The most abundant lipid constituents are triacylglycerols, free cholesterol, cholesterol esters and
phospholipids (phosphatidylcholine and sphingomyelin especially ), though fat-soluble vitamins and anti-oxidants
are also transported in this way
the lipoprotein aggregates should be described in terms of the different protein components or
apoproteins (or 'apolipoproteins'
these classes can be further refined by improved separation procedures, and intermediate-density lipoproteins
(IDL) and subdivisions of the HDL
(e.g. HDL1, HDL2, HDL3 and so forth
Density is determined largely by the relative concentrations of triacylglycerols and proteins
and by the diameters of the broadly spherical particles
Lipoproteins are spherical (VLDL, LDL, HDL) to discoidal (nascent HDL) in shape with a core of non-polar lipids,
triacylglycerols and cholesterol esters, and a surface monolayer, ~20Å thick,
consisting of apoproteins, phospholipids and non-esterified cholesterol,
which serves to present a hydrophobic face to the aqueous phase
the various lipid components should not be considered as absolute,
as they are in a state of constant flux
Apo A1 is the main protein component of HDL
Apo A2 is the second most important HDL apolipoprotein
the main groups are classified as chylomicrons (CM), very-low-density lipoproteins
(VLDL), low-density lipoproteins (LDL) and high-density lipoproteins
(HDL), based on the relative densities of the aggregates on ultracentrifugation
The lipoproteins can be categorised simplistically according to their two main metabolic functions.
The principal role of the chylomicrons and VLDL is to transport triacylglycerols
‘forward’ as a source of fatty acids from the
intestines or liver to the peripheral tissues. In contrast, the HDL remove excess cholesterol from peripheral tissues and
deliver it to the liver for excretion in bile in the form of
bile acids (‘reverse cholesterol transport’).
While these functions are considered separately here for convenience,
it should be recognised that the processes are highly complex and inter-related, and they involve transfer of apoproteins,
enzymes and lipid constituents among the heterogeneous mix of all the lipoprotein fractions.
SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
Plasma SHBG levels tend to increase with increasing age
The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
Testosterone is secreted in a pulsatile fashion
Current clinical guidelines suggest at least two measurements
In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
In older men, the diurnal variation is blunted
it is standard practice for samples to be obtained between 0800 and 1100 h.
Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
DHT remains constant despite the decline of its precursor testosterone
Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
DHT showed no cross-sectional age trend
Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
obesity impairs hypothalamic/pituitary function
Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that has been employed as a treatment for medically refractory epilepsy for 86 years
The hallmark feature of KD treatment is the production of ketone bodies by the liver
almost any diet that produces ketonemia and/or diminished blood glucose levels can induce an anticonvulsant effect.
bioavailable testosterone levels decrease much more with age than does total testosterone or estradiol levels
The decrease in bioavailable testosterone parallels the increase in sex hormone binding globulin with age, a change that accompanies increasing body fat independent of weight change
a graded stepwise decrease in bioavailable testosterone with increasing level of depressed mood
This association was independent of age, weight change, and physical activity, the only three significant confounding covariates of the association between sex hormone levels and BDI scores
I love this abstract. I am going to try and find the full print. As it relates to metabolic dysfunction, elevated Testosterone provides a similar functional picture in women as low Testosterone does in men.
Women with PCOS have associated increased inflammation. This origin is primarily via adipose tissue and associate adipocytokines (TNF-alpha, and IL-6). CRP elevation, as found in this study, is associated with increased CVD.
GH deficiency effectively increases cortisol production in key target tissues including liver and adipose tissue, promoting insulin resistance and visceral adiposity
GH/IGF-I modulation of cortisol metabolism may underpin the pathogenesis of common diseases such as central obesity
Patients with central obesity but with no evidence of hypopituitarism have relative GH deficiency and it is exciting to speculate that low-dose GH treatment in this group, by inhibiting cortisol generation within omental fat, may offer a novel therapeutic approach.
GH plays a key regulating role in obesity. GH deficiency promotes increased cortisone to cortisol production in adipose tissue and liver. This promotes insulin resistance and obesity.
The authors are referencing the increase in the suggestions to use other testing techniques i.e. saliva.
Testosterone therapy can inhibit hepcidin transcription and is associated with increased iron incorporation into red blood cells and increased erythropoietin concentrations
Transdermal TRT has a more favorable adverse effect profile when compared to buccal testosterone formulations
testosterone concentrations should be checked 2–3 months after initiation of therapy and after adjusting the dose
the recommendation for injectable testosterone esters is to check the serum concentration midway between injections
it is recommended for serum testosterone to be evaluated 3 to 12 hours after application of the transdermal patch
Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1)
a study from 1989 utilizing testosterone transdermally containing 5, 10, or 15 mg of testosterone showed that peak concentrations of testosterone were achieved 3 to 8 hours after scrotal application in hypogonadal men
measure serum testosterone any time after the patient has been on treatment with gel for at least 1 week
evaluate serum testosterone at the end of the dosing interval for testosterone pellets
increased amount of fat leads to increased extragonadal aromatase activity, resulting in increased concentrations of estradiol. High circulating concentrations of estradiol down regulate the HPG axis and decrease the amount of circulating testosterone
Up to 80% of plasma estradiol originates from aromatization of testosterone and less than 20% of estradiol in the circulation is secreted by the testes
A PSA concentration, digital rectal examination, and hematocrit should be performed at baseline and at 3 months, 6 months, then yearly after TRT is initiated.
It is used for many medications and has the advantage of high bioavailability, absence of hepatic first pass metabolism, increased therapeutic efficacy, and steadiness of plasma concentrations of the drug
If the hematocrit rises above 54%, treatment should be discontinued
elderly men having higher estradiol serum concentrations than postmenopausal women
In order for leptin to control body weight and metabolism, it must do so from the hypothalamic centers in the brain,
When brain levels of leptin are low due to "leptin resistance" - even if there are high circulating blood levels of leptin - food cravings and weight gain occur because the body believes that it is hungry and goes into a state of continued fat storage.
By reversing "leptin resistance," through the blocking of PTP1 B, the function of the protein hormone leptin is restored so that the hypothalamic center can normally and effectively modulate body weight and metabolism.
Published studies demonstrate that the botanically derived phytochemical, isolated and purified single-peak Isoquinoline Alkaloid Berberine Hel, specifically and potently inhibits human Protein Tyrosine Phosphates 1B (PTP1 B).