GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology


Erectile dysfunction (ED) is a common condition affecting more than 20% of men over 60 years, yet little is known about its genetic architecture. We performed a genome-wide association study of ED in 6,175 case subjects among 223,805 European men and identified one locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71 × 10−14), located between MCHR2 and SIM1. In silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation. Mendelian randomization provides evidence that genetic risk of type 2 diabetes mellitus is a cause of ED (OR 1.11 per 1-log unit higher risk of type 2 diabetes). These findings provide insights into the biological underpinnings and the causes of ED and may help prioritize the development of future therapies for this common disorder.

Main Text

Erectile dysfunction (ED) is the inability to develop or maintain a penile erection adequate for sexual intercourse.

ED has an age-dependent prevalence, with 20%–40% of men aged 60–69 years affected.

The genetic architecture of ED remains poorly understood, owing in part to a paucity of well-powered genetic association studies. Discovery of such genetic associations can be valuable for elucidating the etiology of ED and can provide genetic support for potential new therapies.

We conducted a genome-wide association study (GWAS) in the population-based UK Biobank (UKBB) and the Estonian Genome Center of the University of Tartu (EGCUT) cohorts and hospital-recruited Partners HealthCare Biobank (PHB) cohort. Subjects in UKBB were of self-reported white ethnicity, with subjects in EGCUT and PHB of European ancestry, as per principal components analyses (Supplemental Material and Methods).
ED was defined as self-reported or physician-reported ED using ICD10 codes N48.4 and F52.2, or use of oral ED medication (sildenafil/Viagra, tadalafil/Cialis, or vardenafil/Levitra), or a history of surgical intervention for ED (using OPCS-4 codes L97.1 and N32.6) (Supplemental Material and Methods). The prevalence of ED in the cohorts was 1.53% (3,050/199,352) in UKBB, 7.04% (1,182/16,787) in EGCUT, and 25.35% (1,943/7,666) in PHB (Table S1). Demographic characteristics of the subjects in each cohort are shown in Table S2. The reasons for the different prevalence rates in the three cohorts may include a higher median cohort age for men in PHB (65 years, compared to 59 years in UKBB and 42 years in EGCUT; Table S2), “healthy volunteer” selection bias in UKBB,

a lack of primary care data availability in UKBB, and intercultural differences, including “social desirability” bias.

Importantly, we note that the assessment of exposure-outcome relationships remains valid, despite the prevalence likely not being representative of the general population prevalence.

GWASs in UKBB revealed a single genome-wide significant (p < 5 × 10−8) locus at 6q16.3 (lead variant rs57989773, EAFUKBB [C-allele] = 0.24; OR 1.23; p = 3.0 × 10−11). Meta-analysis with estimates from PHB (OR 1.20; p = 9.84 × 10−5) and EGCUT (OR 1.08; p = 0.16) yielded a pooled meta-analysis OR 1.20; p = 5.71 × 10−14 (heterogeneity p value = 0.17; Figures 1A–1C). Meta-analysis of all variants yielded no further genome-wide loci. Meta-analysis of our results with previously suggested ED-associated variants also did not result in any further significant loci (Supplemental Material and Methods; Table S3), nor did X chromosome analysis in UKBB.

Figure thumbnail gr1
Figure 16q16.3 (Lead Variant rs57989773) Is an Erectile Dysfunction-Associated Locus and Exhibits Pleiotropic Phenotypic Effects

 

The association of rs57989773 was consistent across clinically and therapy defined ED, as well as across different ED drug classes (Figures 1C and S1). No further genome-wide significant loci were identified for ED when limited to clinically or therapy defined case subjects (2,032 and 4,142 case subjects, respectively).
A PheWAS of 105 predefined traits (Table S4) using the lead ED SNP rs57989773 found associations with 12 phenotypes at a p value < 5 × 10−4 (surpassing the Bonferroni-corrected threshold of 0.05/105), including adiposity (nine traits), adult height, and sleep-related traits. Sex-stratified analyses revealed sexual dimorphism for waist-hip ratio (WHR; unadjusted and adjusted for body mass index) and systolic and diastolic blood pressure (Figure 1D; Table S5).
The lead variant at the 6q16.3 locus, rs57989773, lies in the intergenic region between MCHR2 and SIM1, with MCHR2 being the closest gene (distances to transcription start sites of 187 kb for MCHR2 and 284 kb for SIM1). Conditional and joint analysis (Supplemental Material and Methods) revealed no secondary, independent signals in the locus. Previous work has implicated the MCHR2-SIM1 locus in sex-specific associations on age at voice-breaking and menarche.

The puberty timing-associated SNP in the MCHR2-SIM1 region (rs9321659; ∼500 kb from rs57989773) was not in LD with our lead variant (r2 = 0.003, D’ = 0.095) and was not associated with ED (p = 0.32) in our meta-analysis, suggesting that the ED locus represents an independent signal.

To identify the tissue and cell types in which the causal variant(s) for ED may function, we examined chromatin states across 127 cell types

for the lead variant rs57989773 and its proxies (r2 > 0.8, determined using HaploReg v.4.1) (Supplemental Material and Methods). Enhancer marks in several tissues, including embryonic stem cells, mesenchymal stem cells, and endothelial cells, indicated that the ED-associated interval lies within a regulatory locus (Figure 2A; Table S6).

Figure thumbnail gr2
Figure 2Functional Analysis of 6q16.3 Implicates SIM1 in ED Pathogenesis

 

To predict putative targets and causal transcripts, we assessed domains of long-range three-dimensional chromatin interactions surrounding the ED-associated interval (Figure 2B). Chromosome conformation capture (Hi-C) in human embryonic stem cells

showed that MCHR2 and SIM1 were in the same topologically associated domain (TAD) as the ED-associated variants, with high contact probabilities (referring to the relative number of times that reads in two 40-kb bins were sequenced together) between the ED-associated interval and SIM1 (Figures 2B and S2). This observation was further confirmed in endothelial precursor cells,

where Capture Hi-C revealed strong connections between the MCHR2-SIM1 intergenic region and the SIM1 promoter (Figure 2C), pointing toward SIM1 as a likely causal gene at this locus.

We next used the VISTA enhancer browser

to examine in vivo expression data for non-coding elements within the MCHR2-SIM1 locus. A regulatory human element (hs576), located 30-kb downstream of the ED-associated interval, seems to drive in vivo enhancer activity specifically in the midbrain (mesencephalon) and cranial nerve in mouse embryos (Figure 2D). This long-range enhancer close to ED-associated variants recapitulated aspects of SIM1 expression (Figure 2D), further suggesting that the ED-associated interval belongs to the regulatory landscape of SIM1. Taken together these data suggest that the MCHR2-SIM1 intergenic region harbors a neuronal enhancer and that SIM1 is functionally connected to the ED-associated region.

Single-minded homolog 1 (SIM1) encodes a transcription factor that is highly expressed in hypothalamic neurons.

Rare variants in SIM1 have been linked to a phenotype of severe obesity and autonomic dysfunction,

including lower blood pressure. A summary of the variant-phenotype associations at the 6q16 locus in human and rodent models is shown in Table S7. Post hoc analysis of association of rs57989773 with autonomic traits showed nominal association with syncope, orthostatic hypotension, and urinary incontinence (Figure S3). The effects on blood pressure and adiposity seen in individuals with rare coding variants in SIM1 are recapitulated in individuals harboring the common ED-risk variants at the 6q16.3 locus (Figure 1D), suggesting that SIM1 is the causal gene at the ED-risk locus. SIM1-expressing neurons also play an important role in the central regulation of male sexual behavior as mice that lack the melanocortin receptor 4 (encoded by MC4R) specifically in SIM1-expressing neurons show impaired sexual performance on mounting, intromission, and ejaculation.

Thus, hypothalamic dysregulation of SIM1 could present a potential mechanism for the effect of the MCHR2-SIM1 locus on ED.

An alternative functional mechanism may be explained by proximity of the lead variant (rs57989773) to an arginase 2 processed pseudogene (LOC100129854), a long non-coding RNA (Figure 2A). RPISeq

predicts that the pseudogene transcript would interact with the ARG2 protein, with probabilities of 0.70–0.77. Arginine 2 is involved in nitric oxide production and has a previously established role in erectile dysfunction.

GTEx expression data

demonstrated highest mean expression in adipose tissue, with detectable levels in testis, fibroblasts, and brain. Expression was relatively low in all tissues, however, and there was no evidence that any SNPs associated with the top ED signal were eQTLs for the ARG2 pseudogene or ARG2 itself.

As a complementary approach, we also used the Data-driven Expression Prioritized Integration for Complex Traits and GWAS Analysis of Regulatory or Functional Information Enrichment with LD correction (DEPICT and GARFIELD, respectively; Supplemental Material and Methods)

tools to identify gene-set, tissue-type, and functional enrichments. In DEPICT, the top two prioritized gene-sets were “regulation of cellular component size” and “regulation of protein polymerization,” whereas the top two associated tissue/cell types were “cartilage” and “mesenchymal stem cells.” None of the DEPICT enrichments reached an FDR threshold of 5% (Tables S8–S10). GARFIELD analyses, which assesses enrichment of GWAS signals in regulatory or functional regions in different cell types, also did not yield any statistically significant enrichments, therefore limiting the utility of these approaches in this case.

ED is recognized to be observationally associated with various cardiometabolic traits and lifestyle factors,

including type 2 diabetes mellitus (T2D), hypertension, and smoking. To further evaluate these associations, we first conducted LD score regression

to evaluate the genetic correlation of ED with a range of traits. LD score regression identified ED to share the greatest genetic correlation with T2D, limb fat mass, and whole-body fat mass (FDR-adjusted p values < 0.05; Table S11).

Next we performed Mendelian randomization

(MR) analyses to evaluate the potential causal role of nine pre-defined cardiometabolic traits on ED risk (selected based on previous observational evidence linking such traits to ED risk

), i.e., T2D, insulin resistance, systolic blood pressure, LDL cholesterol, smoking heaviness, alcohol consumption, body mass index, coronary heart disease, and educational attainment (Tables S12–S15). MR identified genetic risk to T2D to be causally implicated in ED: each 1-log higher genetic risk of T2D was found to increase risk of ED with an OR of 1.11 (95% CI 1.05–1.17, p = 3.5 × 10−4, which met our a priori Bonferroni-corrected significance threshold of 0.0056 [0.05/9]), with insulin resistance likely representing a mediating pathway

(OR 1.36 per 1 standard deviation genetically elevated insulin resistance, 95% CI 1.01–1.84, p = 0.042). Sensitivity analyses were conducted to evaluate the robustness of the T2D-ED estimate (Figure S5, Table S13), including weighted median analyses (OR 1.12, 95% CI 1.02–1.23, p = 0.0230), leave-one-out analysis for all variants (which indicated that no single SNP in the instrument unduly influenced the overall value derived from the summary IVW estimate

), and a funnel plot (showing a symmetrical distribution of single-SNP IV estimates around the summary IVW causal estimate). The MR-Egger regression (intercept p = 0.35) provided no evidence to support the presence of directional pleiotropy as a potential source of confounding.

We also identified a potential causal effect of systolic blood pressure (SBP), with higher SBP being linked to higher risk of ED (MR-Egger OR 2.34 per 1 standard deviation higher SBP, 95% CI 1.26–4.36, p = 0.007, with MR-Egger intercept [p = 0.007] suggesting presence of directional pleiotropy). LDL cholesterol (LDL-C) showed minimal evidence of a causal effect (OR 1.07 per 1 standard deviation higher LDL-C, 95% CI 0.98–1.17, p = 0.113), and there was limited evidence to support a role for smoking heaviness or alcohol consumption (Table S15). Genetic risk of coronary heart disease (CHD) showed weak effects on risk of ED, suggesting that pathways leading to CHD may be implicated in ED (OR 1.08, 95% CI 1.00–1.17, p = 0.061). Further, we identified no causal effects of BMI (using a polygenic score or a single SNP in FTO) or education on risk of ED.
Genetic variants may inform drug target validation by serving as a proxy for drug target modulation.

ED is most commonly treated using phosphodiesterase 5 (PDE5) inhibitors such as sildenafil. To identify potential phenotypic effects of PDE5 inhibition (e.g., to predict side effects or opportunities for repurposing), we looked for variants in or around PDE5A, encoding PDE5, which showed association with the ED phenotype. Of all 4,670 variants within a 1 Mb window of PDE5A (chromosome 4:119,915,550–121,050,146 as per GRCh37/hg19), the variant with the strongest association was rs115571325, 26 kb upstream of PDE5A (ORMeta 1.25, nominal p value = 8.46 × 10−4; Bonferroni-corrected threshold [0.05/4,670] = 1.07 × 10−5; Figure S6). Given the weak association with ED, we did not evaluate this variant in further detail.

We have gained insight into ED, a common condition with substantial morbidity, by conducting a large-scale GWAS and performing several follow-up analyses. By aggregating data from 3 cohorts, including 6,175 ED-affected case subjects of European ancestry, we identified a locus associated with ED, with several lines of evidence suggesting SIM1, highly expressed in the hypothalamus, to be the causal gene at this locus. Our findings provide human genetic evidence in support of the key role of the hypothalamus in regulating male sexual function.

Mendelian randomization implicated risk of T2D as a causal risk factor for ED with suggestive evidence for insulin resistance and systolic blood pressure, corroborating well-recognized observational associations with these cardiometabolic traits.

Further research is needed to explore the extent to which drugs used in the treatment of T2D might be repurposed for the treatment of ED. Lack of evidence for a causal effect of BMI on ED risk in MR analysis (using multiple SNPs across the genome) suggests that the association of the lead SNP (rs57989773) with BMI arises from pleiotropy and that the association of this variant with ED risk is independent of its association with adiposity.

In conclusion, in a large-scale GWAS of more than 6,000 ED-affected case subjects, we provide insights into the biological underpinnings of ED and have elucidated causal effects of various risk factors, including pathways involved in the etiology of T2D. Further large-scale GWASs of ED are needed in order to provide additional clarity on its genetic architecture and etiology and to shed light on potential new therapies.
Source:www.cell.com

Type 2 Diabetes Could Be a Cause of Erectile Dysfunction


Type 2 diabetes may be a causal factor in the development of erectile dysfunction (ED), with insulin resistance a likely mediating pathway, results of a large-scale genomic analysis suggest. The data also uncovered a genetic locus linked to ED.

Jonas Bovijn, MD, DPhil, Big Data Institute at the University of Oxford, United Kingdom, and colleagues gathered data on more than 220,000 men across three cohorts, of whom more than 6000 had ED.

The researchers initially showed that a region on chromosome 6 is linked to the development of ED. The location suggested that the condition is associated with dysregulation of the hypothalamus.

Next, they performed a Mendelian randomization analysis, which examined the relationship between gene mutations known to be associated, in this case, with cardiometabolic factors and the outcome of ED.

The research, published online December 20 in the American Journal of Human Genetics, showed that a genetic predisposition to type 2 diabetes increased the risk for ED. The risk was driven primarily by susceptibility to insulin resistance.

Bovijn said in a release: “We know that there is observational evidence linking erectile dysfunction and type 2 diabetes, but until now there has not been definitive evidence to show that predisposition to type 2 diabetes causes erectile dysfunction.”

“Further research is needed to explore the extent to which drugs used in the treatment of type 2 diabetes might be repurposed for the treatment of ED,” the team notes.

Co–senior author Anna Murray, PhD, University of Exeter Medical School, United Kingdom, said in the release that “until now little has been known” about the cause of ED.

Previous studies have suggested there is a genetic basis for ED. The new study goes further by demonstrating that a genetic predisposition to type 2 diabetes is linked to ED, according to Murray.

“That may mean that if people can reduce their risk of diabetes through healthier lifestyles, they may also avoid developing erectile dysfunction,” she said.

Michael Holmes, MD, PhD, of the Nuffield Department of Population Health at the University of Oxford, who was one of the senior authors, agreed.

“Our finding is important, as diabetes is preventable, and indeed one can now achieve ‘remission’ from diabetes with weight loss, as illustrated in recent clinical trials.

“This goes beyond finding a genetic link to erectile dysfunction to a message that is of widespread relevance to the general public, especially considering the burgeoning prevalence of diabetes,” Holmes said.

Large Studies Key

Although the prevalence of ED is known to increase with age, rising to 20% to 40% among men aged 60 to 69 years, the genetic architecture of the condition remains poorly understood. This is at least in part due to a lack of well-powered studies.

The researchers therefore conducted a genome-wide association study (GWAS) using data on 199,362 individuals from the UK Biobank cohort and 16,787 people from the Estonian Genome Center of the University of Tartu (EGCUT) cohort, both of which are population based.

In addition, they included information on 7666 participants in the hospital-recruited Partners HealthCare Biobank (PHB) cohort.

The prevalence of ED, which was determined on the basis of self- or physician-reported ED, the use of oral ED medication, or a history of ED surgical intervention, was 1.53% in the UK Biobank, 7.04% in EGCUT, and 25.35% in PHB.

The researchers believe that the difference in prevalence rates between the cohorts may relate to the older average age for men in PHB, at 65 years, vs 59 years in the UK Biobank and 42 in EGCUT. In addition, the prevalence in the UK Biobank cohort may have been affected by a “healthy volunteer” selection bias and a lack of primary care data.

GWAS on the UK Biobank data indicated that there was a single genome-wide significant locus at 6q16.3 between the MCHR2 and SIM1 genes, with rs57989773 the lead variant.

Pooled meta-analysis of the combined cohorts indicated that rs57989773 was associated with ED at an odds ratio of 1.20 per C-allele (P = 5.71 × 10-14).

Synthesizing previous research on SIM1, which is highly expressed in the hypothalamus, in both human and rodent models, the team found that rs57989773 is associated with syncope, orthostatic hypotension, and urinary incontinence.

Moreover, the common risk variant for ED at 6q16.3 is linked to blood pressure and adiposity, as well as male sexual behavior in mice.

The researchers, therefore, suggest that a potential mechanism for the effect of the MCHR2-SIM1 locus on ED could be the hypothalamic dysregulation of SIM1.

The team also performed Mendelian randomization analyses to examine the potential causal role of cardiometabolic traits in ED risk.

Factors included type 2 diabetes, insulin resistance, systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol levels, smoking heaviness, alcohol consumption, body mass index, coronary heart disease, and educational attainment.

The analysis revealed that type 2 diabetes was causally implicated in ED, with the risk for ED increased 1.11-fold with each 1-log higher genetic risk for type 2 diabetes (P = 3.5 × 10-4).

Insulin resistance was found to be a likely mediating pathway for the relationship, with an odds ratio for ED of 1.36 per 1 SD genetic increase in insulin resistance (P = .042).

SBP also had a causal effect on ED risk, at an odds ratio of 2.34 per 1 SD increase in SBP (P = .007).

LDL cholesterol was found to have a minor impact on the risk for ED, at an odds ratio of 1.07 per 1 SD increase in levels (P = .113). There was no association between ED and either smoking heaviness or alcohol use.

Source:Medscape.com

Type 2 Diabetes Could Be a Cause of Erectile Dysfunction


Type 2 diabetes may be a causal factor in the development of erectile dysfunction (ED), with insulin resistance a likely mediating pathway, results of a large-scale genomic analysis suggest. The data also uncovered a genetic locus linked to ED.

Jonas Bovijn, MD, DPhil, Big Data Institute at the University of Oxford, United Kingdom, and colleagues gathered data on more than 220,000 men across three cohorts, of whom more than 6000 had ED.

The researchers initially showed that a region on chromosome 6 is linked to the development of ED. The location suggested that the condition is associated with dysregulation of the hypothalamus.

Next, they performed a Mendelian randomization analysis, which examined the relationship between gene mutations known to be associated, in this case, with cardiometabolic factors and the outcome of ED.

The research, published online December 20 in the American Journal of Human Genetics, showed that a genetic predisposition to type 2 diabetes increased the risk for ED. The risk was driven primarily by susceptibility to insulin resistance.

Bovijn said in a release: “We know that there is observational evidence linking erectile dysfunction and type 2 diabetes, but until now there has not been definitive evidence to show that predisposition to type 2 diabetes causes erectile dysfunction.”

“Further research is needed to explore the extent to which drugs used in the treatment of type 2 diabetes might be repurposed for the treatment of ED,” the team notes.

Co–senior author Anna Murray, PhD, University of Exeter Medical School, United Kingdom, said in the release that “until now little has been known” about the cause of ED.

Previous studies have suggested there is a genetic basis for ED. The new study goes further by demonstrating that a genetic predisposition to type 2 diabetes is linked to ED, according to Murray.

“That may mean that if people can reduce their risk of diabetes through healthier lifestyles, they may also avoid developing erectile dysfunction,” she said.

Michael Holmes, MD, PhD, of the Nuffield Department of Population Health at the University of Oxford, who was one of the senior authors, agreed.

“Our finding is important, as diabetes is preventable, and indeed one can now achieve ‘remission’ from diabetes with weight loss, as illustrated in recent clinical trials.

“This goes beyond finding a genetic link to erectile dysfunction to a message that is of widespread relevance to the general public, especially considering the burgeoning prevalence of diabetes,” Holmes said.

Large Studies Key

Although the prevalence of ED is known to increase with age, rising to 20% to 40% among men aged 60 to 69 years, the genetic architecture of the condition remains poorly understood. This is at least in part due to a lack of well-powered studies.

The researchers therefore conducted a genome-wide association study (GWAS) using data on 199,362 individuals from the UK Biobank cohort and 16,787 people from the Estonian Genome Center of the University of Tartu (EGCUT) cohort, both of which are population based.

In addition, they included information on 7666 participants in the hospital-recruited Partners HealthCare Biobank (PHB) cohort.

The prevalence of ED, which was determined on the basis of self- or physician-reported ED, the use of oral ED medication, or a history of ED surgical intervention, was 1.53% in the UK Biobank, 7.04% in EGCUT, and 25.35% in PHB.

The researchers believe that the difference in prevalence rates between the cohorts may relate to the older average age for men in PHB, at 65 years, vs 59 years in the UK Biobank and 42 in EGCUT. In addition, the prevalence in the UK Biobank cohort may have been affected by a “healthy volunteer” selection bias and a lack of primary care data.

GWAS on the UK Biobank data indicated that there was a single genome-wide significant locus at 6q16.3 between the MCHR2 and SIM1 genes, with rs57989773 the lead variant.

Pooled meta-analysis of the combined cohorts indicated that rs57989773 was associated with ED at an odds ratio of 1.20 per C-allele (P = 5.71 × 10-14).

Synthesizing previous research on SIM1, which is highly expressed in the hypothalamus, in both human and rodent models, the team found that rs57989773 is associated with syncope, orthostatic hypotension, and urinary incontinence.

Moreover, the common risk variant for ED at 6q16.3 is linked to blood pressure and adiposity, as well as male sexual behavior in mice.

The researchers, therefore, suggest that a potential mechanism for the effect of the MCHR2-SIM1 locus on ED could be the hypothalamic dysregulation of SIM1.

The team also performed Mendelian randomization analyses to examine the potential causal role of cardiometabolic traits in ED risk.

Factors included type 2 diabetes, insulin resistance, systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol levels, smoking heaviness, alcohol consumption, body mass index, coronary heart disease, and educational attainment.

The analysis revealed that type 2 diabetes was causally implicated in ED, with the risk for ED increased 1.11-fold with each 1-log higher genetic risk for type 2 diabetes (P = 3.5 × 10-4).

Insulin resistance was found to be a likely mediating pathway for the relationship, with an odds ratio for ED of 1.36 per 1 SD genetic increase in insulin resistance (P = .042).

SBP also had a causal effect on ED risk, at an odds ratio of 2.34 per 1 SD increase in SBP (P = .007).

LDL cholesterol was found to have a minor impact on the risk for ED, at an odds ratio of 1.07 per 1 SD increase in levels (P = .113). There was no association between ED and either smoking heaviness or alcohol use.

 

Source:Medscpe.com

Statins and BP lowering medicines don’t cause Erectile dysfunction


https://speciality.medicaldialogues.in/statins-and-bp-lowering-medicines-dont-cause-erectile-dysfunction/

This heat-activated penile implant could be the answer to erectile dysfunction


For men who no longer have the ability to become erect naturally, the loss of healthy sexual function can be incredibly challenging – but a new penile prosthetic device could restore that missing spark.

Scientists in the US have developed a heat-activated penis exoskeleton using a memory metal called nitinol – a nickel-titanium alloy – that changes its shape depended on what temperature it is.

The idea is that this prosthetic, once implanted in the penis, would remain flaccid while at body temperature. But when the situation calls for it, heating the implant would cause it to harden, expanding into a straightened, elongated shape.

398472398-implant_1024

According to the research team – led by urologist Brian Le from the University of Wisconsin-Madison – that artificially induced hardness could go a long way to making men who’ve lost the ability to become erect feel good about themselves.

“It’s a survivorship issue,” says Le. “[R]estoring function can help people feel whole in their bodies again.”

While existing penile implants use inflatable pumps or rods to help patients become erect, the researchers say these older technologies can be difficult to use and potentially cause tissue damage.

By contrast, the unique properties of nitinol could make for a much more sophisticated device. The super-elastic metal is what’s called a shape-memory alloy, which means it can ‘remember’ an original shape that it reverts to when heated.

In the case of the penile implant, the original shape is the stiffened, elongated form, but once it cools down, the prosthetic changes into a limp, slightly curved form.

You can see the transition in the video below. When the implant is dropped into a small pool of heated water, it instantly straightens out into its remembered position.

Of course, some of you out there reading this – particularly the guys – might be wondering (or worrying) about just how the heat gets applied to this rather sensitive part of the male anatomy?

The answer is a remote-control device that the researchers are currently working on. The team envisages that this remote heating tool will be able to be simply be waved over the penis, heating the nitinol implant via induction.

In other words, men won’t need to dunk their appendage into a steaming hot tub in order to get erect.

And the other good news is the relatively mild temperature the alloy hardens at. According to the researchers, the nitinol will change shape when it’s raised a few degrees above body temperature – so the transition shouldn’t be painful, but hopefully it’s also hot enough that it won’t get triggered at the wrong time.

It’ll take a lot more testing before this kind of implant becomes commercially available, but the scientists are hopeful – provided further trials indicate everything is safe – the prosthetic may hit the market within five to 10 years.

“We’re hoping that, with a better device, a better patient experience, and a simpler surgery, more urologists would perform this operation, and more patients would want to try the device,” says Le.

With as much as 40 percent of men aged 40 experiencing erectile dysfunction, it’s clearly a huge issue, and while many of those individuals can turn to drugs like Viagra, such medications don’t work for everybody.

According to the team, one-third of men with erectile dysfunction between the ages of 40 and 70 don’t respond to the drugs, so better penile implants could be a massive deal for affected males and their partners – and hopefully they don’t have too long to wait.

“The restrictions on this device are not going to come from the research, but from regulatory hurdles that determine whether it can be put inside a person, what kind of trials need to be involved.”

Shape-memory alloys can be made from three different combinations, or alloys – a copper-aluminium-nickel alloy, a nickel-titanium alloy, or less commonly, a zinc, copper, gold and iron alloy. The alloy being used in the video above is a nickel-titanium alloy, which is commercially produced as sold as ‘Nitinol’.

Nitinol was discovered in 1959 by William Buehler, a scientist at the US Naval Ordnance Laboratory, as he searched for materials that could be used in tools for dismantling magnetic mines. Nitinol didn’t end up being much help in that regard, but it’s now widely used in medical technology, including “devices that maintain blood flow within an artery, implants that restore function to a failing heart valve and retrieval devices that remove life-threatening blood clots from deep within the brain”, says US-based Nitinol manufacturer Memry on their website.

Shape memory alloys like Nitinol can be made up of one of two different crystal structures, depending on where they are sitting in relation to a certain, very important temperature, known as the ‘transformation temperature’. If the alloy is below this temperature, its atoms are organised in flexible lattices, which allows it to be bent in all kinds of shapes very easily. But once the metal is heated past its transformation temperature – which for a piece of Nitinol wire will be somewhere between 65 and 80°C – it automatically returns to its original shape.

“Once heated to the critical temperature, Nitinol shows its ‘heat memory’ as it transforms into the austenitic state, where the atoms become locked into their previous rigid arrangement,” says the Grand Illusions website. “When the metal springs into its remembered shape, it does so with so much force that it can be used to do actual work. Small motors have been built using Nitinol wire that passes through different temperatures. Solar panels on some satellites are raised into position by shape memory alloys, activated by the heat of the Sun.”

 

Watch the video. URL:https://youtu.be/FBaIdvgbBAM

 

10 Bogus Facts About Erectile Dysfunction


There’s no shortage of information out there about erectile dysfunction, but the problem is, a lot of it is just not true.

And reading about “miracle” pills or supplements that just don’t work aren’t going to do your penis any good.

erectile dysfunction myths
What you need is real, honest information about what’s going on below your belt. So we’ve compiled a list of the 10 biggest bogus facts about ED—and the real truth you need to know.

1. The falsehood: Erectile dysfunction refers to one specific penis problem

The truth: The definition of erectile dysfunction is not the same for every guy, says Daniel Williams, M.D., an associate professor in the department of urology at the University of Wisconsin School of Medicine and Public Health.

It’s usually defined as the inability to get and keep an erection that’s satisfying enough for sex.

But some guys have problems getting erections in the first place, while others have difficulty maintaining an erection that lasts long enough for sex.

And in other cases, a man may be unable to get an erection that’s strong enough to penetrate during intercourse.

2. The falsehood: Erectile dysfunction only affects older guys

The truth: It’s true that the prevalence of erectile dysfunction does increase with age, but younger guys are by no means immune to it.

According to a study in the American Journal of Medicine, 85 percent of men ages 20 to 39 say they “always” or “almost always” can get and maintain an erection good enough for sex.

That means 15 percent of men have difficulty with their erections at least occasionally during sex.

When looking at men ages 40 to 59, 20 percent say they can usually get a good enough erection, while 12 percent say they only sometimes can, and 2 percent say they never can.

3. The falsehood: If you struggle in the bedroom once, you have erectile dysfunction

The truth: Few guys bat a thousand in the bedroom, and an off night is usually nothing to worry about, says Tobias Köhler, M.D., M.P.H., F.A.C.S., urology chair at Illinois’s Memorial Hospital.

Lots of times the cause can be traced to a temporary issue—say, you drank too much alcohol earlier that night, or were completely exhausted from a tough week at the office—that you don’t need to stress over.

On the other hand, if you notice your difficulty achieving or maintaining an erection lasts for three months or longer, that suggests a more chronic issue may be at play.

Make an appointment with your doctor to see what’s up.

4. The falsehood: Erectile dysfunction is all in your head

The truth: In many cases, erectile dysfunction is a combination of both physical and psychological factors, says Dr. Williams.

For instance, your ED may have a physical cause—usually a problem with your blood vessels that hampers blood flow to your penis.

But the more you stress about your problem, the more stress can play a role in making it even more difficult to achieve an erection.

So before you meet with your doctor, keep a log of when your erectile problems occur. That will help him or her determine what’s driving your ED—and figure out the best way to treat it.

5. The falsehood: ED means there’s something wrong with just your penis

The truth: Your erection—or lack of one—can actually alert you to underlying medical problems throughout your body.

For instance, take heart disease: Conditions like high blood pressure and high cholesterol can damage your blood vessels, impeding blood flow to your penis, Dr. Köhler says.

“The vessels that supply blood to your erection are only one to two millimeters in diameter,” he says. “Your heart’s are twice that size.”

That means your erection may take a hit years before you might suffer chest pains or other symptoms of heart disease.

Problems with your erection can also signal diabetes, low testosterone, or clinical depression.

6. The falsehood: Only a specialist can treat erectile dysfunction

The truth: In most cases, your primary care doctor is a solid place to start for your ED workup, says Dr. Williams.

He or she can order tests to check for related health conditions, such as a lipid panel to test for high cholesterol or a blood glucose test to check for diabetes.

Your primary care doctor can also prescribe first-line erectile dysfunction drugs called PDE5 inhibitors, which you probably know as Viagra or Cialis.

Still, you may need to see a urologist if those treatments don’t work, or if you have other urological issues along with your ED, like problems urinating or prostate problems.

 7. The falsehood: Your bad habits don’t affect your penis

The truth: Your vices aren’t just bad for your health—they might be hurting your erection, too.

Take lighting up: Cigarette smoking can damage your blood vessels, impeding blood flow and making it difficult to get an erection.

One year after quitting, 25 percent of ex-smokers reported improvement in their erections, a study from Iran found.

Most recreational and illicit drugs—including marijuana—have been linked to erectile problems too, says Dr. Köhler.

Plus, cutting down on booze can also improve your erections. It helps the vessels in your body rush blood to your penis, keeping it there so you can perform, he says.

8. The falsehood: All erectile dysfunction drugs are the same

The truth: The meds you are most familiar with—Viagra, Cialis, and Levitra—all belong to the same class of drugs called PDE5 inhibitors.

These drugs all work the same way, by relaxing smooth muscles and increasing blood flow to the penis, says Dr. Williams.

Still, they do affect your body a bit differently, which is important to understand if you want to reap the greatest benefits from each.

For instance, drugs like Viagra and Levitra reach peak effectiveness in one hour, while Cialis takes about two.

Also, eating a heavy, fatty meal before popping Viagra and Levitra can reduce the effectiveness of the drug. So you should wait between 2 to 3 hours after eating a big meal to take those kinds.

9. The falsehood: You’re out of options if Viagra doesn’t work for you

The truth: If first-line ED drugs like Viagra or other PDE5 inhibitors don’t work for you, you have other options.

Your doctor may prescribe an injectable medication called alprostadil—known by the brands Caverject or Edex. These drugs work by relaxing the smooth muscles of your penis, opening up blood vessels and increasing blood flow, says Dr. Williams.

Injecting your penis—yes, with a needle—can be pretty scary, but most men say it doesn’t hurt as much as they feared, he says.

The good news? Not only are these drugs effective, but they also tend to be a lot more affordable than PDE5 inhibitors.

10. The falsehood: Taking testosterone will cure your erectile dysfunction

The truth: If your testosterone levels are in the normal range, raising them higher probably won’t help your erectile issues, says Dr. Williams.

That’s why it’s important to get your levels tested: A level of about 300ng/dl or below is usually considered low, and guys with those levels are considered candidates for treatment.

What’s more, even if you do have low T, bringing your levels up to normal range may not be enough to fix all your erection woes. You still may need help from other ED treatments, like PDE5 inhibitors, he says.

Could a daily dose of vitamin D cure erectile dysfunction?


  • Vitamin D deficiency is known risk factor in diabetes and heart disease
  • New study found low levels of ‘sunshine’ vitamin raise risk of impotence
  • Men who had a vitamin D deficiency were 32% more likely to suffer ED
  • ED affects 40% of men over 40, and 70% of those over the age of 70

A daily dose of vitamin D could prevent men suffering erectile dysfunction the torture of impotence, experts have said.

Vitamin D deficiency has emerged as a risk factor in a range of condition, from diabetes to high blood pressure, and heart disease.

Now, researchers at Johns Hopkins University believe low levels of the ‘sunshine’ vitamin could also fuel erectile dysfunction.

Their findings, presented at the annual meeting of the American Heart Association, revealed a great prevalence of impotence among men with vitamin D deficiency.

Men who were found to have low levels of vitamin D were 32 per cent more likely to suffer erectile dysfunction, a new study by researchers at John Hopkins University found

Men who were found to have low levels of vitamin D were 32 per cent more likely to suffer erectile dysfunction, a new study by researchers at John Hopkins University found

Dr Erin Michos, a preventative cardiologist and associate professor of medicine at Johns Hopkins, said: ‘Vitamin D deficiency is easy to screen for and simple to correct with lifestyle changes that include exercise, dietary changes, vitamin supplementation and modest sunlight exposure.

‘Checking vitamin D levels may turn out to be a useful tool to gauge ED risk.

‘The most relevant clinical question then becomes whether correcting the deficiency could reduce risk and help restore erectile dysfunction.’

Dr Michos and her colleagues do however note, their findings are observational and more research is needed to determine whether the deficiency can cause or directly contribute to ED.

They note that if their results are affirmed in subsequent studies, vitamin D deficiency may become a clinical marker and a possible therapeutic target for ED.

 Checking vitamin D levels may turn out to be a useful tool to gauge erectile dysfunction risk
Dr Erin Michos, Johns Hopkins

Both erectile dysfunction and deficiency are individual markers of heightened cardiovascular risk so researchers say the new findings underscore the system-wide effects that vitamin D has on vascular function throughout the body, including vessels that feed cardiac and genital tissues.

Dr Michos and her team analysed the records of more than 3,400 men aged 20 and older, who participated in a national Health and Nutrition Examination Survey, from 2001 to 2004.

None of the men had overt heart disease, 30 per cent were vitamin D deficient and 16 per cent reported symptoms of erectile dysfunction.

Vitamin D deficiency, defined as vitamin D levels below 20 nanograms per milliliter of blood, was present in 35 per cent of men with erectile dysfunction, compared with 29 per cent without symptoms of impotence.

Those men with vitamin D deficiency were 32 per cent more likely to have erectile dysfunction than men with adequate vitamin D levels.

Researchers said that was the case even after they accounted for other factors commonly known to lead to impotence, including certain medications, alcohol use, smoking, diabetes, inflammation and high blood pressure.

Erectile dysfunction is the inability to achieve or maintain an erection of sexual intercourse, and affects 40 per cent of men over the age of 40, and 70 per cent of men aged 70 and older

Erectile dysfunction is the inability to achieve or maintain an erection of sexual intercourse, and affects 40 per cent of men over the age of 40, and 70 per cent of men aged 70 and older

Erectile dysfunction is the inability to achieve or maintain erection for satisfactory sexual intercourse.

It affects around 40 per cent of men older than 40 and 70 per cent of those over the age of 70, researchers said.

Vitamin D deficiency affects as many as 40 per cent of adult Americans, according to the Centers for Disease Control and Prevention.

Risk factors for the deficiency include being obese or overweight, limited outdoor activity, having darker skin and suffering from certain inflammatory conditions, such as diabetes and inflammatory bowel disease.

The Institute of Medicine recommends cumulative daily vitamin D intake of 600 international units for adults between 18 and 70 years of age, and 800 international units for those over 80.

Vitamin D supplementation is typically reserved only for those with documented deficiency, defined as blood levels below 20 ng/ml.

 

Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma


Importance  The target for the oral erectile dysfunction drugs, phosphodiesterase type 5 (PDE5) inhibitors, is part of a pathway implicated in the development of malignant melanoma. An increased risk of melanoma in sildenafil users was recently reported.

Objective  To examine the association between use of PDE5 inhibitors and melanoma risk, including data on specific PDE5 inhibitors, number of prescriptions, and melanoma stage.

Design, Setting, and Participants  Nationwide, population-based, nested case-control study in the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden, including 4065 melanoma cases diagnosed from 2006 through 2012 and 5 randomly selected controls per case with matching year of birth.

Exposures  Number of filled prescriptions for the PDE5 inhibitors sildenafil and vardenafil or tadalafil.

Main Outcomes and Measures  Risk of melanoma; overall and by stage and risk of basal cell carcinoma in multivariable logistic regression analyses.

Results  Of 4065 melanoma cases, 435 men (11%) had filled prescriptions for PDE5 inhibitors, as did 1713 men of 20 325 controls (8%). In multivariable analysis, there was an increased risk of melanoma in men taking PDE5 inhibitors (OR, 1.21 [95% CI, 1.08-1.36]). The most pronounced increase in risk was observed in men who had filled a single prescription (OR, 1.32 [95% CI, 1.10-1.59]; exposure rate, 4% for cases vs 3% for controls), but was not significant among men with multiple filled prescriptions (for 2-5 prescriptions: OR, 1.14 [95% CI, 0.95-1.37], 4% for cases and 3% for controls; for ≥6 prescriptions: OR, 1.17 [95% CI, 0.95-1.44], 3% for cases vs 2% for controls). PDE5 inhibitors were significantly associated with melanoma stage 0 (OR, 1.49 [95% CI, 1.22-1.83], 13% for cases vs 8% for controls) and stage I (OR, 1.21 [95% CI, 1.02-1.43], 12% for cases vs 10% for controls), but not stage II through IV (OR, 0.83 [95% CI, 0.63-1.09], 6% for cases vs 7% for controls). The risk estimates were similar for sildenafil and vardenafil or tadalafil. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (OR, 1.19 [95% CI, 1.14-1.25], 9% for cases vs 8% for controls). Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk.

Conclusions and Relevance  In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.

Coffee could reduce risk of erectile dysfunction


Coffee perks millions of Americans up each morning, and a new study finds it might help keep men’s sex lives percolating, too.

The study, from the University of Texas Health Science Center at Houston, found that men who consume more caffeine each day had a lower risk of erectile dysfunction. The exception? Men with diabetes — for them, extra caffeine didn’t lower their odds for impotence, the researchers said.

“Even though we saw a reduction in the prevalence of erectile dysfunction with men who were obese, overweight and hypertensive, that was not true of men with diabetes. Diabetes is one of the strongest risk factors for erectile dysfunction, so this was not surprising,” lead author Dr. David Lopez, assistant professor at UTHealth School of Public Health, said in a university news release.

The study couldn’t prove cause-and-effect, but one expert said the findings are in line with current research.

“These findings also support the latest U.S. Dietary Guidelines Advisory Committee position that drinking three to five cups a day reduces the risk of type 2 diabetes and heart disease; two conditions that are well established as significant risk factors for erectile dysfunction,” said Dr. Natan Bar-Chama, director of Male Reproductive Medicine at the Mount Sinai Hospital in New York City.

In the study, Lopez and colleagues looked at data on more than 3,700 men tracked by the U.S. National Health and Nutrition Examination Survey. The men answered questionnaires asking them to recall their caffeine intake from the prior 24 hours.

The amount of caffeine that appeared to reduce the risk of impotence was equal totwo to three cups of coffee a day, the researchers said.

Compared to men in the study who consumed zero to 7 milligrams of caffeine a day, men who consumed 85 to 170 milligrams of caffeine a day were 42 percent less likely to report erectile dysfunction, and those who consumed 171 to 303 milligrams of caffeine a day were 39 percent less likely to report the condition, the Texas team said.

Caffeine sources in the study included beverages such as coffee, tea, soda and sports drinks.

The study authors believe that caffeine may help thwart impotence because it relaxes certain arteries and muscles in the penis, improving blood flow and the ability to have an erection.

Another expert agreed. “More research is needed, but what scientists think is happening here is that coffee and caffeine are causing cavernous smooth muscle tissue (found in the penis) to relax, allowing more blood flow to the area and leading to improved erectile function,” said Dr. David Samadi, chair of urology at Lenox Hill Hospital in New York City.

The study was published online recently in the journal PLOS One.

According to background information in the study, erectile dysfunction affects more than 18 percent of American men 20 and older

Low Testosterone and Heart Disease Linked—But What’s Really Causing Them?


Story at-a-glance

  • After age 30, a man’s testosterone levels begin to decline, and continue to do so as he ages, leading to symptoms such as decreased sex drive, erectile dysfunction, depressed mood, and difficulties with concentration and memory
  • According to a recent analysis, low testosterone may increase a man’s risk for cardiovascular disease. The mechanism of harm in still unknown, and both low testosterone and heart disease may simply be the result of poor overall health
  • Estrogen, the female sex hormone, plays a much bigger role in men’s heath than previously thought. Both hormones have been found to be important for sexual function, and a deficiency in either has a negative impact on a man’s libido
  • While testosterone deficiency accounts for decreases in lean mass, muscle size and strength, estrogen deficiency in men is the primary culprit when it comes to increases in body fat
  • Dietary and exercise changes, particularly limiting sugar/fructose, eating healthy saturated fats and engaging in high-intensity exercises, Power Plate, and strength training, can be very effective at boosting testosterone levels naturally.
  • Heart Problems

Testosterone is an androgenic sex hormone produced by a man’s testicles, and to a lesser degree, in smaller amounts, by the ovaries in women. While testosterone is stereotypically associated with virility, it also plays a role in maintaining muscle mass, bone density, red blood cells, and a general sense of well-being. 

Beginning around age 30, a man’s testosterone levels begin to decline, and continue to do so as time goes on—unless you proactively address your lifestyle.

Chemical exposures, including prescription drugs like statins, can also have an adverse effect on your testosterone production. Symptoms of decliningtestosterone levels include:

  • Decreased sex drive
  • Erectile dysfunction and/or problems urinating
  • Depression
  • Difficulties with concentration and memory
  • Weight gain and/or breast enlargement

According to a recent analysis,1 low testosterone may also increase a man’s risk for cardiovascular disease. As reported in the featured article:2

“To arrive at their findings, the research team examined previous studies that analyzed cardiovascular disease and testosterone levels between 1970 and 2013. The review of the studies revealed modest evidence that low testosterone levels are linked to an increased risk of cardiovascular disease.

However, the researchers note there was little evidence of a link between low testosterone and artherosclerosis – the hardening and narrowing of the arteries that can lead to heart attacks and strokes, and there was no evidence of a specific link between heart attacks and testosterone levels.”

The Importance of Testosterone for General Health

While the exact mechanism linking low testosterone to heart disease could not be ascertained, the researchers suggest the effect might be related to thrombosis or arrhythmia. Thrombosis is when a blood clot develops, and arrhythmia is basically a condition in which your heart beats erratically. Previous research has linked low testosterone with both of these conditions, plus a number of others, including:

  • Increased blood pressure
  • Dyslipidemia
  • Endothelial dysfunction
  • Impaired left ventricular function

Interestingly enough however, they also found that testosterone replacement therapy did NOT have any positive effect on cardiovascular health. This could potentially indicate that low testosterone does not in and of itself promote heart disease, but rather that low T and heart disease are both caused by something else. As stated by lead researcher, Dr. Johannes Ruige:3

“Based on current findings, we cannot rule out that low testosterone and heart disease both result from poor overall health.”

Indeed, I know first-hand that low testosterone is not an automatic outcome of aging, provided you incorporate certain lifestyle strategies that can naturally boost your testosterone levels, which I’ll review below. These strategies are part and parcel of an overall healthy lifestyle, so they also automatically reduce your risk of most chronic disease, including heart disease.

It actually makes logical sense that failure to incorporate these foundational health-promoting strategies could be the root cause of low testosterone, heart disease, and all the heart-related adverse effects listed above.

The Role of Estrogen in the Aging Male

Both men and women make estrogen out of testosterone. As a result, some men can actually end up with close to twice the amount of estrogen found in postmenopausal women. Still, the levels of both testosterone and estrogen both tend to decline with age, and as they do, your body changes. So far, researchers have almost exclusively focused on estrogen’s effect on women, and testosterone’s impact on men. But that may soon change.

A recent article in the New York Times4 highlighted research demonstrating the intricate play of women’s sex hormones in aging men’s health—a factor that has so far been largely ignored:

“Estrogen, the female sex hormone, turns out to play a much bigger role in men’s bodies than previously thought, and falling levels contribute to their expanding waistlines just as they do in women’s. The discovery of the role of estrogen in men is ‘a major advance,’ said Dr. Peter J. Snyder, a professor of medicine at the University of Pennsylvania, who is leading a big new research project on hormone therapy for men 65 and over. Until recently, testosterone deficiency was considered nearly the sole reason that men undergo the familiar physical complaints of midlife. “

The study in question, published in the New England Journal of Medicine5 (NEJM), found that there were significant individual variations in the amount of testosterone required for any particular man to maintain lean body mass, strength, and sexual function.

However, they were able to determine that testosterone deficiency accounted for decreases in lean mass, muscle size and strength, while estrogen deficiency was the primary culprit when it came to increases in body fat. Both hormones were found to be important for sexual function, and a deficiency in either had a negative impact on the men’s libido. According to the lead author, Dr. Joel Finkelstein, an endocrinologist at Harvard Medical School:

“Some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens.”

Despite individual variations, Dr. Finkelstein’s research offers valuable insight into the function and behavior of estrogen and testosterone at different levels in a man’s body. For example, they found that less testosterone is actually needed for muscle maintenance than previously thought. They also found that:

  • In young men, the average testosterone level is about 550 nanograms per deciliter (ng/dl)
  • Muscle size and strength does not become adversely affected until testosterone levels drop below 200 ng/dl, which has previously been considered extremely low
  • Fat accumulation, however, increases at testosterone levels of 300-350 ng/dl, due to its impact on estrogen
  • Libido increases steadily with simultaneous increases in testosterone and estrogen

Please note that men are NOT advised to take estrogen replacement therapy, as this could cause feminization, such as enlarged breasts. As your testosterone levels rise, your body will automatically produce more estrogen, so the key is to maintain your testosterone level—ideally by incorporating the strategies I will discuss below.

How to Raise Your Testosterone Levels Naturally Through Exercise

Personally, I do not recommend using testosterone hormone replacement. If you indeed have low testosterone, you can consider trans rectal DHEA cream, which I’ll discuss below. DHEA is the most abundant androgen precursor prohormone in the human body, meaning it’s the largest raw material your body uses to produce other vital hormones, including testosterone in men and estrogen in women. However, I believe many of you may not even need that, were you to take full advantage of your body’s natural ability to optimize hormones like testosterone and human growth hormone (HGH).

Just like testosterone, your HGH levels also sharply decline after the age of 30, as illustrated in the graph above. Both of these hormones are also boosted in response to short, intense exercise. As I do not take any hormone or prohormone supplements, I’ve been doing Peak exercises for just over three years now, and at the age of 59, my testosterone level (done last month) and HGH levels (listed below) are still well within the normal range for a young adult male without the aid of ANY prescriptions, hormones and hormone precursor supplements:

  • Total testosterone: 982 ng/dl (normal test range: 250-1,100 ng/dl)
  • Free testosterone: 117 pg/ml (normal test range: 35-155 pg/ml)
  • HGH: 14,000 pg, more than three times the normal test range of 1,000-4,000 pg/24 hours

Below is a summary and video demonstration of what a typical high-intensity Peak Fitness routine might look like. As you can see, the entire workout is only 20 minutes, and 75 percent of that time is warming up, recovering or cooling down. You’re really only working out intensely for four minutes. It’s hard to believe if you have never done this, that you can actually get that much benefit from only four minutes of intense exercise, but that’s all you need!

  • Warm up for three minutes
  • Exercise as hard and fast as you can for 30 seconds. You should feel like you couldn’t possibly go on another few seconds
  • Recover at a slow to moderate pace for 90 seconds
  • Repeat the high intensity exercise and recovery 7 more times.

Four Additional Ways to Boost Testosterone and HGH

Besides high intensity exercise, there are several other strategies that will also boost your testosterone levels naturally. These are appropriate for virtually anyone, male or female, as they carry only beneficial “side effects.” For even more tips, please see my previous article, “9 Body Hacks to Naturally Increase Testosterone.”

    • Weight training. When you use strength training to raise your testosterone, you’ll want to increase the weight and lower your number of reps. Focus on doing exercises that work a wider number of muscles, such as squats or dead lifts. You can take your workout to the next level by learning the principles of Super-Slow Weight Training. For more information on how exercise can be used as a natural testosterone booster, read my article “Testosterone Surge After Exercise May Help Remodel the Mind.”
    • Whole body vibration training (WBVT) using a Power Plate. In addition to the Peak Fitness exercises, I do 10 minutes of Power Plate training twice a day and this likely also improved my hormones. WBVT in some ways simulate high intensity exercise by stimulating your white (fast-twitch) muscle fiber. This kick-starts your pituitary gland into making more growth hormone, which helps you build lean body mass and burn fat.
    • Address your diet. This is critical for a number of reasons. First of all, if you’re overweight, shedding the excess pounds may increase your testosterone levels, according to recent research.6 Testosterone levels also decrease after you eat sugar. This is likely because sugar and fructose raises your insulin level, which is another factor leading to low testosterone. Ideally, keep your total fructose consumption below 25 grams per day. If you have insulin resistance and are overweight, have high blood pressure, diabetes or high cholesterol, you’d be well advised to keep it under 15 grams per day.

The most efficient way to shed excess weight and normalize your insulin levels at the same time is to strictly limit the amount of sugar/fructose and grains in your diet, and replacing them with vegetables and healthy fats, such as organic pastured egg yolks, avocado, coconut oil, butter made from raw grass-fed organic milk, and raw nuts.

Saturated fats are in fact essential for building testosterone. Research shows that a diet with less than 40 percent of energy as fat (and that mainly from animal sources, i.e. saturated) lead to a decrease in testosterone levels.7 My personal diet is about 70-80 percent healthy fat, and other experts agree that the ideal diet includes somewhere between 50-70 percent fat. I’ve detailed a step-by-step guide to this type of healthy eating program in my optimizednutrition plan.

  • Intermittent fasting. Another effective strategy for enhancing both testosterone and HGH release is intermittent fasting. It helps boost testosterone by improving the expression of satiety hormones, like insulin, leptin, adiponectin, glucacgon-like peptide-1 (GLP-1), cholecystokinin (CKK), and melanocortins, which are linked to healthy testosterone function, increased libido, and the prevention of age-induced testosterone decline.

Why I Recommend DHEA Over Testosterone Replacement

I personally do not use any hormone or prohormone treatments as I’ve been successful in getting my hormone levels within the healthy young adult range using the protocols described above. However, if you chose to use hormones it is really crucial to use bioidentical versions. There are synthetic and bioidentical hormone products out on the market, but I advise using bioidentical hormones like DHEA if you opt for this route. DHEA is a hormone secreted by your adrenal glands. Again, this substance is one of the most abundant precursor hormones in your body, and it’s crucial for the creation of hormones, including testosterone and other sex hormones.

Production of this prohormone peaks during your late 20s or early 30s. With age, DHEA production begins to decline, right along with your testosterone and HGH levels. Your adrenal glands also manufacture the stress hormone cortisol, which is in direct competition with DHEA for production because they use the same hormonal substrate known as pregnenolone. Chronic stress basically causes excessive cortisol levels, thereby impairing DHEA production, which is why stress is another factor for low testosterone levels.

It’s important to use any DHEA product with the supervision of a professional. Find a qualified health care provider who will monitor your hormone levels and determine if you actually require supplementation.

Also, rather than using an oral hormone supplementation, I recommend trans-mucosal (vagina or rectum) application. Skin application may not be wise, as it makes it difficult to measure the dosage you receive. This may cause you to end up receiving more than what your body requires. Applying a trans-mucosal DHEA cream to your rectum (or if you are a woman, your vagina) will allow the mucous epithelial membranes that line your mucosa to perform effective absorption. These membranes regulate absorption and inhibit the production of unwanted metabolites of DHEA. That said, I do NOT recommend prolonged supplementation of hormones, even bioidentical ones. Doing so can trick your body into halting its own DHEA production and may cause your adrenals to become impaired.

Other Helpful Supplements

Besides DHEA, there are also nutritional supplements that can not only address some of the symptoms commonly associated with low testosterone, but may help boost your testosterone levels as well. These include:

    • Saw palmetto. Besides addressing symptoms of low testosterone, this herb may also help to actually increase testosterone levels by inhibiting up-conversion to dihydrotestosterone.8 Research has also shown it can help reduce your risk of prostate cancer. When choosing a saw palmetto supplement, you should be wary of the brand, as there are those that use an inactive form of the plant. According to industry expert Dr. Rudi Moerck, what you want to look for is an organic supercritical CO2 extract of saw palmetto oil, which is dark green in color. Since saw palmetto is a fat-soluble supplement, taking it with eggs will enhance the absorption of its nutrients.
    • Astaxanthin in combination with saw palmetto. There is also solid research indicating that if you take astaxanthin in combination with saw palmetto, you may experience significant synergistic benefits. A 2009 study published in theJournal of the International Society of Sports Nutrition found that an optimal dose of saw palmetto and astaxanthin decreased both DHT and estrogen while simultaneously increasing testosterone.9
    • Ashwagandha. This ancient Indian herb is known as an adaptogen, which can help boost stamina, endurance, and sexual energy. Research published in 201010 found that men taking the herb Ashwagandha experienced a significant increase in testosterone levels.

Ashwagandha also helps promote overall immune function, and can help increase your resistance to occasional stress.11 It also supports healthful levels of total lipids, cholesterol, and triglycerides already in the normal range. While some adaptogens are stimulants in disguise, this is not the case with Ashwagandha. It can give your morning exercise routine a boost, and when taken prior to bed, it can help you get a good night’s sleep as well. I recommend using only 100% organic Ashwagandha root, free of fillers, additives and excipients, to ensure quality.

Low Testosterone Is Not an Inevitable Fate for Aging Men

I strongly recommend implementing lifestyle strategies that are known to optimize testosterone levels naturally before you do anything else to address the symptoms associated with low testosterone. If you’re still deficient in testosterone after implementing high intensity exercise and strength training, along with the dietary strategies detailed above and, ideally, intermittent fasting, then you could try trans-mucosal DHEA. Again, remember to confer with a qualified health care practitioner and get your levels tested before supplementing with DHEA or any other hormone, including testosterone.

Personally, I’ve been able to maintain both testosterone and HGH levels comparable to that of a young healthy male, simply by implementing high intensity exercise, Power Plate exercises, and intermittent fasting, along with my standarddietary recommendations. I would strongly encourage you to review my nutrition plan if you haven’t already done so.

Add to that some regular sun exposure, and you’ll be well ahead of most people. Vitamin D, a steroid hormone, also helps to naturally increase testosterone levels. In one study,12 overweight men who were given vitamin D supplements had a significant increase in testosterone levels after one year. As in most instances, given half a chance, your body will actively and automatically strive to maintain optimal health. So as long as you incorporate the foundational basics of a healthy lifestyle, you can stay healthy and strong well into your old age.