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Hypogonadism is defined as a clinical condition in which low levels of serum testosterone are associated with signs and symptoms, including diminished libido and sense of vitality, erectile dysfunction (ED), reduced muscle mass and bone density, mild depression, and anemia.1 Hypogonadism is prevalent, affecting 4 to 5 million men in the United States, and is underrecognized, underdiagnosed, and undertreated despite available effective therapies.

Most men with hypogonadism, whether symptomatic or asymptomatic, present first to their primary care clinicians. Because of a lack of awareness, coupled with the time constraints of a primary care practice, hypogonadism often goes undiagnosed. To understand their role in the management of hypogonadism and offer patients the best course of action, it is important for primary care clinicians to become more aware of the prevalence and potential morbidity of the condition, its symptoms, methods of diagnosis, and available treatments.

If primary care clinicians were more aware of the prevalence of hypogonadism and the associated comorbidities, ‘they would be much more active in screening for low testosterone’

Martin M. Miner, MD

Even though many investigations into the potential presence of hypogonadism are initiated by patient complaints, the majority of the male population (91%) does not know at least one of the symptoms of low testosterone.2 Research shows that 33% reported having experienced at least 2 hypogonadal symptoms within the last year, an alarming 97% of whom reported that their physician had never broached the subject of low testosterone as possibly related to their symptoms.2 The impetus is clear for clinicians to be aware of the population at risk and the presenting signs and symptoms of hypogonadism.


The Baltimore Longitudinal Study of Aging (N=890) was one of the first studies to demonstrate that age had significant, independent, longitudinal effects on both testosterone level and free testosterone index (testosterone divided by sex hormone- binding globulin [SHBG]).3 Data-adjusted testosterone and free testosterone index values were used to calculate the percentages of men in each decade who were hypogonadal, defined as having at least one visit in that age decade at which testosterone was <325 ng/dL or the free testosterone index was <4.41 ng/dL. In men aged 40 to 79 years, the percentage of men with hypogonadism (as defined by total testosterone or free testosterone index) increased progressively after age 50 (Figure 1).


Figure 1. Prevalence of Hypogonadism: Baltimore Longitudinal Study of Aging3

N=890. Reproduced with permission. Bar height indicates the percentage of men in each 10-year interval, from the third to the ninth decades, with at least one testosterone value in the hypogonadal range, by the following criteria: testosterone <325 ng/dL (<11.3 nmol/L), free testosterone index <4.41 ng/dL (<0.153 nmol/nmol).

The Massachusetts Male Aging Study, a 10-year prospective observational survey, compared cross-sectional data with longitudinal data and found that additional diseases are more likely to develop as men age.4 This explains why longitudinal data reveal much higher percentages of men who are testosterone deficient than do cross-sectional studies that may exclude men with these conditions.

Araujo and colleagues illustrated that the age trend in the proportion of men with low free testosterone increased at a faster rate than the proportion of men with low total testosterone because of a sharp rise in the proportion of men with elevated SHBG.5 Prevalence of symptomatic testosterone deficiency was significantly greater in the 70- to 79-year-old group compared with all other groups (pairwise comparisons, P<.05). Extrapolating, the authors estimated that, by 2025, more than 6 million American men between the ages of 30 and 79 years will suffer from symptomatic testosterone deficiency, an increase of 38% from year-2000 estimates.

The Hypogonadism in Males (HIM) Study (N=2165) examined the prevalence of hypogonadism (defined as total testosterone <300 ng/dL) in men aged 45 years or older who presented to the offices of primary care clinicians.6 The crude prevalence of hypogonadism was found to be 38.7%. As men age, the risk of hypogonadism increased by 17% for each decade. According to Ridwan Shabsigh, MD, Director of the Division of Urology at Maimonides Medical Center in Brooklyn, New York, 66% of individuals in this study with low testosterone were symptomatic.

Sex steroids and hormones

Katherine Margo, MD, Associate Residency Director at the University of Pennsylvania School of Medicine stated in the Journal of Family Medicine, “I do not think medical schools are teaching very much about testosterone deficiency now.”7

A general knowledge of sex steroids and hormones and how they function in the body is important for all practitioners who will see and treat the majority of men with hypogonadism (Figure 2). Many organs are affected by a man’s androgen status (Figure 3).8

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