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Androgen Deficiency of Aging Male (ADAM) and Hormone Replacement

Dr. Renata Trister DO

Male hypogonadism, or testosterone deficiency syndrome (TDS), results from a failure of the testes to produce adequate androgen. Patients have low circulating testosterone in combination with clinical symptoms such as fatigue, erectile dysfunction and body composition changes. The cause may be primary (primary testicular failure due to genetic anomaly, infection, chemotherapy/radiation) or secondary (defect in hypothalamus or pituitary), but often presents with the same symptomatology. In the older patient, androgen deficiency of the aging male (ADAM) is an important cause of secondary hypogonadism because testosterone levels decline progressively after age 40. Hypogonadal patients have alterations not only in sexual function and body composition, but also in cognition and metabolism. Regardless of the cause, hypogonadal patients who are both symptomatic and who have clinically significant alterations in laboratory values are candidates for treatment. The goal of hormone replacement therapy in these men is to restore hormone levels to the normal range and to alleviate symptoms suggestive of hormone deficiency. This can be accomplished in a variety of ways, although most commonly testosterone replacement therapy (TRT) is employed.

Androgen deficiency of the aging male (ADAM) is a cause of secondary hypogonadism that often goes unrecognized. This phenomenon of hypogonadism due to aging has also been described as testosterone deficiency syndrome, late-onset hypogonadism, and andropause. Symptoms of this condition resemble those of ‘normal’ aging and include changing body composition (osteopenia, increased adiposity, decreased muscle mass), decline in energy and stamina, decreased cognitive function, decreased libido, and erectile dysfunction. On a metabolic level, men with lower androgen levels have demonstrated higher glucose and insulin levels, higher rates of obesity, and an increased incidence of type 2 diabetes. Several studies have shown a significant improvement in insulin sensitivity in diabetic men treated with supplemental testosterone. Studies have also suggested a link between hypogonadism and cardiovascular disease, which is not surprising given the relationship with hypogonadism and  metabolic syndrome. Testosterone levels in men begin to decline in the late third or early fourth decade and diminish at a constant rate thereafter.

Validated questionnaires have been developed to assess symptoms associated with androgen deficiency, such as the ADAM questionnaire and the Aging Male Survey.

Androgen Deficiency of the Aging Male (ADAM) Questionnaire. The ADAM questionnaire is considered positive if the patient answers ‘yes’ to questions 1 and 7, as well as two to four of the other items [Morley et al. 2000].

1.Do you have a decrease in libido or sex drive?

2.Do you have a lack of energy?

3.Do you have a decrease in strength and/or endurance?

4.Have you lost weight?

5.Have you noticed a decreased ‘enjoyment of life’?

6.Are you sad and/or grumpy?

7.Are your erections less strong?

8.Have you noticed a recent deterioration in your ability to play sports?

9.Are you falling asleep after dinner?

10.Has there been a recent deterioration in your work performance?

Many positive responses in the questionnaire may be indicative of other conditions such as depression. It is therefore important to combine the results of these questionnaires and laboratory measurements of androgen levels and other clinical symptoms to formulate a diagnosis of hypogonadism.

Once the diagnosis is established, several methods of testosterone replacement treatment (TRT) are available. The goal of hormone replacement therapy in hypogonadal men is to restore hormone levels to the normal range of young adult males and to alleviate symptoms suggestive of hormone deficiency. Restoration of normal testosterone levels with replacement therapy can improve muscle mass, prevent osteoporosis, maintain mental acuity, and restore libido, especially in elderly males. While these benefits of TRT in hypogonadal men are well described, not all hypogonadal patients receive only testosterone as a means of hormone replacement. In general, treatment is either in the form of direct androgen replacement with testosterone therapy, or in the form of replacement of pituitary gonadotropins to stimulate endogenous androgen production. Treatment of hypogonadism needs to be tailored to the underlying cause. Since most men over the age of 50 have declining levels of testosterone (a so-called ‘relative hypogonadism’), such men should only be considered candidates for hormone therapy if they have clinical manifestations of ADAM in addition to low testosterone.

TRT modality

Dosing regimen

Intramuscular injection Testosterone enanthate/cypionate: every 2-3 weeks
Transdermal gels/patches Androderm: 5mg/day
Testoderm: 40cm2 scrotal patch (1 patch/day)
Gels (Testim/Androgel): 5–10mg/day
Subcutaneous pellets Testopel: 75mg pellets; 6–12 pellets (450–900mg) Q3–6 months