesterol crystals trigger an inflammatory response.

“The response to arterial wall injury is an inflammatory process, which over time becomes integral to the development of atherosclerosis and subsequent plaque instability…In this review, a model of plaque rupture is hypothesized with two stages of inflammatory activity.”

In the first stage buildup of cholesterol crystals inside the “foam” cells that accumulate cholesterol induces their death (“apoptosis”); these dead cells elicit an inflammatory response that gathers more lipids into a vulnerable plaque. In stage two further expansion of crystals leads to intimal (blood vessel wall) injury…

“…which can manifest as a clinical syndrome with a systemic inflammation response…We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion, which can tear the plaque cap. This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome.”

The authors refer to their previous work showing that alcohol, aspirin and statins can dissolve cholesterol crystals. Their conclusion:

“…we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis.”

Of course there are a number of other pathways to  inflammation in cardiovascular disease (please see related posts) but this is one of the reasons why I prefer that patients who have both high cholesterol and evidence of inflammation have the benefit of the natural statin derived from red rice yeast with the necessary supportive and protective cofactors including coenzyme Q10. This paper published recently in the American Journal of Cardiology provides evidence that red rice yeast is as effective and better tolerated than the commonly prescribed drug pravastatin:

“The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia.”

The authors enrolled adults who had to discontinue statins due to muscle pain. Their findings are reassuring for those who prefer a natural alternative to pharma statins:

“The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.”

This is a serious issue. Statin-associated myalgia or the diagnosis rhabdomyolysis does not do justice to the devastating side effects I recently observed in a patient who had a bad reaction to lovastatin.

But how do we know when to intervene since high cholesterol alone is not a reliable risk factor and CRP (c-reactive protein) may not be elevated if the inflammation it is supposed to report is also preventing the liver from making it? One very helpful test for discriminating whether high cholesterol is contributing to vascular disease is the lipoprotein-associated phospholipase A2 (Lp-PLA2, PLAC) test, described here in an earlier post, that is associated specifically with inflammation in plaques. Another relies on the fact that it is cholesterol that has been damaged by oxidation that participates in the vascular lesion. To gauge this we can measure lipid peroxides. As this paper published in the journal Atherosclerosis documents, atherosclerosis is strongly associated with the presence of oxidized LDL:

“We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33–66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness…Regression analysis indicated that the carotid intima-media thickness and…the ox-LDL:LDL ratio…were the only factors associated independently with the severity of coronary atherosclerosis.”

We have also a fascinating study just published in the German medical journal Seminars in Thrombosis & Hemostasis that shows how oxidized LDL taken up by platelets induces inflammation in the blood vessel:

“Platelets are involved in the initiation of atherosclerosis by adherence to inflamed endothelium…In this study we investigated the functional consequences of oxidized low-density lipoprotein (oxLDL) uptake on platelet function and interaction with the endothelium.”

The authors were actually able to visualize the intracellular vesicles (microscopic sacs) containing the oxidized LDL using immunoflorescence microscopy. They made a fascinating observation: the platelets containing oxLDL provoked more cellular stickiness than regular LDL, oxLDL in the bloodstream or platelets without oxLDL.

“Furthermore, oxLDL-laden platelets induced foam cell development from CD34+ progenitor cells. On endothelial regeneration, oxLDL-laden platelets had the opposite effect: The number of CD34+ progenitor cells (colony-forming units) able to transform into endothelial cells was significantly reduced in the presence of oxLDL-platelets, whereas native LDL had no effect.”

This is a striking insight: it was only the oxidized LDL that prevented the endothelial cells (lining the blood vessel wall) from repairing, not the ‘native’ LDL.

Doctors and patients alike need to bear in mind the summary of their findings:

“Our results demonstrate that activated platelets internalize oxLDL and that oxLDL-laden platelets activate endothelium, inhibit endothelial regeneration, and promote foam cell development. Platelet oxLDL contributes significantly to vascular inflammation and is able to promote atherosclerosis.”

But, you may ask, since diabetes and pre-diabetes (metabolic syndrome) are so strongly associated with cardiovascular disease shouldn’t there be some kind of connection here? This study published in the journal Lipids shows the evidence that there is.

“Oxidized low-density lipoprotein (ox-LDL) plays a key role in the progression of atherosclerosis and diabetes complications. The aim of this study was first, to evaluate the association between ox-LDL and diabetes duration, and second, to examine serum level of ox-LDL in patients with prolonged diabetes and a desirable LDL-cholesterol level.”

It’s important to appreciate that the study group had ‘regular’ LDL in the desirable range, so a typical blood test would appear to be fine. Their very interesting observation is that the longer the person had diabetes (= the longer the risk factor for cardiovascular disease was building up) the more oxLDL they had in proportion to regular LDL:

“The ox-LDL-to-LDL ratio was dramatically higher in patients with diabetes duration >5 years in comparison to newly diagnosed patients and healthy participants. Ox-LDL was significantly associated with diabetes duration.”

Their final comments must be borne in mind by anyone caring for patients with both diabetes and a significant burden of insulin resistance:

“In conclusion, this study showed that the serum ox-LDL level increases with the length of diabetes, even though the patients’ LDL-cholesterol level is maintained at a desirable level. Our findings highlight that possibly more attention should be focused on markers of oxidative stress in the management of lipids in diabetic patients.”

Can we reliably measure oxidized LDL as implied by the lab test mentioned above? This study published in the journal Blood Pressure assure us that we can:

“Cardiovascular diseases are accompanied by the presence of active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using malondialdehyde (MDA)-modified low-density lipoprotein (LDL) analyses as a diagnostic and prognostic biomarker.”

MDA-modified LDL is the same as oxLDL. What conclusion did they draw from their data?

“MDA-modified LDL estimation has a diagnostic accuracy and may be used as an independent biochemical marker for atherosclerosis.”

Truthfully, the functional approach to cardiovascular disease encompasses a number of other important aspects, but I’m wondering if you’ve gotten this far. As a reward for your diligence I’ll conclude this limited post with a few interesting items of satisfying practical significance. First we have a paper just published in The Journal of Steroid Biochemistry & Molecular Biology that reassures us of the benefit of vitamin D in the prevention and treatment of cardiovascular disease.

“Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In type 2 diabetics, the prevalence of vitamin D deficiency is 20% higher than in non-diabetics, and low vitamin D levels nearly double the relative risk of developing CVD compared to diabetic patients with normal vitamin D levels.”

The authors endeavored to uncover the mechanism behind vitamin D’s benefit:

“We found that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein (AcLDL) and oxidized low density lipoprotein (oxLDL) cholesterol uptake in diabetics only. …In addition, 1,25(OH)2D3…improved insulin signaling, downregulated SR-A1 expression, and prevented oxLDL- and AcLDL-derived cholesterol uptake.”

You can remember their conclusion when getting your vitamin D level checked:

“The results of this research reveal novel insights into the mechanisms linking vitamin D signaling to foam cell formation in diabetics and suggest a potential new therapeutic target to reduce cardiovascular risk in this population.”

Throw some nuts in there too. A nice original study was published not long ago in The Anatolian Journal of Cardiology evaluated the benefit of hazelnuts (filberts) on atherosclerosis. The authors observed a number of interesting effects:

“Lag time for oxidation and α-tocopherol content of LDL were found to be increased while ox-LDL levels decreased during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo) B and apo B/apo AI ratio were found to be significantly lower while apo AI was higher. In respect to LDL subfraction, ratio of large/small LDL was significantly increased at the end of the study.”

They summed up their ‘take home’ message  on hazelnuts (which earlier posts suggest applies to most if not all nuts) accordingly:

“Hazelnut-enriched diet may play important role in decrease in atherogenic tendency of LDL by lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and increasing the ratio of large/small LDL beyond its beneficial effect on lipid and lipoprotein levels.”

Helicobacter pylori infection is, as you likely know, extremely common—according to WHO the most common infection in the world. It is a causative agent in almost all gastric ulcers. We see it here all the time. Finding out if you have it and getting it treated is another important therapeutic point for cardiovascular disease as this paper just published in the journal Digestive Diseases and Sciences reminds us. The authors investigated the impact of H. pylori infection on coronary atherosclerosis by examining the effects of infection on levels of serum lipid, high-sensitivity C-reactive protein (hsCRP) and oxidized low-density protein (oxLDL). What did their data show?

“The levels of total cholesterol, LDL, apolipoprotein B, serum hsCRP, oxLDL were significantly elevated and the severity of coronary atherosclerosis was significantly increased in H. pylori…group.”

Their conclusion echoes the findings of other investigators:

“More serious coronary atherosclerosis was observed in CHD patients with H. pylori…infection. H. pylori…infection might be involved in coronary atherosclerosis by modifying serum lipids, enhancing LDL oxidation, and activating the inflammatory responses.”

Remember, the most reliable ways to diagnose H. pylori infection are by stool antigens, a provoked breath test, or PCR (DNA amplification). H. pylori antibodies are not dependable.

Although it’s a major topic that deserves more space, mention at least much be made of the autoimmune aspect of cardiovascular disease as described in this recent paper published in the journal Angiology:

“Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis.”

The authors then describe their investigation of immune complexes, antibodies and receptor signaling in this process. Certain cases demand a thorough evaluation of the autoimmune component of their CVD.

It would also not be appropriate to close without at least alluding to the influence of hormones on cardiovascular disease, a topic that has many aspects treated in other posts. This paper recently published in the journal Endocrinology makes a very important but little known point for men (for whom most everyone knows that too little testosterone or excess conversion to estrogen is a big risk factor for CVD). Testosterone is normally converted into its dihydrotestosterone form (DHT) which does a lot of the heavy lifting because it’s ten times stronger than the original. Men with prostate disease are commonly prescribed medications (including saw palmetto) that block the conversion of testosterone to DHT, but without first measuring the levels of the bioactive forms of these hormones. These medications don’t always help because not everyone with a prostate condition has too much DHT. Moreover, DHT is important for protection against cardiovascular disease. The authors…

“…investigated the effect of…dihydrotestosterone (DHT) on the rabbit atherogenesis in relation to…oxidized-low-density lipoprotein receptor-1 (LOX-1) and its downstream molecules.”

What did they find?

“…DHT significantly reduced HCD-induced [high cholesterol diet-induced] foam cell formation…DHT inhibited the formation of foam cells induced by oxidized low-density lipoprotein. Moreover, the expression of LOX-1 and inflammatory cytokines in the cultured macrophages was significantly suppressed by DHT.”

Inappropriately blocking the conversion of testosterone to DHT can thus open a door to cardiovascular disease. So remember, both gentlemen and ladies: no hormone interventions without measuring the free-fraction bioactive levels before and after!

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Not to oversimplify since depression can have multiple contributing causes, but there have been many studies published about brain inflammation as an important component of major and minor depression. An illuminating paper published in the latest volume of the journal Biological Psychiatry undertakes an extensive analysis of accumulated scientific evidence. The authors begin by noting:

“Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls.”

Cytokines are, among other things, signalling molecules that regulate immune system function. This has great practical significance because there is an evidence-based approach in functional medicine to analyzing and treating cytokine imbalances. The authors evaluated 24 studies that included eight different cytokines. Here’s what their data showed:

“This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-α and IL-6 in depressed subjects compared with control subjects…this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.”

You may enjoy the interesting comment on this study just published in Journal Watch.

Although this is a valuable study it’s important to keep a broad perspective. Here’s another paper published not long ago in the journal Pharmacopsychiatry, one among many others on cytokines and depression. It documents cases of brain inflammation with a different cytokine pattern. This paper is also interesting for the therapeutic comparison of Prozac and electroacupuncture:

“An increase in inflammatory response and an imbalance between T-helper (Th) 1 and 2 functions have been implicated in major depression. The aims of the present study were to 1) study the relationship between pro- and anti-inflammatory cytokines and between Th1 and Th2 produced cytokines in depressed patients and 2) evaluate and compare the effect of treatments with electroacupuncture (EA) and fluoxetine on these cytokines.”

Th1 and Th2 are the two primary poles of immune system function, cell-mediated and humoral (antibody). Imbalances result in immune dysregulation. Fluoxetine is Prozac. (The inclusion of electroacupuncture might tip you off that this study was done in Germany.) Their data tells a fascinating story:

“Increased proinflammatory cytokine interleukin (IL)-1β and decreased anti-inflammatory cytokine IL-10 were found in the depressed patients. By contrast, Th1 produced proinflammatory cytokines, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were decreased, and Th2 produced cytokine IL-4 was significantly increased in depressed patients…Both acupuncture and fluoxetine treatments, but not the placebo, reduced IL-1β concentrations in responders. However, only acupuncture attenuated TNF-α concentration and INF-γ/IL-4 ratio towards the control level.”

How interesting that what we call a peripheral sensory nervous system modality (stimulation of the brain through the peripheral sensory nerves, in this case with electroacupuncture) reduced inflammation and TNF-α. This corresponds exactly with my clinical experience employing these modalities for a range of conditions including autoimmune disorders, and explains part of why patients feel so much better after a treatment. Their conclusion is worth noting:

“These results suggest that an imbalance between the pro- and anti-inflammatory cytokines (IL-1 and IL-10), and between Th1 and Th2 cytokines (INF-γ or TNF-α and IL-4) occurred in untreated depressed patients. Both EA and fluoxetine had an anti-inflammatory effect by reducing IL-1β. EA treatment also restored the balance between Th1 and Th2 systems by increasing TNF-α and decreasing IL-4.”

Thus depression involves inflammation, but the cytokine expression can vary.

This topic is multifaceted and a proper synopsis of the functional approach to depression is too long for this forum, but here’s one more paper to keep the horizon open. This study published not long ago in the Journal of Psychiatric Practice investigates the role of low testosterone in depression.

“Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients…The objective of this study was to explore the effect of TT administration on depression using both a systematic review of the literature and a meta-analysis.”

What did the data show?

“Meta-analysis of the data from these seven studies showed a significant positive effect of TT therapy on…depressed patients when compared with placebo. Subgroup analysis also showed a significant response in the subpopulations with hypogonadism…”

This certainly confirms expectations considering the population of testosterone receptors in the brain and their density in the frontal lobe. Hypogonadism means that the testicles are producing too little testosterone in response to stimulation by luteinizing hormone (LH). This validates my common sense practice of always including biologically active free fraction testosterone and LH in workups for male depression. Note: testosterone replacement, especially by a transdermal route (gel, patch, cream) can give a good initial result but end up back-firing. This is a topic for another post. For now just remember there is a better way.

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Here’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….

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A 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?

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Here is more evidence of the strong correlation between erectile dysfunction and insulin. This paper recently published in the Journal of Andrology clearly discerns  the “correlation between erectile function and IR and abdominal obesity.” [IR = insulin resistance. Waist circumference is a metric for abdominal obesity.] Moreover, “IR also appears to alter testosterone production.” Important: a careful reading of this paper also discloses what functional medicine practitioners and Lapis Light patients know: “a negative correlation [with erectile function] was shown only between BT (biologically active fraction) and abdominal obesity. (BT is also termed free-fraction testosterone, measured in our salivary profiles. Total testosterone is not a reliable indicator.)

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I hope this post is widely distributed because, based on the gluten gene sensitivity test results and hormone profiles I am getting (consistent with these findings), a large percentage of men need to see it. Here are just a few research papers from major journals that seem to be largely ignored:

1. Gluten reactions cause tissue resistance to testosterone
2. Hypogonadism (impaired testicular function), infertility, and sexual dysfunction occurring with gluten reactions
3. Pituitary regulation of testicular function disrupted by gluten reactions

Do someone a favor and pass it on.

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