Aging and Endocrinology

Contents

Foreword xiii

Derek LeRoith

Preface xvii

Anne R. Cappola

Growth HormoneAxis and Aging 187

Ralf Nass

Growth hormone (GH) and/or ghrelin mimetics represent potential treat-ment and/or prevention options for musculoskeletal impairment associ-ated with aging. Use of improvement in muscle function as an outcomein studies of GH and ghrelin mimetics is complicated by the lack of a stan-dardized definition for clinically meaningful efficacy of this end point.Based on preliminary study results, the use of ghrelin mimetics may bemore suitable for use in this age group than GH itself. There are still severalunanswered questions related to the use of ghrelin mimetics in the elderly,which prevents recommendation for its use at the current time.

Age-Dependent and Gender-Dependent Regulation of Hypothalamic-Adrenocorticotropic-Adrenal Axis 201

Johannes D. Veldhuis, Animesh Sharma, and Ferdinand Roelfsema

Tightly regulated output of glucocorticoids is critical tomaintaining immunecompetence, the structure of neurons, muscle, and bone, blood pressure,glucose homeostasis, work capacity, and vitality in the human and exper-imental animal. Age, sex steroids, gender, stress, body composition, anddisease govern glucocorticoid availability through incompletely under-stood mechanisms. According to an ensemble concept of neuroendocrineregulation, successful stress adaptations require repeated incrementalsignaling adjustments among hypothalamic corticotropin-releasing hor-mone and arginine vasopressin, pituitary adrenocorticotropic hormone,and adrenal corticosteroids. Signals are transduced via (positive) feedfor-ward and (negative) feedback effects. Age and gonadal steroids stronglymodulate stress-adaptive glucocorticoid secretion by such interlinkedpathways.

Endogenous Sex Steroid Levels and Cardiovascular Disease in Relation to theMenopause: A Systematic Review 227

Carolyn J. Crandall and Elizabeth Barrett-Connor

Heart disease remains a major cause of death among women in the UnitedStates. This article focuses on physiologic endogenous estrogen levelswith a systematic review of literature related to endogenous sex steroidlevels and coronary artery disease (CAD) among postmenopausal womenwith natural or surgical menopause. There is adequate reason to seek

Contentsviii

evidence for associations of circulating estrogen levels and CAD. In thefuture, even if ovarian senescence-associated hormonal changes are con-firmed to be associated with CAD in cohort studies of postmenopausalwomen, there may be other components explaining the gender differencesin CAD patterns.

ReproductiveAging in Men 255

Shehzad Basaria

Aging inmen is associatedwith a decrease in serum testosterone levels dueto attrition in testicular Leydig cells and slowing of the hypothalamic GnRHpulse generator. The practicing endocrinologist is frequently consulted forconsideration of testosterone therapy in older men with late-onset hypogo-nadism (LOH), a condition that many clinicians fail to distinguish fromorganic hypogonadism. Recent data using syndromic definition show thatonly 2% of 40-80-year-old men have LOH. Co-morbidities and obesitystrongly contribute to LOH, suggesting that testosterone is a biomarkerof health. Hence, prevention and treatment of these co-morbidities mightattenuate age-related decline in androgen levels.

TestosteroneAdministration in Older Men 271

Alvin M. Matsumoto

The only indication for testosterone administration in oldermen is testoster-one replacement therapy for male hypogonadism. Compared with younghypogonadal men, the diagnosis and management of male hypogonadismin older men is more challenging. Both the clinical manifestations of andro-gen deficiency and low testosterone levels may be caused or modified bycomorbid illnesses that occur and medications taken more frequently byolder men, resulting in a greater likelihood for overdiagnosis of hypogonad-ism and subsequent inappropriate use of and inadequate response to tes-tosterone treatment. It is important to use a systematic, holistic approach tothe diagnosis and management of older men with hypogonadism.

Thyroid Disorders in OlderAdults 287

W. Edward Visser, Theo J. Visser, and Robin P. Peeters

This article summarizes the current literature about serum thyroid param-eters and thyroid disease during aging. Changes in thyroid function testsmay be part of the physiology of aging, after exclusion of confounding vari-ables. Overt thyroid disease requires immediate treatment. Treatment ofsubclinical hyperthyroidism in the elderly can be advocated, while watchfulwaiting may be an appropriate approach for subclinical hypothyroidism.

Diagnosis and Treatment of Osteoporosis in OlderAdults 305

Dima L. Diab and Nelson B. Watts

Osteoporosis in the elderly is a serious problem that is increasing as thepopulation ages. Diagnosis is established by measurement of bone min-eral density or by the presence of a fragility fracture, especially a spineor hip fracture. Bone-active agents should be prescribed for older patientswith osteoporosis to decrease fracture risk. Nonskeletal risk factors for

Contents ix

fracture and psychosocial impairment must be identified and managed,and therapy must be individualized.

Vitamin D and Aging 319

J. Christopher Gallagher

Age-related changes affect vitamin Dmetabolism and increase the require-ment for vitamin D in the elderly. Also there is an age related decrease incalcium absorption and a higher calcium intake is needed. Increasing cal-cium from dietary sources may be better than supplements, and requiresincreasing the intake of dairy products or other and calcium-fortified foods.Evidence suggests that vitamin D and calcium nutrition can be improved inthe elderly by increasing the vitamin D intake to 800 IU daily together witha total calcium intake of 1000 mg daily. This combination is a simple, inex-pensive strategy that can reduce fractures in institutionalized individualsby 30%.

Diabetes and Altered Glucose Metabolismwith Aging 333

Rita Rastogi Kalyani and Josephine M. Egan

Diabetes and impaired glucose tolerance affect a substantial proportion ofolder adults. Abnormal glucose metabolism is not a necessary componentof aging. Older adults with diabetes and altered glucose status likely repre-sent a subset of the population at high risk for complications and adversegeriatric syndromes. Goals for treatment of diabetes in the elderly includecontrol of hyperglycemia, prevention and treatment of diabetic complica-tions, avoidance of hypoglycemia, and preservation of quality of life.Research exploring associations of dysglycemia and insulin resistancewith the development of adverse outcomes in the elderly may ultimately in-form use of future glucose-lowering therapies in this population.

Age-Associated Abnormalities ofWater Homeostasis 349

Laura E. Cowen, Steven P. Hodak, and Joseph G. Verbalis

Findley first proposed the presence of age-related dysfunction of thehypothalamic-neurohypophyseal-renal axis more than 60 years ago.More sophisticated studies have since corroborated his findings. As aresult, it is now clear that multiple abnormalities in water homeostasis oc-cur commonly with aging, and that the elderly are uniquely susceptible todisorders of body volume and osmolality. This article summarizes the dis-tinct points along the hypothalamic-neurohypophyseal-renal axis wherethese changes have been characterized, as well as the clinical significanceof these changes, with special attention to effects on cognition, gait insta-bility, osteoporosis, fractures, and morbidity and mortality.

Sleep and Hormonal Changes in Aging 371

Georges Copinschi and Anne Caufriez

Age-related sleep and endocrinometabolic alterations frequently interactwith each other. For many hormones, sleep curtailment in young healthysubjects results in alterations strikingly similar to those observed in healthyold subjects not submitted to sleep restriction. Thus, recurrent sleep

Contentsx

restriction, which is currently experienced by a substantial and rapidlygrowing proportion of children and young adults, might contribute toaccelerate the senescence of endocrine and metabolic function. Themechanisms of sleep-hormonal interactions, and therefore the endocrino-metabolic consequences of age-related sleep alterations, which markedlydiffer from one hormone to another, are reviewed in this article.

Frailty, Sarcopenia, and Hormones 391

John E. Morley and Theodore K. Malmstrom

Frailty is now a definable clinical syndrome with a simple screening test.Age-related changes in hormones play a major role in the developmentof frailty by reducing muscle mass and strength (sarcopenia). SelectiveAndrogen Receptor Molecules and ghrelin agonists are being developedto treat sarcopenia. The role of Activin Type IIB soluble receptors andFollistatin-like 3 mimetics is less certain because of side effects. Exercise(resistance and aerobic), vitamin D and protein supplementation, andreduction of polypharmacy are keys to the treatment of frailty.

Index 407