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Curious... Very curious... Who would have thought? After all, testosterone is a must.

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  • Curious... Very curious... Who would have thought? After all, testosterone is a must.

    An interesting study found a correlation between PE and the circulating levels of FREE testosterone, plus very low levels of a lipoprotein.

    The abstract of the study, as well as the whole article (for free) can be found here:

    It seems that high levels of FREE testosterone circulating in the body are not desirable for a man's manhood. It makes sense... If the T is circulating through the body, it means it's not bind where it should be and promoting its effects on wherever (neurons? glands? muscles?).

    I hope this has a followup study and the scientists involved try to experiment with any substance that may help fixing T where it should belong.

    And in the case of the specific lipoprotein? Isn't it curious too?

  • #2
    I had some thoughts on this previously and asked members their experience but little came out .

    The reduced lipoprotein may be a health benifit of free test rather than a part of the pre e problem.


    • #3
      Would a working theory be that increased test increases arousal ?


      • #4
        Originally posted by Pegasus View Post
        Would a working theory be that increased test increases arousal ?
        It could be so... I'm not an expert in the field, but in a layman's perspective it seems that free testosterone, by it's on definition, is circulating in the body, without binding anywhere - any receptor, I mean - and another thing: testosterone must be converted in estrogen via the aromatase enzyme, in order to penetrate its target cells. I wonder if a man having lower aromatase levels would be more prone to the onset of PE also?


        Free testosterone levels were significantly higher in the LPE group than in the control group. Free testosterone levels were also significantly higher in the mild, moderate, and severe LPE subgroups than in the control group. Total testosterone and prolactin levels tended to be lower in the control group than in the LPE group. Very low-density lipoprotein levels were significantly lower in the LPE group and LPE subgroups than in the control group. Triglyceride levels were highest in controls and decreased with progression of LPE.


        There's seem to be a conversion phenomenon here, a complex interplay between hormones and lipoproteins. I think cholesterol, for example, is a precursor to testosterone.

        And from the abstract, it seems that even if you increase the amount of testosterone produced by your testicles, it wont help, because it's not a question of having less T in the body - it's a question of "unemployed" T which stays free, circulating in the body. Whatever that free T should be doing, it is not. It just circulate without binding to the would be specific targets.


        • #5
          Free test is necessary in the body and usually regarded as a positive . I will look at the numbers .


          • #6
            Originally posted by Pegasus View Post
            Free test is necessary in the body and usually regarded as a positive . I will look at the numbers .
            I made a preliminary search and look what I found in Mayo Clinic Labs:

            Most circulating testosterone is bound to sex hormone-binding globulin (SHBG), which, in men, also is called testosterone-binding globulin. A lesser fraction is albumin bound and a small proportion exists as free hormone. Historically, only free testosterone was thought to be the biologically active component. However, testosterone is weakly bound to serum albumin and dissociates freely in the capillary bed, thereby becoming readily available for tissue uptake. All non-SHBG-bound testosterone is therefore considered bioavailable.

            Measurement of total testosterone (TTST / Testosterone, Total, Mass Spectrometry, Serum) is often sufficient for diagnosis, particularly if it is combined with measurements of LH and follicle-stimulating hormone (FSH) (LH / Luteinizing Hormone [LH], Serum and FSH / Follicle-Stimulating Hormone [FSH], Serum). However, these tests may be insufficient for diagnosis of mild abnormalities of testosterone homeostasis, particularly if abnormalities in SHBG (SHBG / Sex Hormone-Binding Globulin [SHBG], Serum) function or levels are present. Additional measurements of free testosterone or bioavailable testosterone are recommended in this situation; bioavailable (TTBS / Testosterone, Total and Bioavailable, Serum) is the preferred assay.

            Reference Values


            Males (adult):

            20-<25 years: 5.25-20.7 ng/dL

            25-<30 years: 5.05-19.8 ng/dL

            30-<35 years: 4.85-19.0 ng/dL

            35-<40 years: 4.65-18.1 ng/dL

            40-<45 years: 4.46-17.1 ng/dL

            45-<50 years: 4.26-16.4 ng/dL

            50-<55 years: 4.06-15.6 ng/dL

            55-<60 years: 3.87-14.7 ng/dL

            60-<65 years: 3.67-13.9 ng/dL

            65-<70 years: 3.47-13.0 ng/dL

            70-<75 years: 3.28-12.2 ng/dL

            75-<80 years: 3.08-11.3 ng/dL

            80-<85 years: 2.88-10.5 ng/dL

            85-<90 years: 2.69-9.61 ng/dL

            90-<95 years: 2.49-8.76 ng/dL

            95-100+ years: 2.29-7.91 ng/dL

            Males (children):

            <1 year: Term infants

            1-15 days: 0.20-3.10 ng/dL*

            16 days-1 year: Values decrease gradually from newborn (0.20-3.10 ng/dL) to prepubertal levels

            *Citation: J Clin Endocrinol Metab 1973;36(6):1132-1142

            1-8 years: <0.04-0.11 ng/dL

            9 years: <0.04-0.45 ng/dL

            10 years: <0.04-1.26 ng/dL

            11 years: <0.04-5.52 ng/dL

            12 years: <0.04-9.28 ng/dL

            13 years: <0.04-12.6 ng/dL

            14 years: 0.48-15.3 ng/dL

            15 years: 1.62-17.7 ng/dL

            16 years: 2.93-19.5 ng/dL

            17 years: 4.28-20.9 ng/dL

            18 years: 5.40-21.8 ng/dL

            19 years: 5.36-21.2 ng/dL

            Females (adult):

            20-<25 years: 0.06-1.08 ng/dL

            25-<30 years: 0.06-1.06 ng/dL

            30-<35 years: 0.06-1.03 ng/dL

            35-<40 years: 0.06-1.00 ng/dL

            40-<45 years: 0.06-0.98 ng/dL

            45-<50 years: 0.06-0.95 ng/dL

            50-<55 years: 0.06-0.92 ng/dL

            55-<60 years: 0.06-0.90 ng/dL

            60-<65 years: 0.06-0.87 ng/dL

            65-<70 years: 0.06-0.84 ng/dL

            70-<75 years: 0.06-0.82 ng/dL

            75-<80 years: 0.06-0.79 ng/dL

            80-<85 years: 0.06-0.76 ng/dL

            85-<90 years: 0.06-0.73 ng/dL

            90-<95 years: 0.06-0.71 ng/dL

            95-100+ years: 0.06-0.68 ng/dL

            Females (children):

            <1 year: Term infants

            1-15 days: 0.06-0.25 ng/dL*

            16 days-1 year: Values decrease gradually from newborn (0.06-0.25 ng/dL) to prepubertal levels

            *Citation: J Clin Endocrinol Metab, 36(6):1132-1142, 1973

            1-4 years: <0.04 ng/dL

            5 years: <0.04-0.07 ng/dL

            6 years: <0.04-0.14 ng/dL

            7 years: <0.04-0.23 ng/dL

            8 years: <0.04-0.34 ng/dL

            9 years: <0.04-0.46 ng/dL

            10 years: <0.04-0.59 ng/dL

            11 years: <0.04-0.72 ng/dL

            12 years: <0.04-0.84 ng/dL

            13 years: <0.04-0.96 ng/dL

            14 years: <0.04-1.06 ng/dL

            15-18 years: <0.04-1.09 ng/dL

            19 years: 0.06-1.08 ng/dL



            0-5 months: 75-400 ng/dL

            6 months-9 years: <7-20 ng/dL

            10-11 years: <7-130 ng/dL

            12-13 years: <7-800 ng/dL

            14 years: <7-1,200 ng/dL

            15-16 years: 100-1,200 ng/dL

            17-18 years: 300-1,200 ng/dL

            > or =19 years: 240-950 ng/dL

            Tanner Stages*

            I (prepubertal): <7-20

            II: 8-66

            III: 26-800

            IV: 85-1,200

            V (young adult): 300-950


            0-5 months: 20-80 ng/dL

            6 months-9 years: <7-20 ng/dL

            10-11 years: <7-44 ng/dL

            12-16 years: <7-75 ng/dL

            17-18 years: 20-75 ng/dL

            > or =19 years: 8-60 ng/dL

            Tanner Stages*

            I (prepubertal): <7-20

            II: <7-47

            III: 17-75

            IV: 20-75

            V (young adult): 12-60


            Total testosterone and general interpretation of testosterone abnormalities:

            In male patients:

            Decreased testosterone levels indicate partial or complete hypogonadism. Serum testosterone levels are usually below the reference range. The cause is either primary or secondary/tertiary (pituitary/hypothalamic) testicular failure.

            Primary testicular failure is associated with increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and decreased total, bioavailable, and free testosterone levels. Causes include:

            -Genetic causes (eg, Klinefelter syndrome, XXY males)

            -Developmental causes (eg, testicular maldescent)

            -Testicular trauma or ischemia (eg, testicular torsion, surgical mishap during hernia operations)

            -Infections (eg, mumps)

            -Autoimmune diseases (eg, autoimmune polyglandular endocrine failure)

            -Metabolic disorders (eg, hemochromatosis, liver failure)


            Secondary/tertiary hypogonadism, also known as hypogonadotrophic hypogonadism, shows low testosterone and low, or inappropriately "normal," LH/FSH levels; causes include:

            -Inherited or developmental disorders of hypothalamus and pituitary (eg, Kallmann syndrome, congenital hypopituitarism)

            -Pituitary or hypothalamic tumors

            -Hyperprolactinemia of any cause

            -Malnutrition or excessive exercise

            -Cranial irradiation

            -Head trauma

            -Medical or recreational drugs (eg, estrogens, gonadotropin releasing hormone [GnRH] analogs, cannabis)

            Increased testosterone levels:

            -In prepubertal boys, increased levels of testosterone are seen in precocious puberty. Further workup is necessary to determine the causes of precocious puberty.

            -In adult men, testicular or adrenal tumors or androgen abuse might be suspected if testosterone levels exceed the upper limit of the normal range by more than 50%.

            Monitoring of testosterone replacement therapy:

            Aim of treatment is normalization of serum testosterone and LH. During treatment with depot-testosterone preparations, trough levels of serum testosterone should still be within the normal range, while peak levels should not be significantly above the normal young adult range.

            Monitoring of antiandrogen therapy:

            Aim is usually to suppress testosterone levels to castrate levels or below (no more than 25% of the lower reference range value).

            In female patients:

            Decreased testosterone levels may be observed in primary or secondary ovarian failure, analogous to the situation in men, alongside the more prominent changes in female hormone levels. Most women with oophorectomy have a significant decrease in testosterone levels.

            Increased testosterone levels may be seen in:

            -Congenital adrenal hyperplasia: non-classical (mild) variants may not present in childhood but during or after puberty. In addition to testosterone, multiple other androgens or androgen precursors are elevated, such as 17-hydroxyprogesterone (OHPG / 17-Hydroxyprogesterone, Serum), often to a greater degree than testosterone.

            -Prepubertal girls: analogous to males, but at lower levels, increased levels of testosterone are seen in precocious puberty.

            -Ovarian or adrenal neoplasms: high estrogen values also may be observed, and LH and FSH are low or "normal." Testosterone-producing ovarian or adrenal neoplasms often produce total testosterone values above 200 ng/dL.

            -Polycystic ovarian syndrome: hirsutism, acne, menstrual disturbances, insulin resistance and, frequently, obesity, form part of this syndrome. Total testosterone levels may be normal or mildly elevated and uncommonly above 200 ng/dL.

            Monitoring of testosterone replacement therapy:

            The efficacy of testosterone replacement in females is under study. If it is used, total testosterone levels should be kept within the normal female range at all times. Bioavailable or free testosterone levels also should be monitored to avoid over treatment.

            Monitoring of antiandrogen therapy:

            Antiandrogen therapy is most commonly employed in the management of mild-to-moderate "idiopathic" female hyperandrogenism, as seen in polycystic ovarian syndrome. Total testosterone levels are a relatively crude guideline for therapy and can be misleading. Therefore, bioavailable or free testosterone also should be monitored to ensure treatment adequacy. However, there are no universally agreed biochemical end points and the primary treatment end point is the clinical response.

            Free testosterone:

            Usually, bioavailable and free testosterone levels parallel the total testosterone levels. However, a number of conditions and medications are known to increase or decrease the sex hormone-binding globulin (SHBG) (SHBG / Sex Hormone Binding Globulin [SHBG], Serum) concentration, which may cause total testosterone concentration to change without necessarily influencing the bioavailable or free testosterone concentration, or vice versa:

            -Treatment with corticosteroids and sex steroids (particularly oral conjugated estrogen) can result in changes in SHBG levels and availability of sex-steroid binding sites on SHBG. This may make diagnosis of subtle testosterone abnormalities difficult.

            -Inherited abnormalities in SHBG binding

            -Liver disease and severe systemic illness

            -In pubertal boys and adult men, mild decreases of total testosterone without LH abnormalities can be associated with delayed puberty or mild hypogonadism. In this case, either bioavailable or free testosterone measurements are better indicators of mild hypogonadism than determination of total testosterone levels.

            -In polycystic ovarian syndrome and related conditions, there is often significant insulin resistance, which is associated with low SHBG levels. Consequently, bioavailable or free testosterone levels may be more significantly elevated.

            Either bioavailable (TTBS / Testosterone, Total and Bioavailable, Serum) or free testosterone (this test) should be used as supplemental tests to total testosterone in the above situations. The correlation coefficient between bioavailable and free testosterone (by equilibrium dialysis) is 0.9606. However, bioavailable testosterone is usually the preferred test, as it more closely reflects total bioactive testosterone, particularly in older men. Older men not only have elevated SHBG levels, but albumin levels also may vary due to coexisting illnesses.


            Early-morning testosterone levels in young male individuals are, on average, 50% higher than p.m. levels. Reference values were established using specimens collected in the morning.

            Testosterone levels can fluctuate substantially between different days, and sometimes even more rapidly. Assessment of androgen status should be based on more than a single measurement.

            The low end of the normal reference range for total testosterone in prepubertal subjects is not yet established.

            While free testosterone can be used for the same indications as bioavailable testosterone, determination of bioavailable testosterone levels may be superior to free testosterone measurement in most situations.


            Last edited by danielmarques; 07-26-2021, 08:28 AM.


            • #7
              Another piece easy to understand:

              Free vs. Total Testosterone: What’s the difference?

              Approximately 98% of the testosterone the body produces is bound to either sex-hormone binding globulin (SHBG), or albumin. This is referred to as “bound testosterone.” The 2% that’s left is known as “free testosterone.”

              This unbound or “free” testosterone is what connects with testosterone receptors within the body’s cells. When a cell absorbs free testosterone, it enables its functionality, such as cell replication in the bones and muscles. Free testosterone is also responsible for the creation of what are known as secondary sexual characteristics in men. These include things like facial hair and a deeper voice.

              As the name suggests, total testosterone is the grand total of all the hormone available in the bloodstream. While some testosterone tests only account for total testosterone, they might not be as helpful as once thought. Here’s why.

              A 98% proportion is normal for bound testosterone – but obviously, anomalies can occur. Limiting testing to total testosterone levels overlooks the possibility of excessive bondage to either SHBG or albumin. Here’s why it matters. The possibility of excessive bondage means that it is possible to have normal levels of total testosterone but still have insufficient free testosterone to perform its essential functions. Too little free testosterone can lead to poor muscle development, irritability, lowered sex drive and a host of other issues that one may not readily associate with too little free testosterone.

              Therefore, while total testosterone levels may appear healthy, low levels of free testosterone could lead to improper diagnosis and treatment plans. For example, a patient may not need more testosterone. They may simply need less of substances that tend to convert testosterone into other substances such as estrogen. This is why it may be critically important to test for free testosterone levels and not just total testosterone alone.

              Bioavailable Testosterone

              Until recently, free testosterone was the only type considered biologically active. It turns out, however, that the portion of the hormone bound to serum albumin tends to become available in the capillary bed. Therefore, non-SHBG-bound testosterone is also deemed as “bioavailable.”

              One way of looking at bioavailable testosterone is that it is like a reserve supply, ready for use when the body is low on free testosterone. However, scientists still don’t know how much bioavailable testosterone goes on to be absorbed by cells in these conditions.

              In most cases, bioavailable and free testosterone run even. Exceptions to this are known to manifest due to certain medical conditions and medications. For example, corticosteroids and sex steroids may cause an increase or decrease in SHBG amounts. In such instances, medical professionals may have difficulty properly diagnosing abnormalities. For this reason, it is critical that men disclose to their doctors all the medications they are taking as a part of their consultation.

              There are also other conditions that may cause diagnostic problems. These include:

              Genetically caused SHBG-binding abnormalities
              Liver disease
              Severe systemic illness

              Increasing Free Testosterone Levels

              There are two ways to improve free testosterone levels. In general, anything that increases total testosterone levels (such as forms of exercise or supplementation) will also elevate free testosterone. The other method involves reducing SHBG bound testosterone.

              While the aging process naturally increases SHBG bondage, other factors can accelerate the process. Levels of certain hormones such as insulin, growth hormone, estrogen, and thyroid hormones are known to affect SHBG bonding. Vitamins and herbs, including vitamin D and boron are thought to lower SHBG.

              Hormonal Imbalances and Erectile Dysfunction

              Testosterone clearly plays a key role in a man’s sexual function. Imbalances in testosterone levels can cause erectile dysfunction (ED) and decreased libido. However, testosterone may be only one of a large number of factors contributing to ED.


              I'm going to read the full article about LLPE, Free T and Lipoprotein with carefull and see if I can get something useful out of it.


              • #8
                Another good one:



                • #9
                  Well, after reading the paper completely, the main takeaways from the study are:

                  Free testosterone levels were significantly higher in the LPE group than in the control group.

                  Free testosterone levels were also significantly higher in the mild, moderate, and severe LPE subgroups than in the control group.

                  Total testosterone and prolactin levels tended to be lower in the control group than in the LPE group - conversely, higher again in the LPE group.

                  Very low-density lipoprotein levels were significantly lower in the LPE group and LPE subgroups than in the control group.

                  Triglyceride levels were highest in controls and decreased with progression of LPE.

                  Testosterone is closely related to blood lipid metabolism. Long-term testosterone therapy improves the lipid profile by reducing total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels, and increasing high-density lipoprotein (HDL) cholesterol levels compared with baseline levels.

                  The mean FT level was significantly higher in the LPE group than in the control group (P < 0.001). However, there were no significant differences in the levels of estradiol, total testosterone (TT), luteinizing hormone, follicle-stimulating hormone (FSH), progesterone, and prolactin between the two groups.

                  Sex hormones levels varied between the control and LPE subgroups. TT and prolactin levels tended to be lower in a healthy condition than with LPE. The mean progesterone level appeared to be higher in the control group than in the mild LPE group. Progesterone and prolactin levels tended to increase and FSH levels tended to decrease with worsening of LPE.

                  FT levels, but not TT levels, were significantly higher in the LPE group than in the control group. Moreover, FT levels were significantly higher in the PE subgroups than in the control group, although there was no significant difference in FT levels among the PE subgroups. Additionally, VLDL levels were significantly lower in the LPE group than in the control group.

                  Keleta et al. showed that long-term treatment with testosterone significantly reduced 5-hydroxytryptamine levels in the brain of rats, which suggested that testosterone might be involved in PE.

                  Previous studies showed that patients with PE had higher FT and FSH levels than healthy men; however, there was no significant difference in TT levels between these two groups.

                  Testosterone and FT are associated with sexual arousal, erection, and ejaculation, and patients with LPE tend to present with a hyperexcitable ejaculatory reflex and hyperarousability. An increase in FT levels may be the cause of these two conditions in these patients. The reasons for higher FT levels in some patients with LPE require further investigation.

                  In our study, FT levels were higher and VLDL levels were lower in the LPE group than in the control group, which suggested a negative correlation between FT and VLDL levels. The reason for the absence of significant intergroup differences in the levels of other blood lipids and the mechanisms underlying regulation of FT and VLDL are not fully understood.

                  Neurophysiological analysis has shown that some patients with PE have penile hypersensitivity, suggesting that, to some extent, PE might be caused by neurological disease.

                  We speculate that PE in some patients may be caused by nerve sheath disease via abnormal blood lipid metabolism, leading to penile hypersensitivity and premature ejaculation. Current research has shown that blood lipids may help control integrity of the myelin sheath, which may affect nerve conduction.

                  Our study showed that FT levels were not significantly different among the LPE subgroups. Additionally, TT, prolactin, and progesterone levels tended to increase, whereas FSH levels tended to decrease as dysfunction worsened. These phenomena may have been caused by clinical factors (anxiety and depression) in patients with PE, changes resulting from an increase in FT levels, bias induced by the small sample size, the effect of the test method (chemiluminescent immunoassay), and other factors.

                  There are some limitations to our study. Blood lipid metabolism is affected by many factors. Although BMI was not significantly different between the groups in our study, other factors can affect blood lipid metabolism, except for LPE, which require further investigation in an experimental control study. Second, testosterone is strongly bound to sex hormone-binding globulin (SHBG). Measurement of FT may be more appropriate than measuring TT because FT is positively associated with total testosterone and strongly negatively associated with SHBG levels. Higher FT levels indicate lower SHBG levels in serum. SHBG levels are lower in obesity, in type 2 diabetes, hirsutism, and metabolic syndrome, which may lead to higher FT levels. Additionally, detecting bioactive testosterone is complex and has not been used in the clinic. Testosterone and FT, but not bioactive testosterone, were detected in our study, although bioactive testosterone can better reflect the state of testosterone in vivo.

                  The pathophysiology of LPE has not been fully determined. High FT levels and low VLDL levels might be used as an objective indicator to diagnose and classify LPE and be used as an indicator of treatment options (e.g., LPE with low VLDL levels can be directly treated with local anesthetics). Although our findings showed significant changes in some patients with LPE, a larger sample size is necessary to improve the design of different interventions and identify the accuracy of our research results.


                  • #10