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Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis. Supplemental calcium is also generally recommended. This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment.This 2-year, randomized, double-blind, multicenter trial enrolled healthy, postmenopausal women with low bone mineral density (BMD). Patients with a dietary calcium intakeor = 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo, alendronate 10 mg/elemental calcium 1000 mg, or alendronate-placebo/calcium 1000 mg (2:2:1). Endpoints included BMD, bone turnover markers (BTMs), and adverse events.Randomized patients (N = 701) were an average of 20.4 years postmenopausal. After 24 months, increases in lumbar spine BMD differed significantly between patients receiving calcium alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium (6.0%) (p0.001). Significant differences were also seen at the trochanter and femoral neck (p0.001). BTMs were significantly lower with alendronate-containing treatments than calcium alone (p0.001). Addition of calcium supplementation to alendronate did not significantly increase BMD compared to alendronate alone (p = 0.29 to 0.97), but did result in a statistically significant, though small, additional reduction in urinary NTx. Adverse events were similar among treatment groups. Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30%, although discontinuation rates were similar among treatment groups.In postmenopausal women with a daily intake ofor =800 mg calcium and 400 IU vitamin D, 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg resulted in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone. Addition of supplemental calcium to alendronate treatment had no effect on BMD and resulted in a small, though statistically significant, additional reduction in NTx.

This study shows that endocrine and vascular etiologies of erectile dysfunction are more common in the older age group, whereas depression and marital discord are more common in the younger age group. There is considerable overlap between various factors pointing to the multifactorial nature of erectile dysfunction. Review of the treatment option chosen reveals that the invasive modalities were least common as compared with the popular vacuum tumescence device (although cumbersome) and testosterone replacement. Persons with low testosterone have an improved efficacy of sildenafil when hypogonadism is treated. Sildenafil with its ease of administration and high efficacy seems to be the logical first choice for most of the patients. If contraindications exist or treatment failures occur, other treatment options should be offered to patients.

PURPOSE the purpose of this study was to assess the ability of older persons with type 2 diabetes to accurately break in half 2 different formulations of micronized glyburide tablets. METHODS Thirty persons with type 2 diabetes, over age 70, were recruited from the St Louis University geriatric clinics. Participants were randomly assigned to 2 groups. Group A broke 30 Glynase Prestabs and 30 generic tablets using 2 different manual tablet-breaking methods. Group B broke 15 Glynase Prestabs and 15 generic tablets without instructions. Visual analog scales were used to assess pain and difficulty of tablet breaking. RESULTS A higher percentage of successful tablet breaking was reported with Glynase Prestabs (80%) compared with the generic tablets (33%). Mean pain scores for breaking Glynase Prestabs were 0.1 (Group A) and 0.9 (Group B). Higher pain scores were obtained for the generic tablets (2.1 for Group A, 3.2 for Group B). Glynase Prestabs were easier to break in both groups, and the resultant half tablets showed less variance from the expected theoretical weight (50% of whole parent tablet weight). CONCLUSIONS Older adults broke Glynase Prestabs more accurately and with less difficulty than generic micronized glyburide tablets. This variation in ease of tablet breaking and accuracy between different tablet formulations affect bioavailability and patient compliance.

Erectile dysfunction is defined as a consistent inability to obtain or sustain an erection sufficient for intercourse in at least 50% of attempts. The term erectile dysfunction has replaced the more pejorative term impotence. A revolution over the past 10 years in the understanding, diagnosis, and treatment of this disorder has enhanced the ability to discuss it more openly than ever before, by both patients and physicians. This disorder affects 10 million to 30 million men in the United States and more than 140 million men worldwide. 12,33 In 1996, there were 1.3 million office visits for the treatment of erectile dysfunction, reported by the National Ambulatory Medical Care Survey, more than double the rate found in 1985. 7,32 There are few disorders that impact quality of life, sense of self and esteem, and relationships with significant others in quite the same way. Although erectile dysfunction is discussed more openly, many myths remain. With aging, the prevalence of erectile dysfunction increases. This prevalence does not represent normal aging, however, any more than hypertension is considered to be normal in an older adult, and erectile dysfunction is not an inevitable effect of aging. Further, a decline in sexual function may relate to matters other than erectile difficulties, such as illness on the part of an individual or his partner, lack of a partner, loss of libido, or environmental issues (e.g., institutional living).

Background. The impact of diabetes on disability and physical functioning in older African Americans and potential causes of the excessive disability associated with diabetes in other studies have been inadequately investigated.Methods. A population-based survey was performed comparing 116 self-reported diabetic inner-city African Americans aged 70 years and older to 522 nondiabetic persons from the same population. A subsample (n = 168) received a physical examination focused on body habitus, upper and lower body strength, balance, and timed physical performance tasks. Blood tests were obtained from 173 subjects.Results. Diabetic individuals reported worse general health (p = .01), instrumental activities of daily living (p = .02), and modified versions of the Rosow-Breslau scale (p < .001) and the Stanford Health Assessment Questionnaire (p = .002). Diabetic persons also reported more falls (0.59 per person vs 0.20, p = .019) and injurious falls (12% vs 6%, p = .025). There were minimal differences in the strength, balance, and timed performance measures (analyzed separately by gender). In multivariable analyses, impairments in visual function and pain and light touch perception appeared to explain some of the association between diabetic status and poor general health, disability, and falls, with lesser contribution from the number of medical problems, number of medications, and glycemic control.Conclusions. Older inner-city diabetic blacks demonstrated worse general health, excess disability, and more falls compared to controls, although deficits in strength, balance, and timed performance could not be demonstrated. The cause of decreased functional status in diabetic elders deserves additional investigation, focusing especially on sensory function, glycemic control, and contribution from specific medical problems and medications.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p 8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.

OBJECTIVE: To target medically ill older home care patients with symptoms of depression in order to reduce their rate of hospitalization. DESIGN: A case-control study. SETTING: A private, nonprofit home care organization, the Visiting Nurse Association of St. Louis. PARTICIPANTS: Home care patients 65 years of age and older with symptoms of depression who were participants of a Total Quality Management (TQM) intervention (n = 81) were compared with an historical control of home care patients 65 years of age and older with symptoms of depression (n = 69). INTERVENTION: Utilization of TQM principles to develop a plan including: (a) an educational seminar on depression for home care staff involved in the project; (b) letters to physicians introducing the TQM project; (c) use of the Geriatric Depression Scale (GDS) for screening; (d) recommendation to the primary physician of a home social service (SS) consultation for patients with a GDS of 10 to 14; (e) recommendation to the primary physician of three interventions for patients with a GDS ≥ 15: home SS consultation + mental health (MH), or gerontological nurse (GN) consultation + antidepressant medication (a pharmacotherapeutic algorithm sent by facsimile to the primary physician upon request). OUTCOME MEASURES: Hospitalization rates of the control group compared with the TQM intervention group, the degree to which part (e) of the plan was implemented, and the effect this had on hospitalization rates. RESULTS: The TQM intervention patients had a higher mean age than the historical control patients but were not different in percent female, percent white race, percent with a caregiver in the home, functional status, and in 15 of 16 diagnostic categories. Overall, the TQM intervention group had a hospitalization rate of 23.5% (19/81) compared with a rate of 40.6% (28/69) for the historical control group (P = .024). For part (e) of the plan (56/81 patients had a GDS ≥ 15), 29/56 (52%) received the recommended SS consultation, 50/56 (89%) received the recommended MH or GN consultation, and 32/56 (57%) received antidepressant medication. One type of intervention did not seem to lower hospitalization rates more than another although having received the MH or GN visits approached significance (12/50, 24%; P = .052) when compared with the control group. CONCLUSION: Utilization of TQM principles and the development of an intervention such as the one described here can decrease hospitalization rates for medically ill older home care patients with symptoms of depression.

To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Although self-assessment of libido was dramatically improved in the testosterone-treated group (P0.0001), approximately one third of the subjects discontinued therapy. In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.

Background Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. Methods Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 μg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. Results During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P

Falls following a meal occur commonly in older persons. These falls have been related to a decrease in postprandial blood pressure due to carbohydrates in the meal. The mechanism by which this occurs is not known. In this study, we examined the possible role of a vasodilatory peptide, calcitonin gene-related peptide (CGRP), which is released following carbohydrate loading in the pathophysiology of postprandial hypotension. Levels were assessed in 29 community-dwelling individuals aged 20-83 years during an oral glucose tolerance test, and heart rate and blood pressure were measured. Five subjects exhibited a postprandial reduction in systolic blood pressure (SBP) greater than 15 mmHg (mean reduction -30 +/- 4 mmHg). Four were aged over 60 (40% of the individuals in that group) and one was middle aged (11%). One individual in the older group was temporarily symptomatic, complaining of light-headedness. Linear regression analysis showed a significant association between the changes in CGRP and in blood pressure: SBP (r = 0.39, P = 0.037), and mean blood pressure (MBP) (r = 0.356, P = 0.06) in the oldest group. Individuals in this group with a greater than 15 mmHg drop in blood pressure, exhibited significantly greater changes in CGRP (SBP: P = 0.001, diastolic blood pressure (DBP): P = 0.05, MBP: P = 0.006). This association of log CGRP delta and BP change was not present in young or middle aged individuals. Thus, increases in CGRP levels were associated with blood pressure reduction, with older individuals more susceptible to these changes than younger individuals. CGRP may play a role in the pathogenesis of postprandial hypotension.

Tests of thyroid function may present a challenge in their use and interpretation, but careful consideration of the patient's clinical state, the role of nonthyroidal disease, or medication on the patient's thyroid function tests can make this task easier

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.

Objective: To determine the effects of long-term use of the thiazide diuretic chlorthalidone on serum bone-related biochemical variables in older persons. Design: Cross-sectional comparison. Setting: Community-dwelling subjects who had participated in the Systolic Hypertension in the Elderly (SHEP) program. Participants: Sixty-six Caucasians (36 male and 30 female), age range 70 to 89 years, of whom 23 were taking a thiazide diuretic. Measurements: 25-hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, calcitonin, and serum bioavailable testosterone. Results: In both groups, there was a high prevalence of low 25 (OHD) levels (30%). Log 25OHD showed a significant inverse relationship to parathyroid hormone (r = .33, P < 0.05). Thiazide users had lower levels of osteocalcin (P < 0.05) and parathyroid hormone levels (P < 0.05) compared with non-thiazide users. Male thiazide users had decreased bioavailable testosterone levels compared with non-thiazide users (P < 0.05). Serum osteocalcin was significantly related to bioavailable testosterone in men not on thiazide (r = .43, P < 0.05). Conclusions: Hypovitaminosis D is a common finding in older individuals with associated elevations in parathyroid hormone. Parathyroid hormone and testosterone concentration (in men) are correlated with serum osteocalcin, a measure of osteoblastic activity. Long-term thiazide use alters these relationships and produces a biochemical profile suggestive of decreased bone formation. Reduced bioavailable testosterone may also play a role in these biochemical changes.

The sexuality of older women has been an area that has received very little investigation until recently. This article explores myths, realities, and alterations in the physiologic function of older women. In addition to hormonal, physical, and functional parameters, other issues also must be considered in this population, such as relationship /interpersonal issues, levels of expectations, "libido mismatch," partner availability, and partner and self-health. Sexual function is a quality of life issue that remains an integral part of successful aging

Comprehensive geriatric assessment has much to offer older women. In this article, differences between comprehensive geriatric assessment and the traditional internal medicine approach are delineated, and specific methods are described for assessing sensory function, continence, nutritional status, risk for falls, upper extremity function, cognition, affect, bone integrity, sexual function, alcohol problems, medication use, socioeconomic milieu, and the home environment. Advanced planning, screening, and prevention also are discussed, and a prototypic form for the initial assessment of the older woman is provided

Malnutrition in the elderly is often unrecognized and untreated. Reduced secretion of growth hormone (GH) has been suggested as a cause of decreased muscle and bone mass with aging. This pilot study characterized the nutritional response of elderly malnourished subjects to recombinant human GH (rhGH). Subjects were included if they were over 60 years of age, if weight was more than 20% below average body weight (ABW), and if serum albumin concentration was less than 3.8 g/dL. Subjects were divided into two groups: one received 100 micrograms/kg rhGH (Protropin, Genentech) intramuscularly (IM) daily for 21 days; the other received a daily control injection of normal saline (Controls -C) (0.1 mL/kg IM) for the same period of time. During the 3-week period, mid-arm muscle circumference (MAMC) increased an average of 0.6 cm in GH patients but fell in C subjects. There was a non-significant trend to a decreased caloric intake in the control group. Weight increased an average of 4.95 lbs (2.2 kg) in the GH treated group, and decreased an average of 4.9 lbs (2.2 kg) in C subjects (P less than 0.05). Urinary nitrogen retention occurred only in the growth hormone treated subjects (P less than 0.05). Somatomedin C (IGF-1) rose significantly in those treated with GH (P less than 0.05), while there was no change in the control group. There was a significant association between weight change and IGF 1 concentration (r = 0.837, P less than 0.05). Neither clinical edema nor hyperglycemia was noted. These findings suggest that GH may be an effective way of maintaining and enhancing weight in malnourished older individuals.

Decreased sexual function commonly occurs with aging but should not be considered a normal event. This article discusses normal physiologic changes and the pathologic events that can lead to erectile difficulties. Proper evaluation can lead to a more appropriate choice of therapeutic agent or device and can benefit the quality of life of the older man and his partner.

Diabetes mellitus is a common condition in the geriatric population. In older subjects it may present in unusual ways and may be associated with unusual conditions. Hyperglycemia produces a variety of effects, including osmotic diuresis and cognitive dysfunction, which seriously impair the quality of life of the older individual. Older diabetics need to have their diabetes well controlled. The approach to diabetic control in older individuals is similar to that in younger individuals, with some notable exceptions.

Female sexuality is an extraordinarily complex process. The physician needs to be aware of the patient's sexuality and whether or not there are sexual concerns. Physiologic changes over the lifespan can interact with sexual performance as can a variety of disease processes. Partner and relationship issues must also be taken into account. Physicians need to include a sexual history as part of their general history and should not be judgmental of their patients' sexual practices. Sexual disorders in women are defined and delineated by those issues causing personal distress. Again, one person's distress may be quite normal to another. The important aspects of care consist of listening, educating, and providing support to the patient. There is increasing interest but a continued need for data in the use of testosterone in women with decreased libido. The use of sildenafil for female sexual dysfunction remains controversial as a benefit. Overall, there is a need for the development of well-organized, randomized, controlled studies on appropriate assessment and intervention for sexual dysfunction in women.

The most important aspect to consider in optimizing the sexual health of the older woman is to ask about it, and determine what might be contributing to any difficulties that are faced. It also behooves all health providers to remind older women (and older men) that age is not a barrier to sexually transmitted diseases. Recognition that healthy sexuality is an important issue for achieving quality of life is an area that patients and their providers need to be cognizant of, but one where far more research and evaluation need to occur.

This study shows that endocrine and vascular etiologies of erectile dysfunction are more common in the older age group, whereas depression and marital discord are more common in the younger age group. There is considerable overlap between various factors pointing to the multifactorial nature of erectile dysfunction. Review of the treatment option chosen reveals that the invasive modalities were least common as compared with the popular vacuum tumescence device (although cumbersome) and testosterone replacement. Persons with low testosterone have an improved efficacy of sildenafil when hypogonadism is treated. Sildenafil with its ease of administration and high efficacy seems to be the logical first choice for most of the patients. If contraindications exist or treatment failures occur, other treatment options should be offered to patients.

The authors evaluated five glucose meters for accuracy, precision, clinical reliability, and patient perceived ease of use. Three meters produced values within the acceptable range for accuracy and precision. The clinical reliability of the meters was determined by patient trials. Twenty-five subjects performed selfmonitoring of blood glucose. Only two meters—the One Touch II and AccuChek III —demonstrated clinical reliability in the acceptable range (within 15% of laboratory values). The Companion-2, the meter rated easiest to use, demonstrated acceptable clinical reliability less than 50% of the time. Laboratory assessments of glucose meters should be supplemented by practical patient trials.

To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women.A cross-sectional study.The Sac and Fox Nation in rural OklahomaSerum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry.A total of 77 Native American women aged 19 to 85 years.Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P.05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P.001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P.001). BMD was lower (P.001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (ror = -0.48, P.001) and body mass index (BMI) (ror = 0.41, P.005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P.05) and femoral (r = .41, P.01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P.05) in premenopausal Native American women, and lower (P0.05) in postmenopausal subjects, compared with white women.In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder.In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales.Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination.Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 ± 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65± 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean ± sem: −2.0 ± 0.9 ng/dL vs. 0.8 ± 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.

Sexual dysfunction is common with advancing age;1–4 frequency of sexual intercourse decreases and erectile dysfunction commonly increases with age. However, decline in sexual function (measured as coital activity) is only indirectly associated with advancing age, is not necessarily inevitable, and varies among individuals. Sexual dysfunction arises from psychologic, physiologic, and pathologic causes within one or more of the following categories5,6: (a) sexual appetite or desire; (b) sexual arousal, including erectile dysfunction; (c) orgasmic, including inhibited orgasm and premature ejaculation; and (d) sexual pain disorders. The first two categories are most commonly seen in older individuals. By age 75, at least 50% of men have developed impotence7 Despite these numbers, sexuality is poorly understood and sexual disorders are frequently underdiagnosed and under-treated in older men.

Menopausal age has not altered substantially since medieval times. In the United States, the average age of menopause is 51 years, and currently over 40 million women are over age 50. Only 1% of women experience menopause prior to age 40.1 Women live one-third of their life span after menopause.

There is limited information concerning bone mineral density (BMD) and its determinants across a wide spectrum of ages in African American females (AAF). Therefore, we have performed a cross-sectional study of 54 AAF and 39 Caucasian females (CF), aged 20-90 yr, to quantify femoral and lumbar bone mineral density, total body calcium, as well as the potential determinants of bone density. BMD decreased with age in all sites after age 40 yr in both racial groups. Bone density was greater in AAF than in CF, although there was considerable overlap between the two groups. There was no significant difference in the rate of age-related bone loss between the two groups. At the femoral neck, BMD was below the fracture threshold in 28% of the postmenopausal AAF compared to 47% of postmenopausal CF. L1-L4 BMD was below the fracture threshold in 8% of postmenopausal AAF and 11% of postmenopausal CF. Serum-25 hydroxyvitamin D (25OHD) was inversely related to age in both othnic groups and lower (P0.05) in premenopausal AAF than CF. Twenty-four percent of the AAF and 22% of the CF had serum 25OHD levels of 8 ng/L or less. Serum PTH was directly related to age (r = 0.43; P = 0.003 in AAF and r = 0.55; P = 0.002 in CF), and 25OHD was inversely related to age (r = -0.43; P = 0.003 in AAF and r = -0.65; P0.001 in CF). PTH was higher (P0.05) in postmenopausal AAF than in CF. Serum testosterone was greater in AAF than in CF (P0.05). Serum estradiol was greater in premenopausal AAF than in CF. Serum dehydroepiandrosterone sulfate was inversely related to age (r = 0.42; P = 0.004 in AAF and r = 0.51; P = 0.005 in CF). Serum osteocalcin was related to age in AAF (r = 0.47; P = 0.001), but not in CF. There was also a trend for an increase in urinary dipyridinoline (expressed per 100 mg urinary creatinine) with age (r = 0.31; P = 0.055 in AAF and r = 0.37; P = 0.066 in CF). Both lean and fat mass were major determinants of femoral neck BMD in AAF. Femoral BMD was directly related to body weight and body mass index in both races. Serum 25OHD and dehydroepiandrosterone sulfate approached statistical significance as independent predictors of femoral BMD in AAF. We conclude that in AAF, 1) bone density is higher than in CF, but there is a significant risk of fracture in a substantial number of subjects on the basis of BMD; 2) there is no difference in rates of age-related bone loss compared to those in CF; 3) both lean and fat mass are significant determinants of bone density; 4) serum estradiol and testosterone were higher than those in CF; and 5) aging is associated with increased bone turnover, 25OHD deficiency, and secondary hyperparathyroidism in both races. The absence of a difference in rates of bone loss between AAF and CF despite higher serum levels of PTH is compatible with the concept of a relative skeletal resistance to PTH in AAF.

Sexuality and aging are not incompatible terms. However, sexual issues are often ignored in older adults. Impacts of altered physiology and pathologic changes, such as cardiovascular disease are discussed in this article. What is clear is that many older adults are interested in remaining sexually active throughout the years.

Nitric oxide has been recently recognized as an intra- and inter-cellular messenger. Animal studies have suggested a role for nitric oxide in the regulation of gonadotropin secretion. In this study of 14 healthy, young males, nitroglycerine administered sublingually was demonstrated to inhibit GnRH stimulated LH secretion from the pituitary (p0.05). There was no significant effect on GnRH stimulated FSH secretion. Nitroglycerine increased basal PTH levels (0.02), but had no significant effect on basal LH, FSH, TSH, cortisol, calcium, or prolactin levels. This study presents evidence that nitric oxide modulates LH and PTH secretion in humans.

Mice were trained to avoid footshock in a T-maze, with retention tested one week later. Adult male CD-1 mice made their first avoidance during acquisition after fewer trials than random cycling females and with less variability. Female mice in diestrus, when plasma levels of progesterone are low, learned to avoid footshock faster than females in estrus. Ovariectomized (OVX) mice learned in fewer trials than intact random cycling mice. Similar differences, though of a smaller magnitude, were found on the retention tests (i.e. males had better retention than females, mice in diestrus showed better retention 8 days later when in the same part of the estrous cycle than those in estrus, and OVX mice had better retention than cycling females). OVX mice with estrogen implants learned faster than those with progesterone implants or progesterone plus estrogen implants. Hormonal status did not affect sensitivity to acoustic or footshock stimuli as measured by a startle reflex, nor did it affect activity. Pretraining administration of amphetamine, picrotoxin and strychnine attenuated the impairing effect of progesterone on acquisition. The possibility that progesterone may impair learning and to some extent, retention by facilitating the GABAergic activity and thereby reducing arousal level is discussed.

Four-month and 12-month-old SAM (Senescence Accelerated Mouse)-P8 and -R1 female mice, either intact or ovariectomized, were trained to avoid foot shock in a T-maze. Mice were trained until they made their first avoidance. Memory retention of this task was then tested 1 week later. The results indicated that P8, but not R1, female mice whether intact or ovariectomized, showed an age-related learning impairment. This impairment was more apparent in ovariectomized mice, as ovariectomy was associated with a significant reduction in the mean trials to make an avoidance in all groups except 12-month P8 females. Of greatest interest was the absence of any age-related impairment of retention in P8 females. In several previous studies, SAM-P8, but not R1, males showed an age-related impairment of learning and memory. These results indicate that age-related impairment of memory in P8 mice may be inherited in a sex-related manner, and suggests that the mechanisms involved in the development of impaired learning and memory are different.

OBJECTIVE: Survey of the association of idiopathic CD4+T cell lymphocytopenia in older persons with protein energy undernutrition and unusual infections/colonizations. METHOD: Retrospective chart analysis. RESULTS: Five subjects aged 61 to 87 years, with unusual organisms and/or either marasmus or kwashiorkor, were noted to have absolute CD4+and CD8+T cell lymphocytopenia. All were HIV negative. CONCLUSION: T cell lymphocytopenia may not be a uncommon finding in malnourished older persons, but additional studies to determine its prevalence need to be undertaken. Its role in disease and impact on therapeutic response needs to be further explored.

Objective: To determine normal serum bone-related biochemical variables in older African-Americans. Design: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. Setting: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. Participants: Thirty-two African-Americans aged 68–93 years and 43 white Americans aged 70–89 years. Measurements: Twenty-five hydroxyvitamin D (250HD), parathyroid hormone, osteocalcin, and calcitonin. Results: Serum 250HD levels in 38% of the African-American men and 38% of African-American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African-Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. Conclusions: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African-Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter.

Objective To examine the effects of testosterone administration to older hypogonadal males (bioavailable testosterone less than 70 ng/dL). Design Alternate-case controlled trial. Setting St. Louis University. Patients Eight males (mean age 77.6 ± 2.3 years) who received testosterone and six males (mean age 76 ± 2.3 years) who served as controls. Selected from alumni of the SHEP trial and attendees at the St. Louis University Impotence Clinic. Interventions Testosterone enanthate (200 mg/mL) was administered intramuscularly to the treatment group every 2 weeks for 3 months. Measurements Serum testosterone, bioavailable testerone and estradiol, weight, % body fat, right hand muscle strength, balance, cholesterol, HDL-cholesterol, hematocrit, BUN, creatinine, albumin, calcium, PTH, 25(OH) vitamin D, 1,25 (OH)2 vitamin D, osteocalcin, prostate-specific antigen, and fructosamine. Results Males who received testosterone had a significant increase in testosterone and bioavailable testosterone concentration, hematocrit, right hand muscle strength and osteocalcin concentration. They had a decrease in cholesterol (without a change in HDL-cholesterol) levels and decreased BUN/Creatinine ratios. Conclusion These preliminary findings support the need for long term studies of testosterone therapy in older hypogonadal males.

Impotence is a highly prevalent condition occurring in 10 million American men over the age of 18 years. Alterations in vascular supply, hormonal changes with age, neurological dysfunction and the use of a variety of medications may combine and contribute to impotence. Impotence should not be considered a normal part of the aging process. Careful attention to evaluation for the aetiology of impotence will lead to making appropriate therapeutic choices.

The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men.

The increase in the numbers of elderly in the United States, and their projected continued increase to 21% or more of the population by 2030, has provided impetus for the growth of geriatrics. Recognition of change that is age-related rather than disease-related, and the ways in which the elderly differ from their young counterparts is vital in the care of the elderly. A functional approach and appropriate geriatric assessment have been shown to be beneficial to the individual.

This study evaluated the use of a vacuum tumescence device in the treatment of impotence in older men. Twenty couples with sexual dysfunction due to erectile impotence and who were interested in restoration of sexual function were treated by providing them with both a vacuum tumescence device to engorge the penis and an obstructing band to impede venous return. Nineteen patients established firm to hard erections lasting an average of 16 minutes and were able to have satisfactory coitus with vaginal ejaculation an average of three times per month. The penile-brachial pressure index, supine and after exercise (a measure of the adequacy of penile arterial flow), exhibited a significant increase following six month's use of the vacuum tumescence device. The only significant complications were mild, self-limited hematomas on three occasions of use. Thus in this limited series the vacuum tumescence device provided a well-accepted, relatively inexpensive therapeutic approach to impotence.

Sexual function decreases markedly with advancing age. In a survey of an outpatient clinic population, Slag et al1 found that one in three patients over 40 years of age had erectile dysfunction. Half of these patients wanted treatment for their impotence. Kinsey et al2 found that the frequency of intercourse decreased from an average of once per week at 65 years of age to once every 10 weeks by the age of 80 years. The reasons for the decline in sexual function with advancing age are multifactorial and include psychological, physiologic, and pathologic processes. The exact role played by each of these processes varies from individual to individual. In addition, a number of changes occur in male hormonal function with advancing age. The effects of these changes on male sexuality are ill defined, and they may also play a role in a number of changes commonly associated with aging, such as decreased muscle strength and osteopenia.