Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, age-invariant, longitudinal effects of age on both T and free T index (free T index = T/SHBG), with an average change of -0.124 nmol/L.yr and -0.0049 nmol T/nmol SHBG.yr. T, but not free T index, also decreased with increasing body mass index. Use of beta-blocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.

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ContextIn men who develop an elevated serum prostate-specific antigen level (PSA) after having undergone a radical prostatectomy, the natural history of progression to distant metastases and death due to prostate cancer is unknown.Objective To characterize the time course of disease progression in men with biochemical recurrence after radical prostatectomy.Design A retrospective review of a large surgical series with median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between April 1982 and April 1997.Setting An urban academic tertiary referral institution.Patients A total of 1997 men undergoing radical prostatectomy, by a single surgeon, for clinically localized prostate cancer. None received neoadjuvant therapy, and none had received adjuvant hormonal therapy prior to documented distant metastases. Main Outcome MeasuresAfter surgery, men were followed up with PSA assays and digital rectal examinations every 3 months for the first year, semiannually for the second year, and annually thereafter. A detectable serum PSA level of at least 0.2 ng/mL was evidence of biochemical recurrence. Distant metastases were diagnosed by radionuclide bone scan, chest radiograph, or other body imaging, which was performed at the time of biochemical recurrence and annually thereafter. ResultsThe actuarial metastasis-free survival for all 1997 men was 82% (95% confidence interval, 76%-88%) at 15 years after surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level elevation. Eleven of these underwent early hormone therapy after the recurrence and are not included in the study. Of the remaining 304 men, 103 (34%) developed metastatic disease within the study period. The median actuarial time to metastases was 8 years from the time of PSA level elevation. In survival analysis, time to biochemical progression (PϽ.001), Gleason score (PϽ.001), and PSA doubling time (PϽ.001) were predictive of the probability and time to the development of metastatic disease. An algorithm combining these parameters was constructed to stratify men into risk groups. Once men developed metastatic disease, the median actuarial time to death was 5 years. The time interval from surgery to the appearance of metastatic disease was predictive of time until death (PϽ.02).Conclusions Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in the design of clinical trials, the identification of men for enrollment into experimental protocols, and counseling men regarding the timing of administration of adjuvant therapies.Estimates are calculated at 3, 5, or 7 years from the time of the initial prostate-specific antigen (PSA) elevation (metastatic-disease free period, based on Gleason score in the surgical specimen, the time of initial biochemical recurrence (Յ2 vs Ͼ2 years), and prostrate-specific antigen doubling time (PSADT) (Ͻ10 vs Ն10 months). CI indicates confidence interval. PSA LEVEL ELEVATION AFTER PROSTATECTOMY

Clinical stage, Gleason score and serum prostate specific antigen (PSA) levels are used separately to predict pathological stage in patients with localized prostate cancer. Because the degree of tumor differentiation has a profound influence on the expression of serum PSA, serum PSA levels alone do not reflect tumor burden accurately. To overcome this obstacle we tested these 3 variables alone and in combinations as predictors of final pathological stage in 703 men with clinically localized prostate cancer at our institution. All patients were assigned a clinical stage by 1 urologist. The Gleason score was determined from preoperative needle biopsy and serum PSA levels were measured on an ambulatory basis. Final pathological stage was determined to be either organ confined, established capsular penetration, seminal vesicle involvement or lymph node involvement. Logistic regression analysis with the likelihood ratio chi-square test determined that serum PSA, Gleason score and clinical stage all predicted final pathological stage well. The results were improved with combinations of the 3 variables (serum PSA, Gleason score and clinical stage) and the combination provided the best separation. From these analyses probability plots and nomograms have been constructed to assist urologists in the preoperative prediction of final pathological stage for patients with clinically localized prostate cancer.

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Objective-To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.Design-Case-control study of men with and without prostate disease who were participants in a prospective aging study. Setting-GerontologyResearch Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.Patients-Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.Outcome Measures-Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.Results-Changesin androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer>BPH>control; P<.01).At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 μg/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively. Conclusions-The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.PROSTATE-SPECIFIC ANTIGEN (PSA) is a serine protease produced by both benign and malignant prostatic epithelium that can be measured in serum samples by immunoassay. 1 Cross-sectional analysis of serum PSA levels in men with and without prostate discent studies suggest that PSA may be useful in the early detection of prostate cancer, 3,4 it is known that PSA elevations occur in men with BPH 2,5,6 and that men with prostate cancer can have normal PSA levels. [4][5][6] are not specific for prostate cancer, and a normal PSA level does not exclude the presence of cancer.The longitudinal changes in PSA that occur with age in men with and without prostate disease have not been reported previously. In addition, although it is well known that PSA is under the influence of androgen, 7,8 the influence of age-related decreases in androgen levels on PSA has not been studied. To better understand the factors that affect PSA levels and potentially improve the use of this valuable clinical marker in men with prostate disease, we evaluated PSA levels in a longitudinal, casecontrol study. METHODS Study GroupsThree groups of men were identified from subjects participating in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing, long-term,prospective aging study of the National Institute of Aging, Bethesda, Md, which has as its goal the study of ...

Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise-induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age-associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss.

This report describes the GRID-Hamilton Depression Rating Scale (GRID-HAMD), an improved version of the Hamilton Depression Rating Scale that was developed through a broad-based international consensus process. The GRID-HAMD separates the frequency of the symptom from its intensity for most items, refines several problematic anchors, and integrates both a structured interview guide and consensus-derived conventions for all items. Usability was established in a small three-site sample of convenience, evaluating 29 outpatients, with most evaluators finding the scale easy to use. Test-retest (4-week) and interrater reliability were established in 34 adult outpatients with major depressive disorder, as part of an ongoing clinical trial. In a separate study, interrater reliability was found to be superior to the Guy version of the HAMD, and as good as the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D), across 30 interview pairs. Finally, using the SIGH-D as the criterion standard, the GRID-HAMD demonstrated high concurrent validity. Overall, these data suggest that the GRID-HAMD is an improvement over the original Guy version as well as the SIGH-D in its incorporation of innovative features and preservation of high reliability and validity.