ANABOLIZING THE FAINT-HEARTED WITH PHYSIOLOGICAL TESTOSTERONE REPLACEMENT

Some 2600 years after the first recorded therapeutic use of  human hormone replacement (in China), and about a century after the first modern hormone use, two new landmark trials with Nebido long-acting testosterone undecanoate DEPOT injection confirm testosterone’s  major  cardiovascular CVS Benefits:

an elegant trial by Guiseppe Rosano’s team at University Rome – Testosterone Benefit on Functional Exercise Capacity, Insulin Resistance, and Baroreflex Sensitivity in Elderly Patients With Chronic Heart Failure;

and Kevin Channer’s 12month trial in Sheffield UK Long term benefits of testosterone replacement therapy on angina threshold and atheroma in men . These confirm the heart-healing benefit of human testosterone replacement, as  we have seen for years in practice.

These findings are in striking contrast to solo estrogen supplement, which greatly improves vasodilation and thus perfusion and hypertension, but has no demonstrable benefit on general muscle or myocardial strength and mass, or arrhythmia; but increases fat mass including in muscle. (Our) metanalysis of all studies with oral estrogen +- progestin confirm   Aloia’s landmark 1995 study,  s that oral estrogen supplement  reduces lean mass (by perhaps 2kg/year)  but increases fat mass (by about 2.5kg/year), the net effect being steady weight gain of about 1/2 kg/year -which gynecologists dismiss as irrelevant, although it turns well women into dumplings- fatness frailty.

Microbiologist Dr Paul de Kruif (1890-1971) was perhaps the first to write the history of the developmental studies on testosterone The Male Hormone (1945) describing exciting clinical experience with it already before WW2 in the hands of medical scientists like Drs  Hammond, Werner  and Lalouche.

Einfeld details the first studies showing testosterone  benefit on CVD published in 1939. And Charbot ea from Paris have just confirmed what Gimeno ea first published from Univ California in 1963, that testosterone is a potent atrial antiarrhythmic drug -which partly explains why older women – normally with  serum testosterone, and testosterone:estrogen ratio only ~ 1:10th  of that of men-  are far more at risk of torsades arrhythmia and CVD in general than men.

William Masters and team had already in 1953 reported in the first RCT of human  bioidentical HRT the dramatic global benefits of injectible testosterone-estrogen even well after 70years of age  in already-institutionalized patients- as he called them, the Third Gender, those neutered by aging’s sexhormone waning.

then Tvedegard Moller & Einfeldt in Denmark ; & Jaffe in USA, reportedtestosterone’s  cardiovascular system CVS benefits .

Ullis Ptacek and Shackman’s thorough 1999  review shows that in USA testosterone only became reputable for study after publication of the landmark trials by Shalender Bhasin ea at UCLA  Drew medical school confirmed that testosterone is highly but safely anabolic on muscle in frail and aging men.

More obliquely, Chapman, Horowitz ea from Adelaide Australia  have just published a small study showing  dramatic benefit of  (oral) Testosterone and a nutritional supplement (475kcals, 9gms protein a day)  on reducing hospital admissions in undernourished older mean 77yrs  men mean BMI 19kg lean mass 43.4kg fat mass 12.8kg, and women mean BMI 18kg/sqm, lean mass 28kg, fat mass 15.8kg; thus the females especially were cachectic; combined supplements abolished hospital admissions over a year,  compared to 70% admission rate (only one patient had elective admissions, for separate hip replacement) without any supplements.It is common cause that such oral testosterone supplement gives very shortlived spikes in serum testosterone, thus does not raise the mean level.

DURATION CONFUSION IN THE ROME TRIAL?: the Rome paper by Caminiti, Rosano ea   perhaps  has a sub-editing typo:  It (the Tables)  clearly says they measured bloodlevels and cardiovascular response  at baseline and at 3 months after commencing testosterone undecanoate injection Nebido 1gm  at baseline and then the  6week shot.

but Nebido  1gm is generally given every 3 months (after the first 3 gms   each 6 weeks apart). This is because  it lasts for 3 months when given on a regular 3monthly basis.The definitive study by Schubert ea in Germany confirmed that the trough TT level over about 30months on 1gm Nebido 3monthly is about 16.3nmol/L – but a peak initially over the first 3weeks post injection to around 30nmol/L- ie rarely outside the physiological range of young men.

Hence the 4th shot would have been due 6months after the 1st shot.  As the Rome  abstract says, it is a 3monthly  administration long term.

So we await clarification that Caminiti & Rosano’s team  actually did the final measurements 3 months after the 3rd shot ie at 6 months ( 24 or 26weeks)? when trough  testosterone TT level  as they report was  predictably  up from ~8 to ~18 nmol/L. Why  would they have done measurements at 3 months (when they gave the 3rd shot) but not at the logical endpoint of 6 months? Otherwise their ‘after’ results would be after only 2gm Nebido over the first 3 months. More plausibly, their rsults are in fact as they say after 6months, after exposure to testosterone  for 6months.

WHAT IS “LONG TERM” IN A DRUG TRIAL? It is puzzling how the authors could call 3 months of replacement long term in their trial? Short term  in the context of human lifespan is surely up to a year (even at a mean of 70yrs age as in this cohort – average life expectancy is about 15years in a first world cohort); medium term would be up to perhaps 5years; and long term surely much beyond that. The only truly longterm RCT  ever done was the 20 year UKPDS.

But the FDA now routinely colludes with the marketing hype of drug companies to claim that even 3month trials are enough to register new designer drugs for chronic use- relying on experience, major adverse effects once the drug is in routine use to indicate if too many gullible patients are being poisoned or killed by the generally non-essential  wannabe new drug before they cancel it.

But it is common cause that serious injuries and degeneration eg of bone, muscle, brain etc can take 2 years or more to heal, before one can no longer expect much more recovery towards optimal function.  Even 6months is very early to expect optimal improvement, heart remodeling  on conservative dose anabolic  HRT equivalent to about 8mg TT a day imi or sc, since 1gm every quarter  has been determined to be an average optimal dose for Nebido, maintaining the blood TT at a minimum of about 16.3nmol/L. . But it depends on individual metabolism, habits, diet, smoking, alcohol and other estrogenic intake, antiandrogens and androgen receptors.

It is common cause that the magic formula for long cardiovascular life for men and women includes not just optimal diet and lifestyle but also  maintenance of  optimal bloodpressure,  and optimal levels by  supplementing  abundant vitamins B,C,D,K, some vitamins A and E,  the essential minerals especially calmag, zinc, iodine, iron, chromium, selenium, manganese, boron; and  the ”co-vitamin” human biologicals that deplete from early adulthood  in particular  EPA+DHA, CoQ10, carnitine, ribose,  arginine, carnosine, proline, and chondroglucosamine, and all our other hormones especially  gonadal, adrenal, thyroid, serotonin, GABA; and the plant prohormone metformin. in case of resistant overweight let alone obesity or diabetes.. A new study from Japan also shows that metformin protects from experimental heart failure.       Even modest boron supplement has potent benefit in reducing excretion of and doubling serum testosterone and estradiol levels in magnesium-repleted postmenopausal women.

But as endocrinologists, specialist physicians or family practitioners experience when interviewing an older patient , the likely answer the GP or specialist receives when enquiring about sex hormones – most patients will rebuff the query with “my gyne / urologist looks after that”.

This despite the fact that most gynecologists and urologists were trained primarily as surgeons and in reproductive organ problems and symptom relief ie short term – not in the pathophysiology of all the other internal diseases and prevention and care of the aging diseases, in which internists, geriatricians, general practitioners are trained and experienced after leaving  undergraduate medical school.

This is the appalling tragedy for the aging,  perpetuated by many cynical health professionals  and drug companies for whom only disease- not prevention- pays : that the most important supplements we  need for dynamic old age – human parenteral balanced sex hormones which deplete in 100% of women and over 50% of men- are dismissed except shortterm for the transient menopause symptoms, or for poor sexual function. .

Oral HT eg premarin, progestin is rightly condemned  much beyond 10 years or age 60yrs precisely because it is too risky (as confirmed by the  monumentally misguided but useful $billion  Women’s Health Initiative) or for sexual problems- which few health professionals are both trained and comfortable to address, and about which older people seldom complain precisely because they are already so impaired by the preventable major aging diseases – cardiovascular, metabolic, mood, mental, muskuloskeletal, malignant etc.

Studies showing the major benefits of testosterone on heart failure and ischemic heart disease of course do not discuss the pros and cons of enterohepatic versus the alternative (parenteral) route;  and to what extent the CVS benefits of TT are mediated by the  muscle-anabolic TT itself as opposed to by its daughter metabolite estrogen – with which no muscle anabolism, strengthening has been described except obviously in the uterus itself, and in promoting vascularization and endothelium. It is sad fact that estrogen alone promotes increasing adiposity while shrinking muscle mass, and dissolving collagen in eg the perineum. This causes the paradox that while estrogen strengthens brain, perfusion, skin, hair and  mucosa, it doubles the incidence and severity of stress urinary incontinence SUI, which SERMS in turn double again; with progestin perhaps halving the degree of SUI.

Only for women, at the behest of the drug industry and their non-human sex hormones, do doctors ignore the physiology, that androgens are the parents of estrogens, with the corollary that having dominance of the daughter- estrogen (whether by being overweight, or taking estrogen or progestin, or in the perimenopause)  suppresses levels and necessary anabolic benefits of androgen. They willfully ignore what is long proven, that estrogen dominance  has no direct benefit antidepressant benefit- if anything, while relieving menopause symptoms, it causes inner hostility- whereas maintaining testosterone balance relieves  depression in 2/3 of postmenopausal depression.

THE CRIMINAL RISKS OF ANY INTRAMUSCULAR INJECTION WHEN ALL THAT IS REQUIRED IS SHORT NEEDLE SUBCUTANEOUS ie SC. Finally, it is a risky and potentially dangerous myth that any routine injections must be  given intramuscularly imi. Unless there is a rare special indication for intramuscular (or intravenous) injection,  insulin   and Nebido and all “imi” injections should simply be given into a pinched fold subcutaneously sc ie under loose skin, ideally the upper outer buttock,  even preferable to the loose abdominal wall skin around which diabetics are advised to rotate insulin injections.

This  works as well sc  as imi –  but why advocate  the grave multiple – potentially paralysing or even fatal- risks of unwarranted  imi injection with a needle longer than about 10mm (the skin being  at most 2 – 3mm thick)  for which health practitioners regularly end up before a court martial when the monotonously predictable mishaps occur with the routine ~25mm long “imi” needle – intramuscular hematoma/abscess if not severe (sometimes permanent)  neuralgic pain or distal paralysis or gangrene from hitting a major nerve or artery, to pulmonary embolism from intravenous injection?

For this reason, a 25g needle usually suffices for most purposes, except  Nebido or eg Primogyn depot injection when a 23g needle is less tedious and slow since these are  suspended in a thicker oil vehicle ( than water-soluble insulin which easily goes through a 27 and even 29g needle). For usual eg depotestosterone cypionate or enanthate, or Mixogen/ Primodian Depot combinations, a 25g needle is ideal.

Imagine accidentally injecting 4ml of Nebido – oil- intravenously into an older male? This cannot happen with short 23g needle subcutaneous injection into the upper outer buttock – which is painless and causes at worst a transient bump.

when even imi Voltaren diclofenac can and does suddenly kill (and in retrospect there is never justification for it imi  since  it can always safely be taken by mouth or as suppository).;

and especially when we have for at least 60 years given subcutaneous pellets sc  eg testosterone up to 1000mg  to men and  in women up to 100mg testosterone with or without estradiol 25 to 100mg?

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2 responses to “ANABOLIZING THE FAINT-HEARTED WITH PHYSIOLOGICAL TESTOSTERONE REPLACEMENT

  1. Thanks. Intereswting, and which oral tetosterone was used? (Probably not methyl test) Is “orabolin” safe?
    Whatr has happened re the testosterone (Depotrone) removal from the market?
    Ben

  2. Pingback: INDEX OF RECENT MAIN TOPICS « Healthspanlife – the Official Life! Blog

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