Late Onset Hypogonadism, ADAM, Andropause: What Is It And What Is The Treatment?

Late-onset hypogonadism (LOH), or androgen decline in the aging male, is a syndrome caused by the well-known decline in gonadal production of androgens in males that occurs with aging. It is characterized by clinical symptoms that accompany low serum androgen levels. LOH affects a wide range of organ systems and has a broad severity of clinical presentations. Sexual dysfunction, including erectile dysfunction (ED), decreased libido, difficulty achieving orgasm, and decreased penile sensation, is usually the presenting complaint, although fatigue, depressed mood, impaired cognition, and decreased muscle mass are other common symptoms. If these symptoms are found in conjunction with low serum testosterone (T), a diagnosis of LOH may be made. Universally accepted guidelines for a level of T to define or treat LOH have not been established. In general, when the T level is found to be at or below the lower limit of normal, in conjunction with symptoms, treatment is appropriate.

The incidence of LOH is rising. Serum T levels decrease with age and according to U.S. Census data from 2000, the U.S. population of men 65 years of age and older is projected to double by the year 2030. An extrapolation from the Massachusetts Male Aging Study found a prevalence of LOH of almost half a million new cases per year in men in their fifth, sixth, and seventh decades of life. The principal treatment for LOH is androgen replacement, also known as testosterone replacement therapy (TRT). With the rising incidence of LOH and better understanding of treatment benefits, the use of TRT has been steadily increasing in recent years. This rise is evidenced by a 500% increase in prescription sales of T since 1993.

The benefits of TRT are easily recognized, primarily because as levels of serum T normalize, desired improvements in sexual function, libido, and mood, as well as in overall quality of life are reached. TRT also has a positive effect on cardiovascular health; one well-documented effect of TRT is a decrease in total cholesterol and low-density lipoprotein (LDL)1. Recent studies have shown a link between hypogonadism and a high-risk and increasingly prevalent syndrome called metabolic syndrome, also known as insulin resistance syndrome, or syndrome X. Metabolic syndrome is characterized by at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL), hyperglycemia, and hypertension2. Laaksonen and colleagues have suggested that hypogonadism is an element of metabolic syndrome based on their large population-based study. Treatment of LOH with TRT may improve the symptoms of metabolic syndrome, and vice versa, treatment of metabolic syndrome may improve the symptoms of LOH.

Despite its benefits, TRT has a number of contraindications, and questions remain regarding its effects on prostate health. Benign prostatic hyperplasia (BPH) is an androgen-sensitive disease which is accelerated by endogenous and exogenous T. The incidence of BPH increases with age, and prostate volume is decreased in hypogonadal men compared to men with normal serum T. Prostate volumes of men with LOH undergoing TRT increase up to the levels of age-matched controls, but TRT has not been shown to drastically increase prostate volume beyond that of eugonadal men of the same age. Similar to BPH, prostate cancer (CaP) is exquisitely androgen sensitive. First-line treatment for metastatic CaP is androgen deprivation, either through bilateral orchiectomy or medical castration with gonadotropin-releasing hormone agonists. While numerous studies have failed to show that exogenous T is a direct cause of CaP, the fact that CaP is androgen sensitive raises the question of whether T can awaken a clinically insignificant CaP or augment a CaP into a higher Gleason grade.

Short-term changes in prostate-specific antigen (PSA) levels during TRT have been reported. Much of this data is derived from relatively small, often retrospective studies. A definitive double-blind, randomized, placebo-controlled study on the effect TRT has on PSA has yet to be published. A systematic review of 18 studies of short-term TRT for men with LOH performed in 2003 found an average PSA increase of 0.3 ng/mL, and a systematic review of 6 other published studies of TRT in slightly older men with LOH found a slightly higher average PSA increase of 0.43 ng/mL. The long-term effects TRT has on PSA, however, have yet to be reported.

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