Low Testosterone in Men: Recommendations on the diagnosis, treatment and monitoring

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* Limitations of using free testosterone by equilibrium dialysis and calculated free testosterone concentrations in practice are the lack of assay standardization, an accuracy-based quality control program, and a harmonized reference range. Until these limitations are addressed, free testosterone by equilibrium dialysis and calculated free testosterone should use reference ranges established by individual laboratories or their specific assay method




CDC Hormone Standardization Program (CDC HoSt) Certified Free Testosterone Procedures?


Sooner or later and SHBG to boot!

When the time comes these will be the only free testosterone assays I will recommend for men to use/rely upon when getting blood work done (pre/post-TRT).




*a lab/assay that is certified by the CDC's HoSt Program
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The above applies to TT, estradiol, and soon enough free testosterone and SHBG!
 
Defy Medical TRT clinic doctor

Note the language precision is somewhat lazy and I don't have a copy of the paper yet. My impression is most of these men were secondary and they measure the same TT with hCG monotherapy as they do with exogenous T use. Note the mention of improved symptom resolution.

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Safety of Human Chorionic Gonadotropin Monotherapy for Men with Previous Exogenous Testosterone Use or Replacement Therapy


Methods​


We retrospectively reviewed 50 charts using exogenous T (including testosterone cypionate, clomid, anastrozole, methandienone, and testosterone gel) and were switched to hCG monotherapy for at least 1 month with follow-up labs. We evaluated changes in hormones [T, LH, follicle stimulating hormone (FSH), and estradiol], hematocrit (HCT), glycated hemoglobin (A1c), and prostate specific antigen (PSA). Results presented as means standard deviation. Student t-test was used to compare pre- and post-treatment values, significance was set at p=0.05. We also evaluated for incidence of thromboembolic events, including stroke, deep vein thrombosis, and myocardial infarction.


Results​


The average age was 43.3±10.2 years with a BMI of 29.4±3.9 kg/m2. Of the patient's reviewed, 46% had used clomid, 18% T cypionate, 15% anabolic steroids, 13% T gel, 4% T pellets, and 4% methandienone. Average follow-up after starting hCG therapy was 163 days, range 28 to 583 days. Average weekly hCG dosage was 2435 IU. Serum T experienced no significant change, from 402.54±281.34 ng/dL to 404.29 ±259.64 ng/dL (p=0.58, n=50). No change was seen in FSH (4.82±6.21 to 3.71±3.24 mIU/mL, n=25), LH (3.12±4.18 to 1.98±1.86 mIU/mL, n=25), PSA (0.79±0.39 to 0.64±0.25 ng/mL, n=6), estradiol (27.84±14.82 to 27.96±13.18 pg/mL, n=31), or A1c (5.51±0.41 to 5.41±0.0.43 %, n=8). There was a statistically significant decrease of HCT (45.05±4.87 to 43.91±4.48 %, n=15). When evaluated for improvement of erectile dysfunction (ED, n=30), low libido (n=30), and low energy (n=32), 57%, 63%, and 66% of patients reported improvement of each symptom, respectively. Only 41% of patients with ED were noted to be on another medication or therapy specifically for ED. No thromboembolic events were observed.

Conclusions​


Weekly hCG dosing appears to have no significant effect on T levels in men with a history of exogenous T use or TRT. The majority of patients reported an improvement in their hypogonadal symptoms. No changes were noted in PSA and A1c. HCT was noted to have a small, but statistically significant decrease and no thromboembolic events were recorded.
 
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*The lack of increase in cardiovascular events with elevated hematocrit may be due to the fact that T acts as a vasodilator and has anti-atherosclerotic effects [223].

Review article of androgen effect on cardiac and VSM cell adrenergic systems:


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Beyond Testosterone Book by Nelson Vergel
AR CAG repeat lengths (short/long)

*The number of cytosine–adenine–guanine triplet (CAG) repeats in androgen receptors differ in men and influences the androgen receptor activity [88,89,90,91] (Figure 1). Hence testosterone sensitivity may vary in different individuals.

*The same applies to androgen receptor gene CAG repeat lengths >24 in the presence of symptoms and normal testosterone levels may be considered as a state of preclinical TD [93]

*In general, it is currently speculated that variable phenotypes of androgen insensitivity exist, mainly owing to mutated androgen receptors. More subtle modulation of androgen effects is related to the CAG repeat polymorphism in exon 1 of the androgen receptor gene: transcription of androgen-dependent target genes are attenuated with the increasing length of triplets.

*As a clinical entity, the CAG repeat polymorphism can relate to variations of androgenicity in men in various tissues and psychological traits: The longer the CAG repeat polymorphism, the less prominent is the androgen effect when individuals with similar testosterone concentrations are compared.

*A strictly defined threshold to TD is likely to be replaced by a continuum spanned by genetics as well as symptom specificity. In addition, the effects of externally applied testosterone can be markedly influenced by the CAG repeats and respective pharmacogenetic implications are likely to influence indications as well as modalities of testosterone treatment of hypogonadal men. Investigation of CAG repeat polymorphism in exon 1 of the androgen receptor gene may be useful in testosterone treatment regimens adjustment

 
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