Distinct roles of age and abdominal visceral fat in reducing androgen receptor-dependent negative feedback on LH secretion in healthy men.

Testosterone (T) impacts luteinizing hormone (LH) secretion through negative feedback via the androgen receptor (AR) in the hypothalamo-pituitary system. An untested postulate is that increasing body mass index (BMI), abdominal visceral fat (AVF) or total abdominal fat (TAF) with ageing decreases LH secretion by heightening T negative feedback via AR. This hypothesis was tested in a prospective, randomized double-blind cross-over study of 19 healthy men comparing the effects of flutamide, a selective non-steroidal AR antagonist and placebo administration on basal and pulsatile LH secretion as a function of age and obesity measures. To this end, serum levels of 2-hydroxyflutamide (2-OHF), a major active flutamide metabolite, were measured by mass spectrometry, and AVF/TAF quantified by abdominal computerized tomography. Statistical analysis showed that antiandrogen administration elevated 6-h mean LH concentrations to 5.4 ± 1.3 IU/L compared with 3.3 ± 1.2 IU/L for placebo (p < 10(-3) ), and total T by 35% (p < 10(-4) ). The LH-T concentration product doubled (p < 10(-8) ). According to deconvolution analysis, flutamide exposure increased total LH secretion (p < 10(-3) ) and pulsatile LH secretion (p = 0.0077), along with LH pulse frequency (p = 0.019). Despite feedback inhibition, the LH-T product declined as a linear function of AVF (p = 0.021) and TAF (p = 0.017). This was explained by the fact that higher BMI was associated with lower 2-OHF concentrations (R = -0.562, p = 0.012). In contrast, age was associated with less pulsatile LH secretion (R = -0.567, p = 0.011) even when LH responses were normalized to antiantrogen levels. In conclusion, increased AVF, TAF and BMI predict decreased LH and flutamide blood levels, whereas older age is marked by impaired stimulation of pulsatile LH secretion even when normalized for antiandrogen levels, suggesting different mechanisms of regulation by adiposity and age.

Biobanks and personalized medicine.

We provide a mini-review of how biobanks can support clinical genetics in the era of personalized medicine. We discuss types of biobanks, including disease specific and general biobanks not focused on one disease. We present considerations in setting up a biobank, including consenting and governance, biospecimens, risk factor and related data, informatics, and linkage to electronic health records for phenotyping. We also discuss the uses of biobanks and ongoing considerations, including genotype-driven recruitment, investigations of gene-environment associations, and the re-use of data generated from studies. Finally, we present a brief discussion of some of the unresolved issues, such as return of research results and sustaining biobanks over time. In summary, carefully designed biobanks can provide critical research and infrastructure support for clinical genetics in the era of personalized medicine.

Elder mistreatment.

Elder mistreatment is a widespread problem in our society that is often under-recognized by physicians. As a result of growing public outcry over the past 20 years, all states now have abuse laws that are specific to older adults; most states have mandated reporting by all health care professionals. The term "mistreatment" includes physical abuse and neglect, psychologic abuse, financial exploitation and violation of rights. Poor health, physical or cognitive impairment, alcohol abuse and a history of domestic violence are some of the risk factors for elder mistreatment. Diagnosis of elder mistreatment depends on acquiring a detailed history from the patient and the caregiver. It also involves performing a comprehensive physical examination. Only through awareness, a healthy suspicion and the performing of certain procedures are physicians able to detect elder mistreatment. Once it is suspected, elder mistreatment should be reported to adult protective services.

Urinary incontinence in the elderly. Drug treatment options.

Urinary incontinence is commonly seen in the elderly. It has multiple complications and is often the reason an elderly person is forced to abandon independent living and enter a nursing home. There are multiple causes of urinary incontinence: it is not a single entity or a specific diagnosis. In most patients, the incontinence can be placed into 1 of the following 4 categories: detrusor overactivity (urge incontinence), overflow incontinence, stress incontinence (outlet incompetence) or functional incontinence. To understand the pathophysiology of urinary incontinence, some knowledge of the urinary tract anatomy and physiology is required. It is also important to know how the anatomy and physiology changes in response to the aging process. Successful treatment depends on the specific cause of the incontinence. If incorrectly diagnosed, various treatments may actually worsen the incontinence or cause other problems. Since most elderly patients do not volunteer a problem of urinary incontinence, questions regarding the presence of symptoms must be asked. In most patients, the specific type of incontinence can be diagnosed with a thorough medical history and physical examination. Several simple and widely available laboratory tests may also be useful in the evaluation. Occasionally, urological consultation or urodynamic testing should be performed. Once correctly diagnosed, there are a large number of pharmacological as well as nonpharmacological treatments (behavioural, surgical) available. This article concentrates on the pharmacological therapies for patients with various types of urinary incontinence. Since most patients with urinary incontinence are elderly, they are more susceptible to the effects as well as the adverse effects of medications. This must be taken into account before any pharmacological therapy is initiated. Although many elderly patients believe their symptoms of urinary incontinence to be a part of growing old, urinary incontinence is never a normal change of aging. With proper evaluation and treatment, the majority of patients with urinary incontinence can be helped or cured.