The Clinical Diagnosis of Androgen Deficiency


Group A: Symptoms and signs suggestive of androgen deficiency in men

• Incomplete sexual development, aspermia, eunuchoid body habitus

• Reduced sexual desire (libido) and activity

• Decreased spontaneous erections

• Breast discomfort, gynecomastia

• Loss of body (auxiliary and pubic) hair, reduced shaving

• Very small or shrinking testis (especially <5 cm3)

• Inability to father children, reduced or absent sperm in ejaculate

• Height loss, soft-trauma fracture, low bone mineral density, osteomalacia

• Reduced muscle mass and strength

• Hot flashes, sweats

Group B: Symptoms and signs associated with androgen deficiency that are less specific than those listed in group A

• Decreased energy, motivation, initiative, aggressiveness, self confidence

• Feeling sad or down, depressed mood, dysthymia

• Impaired concentration and memory

• Prolonged sleep disturbance, increased sleepiness

• Mild anemia (normochromic, normocytic, into the female range)

• Increased body fat, body mass index

• Diminished physical or work performance


Based on data from Bhasin et al. [2]





Presentation by Age


The clinical picture of male hypogonadism varies markedly between patients who have yet to undergo puberty and those subjects that have already reached sexual maturity. It behooves the clinician to be astute regarding certain signs and symptoms that occur at each stage of life. In the pubescent male, the most noticeable signs of reduced testosterone are a lack of age-appropriate virilization and a paucity of secondary sexual characteristics, such as deepening of the voice and temporal hair recession [7]. These patients can display sustained height increase (albeit without a pubertal growth spurt) because of a failure of the epiphyses to close, and exhibit eunuchoid body proportions, where arm span is greater than overall height by >2 cm [8].

Hypogonadism in the pubescent male can indicate of a genetic disorder. In these cases, the classic signs and symptoms of these rare disorders can alert the clinician to the presence of a coincident hypogonadal state. In Kallmann syndrome, low serum levels of testosterone result from reduced or absent gonadotropin releasing hormone (GnRH), and juvenile boys may present with anosmia, delayed sexual development, and midline facial/cranial defects [9]. Although Klinefelter syndrome is the most common genetic cause of hypogonadism, patients typically exhibit a clinically normal phenotype until puberty. At which point, serum LH and FSH levels dramatically increase, inhibin B decreases, and testosterone levels fall, leading to hypogonadal manifestations [10]. Pre-pubertal Klinefelter boys have preserved normal seminiferous tubule architecture with characteristically reduced germ cell counts. In contrast, in Klinefelter patients who have undergone puberty, their seminiferous tubules undergo extensive hyalinization and fibrosis with testicular atrophy [10]. Bilateral congenital anorchia is another potential genetically linked etiology of testosterone deficiency that is easily identified by congenital absence of the testes [11].

Patients who have reached sexual maturity exhibit a different constellation of symptoms, mainly centering on a loss of secondary sexual characteristics. Loss of body hair with a reduced frequency of shaving, decreased muscle mass, physical strength, and atrophic testicles are typical examples [2]. According to the Endocrine Society, other specific symptoms of testosterone deficiency include reduced sexual desire and frequency of sexual activity, decreased spontaneous and nocturnal erections, hot flashes, and breast tenderness or gynecomastia [2].

Often, the symptoms of testosterone deficiency are difficult to distinguish from the physiologic changes that we witness with normal aging. Therefore, testosterone deficiency in the aging male is often not recognized [12]. There are also differences in the presentation of testosterone deficiency in middle-aged men from the geriatric population. Many signs and symptoms of testosterone deficiency are expressed heterogeneously with respect to age in the post-pubertal population [13]. In a series of 1,647 males who were assayed for signs and symptoms of testosterone deficiency, the youngest quartile showed an inverse correlation between testosterone and hypoactive sexual desire, while the oldest quartile demonstrated inverse correlations between testosterone and both severe erectile dysfunction and somatized anxiety [13].


Signs and Symptoms of Androgen Deficiency by System



Sexual Dysfunction


The hallmark of androgen deficiency to the general population is diminished sexual function (see Fig. 3.1). Reduced libido is often observed in men with undersized or soft testicles and erectile dysfunction (ED) [7, 14]. Other sexual dysfunctions associated with androgen deficiency include decreased erectile rigidity, difficulty achieving orgasm, diminished ejaculatory volume, reduced genital sensation, and diminished intensity of orgasm [14].

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Fig. 3.1
Summary of signs of testosterone deficiency by system

Hypogonadal men with low libido and ED have been observed to have long-term improvement in their sexual desire with exogenous testosterone supplementation. However, their resolution of ED is short lived, when measured using validated questionnaires [15, 16]. Nevertheless, it is important to recognize a correlation between ED and testosterone deficiency, and that a new onset of ED can be a harbinger of future vascular morbidity and mortality [17].


Cognition and Mood Changes


Chronic fatigue and lack of energy are the most common mood abnormalities associated with testosterone deficiency [18]. Depression, irritability, and reduced motivation are common entities witnessed in the hypogonadal state [2, 19]. Sleep disturbance and decreased work capacity are nonspecific symptoms that are often associated with reduced testosterone [2]. Other cognitive effects seen in men with subnormal testosterone levels include memory impairment and worsening visuospatial performance [20].


Metabolic Syndrome


The metabolic syndrome (MetS) is a group of coincident disease processes that increases an individuals’ risk of cardiovascular events although multiple definition and content have been proposed. According to the International Diabetes Federation, the major entities that comprise the MetS are hypertension, insulin resistance, abnormal body fat distribution, and dyslipidemia [21]. Studies have clearly noted an association between testosterone deficiency and the MetS [22, 23], an association that persists in non-obese males [24]. Cardiovascular complications associated with MetS and low testosterone include large vessel atherosclerosis [25] and angina pectoris [26]. Since testosterone therapy has been shown to be more effective than exercise and diet alone in treating MetS among patients with subnormal testosterone [27], it is vital to determine if the MetS patient is a candidate for testosterone replacement therapy [18].


Body Composition


There is an annual 1.5–2% reduction of testosterone production during the normal aging process in adult men [28]. Likewise, there is decrease in muscle mass and an associated increase in adipose tissue, which alters overall body shape and composition [28]. Studies of men with hypogonadism reveal decreases in lean body mass and increases in overall body fat mass paralleling falling androgen levels [29] (Fig. 3.1).

In addition to its effects on overall body composition, testosterone has an effect on regional body distributions of various tissues. Analysis of a cohort of men, aged 50–89, from the California community of Rancho-Bernardo documented that total testosterone levels were inversely correlated with central adiposity [30]. Testosterone replacement therapy in hypogonadal men increased lean body mass and decreased the total amount of adipose tissue while simultaneously altering its distribution [31].


Skeletal Changes


Testosterone deficiency contributes to reduced bone mineral density and the development of osteoporosis by interrupting the normal inhibition of osteoclastic bone resorption and decreasing the estrogen-dependent stimulation of osteoblasts, by way of the inability of testosterone to be aromatized into estrogen [32]. Low serum testosterone levels correlate with frailty because of decreased bone mineral density in elderly males [33].

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Apr 6, 2017 | Posted by in UROLOGY | Comments Off on The Clinical Diagnosis of Androgen Deficiency

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