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advanced age, obesity, a diagnosis of metabolic syndrome, and poor general health status were predictors of LOH

Diabetes mellitus was correlated with hypogonadism in most studies

coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with the incidence of low testosterone

LOH can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol/L (3.2 ng/mL) and a free testosterone level of less than 220 pmol/L (64 pg/mL)

Mean weight decreased

Waist circumference decreased

Total cholesterol decreased

Low-density lipoprotein decreased

Triglycerides decreased

High-density lipoprotein (HDL) increased

ratio of total cholesterol to HDL improved

Prostate volume increased

PSA increased

The benefits for men older than 65 years of age were compared with those of younger men, and the improvements in body weight, metabolic factors, psychological functioning, and sexual functioning were of the same magnitude in both age groups

weight loss was progressive over the 6-year period, effects of testosterone on lipids and on psychological and sexual functioning reached a plateau after approximately 3 years and these effects were sustained

Effects of testosterone on hematopoiesis, on the prostate, and on bladder function were not more severe in older men than in younger men

observe a mild increase in prostate volume and serum PSA over time, which is a normal finding in aging men. Maybe somewhat surprising, postvoiding residue and the IPSS did not deteriorate with aging but showed a degree of improvement

the severity of the metabolic syndrome is associated with the severity of lower urinary tract symptoms

The symptoms of the metabolic syndrome improve upon testosterone treatment and testosterone may thus have a favorable effect on lower urinary tract symptoms

it seems reasonable to conclude that the risks of testosterone administration to elderly men are not disproportionately higher in elderly men than in younger men.

Despite evidence to the contrary, physicians still harbor a wrongful association between testosterone and the development of prostate pathology (prostate cancer and benign prostate hyperplasia)

Not surprisingly, the incidence of prostate cancer was higher in older men; however, it was lower than expected in both groups

These observations suggest that the incidence of prostate cancer in patients receiving testosterone therapy, both in the younger and in the older group, was not greater than in the general population not receiving testosterone treatment

The historical fear that raising testosterone levels will result in more prostate cancer has been dispelled, particularly by the work of Abraham Morgentaler

Higher serum testosterone levels fail to show an increased risk of prostate cancer, and supraphysiological testosterone does not increase prostate volume or PSA in healthy men

This apparent paradox is explained by the "saturation model,"

Recent studies indicate no increased risk of prostate cancer among men with serum testosterone in the therapeutic range

In the present observational study, no cases of major adverse cardiovascular events occurred.

the benefits of testosterone therapy are fully achieved only by long-term treatment

To achieve maximal benefits, good patient adherence is a prerequisite

primary hypogonadism (probably the genuine form of LOH) is strongly associated with age

Compensated hypogonadism represents a distinct clinical entity that warrants continued monitoring to prevent or preempt further deterioration

Bioavailable and free testosterone are known to correlate better than total testosterone with clinical sequelae of androgenization such as bone mineral density and muscle strength

peak levels seen in the morning following sleep, which can be maintained into the seventh decade

Samples should always be taken in the morning before 11 am

The reliable measurement of serum free testosterone requires equilibrium dialysis. This is not appropriate for clinical use as it is very time consuming and therefore expensive.

With increasing age, a greater number of men have total testosterone levels just below the normal range or in the low-normal range. In these patients total testosterone can be an unreliable indicator of hypogonadal status.

It is advised that at least two serum testosterone measurements, taken before 11 am on different mornings, are necessary to confirm the diagnosis.

Patients with serum total testosterone consistently below 8 nmol/l invariably demonstrate the clinical syndrome of hypogonadism and are likely to benefit from treatment. Patients with serum total testosterone in the range 8–12 nmol/l often have symptoms attributable to hypogonadism and it may be decided to offer either a clinical trial of testosterone treatment or to make further efforts to define serum bioavailable or free testosterone and then reconsider treatment. Patients with serum total testosterone persistently above 12 nmol/l do not have hypogonadism and symptoms are likely to be due to other disease states or ageing per se so testosterone treatment is not indicated.

Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year.

With advancing age there is also a reduction in androgen receptor concentration in some target tissues and this may contribute to the clinical syndrome of LOH

Metabolic clearance declines with age

Gonadotrophin levels rise during aging (Feldman et al 2002) and testicular secretory responses to recombinant human chorionic gonadotrophin (hCG) are reduced

There are changes in the lutenising hormone (LH) production which consist of decreased LH pulse frequency and amplitude, (Veldhuis et al 1992; Pincus et al 1997) although pituitary production of LH in response to pharmacological stimulation with exogenous GnRH analogues is preserved

the decreases in testosterone levels with aging seem to reflect changes at all levels of the hypothalamic-pituitary-testicular axis