HPTA is a homeostatic mechanism, providing balance.
The administration of exogenous steroid hormones will suppress HPTA’s function, hence the endogenous hormone production.
Time and dose of AAS abuse will result in testicular shrinkage eventually; this is a typical homeostatic mechanism, regulated from HPTA.
Testosterone Replacement Therapy (TRT) is the solution to this hormonal defect.
Considering that andropause exists after the age of fourty, HPTA is hardly to get restored with a regular Post Cycle Therapy protocol.
As a result, we should provide the appropriate amount of androgen, in order serum testosterone levels to be within the optimal range.
Before starting patients on HRT, doctors must rule out contraindications to treatment.
Inhibitory, high-risk factors for potential adverse outcomes from hormone replacement therapy are:
– erythrocytosis (hemoglobin> 18)
– obstructive sleep apnea (OSA)
– benign prostatic hypertrophy (BPH=PSA> 4). The presence of a clinical prostatic carcinoma is an absolute contraindication for HRT and should be carefully excluded by PSA, rectal examination and biopsy before starting any therapy.
– dyslipidemia with HDL <40
Testosterone could be administrated either intramuscularly (IM) or subcutaneous (SC) (parenterally), by gel- skin patch (transdermal), orally (per os), or even as a mucoadhesive buccal tablet.
The testosterone esters that are used are usually slow, with enanthate and cypionate (70% release), while the decanoate is implemented with a larger dosage of 1000mg, having a slower half life
The frequency of intramuscular (IM) or subcutaneous (SC) injections varies from daily, twice weekly, weekly, or even every three months (testosterone undecaonate).
Subcutaneous administration delays absorption and offers prolonged pharmacokinetics, due to lesser vascularity of fatty tissue.
The suspicion that the administration of testosterone subcutaneously, would increase the chances of aromatization would valid for patients with a subcutaneous rate >15%.
However, according to Dr.Justin Saya, the fact that testosterone is released from the ester after entering the bloodstream, breaks this claim.
Therefore, increasing of beta estradiol (E2) does not occur by SC injections.
The use of transdermal testosterone has beneficial effects on libido, since the skin has an increased concentration of the enzyme 5a reductase enzyme receptors.
In order to ensure proper spermatogenesis and testicular size, Human Chorionic Gonadotropin (hCG) is prescribed along with testosterone.
As Dr. John Crisler mentions, a frequent small amount of HCG will mimic the natural testosterone production by Leydig cells in the testicles.
According to Dr.Saya, hCG should be better used on the day before weekly administration.
The day before the injection, serum testosterone levels will be lower.
Therefore, the administration of hCG would give a boost and increase endogenous testosterone’s production.
According to papers of Nelson Vergel, author of the book ‘’Testosterone, a man’s guide’’, HCG use can provide a better hormonal environment for basic steroid hormones: pregnenolone, progesterone and dihydroepiandrosterone.
DHEA is a pro hormone, released by the adrenal glands, also called as ‘’the mother of all hormones’’.
In men, it is converted to estrone (E1), through androstenedione.
Therefore in males, DHEA is slightly aromatised, especially in doses over 50mg per day. However DHEA, improves cognitive function, mood, libido, bone mineral density (BMD), body composition and provides prevention against cancer.
Testosterone is converted to estradiol, by the aromatase enzyme in adipose tissue, mamary gland, liver and brain.
Therefore, anti-estrogens will ensure beta estradiol does not elevate above optimal range.
E2 is necessary for proper libido, joints lubrication, muscle glycogen formation, proper BMD, well being feeling and Androgen Receptors affinity.
However, estrogens should be within a certain range, as Dr.Crisler names it as ‘’sweet spot’’.
Antiestrogens are usually Aromatase Inhibitors (AIs) such as anastrozole, letrozol, exemestane), or even the old generation of antiestrogens the Selective Estrogen Receptors Modulators (SERMs), such as tamoxifen citrate.
Each individual has a different Estrogen Receptor (ER) affinity, therefore AIs dosage and frequency of use is strictly personalized.
It should be noted that, elevated levels of estrogen increase the risk of coagulopathy.
Anti androgens, drugs that block the 5a reductase enzyme action, are better not to be used within HRT.
Finasteride and dutasteride are responsible for dihydrotestosterone’s (DHT) crush.
Relative to testosterone, DHT is considerably more potent (5x times more) as an agonist of the androgen receptor.
As known, testosterone is reduced to DHT.
One way to increase serum level price of free testosterone (FT), is the use of synthetic forms of DHT (mesterolone, drostanolone), or even danazol.
Androgens bind tightly to SHBG; therefore more FT is able to circulate.
DHT has beneficial effects on libido, self esteem, aggression, strength and cognitive function.
However DHT is responsible for Benign Prostatic Hyperplasia (BPH) and Male Pattern Baldness (MPB) – androgenic alopecia.
DHT receptors are located in scalp, epidermis and prostate gland.
If someone has androgenic alopecia issues, or prostate hypertrophy, using 5a reductase inhibitors will improve both hair thinning and prostatic enlargement.
However, the post finasteride syndrome (post fina syndrome by Dr John Crisler) is characterised by persistent sexual, neurological, and physical adverse reactions, such as depression, gynecomastia, chronic fatigue, increased fat deposition, obesity, erectile dysfunction and loss of sexual drive.
In other words, a male feels like being castrated.
The risks of testosterone replacement therapy depend upon age, life circumstances, and other medical conditions. These include:
– erythrocytosis (Hg>18 and Htc> 54%). Androgens stimulate erythropoiesis directly in the bone marrow, by promoting erythropoietin (EPO) synthesis in the kidney and by enhancing intestinal iron absorption from small intestine (jejunum-ileum), iron incorporation in red blood cells and hemoglobin synthesis.
Erythrocytosis increases blood viscosity and the risk for thrombosis in the coronary, cerebrovascular, or peripheral circulation.
This is the main reason for a frequent (every other day-twice per week) protocol, in order to avoid DHT & E2 spiking.
Salicylic acid (aspirin) at 80mg is a preventive method against coagulation.
For those who have G6PD enzymatic deficiency, the use of fish oil (DHA/EPA), will act on a similar way, as anti-thrombotic agent.
– the increased amount of testosterone (>150mg) leads to decreased levels of High Density Lipoprotein (HDL), which acts cardioprotective in arterial endothelium.
– worsening symptoms of benign prostatic hypertrophy.
Prostate cancer is not testosterone dependent after all.
According to late studies, what has been found in middle-aged people with BPH is a predominance of estrogen versus androgen, such as in obesity, or Metabolic Syndrome. Prostate cancer might be a contraindication in order to start hormone replacement, as a marginally increased level of prostate PSA antigen (BPH).
– worsening symptoms of sleep apnea, perhaps due to pharynx thickening
Follow up assessment should be done one month after the beginning of TRT, in order to evaluate serum levels, until the patient reaches a stable hormonal environment.
These include PSA, hemoglobin, hematocrit, lipid profiles, liver function tests and should be also checked at 3, 6 months and then annually.
A digital rectal examination is necessary for those who are over fifty.
Also a BMD of lumbar spine or femoral neck should be measured every 1 to 2 years in hypogonadal men with osteoporosis or low trauma fracture.
As Dr. John Crisler mentions: “the ultimate goal of TRT is to optimize health and happiness in patients, which means producing an environment where we have elevated testosterone to sufficient levels, with the body responding as if it is unaware of the exogenous manipulations”.