Abnormal Liver Function

- hi everybody, nelson vergelhere with excelmale.com i'll be speaking today aboutthe role of estradiol in men, it's a very confusing subject,a lot of misconceptions, a lot of wrong informationon different online forums. not on excelmale, we dodiscuss every single study. i tend to be veryconservative when it comes to the topic of estradiol. i think a lot of clinicsare treating estradiol too aggressively, they arecrashing men's estradiol,

which is not good, i'llbe showing some data on what happens when yourestradiol is too low. and i think most men do notneed to be too concerned about estradiol, their bodyactually keeps a balance between testosterone andestradiol, and unless you have health issues like liver disease or extreme fat content, mostmen, or a genetic mutation, most men do not reallyover-produce estradiol. some men are very concernedabout estradiol since

it's been vilified online,like the evil female hormone that causes water retentionor erectile dysfunction, gynecomastia, when in fact a lot of the symptoms have nothing to do with estradiol. they're all related to otherissues, related to men's testosterone or other health issues. so obviously i have verystrong biases, but estradiol, as i said, excessiveestradiol can obviously cause some issues when it comesto cardiovascular disease,

and yes, in growth of the mammary gland, and cause gynecomastia related issues. so i'm not saying estradiol is all good, obviously nobody has reallyproven that estradiol, high estradiol causesanything in particular. there's only one studyi'll be talking about. so let's review the data thatwe have from different studies, you can also find moreinformation on excelmale.com, since i have a very longpost there that goes through

all the data that i'll be showing today. estradiol is produced fromthe conversion of testosterone through the aromataseenzyme in the liver and in fat cells, mostlysubcutaneous fat cells, under the skin. it has, as i said, benefitsin target tissues like the estrogen receptors inthe brain, in the heart, obviously in the breasttissue in the mammary glands, liver, and the reproductivetract in men and women,

and in bone. so estradiol is neededfor bone health, for reproductive and sperm production, and ovary production of the eggs. liver metabolism, cardiovascular health, estradiol plays a rolein lipids and also mood and sexual function. so estradiol is veryimportant, it is a hormone associated with females somen think it is not a good

hormone for them, but likewomen need testosterone, men also need estradiol,otherwise nature and evolution would not have put itdownstream from testosterone. so really testosterone isa precursor of estradiol. this is a hopefully nota too complicated diagram of what happens with the hormonalcascade in what we call the hpta axis, or hptg axis, hypothalamic-pituitary-testicular axis. the hypothalamus, right, inthe brain, sends a signal

.......with a hormone called gonadotropin-releasing hormonethat tells the pituitary gland to produce luteinizing hormone and follicle-stimulating hormone. these two hormones workon the leydig cells and the germ cells inthe testicles to produce testosterone or sperm. once it starts to be producedmost of it is actually is metabolized and discharged from the body.

and some of it becomesfree testosterone or bound testosterone to albumin orsex hormone binding globulin. 0.3% or so of of testosterone converts to estradiol in healthy menand around six to eight percent of t converts into dht, dihydrotestosterone. dht is linked to sexual function,mood, however excess dht can cause an increase in acnein some men, not all of men, hair loss, especially in thosewith genetic predisposition to hair loss, and even prostaticinflammation, in some men.

so dht is important, once againexcessive dht obviously is not a good thing to have. so, once again,testosterone 0.3% gets converted into estradiol, and i alreadytold you about the benefits. so both estradiol andtestosterone have been shown to send signals to the upstream glands, the hypothalamus and pituitaryglands to either slow them down or increase their activity depending on the level of testosterone.

so the body actually self regulates and tells the hp part of the axis to slow down or increase its rate of production. so when we increasedtestosterone with an injection or with gels or pellets, we're basically shuttingdown this cascade, because the body says "well we don't need to produce any testosterone,this guy is giving us some extra testosterone from theoutside world", so as i said,

the axis is regulated. testosterone still convertsto dht and estradiol, we just do not have lh and fsh, the sperm production drops to almost zero, but t levels are obviously preserved by testosterone replacement therapy options. this is the firststudy actually published in 2013 in the new englandjournal of medicine that was very well done.

the researchers enrolled young men, healthy young men, they gavethem a medication to shut down their testosterone and theirestradiol to zero. basically these men werevolunteeringto get their hormones shut down, and then the researchersgave them injections of testosterone at different dosages. they followed these men for a few months, measured their body composition,muscle, fat, all that. and sexual function questionnaires, etc.

they were able to reallyin a very clean manner, a very well done, controlledstudy, to prove that low estradiol and low testosteronewere linked to increases in fat mass and also decreases in sexual function, libido, et cetera. so estradiol on its owncan do the same things as testosterone, it's anenhancer of the effects of testosterone, and crashing your estradiolby taking either anastrozole or any other medications thatmay decrease estradiol is

actually not a good thing. obviously we know thatlow estradiol can also cause bone loss so men need estradiol. do not over-treat estradiol, be careful with anything youdo to reduce your estradiol because you actually maylose sexual function, get fatter, and lose bone density. and there's also some cognitive issues. very well done study,you can find out more

about this study either bygoogling the reference here or by going to excelmale since i gointo details with different graphs and and other facts. another study, this is a study that really created a lot of thehysteria around estradiol. it actually enrolled oldermen around 58 years of age average, in poland. it was an observational study so there was really no intervention.

501 men with kind of lowtestosterone....they had an average was around320 nanograms per deciliter, so these men were really, by our definition in the united states, were hypogonadal, theyhad low testosterone. they separated the men intofive groups depending on their estradiol blood levels, and by the way this study obviously used the old test. it's a very important thingfor me to focus on right now

because i don't have a slide on it. the fact that estradioltesting has evolved. we used to use an old testthat was based on eclia, it's an old immunoassay testthat used to overestimate estradiol in men. men with higher c reactive protein bloodlevels tended to have an overestimation of estradiol,artificially high estradiol so people would freakout and really that was, we found out later, thatdoing a test called,

based on liquid chromatographyand mass spectrometry gives a better indication ofthe actual value of estradiol. but anyway, so this studyactually used the old test, like most research studies out there, except the previous one ishowed, actually they used liquid chromatography. it separated men in five groups, those that had very lowestradiol under 12.9 picograms per milliliter, to thefifth quartile which was

men with over 37.4picograms per milliliter, and they followed themfor three years to see their survival rate. these men had chronic heart disease, all of them had either ahistory of heart attacks or a heart disease sothese were not healthy men, they were 58 years oldmen with low testosterone, cardiovascular issues, and they were followed to see who died,how many people died.

they found obviously menwith lower estradiol died faster, their chances, their survival rate, three year survival rate, was 44.6 %. and the men with reallyhigh estradiol had a survival rate of 37.4 %, had also actually aneven higher incidence of, sorry, survival rate. the control group, quartile three, is reallya control group because it has the estradiol levels of 20 to 30

.......... most of them survived, 82% or so. so we can tell lower estradiolhas a very low survival rate, meaning only 44% of the menwere alive three years later. high estradiol basically37% of men were alive three years later, so thisactually freaked some people out, we know obviously we know verywell high estradiol is not good for you but cliniciansstarted using the 37 picograms per milliliter as the cutoff for

health related issues on estradiol. it's an observationalstudy, using the old test, if we had used only thechromatography test maybe it would be lower, but really mosthealthy men have 20 to 40 to 50 picograms per milliliter. the higher the testosteronethe higher the estradiol. these are men with lowtestosterone obviously. men using testosterone replacement, most of them have testosteroneover 500 nanograms/ml,

most are actually sittingaround 800 to 1000 nanograms. so you expect higher estradiollevels because 0.3% of testosterone gets converted. so don't freak out just becauseyour estradiol has gone up when you get on testosteronebecause it is an expected response from the body tobalance the effects of, and boost the effects of testosterone. this next study actually observational, basically chart review by the folks from

baylor college ofmedicine here in houston, dr. lipshultz's group, thatlinked higher testosterone and higher estradiol to better libido and sexual function in men. i know it created a lotof controversy out there because most men and cliniciansthink that higher levels of estradiol are bad for you. but in fact these guyswith higher levels of both testosterone and estradiol seemto be doing better sexually.

so the cutoff was 50picograms per milliliter. you can see more details on excelmale.com. another study, i don't havethe reference i'm sorry, you can find it onexcelmale.com, found that that the higher thetestosterone to estradiol ratio, when you divide the numbers,the better the testicular function and sperm production. so men that actually impregnatedtheir wives tended to have testosterone to estradiol ofratio of 14 and above, and

those that did have problemswith having pregnancy effects did have low testosterone to estradiol ratio. so what does this mean?, should we be following up men by dividing testosterone into estradioland seeing the ratio?, there's no real agreement,i don't think any doctor really follows the ratio,most studies don't. i'd like to see more dataobviously on the ratio of testosterone to estradiol,does that really,

is that really the mostimportant factor to follow since testosterone goes up withestradiol?...it's the ratio, really the most importantthing to look at?. we have no data, so hopefullyif any investigators who may be watching this video: hint: this is a good thing tofollow in a research study. measure testosterone andestradiol, give people different doses of testosterone andfollow them for a few years and see who has betterbody composition and/or

sperm production, and/or sexual function. that would be a great, great study. so what happens when eitheryoung men or old men use testosterone injections? what happens to their estradiol? you probably won't be able to see, these graphs are verybusy, it's from a study published in 2010 in the journal of clinicalendocrinology and metabolism.

this study once againshut down blood levels of testosterone in older andyoung men and started giving them testosterone enanthatein different doses, anywhere from 25 milligrams a week up to 600 milligrams a week. very low dosage to a very highbodybuilding-type of dosage. the white bars are old men and the black bars are young men, alright? so this is total estradiol,obviously as the dose increased

estradiol increased, that's obvious. but it actually increaseda lot more in older men. they couldn't really explainif it's the fact that (they didn't do body composition analysis), but was it the fact that allthe older men usually have more fat mass or even medication-inducedliver dysfunction that could be causing more aromatization. but it is a very interestingobservation that older men tend to produce more estradiolper milligram of testosterone

than younger men. this is actually dht... dhtwas not very different. dht production by youngand older men was basically the same at different dosages, and this is something we hardly measure, we should look into free estradiol?, not bound to a sexhormone binding globulin. something that most of usdon't think about is the fact estradiol, like testosterone,gets bound up by

sex hormone binding globulin. some of it is free and some ofit is not free to do its job, ...... so actually the higher thetestosterone dosage the lower the free estradiol, whichis very interesting too, seems like the higherthe dose of testosterone, the more estradiol gets bound up. so this is pretty clear i meanolder men obviously produce more than younger men when itcomes to different dosages,

and when it comes to dht we don't seem to see a difference. of course there's an increaseper dose which is expected. symptoms of estradiol in excessare very controversial too because there is actually littleto no data on most of them. nipple sensitivity, testosteroneincreases the sensitivity of the nipple area in many men,some men actually freak out, they think they're goingto get gynecomastia. nobody has really studiedwhether sensitivity in the nipple

area has been linked to a higherincidence of gynecomastia, so that's one of my doubts. fluid retention, we are assuming because we're coming from data in women that higher estradiol can cause pms-like symptoms and bloat. there is not a single studyin men that actually proves that, we're speculating, we're assuming, some people might besold, i don't believe that

the edema, or water retention, caused by testosterone hasanything to do with estradiol. there are other effectsand i'll be covering that in another video, of whythis happens in some, the minority of men. elevation of blood pressurerelated to the water retention, that could also be an issue that has nothing to do with estradiol. decreased libido, we foundobviously that lower estradiol

can decrease libido, we have not a single, not one single study that shows that high estradiol causes decreases in libido. we just don't have any data,we're just speculating, so any time you hear that,it's basically a speculation, possibly a right one or possiblya wrong one but i just believe the data is important. so we have to educate aboutthe dosing of anastrozole. anastrozole is a drug, thebrand name is arimidex,

that can decrease estradiol. and men, some men call theirdoctors or their clinics when they're having sensitivityon their nipples and they start freaking out, the doctor may actually choose to put them on anastrozole, low dose. what i'm seeing the most onexcelmale.com is that men are being overdosed with anastrozole. they're coming in sayingthat the doctors have

put them on one milligrama day, or one milligram of anastrozole three times aweek, and obviously their estradiol is zero. and they're feeling all thesymptoms of low testosterone, even though theirtestosterone is high because they're using injections. so that's my main concern,it's happening a lot, so for the clinics out there, hopefully anybody watching this video,

please stop doing that. if you're going to treat aman, start him very low dose, 0.5 milligrams a week maybeand retest estradiol four weeks after you do this to makesure that the person, the man does not have estradiol under 20 picograms per milliliter. some men may need one milligram a week, but most men do not need anastrozole. i've never taken anastrozole in 25 years

so obviously i'm not ahigh estradiol producer, i've never had gynecomastia,history of gynecomastia, so some of us just don't have to take it, if our estradiol levels,and even if we had, i believe if we have estradiol of 50 or 60 and you have no symptoms youshouldn't be treating it. but obviously many doctors in the business criticize me for that point of view. i really think estradiol,blockage of the receptor,

eventually has long-termeffects on cognitive function, bone density and even sexual function. but that's me so, don'ttake my word for it. we'll probably hopefullysee more data on this, it's becoming a hot topic that more researchers are looking at. factors that increase estradiol, age, as you saw in the graph before, older men tend to produce more estradiol,

either because we're getting fatter, a metabolic issues, hormonaldifferences, liver metabolism. obesity, the more fat themore aromatization in men. some drugs, in this caseit's a drug used in hiv, has actually been reportedto cause gynecomastia, there are other drugs like finasteride, i'm sorry not finasteride, ketoconazole, that decrease testosterone, or tagamet, acid reducercan decrease testosterone,

and once you decreasetestosterone, the testosterone estradiolratio might be going down and that may actually causeissues with gyno and all that. alcohol overconsumption,you know one or two drinks a day in is not going toincrease your estradiol, but for those who areover-consuming, especially beer, some data i have to say that it's a little bit of a speculation there. liver disease definitely,most of aromatization

happens in the liver tissue. zinc deficiency, we havei think one reference that estradiol does increasein men with deficiency so some men take 50 milligrams of zinc and 2 milligrams of copper, to balance the zinc efficacy. there's one referenceon vitamin c deficiency, one reference on excessive dhea, i'm going to show thatreference right now,

xenoestrogens including plastics, iv bags, exposure to mostlyplastic related containers and environmental toxins, that has actually beencovered a lot in the media, lavender, tea tree oil, soyconsumption and flax seed. flax seed actually is good, it has fiber, and good oils butexcessive use of flax seed, there are two references on that. so the fear that,especially in bodybuilders,

obviously you can tellthis guy is a bodybuilder, is the increase in the nipplesize and the breast tissue under the nipple, whichis called gynecomastia, it's pretty obvious insome men like in this case before and after gyno, and it can obviously getreally bad in some men, due to excessive size. arimidex, or anastrozole,some doctors also may use tamoxifen to decrease estradiol.

this is actually one of, evenmore effective for really severe cases of gynecomastia. when it gets to be really severemen have to go for surgery to remove the breast tissue,that's actually in the worst cases that's the only way to treat it. let's talk a littlebit about anastrozole, it's use in men is off the label so insurancecompanies don't pay for the use of anastrozole in men, it's actually a breastcancer drug used in women,

it's the best single reliableway to control anastrozole, i'm sorry, estradiol blood levels. i'm not saying is the best, there are actually fourdifferent compounds used, there is the mostcommonly used like i said, zinc-copper supplementation, and chrysin seems to work in some men, i really believe that wayof treating anastrozole, sorry i keep changing anastrozole for estradiol,

estradiol is not very effectivebut i'm not going to fight against some references on the subject. compounded anastrozole isavailable from compounding pharmacies very cheap, one, 0.5, 2.5 milligramcapsules depending on what your doctor orders, as i said, 0.5 to one milligram a week, most men that's all they need, although they're gettingtreated with a lot more.

many men don't need it, andpatients can be instructed to take it as needed if sensitivity develops in the chest and nipple area. although as i said i havedoubts that that's linked. but i could have all the doubtsin the world and you still, without data i'm speculating also. all right so i'm goingto go through this one. this is very interesting,people ask me a lot about the supplementation using dhea tofeel better or to increase our

testosterone or to improveyour cognitive function. there are a lot of studies on dhea. dhea has not really been found to increase testosterone in men, there's some good data in women that showed that it does increase testosterone in them. there's some studies thatshowed improved cognitive function, energy levels,especially for men

that have low dhea levels. but dhea can also increase estradiol and if you're very concernedabout estradiol then that's something you need to know. the slide is a review of different papers and the estradiol blood levels, this is no change and thisis increases, and decreases. most studies show an increasein estradiol blood levels using dhea, so if you are goingto take dhea at least have

your estradiol tested afew weeks after you start. 25 to 15 milligrams a dayis what people are using when it comes to dhea sojust keep that in mind, especially if you are really,really freaked out and obsessed about estradiol, which i think some men are justobsessing a little too much. how about hcg, i get that question too. hcg obviously is used for prevention and reversal of testicular atrophy,

we have some anecdotal data,i'm very biased for it, i think hcg is a booster of testosterone when it comes to sexual function. it actually has been shownto be, when you use it with testosterone to improvefertility and sperm production and quality so that's another benefit. i have a video that just talksabout hcg so check it out on excelmale's youtube channel,or on excelmale.com. so make sure after youwatch this estradiol video,

you watch my hcg video. so i'm going to talkabout hcg and the studies, is actually a study once againthat looked at high doses and low doses of hcg and what happened a few hours later, to estradiol. i really like studies,i'm a chemical engineer and i tend to thrive on data. it's very frustrating for me in this field because we don't have asmuch data as we should.

however these guys here from the european journal of endocrinology 2008 took time to look at this. this is a study, the left hand side, of these two graphs arelower doses of hcg, 50, 500, and 5000 ius, only one shot, and this side of the graph is5000 and 6500 iu injections. high dose, lower dose, anddifferent curves right here, this is testosterone and estradiol.

one, three, five, 24, 48, and 72 hours. so basically over thecourse of three days. so yes the higher the hcg dosage, and these guys werenot using testosterone, only hcg one shot right here, one shot. so you do see an increase in estradiol, their baseline wasaround something like 28, 23 to 28 picograms, and obviously the really highdose of 5000 had a spike.

the 500 iu dose only basically spiked a little bit of estradiol a day later, 24 hours and then startedcoming down to a baseline of 72. so yes, if you get on hcg,especially hcg with testosterone, it's a good idea to follow upon your blood work or on your blood levels of estradiol. i believe that maybe the effectof hcg on sexual function, the boosting of sexual functionhas to do a lot with a boost in estradiol blood levels.

obviously the higherdoses had a very high peak that started coming down, even at 72 hours you see the levels notreturning to base line. so the effect takes a while,and one shot of the hcg at 5000 or 6500 ius hasan effect that lasts probably four to five days or longer. so nobody has reallyfollowed this behavior beyond the three day period. for more information you can find it

once again on excelmale.com. this is an evolvingfield, we'll probably see more and more data that willeither prove me right or wrong about the abuse of anastrozole,estradiol management with anastrozole. just askanything you need to ask on excelmale.com. we have 14,000guys on the forum and we have eight guys that are verymuch experts on the subject, they answer questions including myself. we have some doctors too,that answer questions,

and pharmacists and dietitiansand exercise trainers so we'll see you there andstay tuned for my next video. thank you.