Androgen Replacement

Discussion in 'Men's Health Forum' started by Michael Scally MD, Sep 30, 2010.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    IMO, for the most part hyperbole [BS]. And, it does not touch on the issues of AIH.

    testosterone Chases viagra in Libido Race as Doctors Fret
    Testosterone Chases Viagra in Libido Race as Doctors Fret - Bloomberg

    By Shannon Pettypiece
    May 1, 2012

    Eli Lilly & Co. (LLY) and Abbott Laboratories (ABT) are offering help to the 13.8 million American men who have low levels of testosterone. Doctors warn demand for the treatments could lead to overuse with deadly side effects.

    In what may become one of the most sought after sex enhancement treatments since the introduction of Viagra 14 years ago, new testosterone drugs from Abbott, Lilly and other drugmakers are in hot demand. Prescriptions for testosterone replacement therapies have more than doubled since 2006 to 5.6 million, according to data compiled by Bloomberg. Sales are expected to triple to $5 billion by 2017, according to Global Industry Analysts Inc.

    In clinics and treatment centers sprouting up around the country, men are lining up to get shots, gels and patches to boost their testosterone. Michael Murray, 43, a home stager in New York and Chicago, is one of them.

    “Am I making a deal with the devil? A little bit, but I have to think about my quality of life.” said Murray. “It is like I’m in my 20s again.”

    Murray said he doesn’t have any obvious symptoms of low testosterone levels. He simply wants to raise his energy level and give his body building regime a boost. That sort of endorsement may offer promise to the pharmaceutical industry. Still, a growing number of doctors warn that relying on the drug as a fountain of youth risks serious health consequences.

    Loss of Libido

    Like the millions of women who have opted for hormone replacement therapy, men are choosing to get their hormone levels in line. As many as 13.8 million men older than 45 in the U.S. have low levels of testosterone, according to a 2006 study in the International Journal of Clinical Practice. The male sex hormone begins to decline after age 30, and tends to drop about one percent each year, though the level of decline varies. Lower than normal levels can lead to a loss of libido, a decrease in bone and muscle mass, and depression, according to the Cleveland Clinic.

    Problems may occur when the drug is taken by those who don’t need it, according to health experts. Testosterone can increase the growth of prostate tumors and cause blood clots, infertility and liver damage, said Edmund Sabanegh, chairman of urology at the Cleveland Clinic. He said he is careful to prescribe the drugs only to patients with a medical need and has seen a rise in patients coming to him seeking a prescription for testosterone who don’t need it.

    ‘Highly Addictive Drug’

    “There are a lot of really bad things that can happen” from misuse of testosterone, said Sabanegh. “I think it is a highly addictive drug and I think we need to be very careful about treating patients appropriately.”

    Abbott and Lilly said they don’t condone the use of testosterone treatments by men who don’t have clinically low levels of the hormone. Lilly said its testosterone therapy, Axiron, was approved by U.S. regulators in 2010 based on a study of 155 men who were followed for as long as six months.

    Abbott only promotes use of its androgel for Food and Drug Administration approved uses in men diagnosed with low levels of testosterone by a doctor, said Greg Miley, a company spokesman. Abbott said its marketing is intended to raise awareness about low testosterone.

    Both companies said that when used properly, their products provide tremendous help to men with manageable side effects. They said men taking the treatments should be monitored for prostate cancer.

    Disease Awareness

    “Low testosterone is a chronic, but treatable disease and our marketing efforts around disease awareness are designed to raise awareness about this,” Miley said.

    Abbott spent $20.8 million on testosterone advertising in 2011, according to Nielsen Holdings NV. (NLSN) One television ad opens with a silhouette of a man sitting on the bench as his friends play basketball. The voice-over asks viewers if they have “lost their appetite for romance?” or are “feeling like a shadow of your former self?”

    The ads direct viewers to a website called On the website is an image of a troubled-looking man sitting on the edge of a bed, his back toward a woman. Another image shows an overweight man on a scale and there is also a quiz to help determine low testosterone levels.

    Lilly began running television, online and print ads last year for Axiron, which is applied under the arm through a device similar to a deodorant stick. The ads tout the product as “the only underarm testosterone treatment.” The company doesn’t disclose how much it has spent on marketing.

    The ads are intended to “help educate men about low testosterone and encourage them to seek treatment,” said Teresa Shewman, a Lilly spokeswoman.

    Testosterone Clinics

    While growing, sales of the drugs aren’t on par yet with those of erectile dysfunction treatments. The U.S. market for testosterone replacement therapies was $1.6 billion last year, according to data compiled by Bloomberg. Sales of Pfizer Inc. (PFE)’s Viagra were $1.98 billion and Lilly’s cialis were $1.88 billion in 2011.

    To meet the growing demand for testosterone treatments, clinics are opening across the country. Johnny Mitias, an orthopedic surgeon in Mississippi, decided to open a chain of clinics, called Ageless Men’s Health, after he saw the benefits first-hand by treating his own low testosterone. He now has 15 offices and plans to double the number next year. Mitias said he has 5,000 patients, who each pay $250 a month for testosterone injections.

    Strict Guidelines

    Blood tests to measure for low testosterone, though, can be unreliable as testosterone levels tend to fluctuate throughout the day, said Peter Snyder, a University of Pennsylvaniaendocrinologist. He requires men take multiple blood tests in the morning to ensure their levels are below the normal range of 300 to 1,200 nanograms per deciliter.

    “It’s likely the dramatic increase in use of testosterone is mostly for people whose blood test is a little bit low, but for no obvious reason other than age,” Snyder said. “It really isn’t clear that those people are going to benefit.”

    Snyder, who is studying the effects of testosterone in older men, said the increased popularity signals an overuse of the drugs. He said he won’t prescribe testosterone unless a patient has significantly low testosterone and symptoms, like depression, low sex drive or fatigue.

    Other experts worry that some doctors are misprescribing testosterone as a cure-all for a variety of problems. The Cleveland Clinic’s Sabanegh said he sees men taking testosterone to help with erectile dysfunction or low libido when they are trying to conceive a child. Yet testosterone treatments can make men infertile, a side effect doctors sometimes fail to consider, he said.

    Younger Than 60

    Mitias said his clinic has strict guidelines on treatment eligibility. Most patients at Ageless Men’s Health are younger than 60 and have testosterone levels below the normal rage recommended by the Endocrine Society, a professional organization for endocrinologists, he said. The clinic also routinely checks for prostate cancer.

    Mitias never thought he’d be a guy with low testosterone. He worked out regularly, had a busy surgical practice and was keeping up with his three kids. That started to change around age 40. He said he began feeling very tired, was having trouble sleeping and cut back on the gym and playing with his kids.

    He went to the doctor and got his testosterone checked. Even though his levels were within the normal range, Mitias says he decided to try taking testosterone because he had many symptoms. He saw an immediate improvement.

    “I got an injection on Friday and by Monday it changed my life,” Mitias said. “I told my friend and business partner how great I felt. He got tested and found out he was low, got an injection and it changed his life.”
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Risk Factors Associated With Cardiovascular Events During testosterone Administration

    The Testosterone in Older Men with Mobility Limitations (TOM) Trial was a placebo-controlled randomized trial, whose aim was to determine whether testosterone therapy in older men with mobility limitation and low total or free testosterone levels improves lower extremity muscle strength and physical function. Because of significantly higher incidence of cardiovascular adverse events in men assigned to the testosterone arm (23 vs 5 men in placebo group), in December 2009, the trial's Data and Safety Monitoring Board recommended that further enrollment be stopped and administration of study medications to participants be discontinued. In this study, we investigated the risk factors that were associated with cardiovascular events in the TOM Trial.

    The divergence in the cardiovascular events between the placebo and testosterone arms of the TOM Trial was apparent within weeks after randomization, making de novo or accelerated atherogenesis a less likely mechanism responsible for these events. Furthermore, the diversity of these cardiovascular events pointed against a single unifying mechanism.

    Researchers evaluated the relative changes in testosterone and estrogen levels in men who experienced cardiovascular events versus those who did not. Estrogens are prothrombotic, and their administration to men with prostate cancer and for secondary prevention of coronary disease has been associated with an increased risk of myocardial infarction and mortality. Similarly, novel markers of inflammation such as C-Reactive Protein (CRP), interleukin 6 (IL-6), and fibrinogen have been associated with cardiovascular disease and mortality.

    Therefore, they evaluated whether differential changes in serum testosterone and estrogen levels, along with biomarkers of inflammation and coagulation, were associated with cardiovascular events in the two intervention arms. Accordingly, they compared changes in the sex-steroid levels and biomarkers of cardiovascular risk between the testosterone and placebo groups, and within the testosterone group, between those who experienced cardiovascular events and those who did not.

    In conclusion, mobility-limited older men who experienced cardiovascular events in the TOM Trial had greater increase in serum free testosterone levels than those who did not. Research on alternative strategies that may benefit mobility-limited men is needed. In the interim, the benefits of testosterone supplementation in this population should be weighed against the risk of adverse events.

    Basaria S, Davda MN, Travison TG, Ulloor J, Singh R, Bhasin S. Risk Factors Associated With Cardiovascular Events During Testosterone Administration in Older Men With Mobility Limitation. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences.

    Background. Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of cardiovascular events in men randomized to testosterone, resulting in enrollment cessation by trial's Data and Safety Monitoring Board. We evaluated changes in gonadal hormones and markers of inflammation and coagulation to elucidate risk factors associated with cardiovascular events.

    Methods. Men aged 65 years or more, with mobility limitation, total testosterone 100–350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Changes in total and free testosterone, estradiol and estrone, C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor-1, and pro-brain naturetic peptide were compared between groups and within the testosterone group between subjects who experienced cardiovascular events and those who did not.

    Results. Of 209 men randomized (mean age 74 years), gonadal hormones and biomarkers were available in 179 men. Baseline body mass index, gonadal hormones, lipids, Framingham risk scores, and other biomarkers were similar in the two treatment groups. Within the testosterone group, the 6-month increase in free testosterone was significantly greater in men who experienced cardiovascular events than in those who did not [mean (95% confidence interval), 10.6 (4.6–16.7) vs 5.2 (3.0–7.5) ng/dL, p = .05]. In multivariable logistic regression analysis, the change in the serum levels of free testosterone was associated with cardiovascular events.

    Conclusion. Mobility-limited older men who experienced cardiovascular events had greater increases in serum free testosterone levels than those who did not.
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Exogenous testosterone, Cardiovascular Events, And Cardiovascular Risk Factors In Elderly Men

    Increasing interest in the use of supplemental testosterone has also led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk. Interest in the potential role of testosterone in cardiovascular disease (CVD) is primarily based on two seemingly contradictory epidemiologic observations. First, male sex and age are both well-defined risk factors for CVD, as is noted in cardiovascular risk scores. The assumed positive relationship between testosterone and CVD has been attributed to a putative detrimental effect of male sex hormones in general, and testosterone in particular, on the cardiovascular system. The higher incidence of CVD in men than in women of similar age, and its increase in women after the cessation of ovarian cycling with menopause, coupled with the higher CV risk profile of women with hyperandrogenism, all have led to the speculation that gender-related differences in sex steroid hormones may play a key role in the development of atherosclerosis and CVD. In particular, these data have generated the speculation that endogenous estrogens exert a protective effect, while endogenous androgens have a detrimental effect on the development of CVD.

    The second observation is that the population risk for CVD in elderly men increases at a time when serum testosterone levels are actually decreasing. Testosterone levels fall with age such that 20% of men >60 years old have serum testosterone levels below the normal range for young men, and by age 75, men have about 66% of the total serum testosterone level of men at age 25. Epidemiologic studies support the concept that low testosterone increases the risk of mortality in men and that a major component of the increased mortality is related to the effects of testosterone on cardiovascular risk factors. In a longitudinal follow-up study, low serum testosterone, measured as either total testosterone or free testosterone, has been shown to be significantly predictive of all-cause and vascular mortality in patients with coronary artery disease (CAD). Similarly, multivariate analysis of data from a longitudinal follow-up study in men with heart failure (HF) indicated that reduced serum levels of either total testosterone or free testosterone were independently related to increased risk of all-cause mortality.

    The correlation between increased cardiovascular risk and falling testosterone levels may occur because both events are a consequence of aging, but the observation that a significant relationship exists between testosterone plasma level and the severity of coronary atherosclerosis could also imply that low testosterone levels may be one of the causes rather than a consequence of CVD in men. At present, the issue of whether low testosterone levels are a cause or a consequence of CVD has not been resolved. Current evidence suggests that it may play both roles in patients with atherosclerosis. The systemic inflammatory state associated with atherosclerosis can suppress testosterone, which can in turn have adverse effects on a variety of cardiovascular risk factors. Whether testosterone plays a similar role in other forms of CVD remains to be determined.

    Attempting to predict the overall effect of testosterone administration on cardiovascular events and risk of CVD is difficult, based on the diverse and contradictory array of in vitro and in vivo effects that this hormone exerts. The results of such studies provide biologically plausible mechanisms for virtually any observation, according to the model tested. This paper will examine the cardiovascular safety of exogenous testosterone administration by reviewing the incidence of cardiovascular events and changes in cardiovascular risk factors. The ultimate goal of this exercise is to determine, based on available clinical trial data, whether exogenous testosterone administration in middle-aged to elderly men confers cardiovascular benefits or increases cardiovascular risks, and whether these effects differ in hypogonadal and eugonadal subjects.

    Based on the studies reviewed in this paper, treatment of elderly hypogonadal and/or eugonadal men with exogenous testosterone such that physiological levels of testosterone are maintained or achieved does not appear to increase cardiovascular risk. In addition, there are few consistent indicators that testosterone therapy has any detrimental effect on potential cardiovascular risk factors, with the possible exception of HDL-C, which may be decreased, and hematocrit, which is typically increased. Any effect of testosterone on lipids is presumably modulated by background statin use in the majority of subjects with CVD and/or diabetes. The effect of testosterone to increase hematocrit, while a potential risk in subjects with a normal hematocrit at baseline, may actually improve the chronic anemia that is seen in many elderly subjects and thus be a positive rather than a negative effect of hormone supplementation.

    Carson CC, 3rd, Rosano G. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: a review of trial data. J Sex Med 2012;9(1):54-67.

    INTRODUCTION: Increasing interest in the use of supplemental testosterone has led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk. AIMS: To evaluate, based on available clinical trial data, whether exogenous testosterone administration in middle-aged to elderly men increases cardiovascular risk, and to assess whether these effects differ in hypogonadal vs. eugonadal subjects.

    METHODS: MEDLINE search from 2004 to present of all meta-analyses and randomized, controlled clinical trials of testosterone administration in male subjects >/= 45 years old that included measurements of cardiovascular outcomes or known cardiovascular risk factors before and after treatment with testosterone.

    MAIN OUTCOME MEASURES: The effects of testosterone treatment on cardiovascular events and cardiovascular risk factors were assessed.

    RESULTS: In clinical trials where testosterone has been used in patients with preexisting cardiovascular conditions, the effect on disease symptoms has typically been either neutral or beneficial. Based on clinical trial data, testosterone treatment has minimal effect on cardiovascular risk factors with the exception of an increase in hematocrit, which is consistently seen with testosterone treatment, and a decrease in high-density lipoprotein cholesterol, which is an inconsistent response. Responses of hypogonadal and eugonadal men to testosterone treatment in terms of cardiovascular risk are generally similar. Testosterone treatment has not been reported to increase the incidence of cardiovascular events with the possible exception of one trial in frail elderly men.

    CONCLUSIONS: Available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk nor does it unfavorably modify cardiovascular risk profile. Prospective data from large, well-designed, long-term trials of testosterone treatment are lacking and will be required to verify the cardiovascular efficacy/safety of chronic treatment.
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lang PO, Samaras D, Samaras N. testosterone Replacement Therapy in Reversing "Andropause": What Is the Proof-of-Principle? Rejuvenation Res. Testosterone Replacement Therapy in Reversing “Andropause”: What Is the Proof-of-Principle? | Abstract

    Testosterone replacement therapy is often equated with the macho male physique and virility and is viewed by some as an antiaging tonic. The growth in testosterone's reputation and its increased use by men of all ages has seemed to outpace the scientific evidences. This review will aim to examine the uncertainty regarding the nature and the clinical importance of the age-related reduction in the testosterone levels. Considerations will be given both to clinical symptoms, biochemical and clinical diagnostic criteria, and to the risk-to-benefit ratio of reversing late-onset hypogonadism in aging and older men.
  5. BBC3

    BBC3 Member

    The reason I say is this. Keep in mind that todays "lowT Male" is the sedentary office/couch potato who is fat and not exercising. Fat is the biggest factor.

    I get a big chuckle seeing medical science refer to SynT as an "androgen". While it CAN BE, it can also be an ESTROGEN. Which is what it is in LowT Males. And not much more at all.

    Todays "safe play" for big pharma is the concept of "If the benefit outweighs the risk". This is how they justify the drug sales. So consider, does a cholesterol drug keep a 32 year old guy who could eat salads his entire life and still fall over dead with clogged arteries at 33 from dying? Perhaps indeed. Does giving a fat Low T male testosterone benefit him at all? I really doubt it. Really, the operative prescribing factor has become How quick will it kill ya.....

    So its kinda like history with longer drug experience is also blending with newer ones on ASSUMPTION - and discounting the fact the one carbon chain difference is night and day in out come. So they started "off Label" prescribing with drugs with solid experience/histories, and this has transferred to "ready writing of scripts for everything". This was the point of transition I think.

    So the difference in a cholesterol drug and testosterone is still minor. However, considering the liver implications(and other) of cholesterol drugs they are the worse. But still neither will kill anyone quick. The REAL DIFFERENCE is that folks would die without the cholesterol drug, which is why the increased risk is allowed. The FACTOR is that the subject does not have to do anything in conjunction with the cholesterol drug for success. With testosterone, the subject must change lifestyle dramatically (diet and exercise) to benefit from TRT - else he is just blasting his tits and prostate with estrogen, which more than likely is going to result in increased cancers in the long run.

    1. So neither will kill ya quick.
    2. The "acceptable risk level" is directly proportion to BOTH the chance on interaction, poor reaction, and effective success intended related to NEEDED".
    3. The line drawn as to who is a candidate for presciption is somewhere in this matrix.
    4. Its disturbing the social implications/political as to what is ok. Test wont kill ya for 40 years probably if you are going to have a negative response to high Es, allthough the likelyhood of this poor reaction is much greater than liver failure due to cholesterol drugs per say. Yet NEW drugs are purpetrated on the market daily based on the politics of STIGMA, and it took testosterone 60 years to go mainstream tried and true.

    Consider Adderall (AMPHETAMINES) for example. IT was written mainstream, and stronger, in the 70s for weight loss, mood boost, etc. Then became taboo. Its actually rebounding as of late and due to the success in ADHD. But the point is that its tried and true. We know what it will do. Which is nothing if taken correctly (thats a whole nother vector). Then due to political stigma, they have marketed non-stim ADHD meds that we KNOW NOTHING ABOUT. So people are taking their kids off adderall and putting them on stratera. Who the fuck knows if they are not all gonna have Parkinsons from this - or whatever.

    The real prescription for Low T is ANDROGENS. These are not being prescribed. The crap Mark Mcguire took was more andrognenic in a low t male than testosterone by far I suspect. Testosterone is too damn likely to turn to Es and with the cyp ester its a nasty slow incideous issue of poor choice administration.. Really, how many thin folks qualify for a testosterone prescription!?!?!?!!! how many fat ones just make more Estrogen......:)

    When testosterone prescribing takes its toll - no one will be the wiser. No one will be able to point a finger at all. It is going to take too long. Look at The smoking cessation drug (chantix)that is giving folks heart attacks by the dozens. And they just say "well he was due a heart attack from the smoking". W....T.....F.....? and still its written. You think anyone will successfully sue for prostate cancer? They will have to document over many years that the drug has altered "genetic propensity" and by administration. If they are gambling that the world will just decide that it dont work that good and "fad" off of it - this is not going to happen. Do to two factors:
    1. The STIGMA has made it a legend to the point that people just cant believe its hurting them.
    2. The dosing regimen with cypionate has an incideous pattern of giving an "instant boost" androgenically for a day maybe two, and then the Es resound again. All the time climbing in action, all the time justified false positive with every pin....

    So drugs are at a wierd period that this kind of proliferation brings with the ignorance that is in place. 30 years ago prescriptions were very cautious compared to today, and more strictly "as needed", not "good outweighing bad"

  6. bax

    bax Member

    Again BBC broad brushing everything and saying "today's low T male is a fat couch potatato". Your theory would make more sense if this was 100 percent true as you claim. You seem to find the fact that any male with low T could possibly be low fat as well. Ah ignorance. I've seen yoU try and pass this off as fact do much it's absurd. As if being fat and not exercising are absolutes for today's "low T male". Until you clean up this very flawed logic, the rest of your trite theories on trt remain useless, mr. 200mg/ wk. oh the irony.
  7. bax

    bax Member

    Oh, and btw, testosterone IS an androgen, you twit. No ones ginna jump on your bandwagon that "real" trt should be fucking dianobil mixed with some horse adrenaline on top. You do realize that most steroid users consider "test the best" right? You act like 25 mg of t per week will send someone's nipples into D cup land. Get a grip. I saw you berate M_ob the other day for asking questions about his treatment and telling him he's playing with fire, yet here you are saying "real trt" is potent androgens, notwithstanding the fact this is all coming from a FAT TRT abuser who uses way more T per week than he needs. Could it be your a fucking hypocrite? Could it be you are using your own frustrations and projecting them in others who truly NEED treatment because you've done fucked up and made your fat ass fatter by overdosing on T and fucking up a good thing, cuz your a greedy hypocritical piggy? I know the answer. Now if you'd just admit it to yourself and spare us the bullshit, maybe we could take u seriously. Until then, your a chaticature more "androgens" than hus tits can handle... Oh wait, test isn't an androgen. I gots an idea pops, how bout u Practce what you preach. Stop the T, get your fat ass to a track, and in 6 months tell us how you feel. Let's see how theory holds up to reality. C'mon. Show us something instead if all the bravado.
  8. BBC3

    BBC3 Member

    How about I just take you back to the woodshed and whip yur ass... We should meet some time. You are def Proving a nuisance with no general premise or realistic subversion. Till then - give yur mama my regards. Keep in mind there is no way you r mine cause I only pin her in the ass...

    Everything you wrote there just disqualified you from any false premise of meriting future response. You are a troll...
  9. bax

    bax Member

    Haha you completely avoided every point I made. Probably flew over that half baked brain of yours. Fair enough. But if you can't back up your own drivel, I encourage you to not berate others about their treatments they need help with, mr 200mg/wk hypocrite. Again, get off the T, get ur fat ass to the local track, and come back in 6 months and tell us what happens. If you are so confident in your "exercise/body fat" hypothesis I'd think you'd jump all over this, as this would seem to be the path you are recommending. I doubt you have the balls or wherewithal to do it, as you'd rather shoot steroid levels of T and then chide everyone who's trying to get healthy with T. Again, YOU are the troll and hypocrite. Back up your talk, fatty.
  10. BBC3

    BBC3 Member

    Lol. Bax, the problem is that you completely stepped yur knowledge bounds with your rebuttal. You just went too far off in too many ways. Tell ya what, let me get my buuuoooze on, and perhaps I'll review again and further yur education. Fuker..
  11. bax

    bax Member

    Yeah that's it.. Go on and booze and shoot your weekly dose. That'll help those estrogen levels. Guess I was right. The track don't sound so tempting without the needle does it, mr 200mg/wk? Hypocrite.
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Yeap BB, Alfonso H, Chubb SAP, et al. Reference Ranges and Determinants of testosterone, Dihydrotestosterone, and Estradiol Levels Measured using Liquid Chromatography-Tandem Mass Spectrometry in a Population-Based Cohort of Older Men. Journal of Clinical Endocrinology & Metabolism. Reference Ranges and Determinants of Testosterone, Dihydrotestosterone, and Estradiol Levels Measured using Liquid Chromatography-Tandem Mass Spectrometry in a Population-Based Cohort of Older Men

    Context: Testosterone (T) levels decline with increasing age. Controversy exists over the threshold for classifying T as low vs. normal in older men. The relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) remains unclear.

    Objective: We assessed the associations of T, DHT, and E2 in men aged 70 yr or older and established reference ranges for these in healthy older men.

    Participants: Community-dwelling men aged 70–89 yr residing in Perth, Western Australia, Australia, participated in the study.

    Main Outcome Measures: Plasma T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples from 3690 men.

    Results: Increasing age, higher body mass index and waist to hip ratio, dyslipidemia, diabetes, and higher LH were independently associated with lower levels of T and DHT. Increasing age, diabetes, and higher LH were associated with lower E2. In a reference group of 394 men aged 76.1 ± 3.2 yr reporting excellent or very good health with no history of smoking, diabetes, cardiovascular disease, cancer, depression, or dementia, the 2.5th percentile for T was 6.4 nmol/liter (184 ng/dl); DHT, 0.49 nmol/liter; and E2, 28 pmol/liter. Applying these cutoffs to all 3690 men, those with low T or DHT had an increased odds ratio for frailty, diabetes, and cardiovascular disease. Men with both low T and DHT had a higher odds ratio for these outcomes.

    Conclusions: The 2.5th percentile in a reference group of healthy older men provides age-appropriate thresholds for defining low T, DHT, and E2. Additional studies are needed to test their potential applicability and clinical utility in older men.
  13. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The All-Time Worse Publication On Anabolic-Androgenic Steroids (AAS)

    Promoted False Theories, Facts, & Myths Causing More Damage And Harm To The Public

    Wilson JD. Androgen Abuse by Athletes. Endocrine Reviews 1988;9(2):181-99.

    ANDROGEN abuse by athletes constitutes only a portion of the problem of androgen misuse by the general population (1) and only a minor aspect of the doping of athletes with drugs presumed to enhance athletic ability (2, 3). Indeed, of the drugs banned by the International Olympic Committee, steroids account only for about 15% (4).

    This particular form of drug abuse stems from the convergence of several separate misconceptions.

    The first was the recognition that the administration of androgens to hypogonadal males causes an increase in nitrogen retention and an increase in muscle mass and lean body weight (5). It followed that the differences in muscle mass between men and women are largely due to differences in testosterone levels, and it was assumed that the administration of androgens in supraphysiological amounts to normal men would do even more than the normal amount.

    The second misconception was that the anabolic (muscle promoting) and androgenic (virilizing) actions of the hormone are exerted by different mechanisms and that pure anabolic agents could be devised that would be devoid of or have minimal androgenic effects (6, 7). In fact, androgenic and anabolic effects are not due to different actions of the hormone but result from interaction of the hormone with the same receptor molecule in different tissues (1). In men with normal levels of plasma androgens the androgen receptor in most tissues appears either to be saturated or downregulated. Thus, it has not been possible to separate the two types of actions at the pharmacological or physiological levels, and in normal men any anabolic actions obtained from exogenous androgens are inevitably limited in scope.

    The third misconception, at least in the United States, stemmed from international competitiveness in sports. According to a widely accepted account, John B. Ziegler, a physician for the US weight lifting team, was told by a Russian team physician at the 1954 world weight lifting championship in Vienna that some members of the Russian team used androgens (8-10). Ziegler assumed that androgens would enhance athletic performance, and he began to experiment in American weight lifters with the various agents that had been developed as candidates for pure anabolic steroids (8). He subsequently concluded that the effects of androgens are purely psychological (9, 10).
  14. newbie23

    newbie23 Member

    Re: The All-Time Worse Publication On Anabolic-Androgenic Steroids (AAS)

    Good Read
  15. solo47

    solo47 Member

    Re: The All-Time Worse Publication On Anabolic-Androgenic Steroids (AAS)

    Sorry, can't accept that the growth & energy I experienced in my 50s was all just psychological.

  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Morales A. The Long and Tortuous History of the Discovery of testosterone and Its Clinical Application. The Journal of Sexual Medicine. The Long and Tortuous History of the Discovery of Testosterone and Its Clinical Application - Morales - 2013 - The Journal of Sexual Medicine - Wiley Online Library

    Introduction The testis importance in homeostasis was recognized for millennia, but a consistent interest in exploring their endocrine function only goes back to about a century.

    Aim The aim of this study is to provide a succinct perspective of the events leading to the discovery of testosterone, the mind-boggling early attempts at therapy and today's situation.

    Method The literature was reviewed with searches in OvidSP Medline, PubMed, and Google Scholar under the headings of testosterone/androgens history. Due to the explosion of reports between the late 19th and early 20th centuries, a manual review of the collection of the period's journals at the university's library was performed. Pertinent books were consulted for specific biographical details.

    Results There is a robust body of literature dealing with testicular function for the period starting in the late 1800s. It is illustrative to learn the painful efforts of many well-intentioned and honest scientists with more conviction and determination than knowledge. Among them, unfortunately, a number of charlatans and profiteers tainted the concept of hypogonadism and its treatment with repercussions lasting until this day. The discovery and synthesis of testosterone represent the effort of brilliant minds (two Nobel Prizes) in various countries and frequently working for the pharmaceutical industry. Shortly after testosterone became available, controversy arose about its application, use, abuse, and potential detrimental effects. Over the decades, the hullabaloo about hypogonadism and its treatment has focused on a variety of issues ranging from absurd efficacy claims to solid studies and from doubts of its existence to convincing proof of a detrimental age-associated deficit in testosterone production.

    Conclusions The history of testosterone discovery, synthesis, and introduction into the therapeutic armamentarium is an outstanding example of human curiosity, ingenuity, greed, and skepticism. Despite the vast progress in the field, many issues remain unresolved, but thoughtful science augurs well for its future.
  17. BBC3

    BBC3 Member

    This looks like some interesting reading...!

    Here are some of the titles that catch attention:

    Conventional and Unconventional Cardiovascular Risk Factors in Men with Erectile Dysfunction (pages 305–308)

    Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior (pages 350–361)

    Development and Validation of the Polish Version of the Female Sexual Function Index in the Polish Population of Females (pages 386–395)
    W…T…F…??? LOL

    The Sexual Disgust Questionnaire; a Psychometric Study and a First Exploration in Patients with Sexual Dysfunctions (pages 396–407)

    Is Female Sexual Function Related to the Male Partners' Erectile Function? (pages 420–429)

    Persistent Genital Arousal Disorder: Characterization, Etiology, and Management (pages 439–450)

    Altered Sexual and Reproductive Functions in Epileptic Men Taking Carbamazepine (pages 493–499)

    Hungarian “Jailhouse Rock”: Incidence and Morbidity of Vaseline Self-Injection of the Penis (pages 509–515)
    *** In all my days and demented research, I have never ever heard of the above…

    Long-Term Changes of Sexual Function in Men with Obstructive Sleep Apnea after Initiation of Continuous Positive Airway Pressure (pages 524–531)

    The Female Prostate: Correcting the G-Spot (page 612)

    Insecure Attachment is Related to More Anal Sex and Vibrator Orgasm but Less Vaginal Orgasm (pages 614–615)

    Feel free to loan me a copy of this one....

    Michael Scally MD likes this.
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone - A Metabolic Hormone In Health And Disease

    Kelly DM, Jones TH. Testosterone: a metabolic hormone in health and disease. Journal of Endocrinology. Testosterone: a metabolic hormone in health and disease

    Testosterone is a hormone which plays a key role in carbohydrate, fat and protein metabolism. It has been known for some time that testosterone has a major influence on body fat composition and muscle mass in the male. Testosterone deficiency is associated with an increased fat mass (in particular central adiposity), reduced insulin sensitivity, impaired glucose tolerance, elevation of triglycerides and cholesterol and low HDL-cholesterol. All of these factors are found in the metabolic syndrome and type 2 diabetes, contributing to cardiovascular risk.

    Clinical trials demonstrate that testosterone replacement therapy improves the insulin resistance found in these conditions as well as glycaemic control, and also reduces body fat mass in particular truncal adiposity, cholesterol and triglycerides. The mechanisms by which testosterone acts on pathways to control metabolism are not fully clear. There is however an increasing body of evidence from animal, cell and clinical studies that testosterone at the molecular level controls the expression of important regulatory proteins involved in glycolysis, glycogen synthesis, lipid and cholesterol metabolism. The effects of testosterone differ in the major tissues involved in insulin action which include liver, muscle and fat suggesting a complex regulatory influence on metabolism. The cumulative effects of testosterone on these biochemical pathways would account for the overall benefit on insulin sensitivity observed in clinical trials.

    This review discusses the current knowledge of the metabolic actions of testosterone and how testosterone deficiency contributes to the clinical disease states of obesity, metabolic syndrome and type 2 diabetes and the role of testosterone replacement.
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The Hypogonadal-Obesity-Adipocytokine-Hypothesis


    High aromatase activity in adipocytes converts testosterone to oestradiol (1).

    Reduced tissue testosterone facilitates triglyceride storage in adipocytes by allowing increased lipoprotein lipase activity (2) and stimulating pluripotent stem cells to mature into adipocytes (blue arrow). Increased adipocytes mass is associated with greater insulin resistance (3).

    Oestradiol and adipocytokines TNF?, IL-6 and leptin (as a result of leptin resistance in human obesity) inhibit the hypothalamic-pituitary-testicular axis response to decreasing androgen levels (4).

    Kisspeptin neurons are inhibited by oestradiol, inflammation and leptin resistance and thus reduce gonadotropic releasing hormone (GnRH) stimulation of the pituitary and subsequent luteinising hormone (LH) release. Reduced LH pulse decreases gonadal stimulation and testosterone release thus causing a state of hypogonadotrophic hypogonadism. Furthermore, leptin also directly inhibits the stimulatory action of gonadotropins on the Leydig cells of the testis to decrease testosterone production.

    +, positive effect;
    -, negative effect.

    Attached Files: