ANDROGEN INSUFFICIENCY

Question 0

Describe the relationship of aging,obesity and testosterone levels.

Answer 0

Serum testosterone falls with age. SHBG increases with age. Up to 70% of men age 70 have hypogonadism as measured by free testosterone. But only 20 to 30% will have low total testosterone levels.

SHBG decreases with obesity. *In obese patients measuring serum testosterone alone will over-diagnose testosterone deficiency. In obese patients it’s important to measure free thyroxine.

As men age, serum gonadotropin concentrations increase, follicle-stimulating hormone (FSH) more than luteinizing hormone (LH), but the rise is not so great as one would expect from the fall in testosterone, **suggesting that the fall in testosterone with aging is due to both secondary and primary hypogonadism.

In the European Male Aging Study, the fall in testosterone with age was associated with an increase in LH, suggesting a degree of primary hypogonadism [12], but the fall in testosterone with obesity alone (without aging) was not, suggesting that the effect of obesity was mediated by secondary hypogonadism.

**Thus it is very important measure free testosterone in older and in obese patients!

Question 1

Describe the various measurements of serum testosterone

Answer 1

60-80% of the serum testosterone is bound to SHBG(not biologically active) and 20-40% is weakly bound to albumin(biologically active)…..
2% is free testosterone…. Albumen bound testosterone+ free testosterone = biologically active component.

Question 2

Is the fall in testosterone and free testosterone with aging a normal physiologic effect of aging or a condition that needs treatment?

Answer 2

The answer is not clear. There are not enough studies presently to answer this question.

Question 3

What are some of the signs and symptoms of androgen deficiency?

Answer 3

• decreased libido and erectile dysfunction
• change in body composition, with loss of lean muscle mass and increase in fat
• osteoporosis
• normochromic and normocytic anemia
• fatigue, decreased stamina and muscle weakness
• possible decreased cognitive function
• depressive symptoms

Question 4

What is the evidence that administering testosterone to aging patients will improve their signs and symptoms?

Answer 4

The studies concerning the effects of administering testosterone, particularly long-term testosterone in older patients have been few number.

• giving testosterone will increase muscle mass and decrease fat
• in the one study on aging patients giving testosterone did not increase muscle strength
• in one study giving testosterone reduced depression in men with testosterone deficiency
• A meta-analysis suggests that IM testosterone raised bone mineral density modestly in the spine but not in the hip. In the absence of bone fracture data the current evidence for improvement with testosterone was weak at best
• several clinical trials did not document evidence of improvement in overall physical function but one did
• in a meta-analysis of 17 trials libido improved but erectile dysfunction did not and satisfaction did not

Question 5

What are some of the possible adverse effects of administering testosterone?

Answer 5

• erythrocytosis
• sleep apnea
• increased cardiovascular risk(studies so far conflicting)
• possible increased risk of prostate cancer(several short-term studies have shown no increased risk but there have been no long-term studies)
• theoretical possibility of increasing BPH but the number of studies is too small to make any conclusions

Question 6

What is the position of Institute of Medicine RE: androgen replacement therapy in older age?

Answer 6

On the basis of most of the studies described above and others, the Institute of Medicine’s committee on testosterone concluded that there is insufficient evidence to conclude that testosterone treatment of older men has any well-established benefit. The committee recommended that a coordinated set of randomized, placebo-controlled clinical trials should be performed to determine if testosterone does improve muscle strength, physical function and frailty, vitality, sexual function, cognition, and quality of life [49].

Until the results of such studies are available, we recommend more conservative criteria for testosterone treatment of older men who have low testosterone for no apparent reason other than age, than for men who have obvious pituitary, hypothalamic, or gonadal disease.

Question 7

What is the position of the Endocrine Society (and UpToDate and Epocrates) regards and replacement therapy?

Answer 7

However, other expert groups argue that there may be a role for testosterone therapy in selected patients. The Endocrine Society first published evidence-based clinical guidelines for testosterone therapy in adult men with testosterone deficiency in 2006; updated guidelines were published in 2010. We agree with their approach in older men, which is outlined below. (See ‘Suggested approach’ below.)

●In the absence of known pituitary or testicular disease, we suggest testosterone therapy only for men with low serum testosterone concentrations on more than one occasion and symptoms of testosterone deficiency. Clinicians must discuss the uncertainty about the risks and benefits of testosterone therapy before recommending this approach.
●The target serum testosterone concentration in these men should be lower than that for younger men, for example, 300 to 400 ng/dL (10.4 to 13.9 nmol/L), rather than 500 to 600 ng/dL (17.4 to 20.8 nmol/L), to minimize the potential risk of testosterone-dependent diseases.

Question 8

What is the suggested approach for treatment from the Endocrine Society? And what are some other suggested approaches regards evaluating testosterone levels?

Answer 8

●If a man has symptoms or conditions that suggest testosterone deficiency, such as decreased libido, energy, or mood, or osteoporosis or anemia, we suggest measuring the serum total testosterone concentration in the morning (eg, 8 to 10 AM). If it is less than 300 ng/dL (10.4 nmol/L), we suggest measuring it twice more, since testosterone concentrations fluctuate.
●Free testosterone should be measured (by equilibrium dialysis or calculated from total testosterone and sex hormone binding concentration [SHBG]) only in men who are obese.
●If the total testosterone is less than 200 ng/dL (6.9 nmol/L), we recommend evaluation for known causes of hypogonadism. In the absence of documented pituitary or testicular disease, we recommend considering treatment with testosterone only if the testosterone concentration is consistently less than 200 ng/dL (6.9 nmol/L), and only after discussion with the patient of the potential benefits and risks [77]. (This recommendation is the same as by some members of the Endocrine Societies Clinical Guidelines Committee, but more stringent than recommended by others.)

***** others would change this 200 level to 230….. Some would recommend a trial of androgen RX with a level of 230 -350 in symptomatic individual

Question 9

What are some of the conditions that can cause low testosterone levels because they reduce SHBG? And what additional test should be done in these patients?

Answer 9

• obesity
• hypothyroidism
• insulin resistance and diabetes mellitus
• Atorvastatin use
• Cushing’s disease

IN THESE CONDITIONS YOU NEED TO ORDER FREE THYROXINE

Question 10

What are several important caveats about ordering serum testosterone levels?

Answer 10

Best to do the testosterone level as close to 8 AM as possible. 8-11 ok
Best to do two or even three levels of testosterone(30% of patients with low testosterone on the first test will have normal testosterone on repeat tests)