Low Testosterone: The Science
Low testosterone is a clinical as opposed to a laboratory diagnosis. It is not simply “low testosterone” on blood testing. What constitutes “low” for one individual may be different than what is considered low for another. So-called “normal” testosterone constitutes levels that fall within a huge range (roughly between 350 ng/dl and 1,100 ng/dl). And herein lies the problem. You may have symptoms of hypogonadism (fatigue, loss of muscle mass, poor libido, etc.) and have T levels within the “normal” range. Likely you would benefit from testosterone replacement therapy regardless (provided other causative etiologies have been ruled out).
The risks of testosterone treatment are minimal despite the media’s ranting and raving. Side effects such as alopecia (accelerated hair loss), enlarged prostate (Testosterone does not cause prostate cancer!), polycythemia, low sperm count and in the case of injectable T, infection, can all be minimized with proper dosing and treatment. Moreover, these risks are far outweighed by the benefits of supplemental testosterone.
For how long does one remain on testosterone replacement therapy (TRT)?
TRT is a lifelong commitment. . In recent times, patients as young as their 20’s have noticed precipitating declines. Testosterone replacement therapy should be considered when a man (or woman) develops symptoms of deficiency in the context of low serum levels. Attempts can be made to restore natural hormone production with Clomid and certain dietary-lifestyle changes, however in the event of failure, TRT should be initiated. And continued indefinitely (barring any unforeseen side effects).
Testosterone is not “cycled.” Does your body synthesize testosterone for 8-12 week intervals and then halt production? No. So why would periods of “on” and “off” be recommended? Cycling protocols are utilized by bodybuilders to minimize toxicity of the massive doses of hormones (most of which are dangerous synthetics) necessary to remain competitive at higher levels of competition. These in no way mimic the body’s natural production of testosterone.
We at the clinic aim to restore a youthful hormone profile and concomitantly minimize side effects, lifelong. This is NOT about “gearing up” for the next bodybuilding competition. It IS about health and Vitality.
What is the correlation between Free testosterone and Sex Hormone-Binding Globulin (SHBG)? What is the difference between the Free and Total testosterone levels?
The majority of circulating testosterone is protein-bound. Albumin binds testosterone “reversibly.” It has affinity for the molecule but freely releases into the tissues. Sex hormone-binding globulin has a higher affinity for testosterone (and other sex hormones) and binds them “irreversibly.”
Once bound, testosterone is unavailable to muscle, as SHBG does not readily release its grip on the molecule. That said, an SHBG level must be obtained as part of your baseline lab studies. Noting all three levels, your AVN physician will best be able to tailor your therapy. You may have high-normal Total T levels but very low Free T due to high levels of circulating SHBG. This can be remedied easily with the addition of some natural herbal remedies or certain Rx medications prescribed by your AVN Health Care Fiduciary Physician. Obtaining these values (Free or Total testosterone) in isolation is of little value. All Three Bio-Markers must be taken into account.
There are many ways to dose injectable testosterone, some better than others. What is your practice paradigm? How do you avoid the “roller-coaster” effects of intermittent dosing?
Testosterone Cypionate is the most commonly prescribed form of TRT and dosed according to knowledge of its half-life. That said, injections are prescribed once or twice weekly (at half the dosage).
Patient feedback is paramount to optimize one’s response to TRT. If one feels better on twice weekly dosing, do it! Levels of both T (total and free) and estradiol are checked frequently as to avoid any significant deviations from optimal levels. There tends to be a less aggressive approach in the medical community however. Cookie Cutter TRT clinics are all about maximizing Profit. $150 bottle of Testosterone Cypionate can cost Patients over $2000.00 in accumulated monthly fees. Moreover, Patients of such clinics have been given prescriptions for Testosterone injections once every 2 weeks and even some 1x monthly to further maximize profits. This carries with it significant risks, namely marked fluctuations in testosterone and estradiol levels in addition to dramatically stressing (and suppressing) the central nervous system’s hormonal regulation machinery (HPTA). Patches and Creams are less effective, but have their place in those not as interested in improving body composition while increasing libido. Injectable (Surgically implanted pellets look more promising), again, discuss the options with your AVN physician to see which method best fits YOUR goals and objectives.
What is HCG? Is its use warranted in TRT protocols?
HCG or human chorionic gonadotropin is the “pregnancy hormone” which, through the actions of progesterone, supports the placenta during the first trimester.
Interestingly, there is biochemical similarity between HCG and the pituitary hormone known as “Luteinizing Hormone” or LH. LH stimulates testicular production of testosterone (and as stated above, progesterone in females); as does HCG
HCG is used to support testicular production of testosterone in males of childbearing age on TRT. Males even considering fathering children in the future will be prescribed HCG to prevent the natural shutdown of sperm production induced by testosterone (through the negative feedback loop on the HPTA Axis). That said, males of childbearing age are often prescribed HCG and or Clomiphene Citrate as a primary therapy outside of TRT.
The purpose is two-fold:
- Increase testosterone production via normal mechanisms (testicular production) as opposed to undergoing injections of the bio-identical hormone (with its potential to suppress normal testosterone and sperm production)
- Stimulate spermatogenesis (sperm production).
So yes, the usage of HCG in the context of the above is warranted. Other compounds are being studied in conjunction with HCG for improving Spermatogenesis: HMG and FSH (If HCG alone is not enough) in the treatment of infertile men generally due to long duration Steroid Cycles without the use of HCG. Seek a referral from an AVN Health Care Fiduciary Physician if fertility is a concern.
TRT and cardiovascular risk. Recent studies suggest an increased risk of cardiovascular events in males on testosterone replacement. Is this true?
In short, the studies are flawed, as are many published in peer-reviewed journals.
There are several major flaws in the 2013 JAMA study, for example:
- The men were not properly monitored and the dosages of T therefore were not restorative. The men enrolled in this study only boosted their mean total T to 332 ng/dL. This is low in the context of cardiac protection (testosterone levels > 500-550 ng/dL have been shown to confer protection). (Consensus for Ideal Cardiac function was in the 700-900ng/dl range)
- Estrogen levels were not routinely assayed. Likely many of the subjects, by virtue of aromatization, had high serum estradiol levels. Excess circulating estrogen predisposes individuals to thrombotic events. It is critical therefore to not only monitor free and total testosterone, but also estradiol levels.
Bottom line: Testosterone (TRT Therapy) in physiologic doses is cardio-protective. How could the resultant increase in vitality (and tendency to exercise, which itself confers protection from cardiovascular disease), muscle mass and libido be associated with elevated risk of heart disease? Sounds more like the fountain of youth!
Substantiating the beneficial effects of testosterone replacement therapy are numerous studies, correlating increased mortality with low testosterone:
- Pye SR, Huhtaniemi IT, Finn JD, et al. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014 Apr;99(4):1357-66.
- Yeap BB, Alfonso H, Chubb SAP, et al. In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality. Journal of Clinical Endocrinology & Metabolism. 2014;99(1).
- Li L, Guo CY, Jia EZ, et al. Testosterone is negatively associated with the severity of coronary artery disease in men. Asian Journal of Andrology. 2012;14:875–878.
- Hyde Z, Norman PE, Flicker L, et al. Low free testosterone predicts mortality from cardiovascular disease but not other causes: the health in men study. Journal of Clinical Endocrinology & Metabolism. 2012;97(1):179–189.
- Araujo AB, Dixon JM, Suarez EA, et al. Endogenous testosterone and mortality in men: a systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2011;96(10):3007–3019.
- Haring R, Völzke HV, Steveling A, et al. Association of low testosterone levels with all-cause mortality by different cut-offs from recent studies. European Heart Journal. 2010;31:1494–1501.
- Corona G, Monami M, Boddi V, et al. Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. Journal of Sexual Medicine. 2010;7(4):1557–1564.
- Malkin CJ, Pugh PJ, Morris PD, et al. Low serum testosterone and increased mortality in men with coronary heart disease. 2010;96(22):1821–1825.
- Tivesten Å, Vandenput L, Labrie F, et al. Low serum testosterone and estradiol predict mortality in elderly men. Journal of Clinical Endocrinology & Metabolism. 2009;94(7):2482–2488.
- Vikan T, Schirmer H, Njølstad I, et al. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø study. European Journal of Endocrinology. 2009;161(3):435–442.
- Yeap BB, Hyde Z, Almeida OP, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. Journal of Clinical Endocrinology & Metabolism. 2009;94(7):2353–2359.
- Khaw K-T, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. 2007;116(23):2694–2701.
- Maggio M, Lauretani F, Ceda GP, et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the chianti area (InCHIANTI) study. Archives of Internal Medicine. 2007;167(20):2249–2254.
- Shores MM, Matsumoto AM, Sloan KL, et al. Low serum testosterone and mortality in male veterans. Archives of Internal Medicine. 2006;166(15):1660–1665.
- Oh J-Y, Barrett-Connor E, Wedick NM, et al. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002;25(1):55–60.
“Men with low testosterone usually present with bothersome symptoms, particularly ED, and require treatment to address those problems, not simply for cardiovascular prevention purposes. The benefits of conventional cardiovascular risk reduction with exercise and weight reduction are fundamental to management but are frequently unsuccessful. There is a considerable body of evidence that low testosterone is associated with increased cardiovascular and cancer mortality. A policy of taking little or no action for these men based on concerns of increased cardiovascular and cancer risk associated with physiological replacement would seem illogical. There is considerable evidence of modest cardiac and metabolic benefits that are shown to reduce cardiovascular risk plus sexual, mood, and quality of life changes associated with restoring testosterone levels. These may add up to substantial benefit to many patients. These benefits may potentially denied to patients by fears over prostate and cardiac risk that is not currently supported by evidence.”
[Source: G. Hackett, M. Kirby and A. J. Sinclair. Testosterone Deficiency, Cardiac Health, and Older Men. Int J Endocrinol. 2014.]
In Conclusion: Numerous studies support the benefits of restoring of a youthful hormone profile while only a few negate this. The negative studies were of poor design. As with many evolving medical treatments, there will always be resistance to their acceptance and integration into mainstream.
The fact that estradiol (an estrogen subtype) levels were not routinely assayed (nor controlled) is a purported flaw in the 2013 JAMA study that vilified TRT. Why is this important? What bearing does estradiol have on one’s health?
Circulating testosterone is subject to “aromatization” and biochemical conversion to estradiol (E2). Estradiol maintains bone mineral density, is cardio-protective and supports sexual function. Bottom line? Both men and women need estradiol. It is not a gender-specific sex hormone, although levels in females are higher than those in males. Estradiol is also a growth factor and has been implicated in tumor progression in various hormone-sensitive cancers (i.e., breast). Control of estradiol levels is therefore important. More importantly in women, a balance between estradiol and progesterone is critical.
Progesterone keeps the growth-promoting effects of estradiol in check. Therefore, female HRT candidates are generally always placed on combination therapy with both estrogen and progesterone.
Elevated levels of estradiol in men are not only associated with obesity, sexual dysfunction and gynecomastia, but also with thrombotic events (blood clotting within a vessel and resultant stroke, heart attack, mesenteric thrombosis or pulmonary embolism). Undoubtedly, a percentage of patients in the JAMA study cohort had elevated levels of estradiol due to aromatization of the exogenous (supplemental) testosterone, predisposing them to coronary events. Estradiol levels were not routinely assayed however and contribute to the spurious nature of the study conclusions.
It is imperative to control estradiol levels in male patients on TRT. Akin to the necessary balance between progesterone and estradiol in females, there is a critical balancing act between testosterone and estradiol in males. Typically, males fare well with estradiol levels approximating 20 pg. /ml.
This is not always the case however. More important than the absolute value is the ratio between testosterone and estradiol. And there is no “one size, fits all.” We are all biochemically distinct. An optimal T: E ratio for you is likely to be different from that of your sibling, for example. You may function well with an estradiol level of 20 pg. /mL, while he may experience hot flashes or erectile dysfunction (symptoms of low estradiol). He may function optimally with an estradiol level of 35 pg. /mL, while you may experience nipple sensitivity (from relatively high estradiol). This is precisely why there must open communication lines between the AVN physician and patient. Treatment will require modifications to meet the needs of each respective individual.
To manipulate circulating estradiol levels in males on TRT, one routinely prescribes Anastrozole or Aromisin, also called an “aromatase inhibitor”. Other estrogen modulators include tamoxifen, Chrysin and Zinc, the latter two being OTC.
Is therapeutic phlebotomy a treatment for testosterone-induced polycythemia? How many times a year should a man on TRT have his hemoglobin and hematocrit tested?
Many TRT patients are routinely phlebotomized. Hematocrit levels above 50 warrant attention and anything higher, generally requires therapeutic phlebotomy (Blood Donation).
Better TRT Physicians tend to be aggressive about phlebotomy to avoid any potential issues due to “blood- thickening.” That said, patients undergo laboratory testing at 3-month intervals initially. After optimizing their hormone levels, patients are seen (and obtain labs) every 6 months. In the interim, they are being phlebotomized per schedule (which ultimately depends upon their response to the prescribed blood draws: a STAT hematocrit is obtained prior to every phlebotomy session).
Aging and low testosterone, is there a correlation?
“There is indirect evidence that aging is 75-80% environmental in etiology. Keep in mind that “environment” encompasses ALL factors to which the body is exposed: nutrition, physical and psychological stressors and toxins to name a few. That said, many conditions such as type II diabetes and obesity, both of which have their underpinnings in insulin resistance, can cause hypogonadism.
The proverbial “quick fix” is to place a patient on restorative testosterone therapy, thereby correcting one’s lab values. This however is a short-sighted approach, in essence addressing the epiphenomenon, as opposed to the phenomenon (type II diabetes in this case), or treating the effect and not the cause. Patients are routinely screened for disease risk factors (Lab Work Imperative). In this context, BOTH the low testosterone AND said risk factors are evaluated concomitantly. One is not addressed without the other.
Patients are started on a rigorous exercise program, advised as to proper nutrition, supplementation, and diet and placed on the proper anti-aging –bio identical TRT medications the effects of which are synergistic. Lowering disease risk factors (inflammation and insulin resistance) increases testosterone levels. Supplemental testosterone, in a reciprocating manner, reduces risk factors for disease. It’s a WIN-WIN for the patient/client.”
Dr. Brett Osborn, Neurosurgeon and Anti-Aging Regenerative Medicine Physician.
In the wake of the FDA’s recent ruling mandating “black box” label warnings on all testosterone products, is the climate for men seeking to optimize their hormones becoming better or worse?
Answer: Neutral. I believe the FDA is simply looking out for the pharmaceutical industry and the populace at large. By virtue of their labeling, the FDA is exonerating itself as a governing body by indirectly publicizing the results of the recent TRT study, albeit flawed.
This should be held in the same regard as commercial-embedded warnings issued by pharmaceutical companies. And while attorneys may be chomping at the bit to vilify prescribing physicians in the wake of such labeling, this is by no means proof of danger (and likely is the opposite in fact). Answering your question, sometimes perceived “negative” publicity serves an antithetic function, and hopefully in this case will raise awareness of the health-promoting benefits of TRT in select individuals.
How do I inject myself, if that is the methodology that best meets my needs? And will it hurt?
The trivial “pain” associated with an intramuscular injection is mostly due to apprehension and the anxiety of self-administration. One quickly becomes habituated to this practice and the perceived pain diminishes. This is provided proper injection techniques are utilized:
- Wash your hands thoroughly with soap and dry them completely.
- Uncap the needle by holding the syringe (preloaded with medication) with your writing hand and pulling on the cover with your other hand.
- Hold the syringe in your dominant hand. Place the syringe under your thumb and first finger. Let the barrel of the syringe rest on your second finger.
- Swab the target skin area with an alcohol wipe and allow it to dry. [Ideally, IM injections should be performed after a shower for antiseptic reasons.]
- Depress and pull the skin taut with your free hand (using your thumb and first finger).
- Use your wrist to inject the needle at a 90-degree angle (straight in). Do not slowly push the needle in nor jab the skin. The action should be deliberate. The needle should be advanced into the muscle nearly to the hub. The depth of needle insertion is unrelated to the perceived pain. It is rather a function of insertion technique (site selection and continuous insertion pressure).
- Release the skin. As you let go of the skin, hold the syringe so it stays pointed straight in.
- Pull back on the plunger slightly to assure you are not in a blood vessel. [In the event of blood return into the needle, remove the needle, and discard it. The procedure should be repeated on the opposite side.]
- Push down on the plunger to inject the medication. Sometimes this will cause subtle twitching of the muscle into which the medication is being injected.
- Remove the needle and apply pressure to the injection site for 1 minute.
- Discard the needle in a Sharps container.
This technique will be demonstrated during your clinic appointment if requested.
The staff is available to assist you virtually (via a HIPAA-compliant videoconferencing platform) should the need arise. You will gain confidence in no time!
Sub-Q injections (Bio-Identical HGH: Semorelin /CJC with DAC, HGH)
- Hold the syringe in your dominant hand. Place the syringe under your thumb and first finger. Let the barrel of the syringe rest on your second finger.
- Swab the target skin area with an alcohol wipe and allow it to dry.
- Grasp the skin with the hand your free hand.
- Holding the syringe barrel tightly with your writing hand, use your wrist to insert the needle through the skin at a 45-degree angle. Remember, this injection is superficial.
- Once the needle is all the way in, push the plunger down slowly to inject the syringe’s contents. If a small bubble if fluid is noted beneath the skin or the injection was painful, do not become alarmed. Inject slightly deeper the next time (the needle should enter the skin at > 45-degree angle).
- Remove the needle and apply gentle pressure with a cotton swab for 1 minute or less.
- Discard the needle in a Sharps container.
Subcutaneous injections are typically performed in the lower quadrants of the abdomen. Other potential sites are the upper arm and thigh. Again this is patient-dependent and a matter of comfort.
How do I store the medication?
Transdermal hormone preparations are typically refrigerated. Injectable testosterone (Cypionate and Enanthate for example) is stored at room temperature and should be shielded from light (to prevent oxidation). Reconstituted HCG is to be refrigerated. Oral HCG can be kept at room temperature -away from light. HGH and Bio-Identical HGH needs to be refrigerated once constituted. HGH in pen format still needs to be refrigerated when not being used –generally 20 min prior to injection it is brought to room temperature before injecting, otherwise refrigerated.
When will I feel the medication starting to work?
The effects of HRT are typically experienced within the first several weeks in both males and females. In females on dual estrogen/progesterone therapy (+/- testosterone), sleep patterns tend to improve, as does vitality. Males on TRT typically experience similar effects and often notice return of morning erections.
If started on thyroid replacement you will likely notice an increase in energy levels in a similar time frame.
What if I travel for work? Miss a shot?
If you are scheduled to be away from home for more than a couple weeks, plan to take your medications with you. This obviously includes needles and syringes as well. Injectable testosterone (also in a small vial) should be maintained at room temperature. If you are travelling by plane, be prepared to present copies of your prescriptions to the TSA agents if asked. Remember, testosterone is a schedule III drug.
How much does Hormone Replacement Therapy (HRT) cost?
Sex Hormone replacement therapy (medications only) costs $100-$150 per month (TEST/Estrogen-Progesterone/HCG/Aromisin-Arimidex) and upwards of $500 a month if Bio-Identical HGH-Actual HGH are prescribed. This does not include clinic visits, laboratory studies and other diagnostic tests, nor the recommended nutritional supplements. Your AVN Health Care Fiduciary Physician will provide you the option to invest in your medication up front (purchase the medication outright) at a significant discount for those that are AVN Members. Many HRT docs charge monthly fees that end up costing you up to if not more than 10x the real cost of the medication itself and require you to come into their offices (generally 1x week) for administration which can prove time and $ consuming. Please refer to the AVN service model agreements to access cost saving potential in working with the BEST of the BEST Health Care Fiduciary TEAM. Your Health and Vitality will improve, as will the investment in the NEW YOU!
What does AVN see on the horizon for TRT/HRT front over the next 5-10 years?
As long as there is misinformation via the Main Stream Media and litigious attorneys looking to make a buck, there will always be resistance as Big Pharma and Large Medical Administrators have their agenda. Millions of men and women are successfully utilizing HRT currently and regaining their vitality and lust (PUN INTENDED) for life. Those numbers will increase dramatically as properly prescribed, HRT is safe and effective. Its acceptance is simply a matter of its gaining momentum through documented treatment successes. An educated AVN patient-client will provide the momentum for moving towards a preventive health care paradigm and ultimately into one of human optimization: The definition of Vitality! The AVN Difference!