Appendix K: Abbreviations and Glossary K

low-density lipoprotein 1,25 OH2D3 calcitriol or 1,25 LDL

dihydroxyvitamin D3 cholesterol ACOG American College of MI myocardial infarction Obstetricians and Gynecologists MPA medroxyprogesterone acetate AHCPR Agency for Health Care Policy MRI magnetic resonance imaging and Research (DHHS) NCI National Cancer Institute (NIH) AMI acute myocardial infarction NHLBI National Heart, Lung, and Blood BMC bone mineral content Institute (NIH) BMD bone mineral density NIA National Institute on Aging (NIH) CEA cost-effectiveness analysis NIAMS National Institute of Arthritis, CHD coronary heart disease Musculoskeletal and Skin CVA cerebrovascular accident Diseases (NIH) CVD cardiovascular disease NIDDK National Institute of Diabetes and DES diethylstilbestrol Digestive and Kidney Diseases DEXA dual energy x-ray absorptiometry (NIH) DHHS U.S. Department of Health and NIH National Institutes of Health Human Services (DHHS) DPA dual photon absorptiometry NOF National Osteoporosis Foundation ERT estrogen replacement therapy OB-GYN obstetrics and gynecology FDA Food and Drug Administration OHTA Office of Health Technology (DHHS) Assessment (AHCPR) HCFA Health Care Financing OTA Office of Technology Assessment Administration (DHHS) PEPI Postmenopausal Estrogen/ HDL high-density lipoprotein Progestin Interventions Trial cholesterol PERT combined estrogen/progestin HRT hormone replacement therapy replacement therapy IHD ischemic heart disease PHS Public Health Service IU international units QALY quality-adjusted life year IV intravenous 1213 214 Cost Effectiveness of Screening for Osteoporosis

QCT quantitative computed USP DI U.S. Pharmacopoeia Dispensing tomography Information SC subcutaneous VLDL very low-density lipoprotein SPA single photon absorptiometry cholesterol SXA single photon x-ray absorptiometry

19-nortestosterone Anovulation A form of progestin. The absence of ovulation (development and re- lease of an ovum from the ovary). Amenorrhea The absence or abnormal cessation of menstrua- Appendicular skeleton tion. The bones of the extremities, including all of the bones of the limb girdles. Anabolic steroid Any of a group of synthetic derivatives of the an- Arteriography drogen testosterone (a sex steroid or hormone) A diagnostic procedure that allows blood vessels having pronounced anabolic properties and rela- to be seen on X-ray film after the injection of con- tively weak androgenic properties. Anabolic ste- trast material into the bloodstream; used to detect roids such as dromostanolone, ethylestrenol, abnormalities such as obstructions, aneurysms, nandrolone, oxandrolone, oxymetholone, and sta- clots, tumors, and injured organs. nozolol are used clinically mainly to promote Arteriosclerosis growth and repair of body tissues in senility, de- A general term that describes thickened and hard- bilitating illness, and convalescence. ened arteries, the condition that leads to most Androgen (or androgenic hormone) cases of heart disease and a significant proportion of cerebrovascular disease in the United States. Naturally occurring male sex hormones (e.g., testosterone, androsterone, and dehydroepiandros- Atherogenesis terone) and substances that exert biological effects The formulation of patchy plaques of fatty or lipid characteristic of these hormones (e.g., the synthet- material on the inner lining of the arteries, restrict- ic compound methyltestosterone). Androgens in- ing blood flow and encouraging the development hibit bone resorption and increase calcium of blood clots; can result in sudden stoppage of absorption in the intestine, but also have serious blood flow to the heart. side effects. Atherosclerosis Androgenic A descriptive term for thickened and hardened lip- Any substance, e.g., androsterone and testoster- id-rich lesions of the medium and large muscular one, that stimulates male characteristics. arteries; classified into two forms: early lesions, consisting of fatty streaks, and advanced lesions, Angina consisting of fibrous plaques; commonly occurs Any spasmodic, choking, or suffocating pain. The in arteriosclerosis, in which deposits of fibrous term is often used to denote angina pectoris—a and cellular tissue, cholesterol, and fat accumulate condition characterized by severe, transient chest in large and medium-sized arteries, impeding pain, accompanied by a feeling of suffocation, is blood flow; responsible for the majority of cases due to a deficiency in blood supply to the heart. of myocardial and cerebral infarction. Angiography Axial skeleton See arteriography. The spine, ribs, sternum, and skull. Appendix K Abbreviations and Glossary 1215

Bilateral oophorectomy Bone Surgical removal of both ovaries. A specialized connective tissue in which a matrix Bioavailability consisting of collagen fibers, a large variety of The degree to which a drug or other substance be- other proteins and ground substances is impreg- nated with a solid mineral. Bone is the dynamic comes available to the target tissue after adminis- and complex tissue of which the bones in the adult tration. skeleton of humans and other vertebrates is large- Bioequivalence ly composed. The skeleton is composed of two The requirement that a generic product include the kinds of bone: an outer, dense shell of cortical (or same therapeutic ingredient, and that its rate and compact or haversian) bone and an inner, open, extent of absorption be the same as the innovative sponge-like region of cancellous (or trabecular) product. bone. About 80 percent of the mass of the skeleton Bisphosphonates is cortical bone, and 20 percent is cancellous bone. Chemical compounds developed during the past Bone densitometry 20 years for treatment of various bone diseases. A term used to refer to a range of noninvasive Basically, they are carbon-substituted analogues techniques that use a densitometer to measure the of pyrophosphate (an endogenous physiologic in- density of bone (e.g., SPA, DEXA, DPA, SXA) hibitor of bone mineralization). and is used to detect osteoporosis. Several bisphosphonates are under investiga- tion as therapeutic agents for osteoporosis, among Bone density them etidronate, clodronate, tiludronate, pa- The mass of bone substance per unit volume 3 midronate, risedronate, and alendronate. Bis- (g/cm ). phosphonates are considered experimental Bone mineral content (BMC) (investigational) in the prevention and treatment The mass of bone divided by the one dimensional of osteoporosis in the United States. length of bone measured expressed as grams per Blinding cm. A technique used in a randomized clinical trial Bone mineral density (BMD) (RCT) to prevent bias by preventing the patients The mass of bone divided by the two dimensional and/or investigators involved in the trial from projected area of the bone measured, expressed as knowing which participants are receiving which mass per unit area (g/cm2). treatment. In a single-blind RCT, the patients in the trial are “blind” as to which individuals in the Calcaneus study are receiving the experimental or control The heel bone. treatment. In a double-blind RCT, both the in- Calcitonin, human vestigators and the patients are “blind” as to which One of the three calcium-regulating hormones in individuals in the study are receiving the exper- humans, the others being human parathyroid hor- imental treatment and which are receiving control mone (hPTH) and calcitriol. treatment. Additional layers of blinding can be added, as, for example, when a third individual Calcitriol (1,25 OH2D3, 1,25-dihydroxy-

(usually the evaluator of outcomes, the individual vitamin D3 or 1,25-dihydroxychole- analyzing the data) also is unaware of treatment calciferol) assignments. One of several vitamin D metabolizes. Body mass index (BMI) Calcium Weight in kilograms divided by height in meters The most abundant mineral element in the human squared. A measure used to define normal ranges body. In humans, calcium is an essential nutrient of body weight. not only for the normal mineralization of bones 216 Cost Effectiveness of Screening for Osteoporosis

and teeth but also for regulating intracellular Cerebral infarction events in most, if not all body tissues. An area of dead tissue in the cerebrum caused by an interruption of blood circulation due to func- Cancellous (or trabecular) bone tional constriction or actual obstruction of a blood The inner, open, sponge-like region of bone prev- vessel, hemorrhage, etc. Also known as a stroke alent in the vertebrae and in the pelvis, the main or cerebrovascular accident (CVA). sites of osteoporotic fractures. About 20 percent of the mass of the skeleton is cancellous bone. Cerebrovascular disease Compare cortical bone. Any disease of the blood vessels supplying blood to the brain or of the brain’s covering membranes Carcinogen (meninges), characterized by rupture of the blood An agent that causes cancer (e.g., certain chemi- vessels or inadequacy of blood to the brain. Com- cals, ionizing radiation, tobacco smoke, asbestos mon causes include atheroma, hypertension, cere- fibers, and estrogen). bral thrombosis, or embolism. Carcinoma Cholecystectomy A cancer arising from epithelial cells, including Surgical removal of the gall bladder. the external epitheliums (mainly skin and linings Cholesterol of the gastrointestinal tract, lungs, and cervix) and A sterol present in animal tissues (e.g., cell mem- the internal epitheliums that lines various glands branes, blood plasma, and lipoproteins), involved (e.g., breast, pancreas, uterus, and thyroid). in physiological processes, such as the manufac- Cardiac arrhythmias ture of bile acids, sex hormones, and adrenocorti- Variations from the normal rate or rhythm of heart coid hormones; also involved in the development beats. of pathological processes such as atherosclerosis. See also high-density lipoprotein cholesterol and Cardiac catheterization low-density lipoprotein cholesterol. Passage of a small catheter through a vein or artery Climacteric into the heart for the purpose of securing blood The syndrome of endocrine, somatic, and psychic samples, determining intracardiac pressures, and changes occurring at the end of the female repro- detecting cardiac anomalies. ductive period (menopause). Cardiovascular disease (CVD) Clinical trial (also called therapeutic Any of a diverse group of diseases affecting the trial) heart, blood vessels, and/or blood circulation. A research activity that involves the administra- CVD includes diseases of the heart muscle itself, tion of an experimental prophylactic, diagnostic, ischemic heart disease, hypertension, cerebrovas- or therapeutic agent, device, regimen, procedure, cular diseases, and various other conditions. etc. to humans to evaluate its safety and effective- Case-control study ness. The term is subject to wide variation in A type of observational study, where the frequen- usage, from the first use in humans without any cy of a suspected causative factor, such as estrogen control treatment to a rigorously designed and use, is compared in a group of people who have a executed experiment involving test and control disease (cases) and those who do not (controls). If treatments and randomization. See also random- this factor is found with greater frequency in those ized clinical trial (RCT). with disease, a causal association may be sus- Coagulation pected. Results of the comparison may be ex- The process of certain particles joining together to pressed as the relative risk. See relative risk. form larger masses. Appendix K Abbreviations and Glossary 1217

Coagulation proteins trogens have pharmacologic effects similar to Proteins found in the plasma that aid in the coagu- those of endogenous estrogens. lation process of blood (e.g., Factor VIII, Factor Consensus conference IX. antihemophilic factor, or prothrombin). Also A meeting of scientists, medical practitioners, and called “clotting factors.” informed lay people to review scientific in- Cohort study formation about biomedical technologies and to A type of observational study, where the investi- develop a consensus statement on the clinical ap- gator begins with a group of subjects (the “CO- plication of current medical findings. hort”), some or all of whom are exposed to a Coronary artery bypass graft (CABG) suspected causative factor, and follows this cohort surgery over time for development of a disease. Compari- A surgical procedure in which a vein or an artery son is made with a control group composed of un- is used to bypass a constricted portion of one or exposed members of the cohort (internal more coronary arteries. This procedure has be- controls), or to subjects outside the cohort who come the primary surgical approach to the treat- are similar to members of the cohort, but who have ment of coronary artery disease. not been exposed to the suspect factor (population, community, or external controls). Coronary artery disease (CAD) Narrowing or blockage of the coronary arteries, Cones fracture which usually results in reduced blood flow to the Fracture of the wrist. heart muscle. Compact bone Coronary perfusion See cortical bone The pumping of a fluid through the heart by way Comparison group of an artery. In a cohort study, the group of unexposed mem- Cortical (or compact or haversian) bone bers to which the exposed members are compared. The dense outer shell of bone. One of the two gen- In case-control studies, the group of subjects with- eral structural categories of the bone tissue mak- out disease to which the subjects with disease (the ing up the skeleton, cortical bone consists of cases) are compared. tightly packed layers of bone. It forms the outer Confidence interval shell of all bones and is prevalent in the shafts of Conventionally, a 95-percent confidence interval the long bones of the arms and legs. About 80 per- is used, which implies that there is a 95-percent cent of the mass of the skeleton is cortical bone. chance that the true relative risk being measured Compare cancellous bone. falls within the interval, and a 5-percent risk that Cost-effectiveness analysis (CEA) it does not. An analytical technique that compares the costs of Confounding variables a project or of alternative projects to the resultant Variables related to both the disease and the expo- benefits, with costs and benefits/effectiveness ex- sure under study that can explain or alter all or part pressed by different measures. Costs are usually of an observed association. expressed in dollars, but benefits/effectiveness are Conjugated estrogens ordinarily expressed in terms such as “lives An amorphous preparation of naturally occurring, saved,” “disability avoided,” “quality-adjusted water-soluble, conjugated forms of mixed estro- life-years saved,” or any other relevant objectives. gens, chiefly sodium estrone sulfate, extracted Cross-sectional study from the urine of pregnant mares; suitable for pa- In epidemiology, an observational study that ex- renteral, oral, and topical administration and used amines the relationship between diseases (or other in estrogen hormone therapy. The conjugated es- health-related characteristics) and other variables 218 Cost Effectiveness of Screening for Osteoporosis

of interest as they exist in a defined population at or spine. DPA is sometimes used to measure bone one particular time. The temporal sequence of mass in the whole body and can be used to mea- cause and effect cannot necessarily be determined sure bone mass in the forearm, distal radius in a cross-sectional study. (wrist), and calcaneus (heel). Cyclic regimen Duration of exposure Interrupted episodes with ongoing medication. In The length of time a person or test animal is ex- cyclic regimens of estrogen and progestin, estro- posed to a chemical. gen is usually given for 21 days each month, and Dysmenorrhea a progestin is given with estrogen for the last 7 to Difficult and painful menstruation. 14 days of those 21 days. Dyspareunia Densitometry Difficult or painful coitus/intercourse in women. See bone densitometry Dysuria Diethylstilbestrol (DES) Painful or difficult urination. A synthetic estrogenic compound used to treat menopausal symptoms, vaginitis, and suppressed Effectiveness lactation. The same as efficacy (see below) except that it re- Discounting fers to “. . . average or actual conditions of use.” A procedure used in economic analysis to express Efficacy as “present values” those costs and benefits that The probability of benefit to individuals in a de- will occur in future years. Discounting is based on fined population from a medical technology ap- two premises: 1) individuals prefer to receive plied for a given medical problem under ideal benefits today rather than in the future; and 2) re- conditions of use. Efficacy is generally evaluated sources invested today in alternative programs in controlled trials of an experimental therapy and could earn a return over time. a control condition. Compare to effectiveness. Double blind Endogenous See randomized clinical trial (R CT) and blinding. Produced within or caused by factors within the Dual energy x-ray absorptiometry organism. (DEXA) Endometrial biopsy A bone densitometry technique similar to DPA The microscopic examination of a sample of cells, but uses an x-ray machine rather than a radioactive obtained from the lining of the uterus, in order to material to produce a dual-energy radiation beam. evaluate ovulatory function and/or to detect the Different manufacturers use different terms for presence of hyperplasia, dysplasia, or cancer. this technology (e.g., quantitative digital radiog- Endometrium raphy (QDR), dual-energy radiography (DER), The tissue lining the inner uterus, the thickness dual energy radiographic absorptiometry (DRA), and structure of which vary with the phase of the and dual x-ray absorptiometry (DXA). menstrual cycle. Dual photon absorptiometry (DPA) Endothelium A bone densitometry technique that uses a dual- The layer of epithelial cells that lines the cavities energy radioactive material (usually gadolini- of the heart and of the blood and lymph vessels, um- 153) as the source of a dual-energy radiation and the serious cavities of the body. beam; the dual-energy beam allows measurement of bone and soft tissue without the necessity of en- Epidemiological studies casement in water required in SPA or SXA. The Studies concerned with the relationships of vari- site of measurement for DPA is typically the hip ous factors determining the frequency and dis- Appendix K Abbreviations and Glossary 219

tribution of specific diseases in a human approved by FDA for osteoporosis. As of 1995, community. etidronate was the only bisphosphonate available Epidemiology on the U.S. market. Neither etidronate nor any The scientific study of the distribution and occur- other bisphosphonates have been approved by rence of human diseases and health conditions, FDA for indications related to osteoporosis. and their determinants. Etiology Equine estrogen The cause or origin of disease. Estrogen pertaining to, characteristic of, or Exogenous estrogen derived from the horse. See conjugated estrogens. Estrogen that is not produced within the body but Erythema is provided by other means, e.g., tablets, injection, Redness of skin due to congestion of the capil- cream. laries. External controls Esterified estrogen In a cohort study, individuals not part of the cohort A mixture of the sodium salts of sulfate esters of and who have not been exposed, with which the estrogenic substances; used for oral estrogen ther- exposed members of the cohort are compared. In apy. a clinical trial, individuals not formally enrolled Estradiol in the trial who have had an alternative treatment, with which the experimentally treated group is The most potent naturally occurring estrogen in compared. External controls may be historical or humans. concurrent. Estrogen A generic term for estrus-producing compounds; External validity the naturally occurring female sex hormones, in- A measure of the extent to which study results can cluding estradiol, estriol, and estrone. The term be generalized to the population that is repre- also refers to substances occurring in plants or sented by individuals in the study, assuming that made synthetically (as benzestrol or diethylstil- the characteristics of that population are accurate- bestrol) that have biologic activity similar to that ly specified. of estrogens produced in the ovaries of female Femur mammals. The thigh bone, the bone that extends from the hip Estrogen replacement therapy (ERT) to the knee. It is the longest and largest bone in the The use of estrogen for the relief of menopausal body. symptoms, e.g., hot flashes, the prevention of Fibrin heart disease, and the prevention of osteoporosis. A white insoluble protein formed at the site of an Estrone injury from fibrinogen that becomes the founda- An estrogen isolated from pregnancy urine, the tion of a blood clot. human placenta, and palm kernel oil, and also pre- Fibrinogen pared synthetically. A soluble plasma protein synthesized in the liver, Etidronate which is involved in blood coagulation as the pre-

A bisphosphonate (C2H6NA207P2) that was pat- cursor of fibrin. Also called “Factor I.” ented as a therapeutic agent for calcium disorders Fibroblast in 1972 by Procter& Gamble, parent company of A connective tissue cell, found in the skin. Norwich Eaton Pharmaceuticals, Inc. Oral etidronate is indicated for the treatment of Paget’s dis- First-pass hepatic effect ease and some other conditions, but it has not been See hepatic effect. 220 Cost Effectiveness of Screening for Osteoporosis

Functional impairment uals are compared. In a cohort study, unexposed A deficit in an individual’s ability to function in- individuals outside of the cohort, at some time dependently. Functional impairments in elderly previous to the cohort observation period, against people are often described in terms of deficits in which the exposed members of the cohort are activities of daily living (ADLs) and instrumental compared. activities of daily living (IADLs). Hormone Grade A specific organic product of living cells that, The histological appearance of a cancer cell. In transported by body fluids, produces a specific ef- oncology, the classification of cancer according to fect on the activity of cells remote from its point the degree of differentiation of the cancer cell. of origin (e.g., metabolism, growth, and the devel- More differentiated cell types are generally less opment of secondary sex characteristics, such as malignant. breasts and facial hair). Examples of such hormones include insulin, estrogen, progestin, tes- Haversian bone tosterone, adrenaline, and thyroxine. Also a See cortical bone. synthetic substance that resembles a naturally oc- Healthy user effect curring hormone in producing a specific biologi- A phenomenon in epidemiologic studies in which cal effect. subject participants exhibit lower incidence of Hormone replacement therapy (HRT) morbidity or mortality than the general population This term describes either estrogen replacement because they are generally in good health while therapy or combined estrogen and progestin re- the less healthy either choose not to participate in placement therapy when a distinction is not neces- the study or are excluded. sary. Hemostatic Hospital-based case-control studies The arrest of bleeding, whether by the physiologi- In this type of study, all cases diagnosed with the cal properties of vasoconstriction and coagulation disease under study in one or more hospitals are or by surgical means. compared with patients in the same hospitals who Hepatic effect do not have the disease. Pertaining to the liver, the metabolism of estrogen Hot flash by the liver. Sudden sensations of heat and flushing of the face Hepatobiliary and torso, associated with menopause. Related to the gallbladder. Hypermenorrhea High-density lipoprotein cholesterol Excessive menstrual bleeding, but occurring at (HDL) regular intervals and being of usual duration. A class of cholesterol; low levels of HDL are Hyperplasia associated with an increased risk of heart attack. Abnormal increase in the number of normal cells Histology in normal arrangement in an organ or tissue, Microscopic anatomy. The study of the minute which increases its volume. anatomical structure, composition, and function Hypertension of the tissues. Elevated pressure, usually referring to high blood Historical controls pressure—a common and significant cardiovas- In nonrandomized clinical trials, individuals cular disorder characterized by persistently high treated with a “control treatment” outside the arterial blood pressure, usually greater that study proper, at some time previous to the trial, 140mm Hg systolic and 90mm Hg diastolic pres- against which the experimentally treated individ- sure. Appendix K Abbreviations and Glossary 122I

Hypertriglyceridemia Ischemic heart disease (IHD) An excess of triglycerides in the blood. A spectrum of conditions caused by insufficient Hysterectomy oxygen supply to the heart muscle, and the leading Surgical removal of the uterus, in some cases also cause of death in the United states. The most com- including the cervix, ovaries, oviducts, and pelvic mon manifestations of IHD are angina. acute myocardial infarction (heart attack), and sudden lymph nodes. death. In vitro Latency Literally “in glass”; pertaining to a biological pro- Time since first exposure to a suspected causative cess or reaction taking place in an artificial envi- factor. ronment, usually a laboratory. Latent effect In vivo A reaction to a substance that is not immediately Literally “in the living”; pertaining to a biological evident but that appears later in life; also referred process or reaction taking place in a living cell or to as a silent effect. organism. Life expectancy Incidence An expected number of years of life based on sta- In epidemiology, the number of new cases of dis- tistical probability. ease, infection, or some other event having their onset during a prescribed period of time in relation Lipids to the unit of population in which they occur. The A group of organic compounds, classified into incidence rate is the number of new cases of spe- complex lipids (e.g., fatty acids, phospholipids, cified disease divided by the number of people in cholesterol) and simple lipids (e.g., steroids). Lip- a population over a specified period of time, usu- ids are central to a wide variety of metabolic and ally 1 year. structural functions in the body, such as energy storage, formation of hormones and bile acids, Infarction and structure of cell membranes. Necrosis (death) of tissue, resulting from the interruption of blood supply (e.g., as in a heart attack Lipoprotein (myocardial infarction)). Compounds consisting of lipids (fatty substances such as cholesterol) and proteins, the form in Internal controls which lipids are transported in the blood and A control group composed of unexposed mem- lymph fluid. Lipoproteins form the main structur- bers of a cohort. See cohort study. al components of cell membranes and cell organ- Internal validity elles. They are classified as very low-density A measure of the extent to which study results re- (VLDL), low-density (LDL), and high-density flect the true relationship of a “risk factor” (e.g., (HDL) lipoprotein cholesterol. treatment or technology) to the outcome of inter- Low-density lipoprotein cholesterol est in study subjects. (LDL) Ischemia A class of cholesterol; high levels of LDL are Insufficient blood supply to meet the full physio- associated with a greater risk of heart attack. logic needs of the tissue for oxygen (but short of Magnetic resonance imaging (MRI) the degree of ischemia that results in necrosis), A diagnostic technique that produces cross-sec- usually due to atherosclerosis, but also due to inju- tional images of organs and structures in the body ry to blood vessels, muscle spasm, or inefficient by measuring the reaction of nuclei (typically of pumping of the heart. hydrogen protons) in magnetic fields to radio fre- 222 Cost Effectiveness of Screening for Osteoporosis

quency waves. MRI has also been used to measure Menopausal syndrome bone density. Symptoms associated with menopause, e.g., hot Matching flashes, vaginal dryness, osteoporosis. A method of minimizing the impact of confound- Menopause ing factors. Controls may be matched to cases to Cessation of menstruation; the immediate postre- try to minimize other differences between groups. productive phase of a woman’s life, when Matching may be done with groups of subjects menstrual function ceases due to failure to form (stratification) or with individuals, and may be ovarian follicles and ova. Menopause occurs natu- done with highly specific characteristics, such as rally around the age of 50. Menopause is also a age, age at menopause, family history of the dis- secondary consequence of surgical removal of the ease, etc. ovaries, and of certain illnesses (e.g., premature ovarian failure). Medicare A nationwide, Federally administered health in- Menorrhagia surance program authorized by Title XVIII of the Excessive menstruation. Social Security Act in 1965 to cover the cost of Menses hospitalization, medical care, and some related The monthly flow of blood from the female geni- services for eligible persons over age 65, persons tal tract. receiving Social Security Disability Insurance Meta-analysis payments for 2 years, and persons with end-stage A statistical process used to pool results from a renal disease. Medicare consists of two separate number of studies (e.g., from many small random- but coordinated programs—hospital insurance ized clinical trials) to enable the demonstration of (Part A) and supplementary medical insurance statistically significant differences when the re- (Part B). Health insurance protection is available sults are combined. to insured persons without regard to income. Metastasis MEDLINE database The process by which malignant cells spread to The original, largest, and most utilized database in distant body sites via the lymphatic circulation the National Library of Medicine’s computerized of the bloodstream; also, a secondary malignant retrieval and technical processing system. MED- tumor. LINE contains references to biomedical and other Metrorrhagia literature relevant to health and health services. Uterine bleeding, usually of normal amount, oc- Medroxyprogesterone acetate (MPA) curring at completely irregular intervals, the peri- A form of progestin. Also known as Provera od of flow sometimes being prolonged. (Wyeth-Ayerst). In the United States, MPA is the Morbidity most commonly used progestin in combined es- The condition of being ill or otherwise afflicted trogen/progestin replacement therapy. with an unhealthful condition. Membership bias Morbidity rate Bias introduced when the group or cohort being The rate of illness in a population, calculated as studied is unrepresentative of the population at the number of people ill during a time period di- large, so that comparisons and extrapolations to vided by the number of people in the total popula- the population group are unjustified. tion; used to refer to incidence or prevalence rates of disease. Menarche Mortality rate The onset of menses at puberty. The death rate, often made explicit for a particular characteristic; e.g., age, sex, or specific cause of Appendix K Abbreviations and Glossary 223

death. A mortality rate contains three essential (e.g., case-control studies, cross-sectional studies, elements: 1 ) the number of people in a population and cohort studies). Such studies are the tradition- group exposed to the risk of death (the denomina- al source of information on suggestive associa- tor); 2) a time factor; and 3) the number of deaths tions in epidemiology. occurring in the exposed population during a cer- Occlusion tain time period (the numerator). In the context of the vascular system, the blocking Myocardial infarction (Ml) off or obstruction of blood flow through a vessel. Heart attack. Sudden necrosis (death) of tissue in Odds ratio the myocardium (heart muscle) characterized by A measure of association closely related to rela- severe, unremitting chest pain. leading to arrhyth- tive risk; the ratio of the odds of a disease occur- mias and/or heart failure; in most cases, caused by ring in individuals exposed to the risk compared coronary atherosclerosis (obstruction of coronary to those unexposed. For large samples, the odds vessels, leading to insufficient blood supply to the ratio is essentially equal to the relative risk. heart muscle). Oligomenorrhea Myocardium Abnormally infrequent menstruation. Muscle of the heart. Natural estrogen Oophorectomy An estrogen derived from natural sources, (i.e., Excision of one or both ovaries. not synthetic), such as conjugated equine estro- Opposed estrogen gens, estradiol, or estriol. Estrogen used in conjunction with progestin. Natural menopause Osteoblast Menopause that occurs as a natural part of the ag- A cell arising from a fibroblast, which, as it ma- ing process; not surgically induced. tures, is associated with bone production. Naturally occurring estrogenic Osteopenia hormones A reduction in the amount of bone mass, leading Female sex hormones produced by the ovaries, the to fractures after only minimal trauma. placenta, testes, and possibly the adrenal cortex. Osteoporosis Neoplasm A systemic skeletal disease characterized by low Uncontrolled and progressive growth of tissue, ei- bone mass and microarchitectural deterioration of ther benign or malignant; a tumor. bone tissue, with a consequent increase in bone Nested case-control studies fragility and susceptibility to fracture. Case-control studies conducted, or “nested,” P value within a cohort group. In epidemiologic studies, the probability of con- Nonischemic heart disease cluding that a statistical association exists be- Heart disease from causes other than coronary tween, for instance, a risk factor and a health artery disease (e.g., congenital heart disease, myo- endpoint, when, in fact, there is no real associa- cardiopathy). tion; the likelihood that an observed association in Norethidrone acetate a study is due to the play of chance. Also called .4 progestational agent similar in action to proges- “Type I error” or “alpha,” and commonly called terone. the level of significance. See significance level. Observational study An epidemiologic study in which the experiences of the groups being compared are simply observed 224 Cost Effectiveness of Screening for Osteoporosis

Parathyroid hormone (PTH) or human the blood vessels) of large and medium-sized parathyroid hormone (hPTH) veins. A polypeptide hormone which regulates the con- Platelets centration of extracellular fluid calcium. Disk-shaped tissue, found in the blood of mam- Parenteral mals, which responds to injury elsewhere in the Administration through routes other than the ali- body. Platelets are known for their role in blood mentary canal. Parenteral administration includes coagulation (clotting). Also called “thrombo- intravenous. subcutaneous, transdermal, intraoc- cytes.” ular, and intranasal administration. Population-based case-control studies Pathophysiology In this type of study, all cases diagnosed in the The physiology of disordered function. community or in a sample of the general popula- Percutaneous tion are compared with controls selected from the Literally, “through the skin”; refers to a surgical community or a sample of the general population. procedure that requires only a very small incision, Postmenopause such as a biopsy, or aspiration of fluid beneath the The period of time after the menopause. skin using a needle, catheter, or syringe. Power Perimenopause The power of the study refers to the chance of find- The time around the menopause. ing a true difference in risk and labeling it as statis- Peripheral conversion tically significant. Thus the power of the study is Conversion of estrogen outside of the liver, in pe- equal to 0.80 when the sensitivity level is 0.20 ripheral tissues. (i.e., 1- 0.20= 0.80). Peripheral nervous system Predictive test The autonomic nervous system, the cranial A medical test generally applied to asymptomatic nerves, and the spinal nerves including associated individuals to provide information regarding the receptors. future occurrence of disease. Pharmacodynamics Premarin The study of the actions of drugs on living sys- Wyeth-Ayerst’s brand of conjugated estrogen. tems. The most commonly used estrogen for HRT in the Pharmacokinetics United States. See conjugated estrogens. The rate of change in a physical or chemical sys- Premature ovarian failure tem, specifically in relation to drugs. Condition characterized by the failure to ovulate Placebo before the normal age of menopause. A drug or procedure with no intrinsic therapeutic Premenopause value. In a placebo-controlled randomized clini- The stage of life before menstruation stops. cal trial, a placebo is given to patients in control groups as a means to blind investigators and pa- Premenstrual syndrome tients as to whether an individual is receiving the The pattern of symptoms related to the menstrual experimental or control treatment. See random- cycle. ized clinical trial (RCT). Preovulation Plaques The first 14 days of a woman’s menstrual cycle, Yellowish fatty deposits formed within the intima when estrogen levels are rising before ovulation and inner media (innermost and middle coats of takes place. Appendix K Abbreviations and Glossary 225

Prevalence prevention of osteoporosis; progestin opposes the A measure of the number of individuals in a given carcinogenic effects of estrogen on the endome- population who have a specific disease or other trium. condition at a designated time (or during a particu- Progestogen lar period). See progestin. Primary prevention A category of health and/or related interventions Prospective study that aim to eliminate a disease or disordered state An epidemiologic study in which data are gath- before it can occur. Compare secondary preven- ered after a hypothesis has been generated and the tion. study approved. In a prospective study, the inves- tigator first identifies the subjects and then fol- Progestational lows them over time for development of disease. Favoring pregnancy; conducive to gestation; hav- Compare retrospective study. ing a stimulating effect upon the uterine changes essential for the implantation and growth of the Provera fertilized ovum. Referring to progesterone, or to Wyeth-Ayerst’s brand of the progestin medroxy- a drug with progesterone-like properties. progesterone acetate (MPA). The most commonly used progestin for HRT in the United States. See Progesterone (also called progestational progestin, progesterone. hormone) An antiestrogenic female sex hormone secreted by Quality-adjusted life-year (QALY) the ovaries (specifically by the corpus lutetium, In cost-effectiveness analysis, a measure of health formed immediately after ovulation), by the pla- impact used to compare the benefit or effective- centa during pregnancy to prepare the inner lining ness of alternative health interventions, such as of the uterus for implantation of an ovum, and in the value of an extra year of life gained through small amounts by the adrenal glands and testes, kidney transplantation versus dialysis for patients and prepares the inner lining of the uterus for preg- with end stage renal disease; involves some de- nancy. Receptors for progesterone have been iden- gree of arbitrary valuation and weighting of differ- tified on osteoblasts, and although the data are not ent conditions. entirely clear, it appears that progesterone may Quantitative computerized tomography stimulate bone formation. Progesterone and other (QCT) agents capable of producing some or all of the bio- A bone densitometry technique similar to DEXA logical effects similar to those of progesterone are which measures the central, trabecular portion of called progestins (or progestogens). the vertebral body, the spongiosa. Techniques Progestin have been developed to allow for quantitative Originally, the crude hormone of the corpus lute- measurement on most commercially available CT tium of the ovary; it has since been isolated in pure scanners. form and is now known as progesterone. The ge- Radiographic densitometry neric term for any substance, natural or synthetic, Noninvasive measurement of bone mass in vivo that effects some or all of the biological changes was first performed by quantifying radiographs produced by the hormone progesterone. See pro- with an optical densitometer. The film densitv gesterone. . . over the bone is compared to that over the soft tis- Progestin/estrogen replacement therapy sue, and the resultant absorption is related to that (PERT) obtained over a series of standards with known The use of estrogen combined with progestin for mineral content. Because of technical errors re- the treatment of menopausal symptoms, e.g., hot lated to the polychromate nature of the radiation flashes, the prevention of heart disease, and/or the source and differences in x-ray film characteris- 226 Cost Effectiveness of Screening for Osteoporosis

tics, this technique has many errors and is rarely measuring the effects of several factors concur- used clinically today. rently. Radiogrammetry Relative risk X-rays of the hand and radius, using fine grain in- A measure of a relationship, defined as the chance dustrial film, have been used to measure the corti- of an outcome, such as breast cancer, among a cal thickness of these tubular bones as an indicator group of persons having a suspected causative fac- of cortical bone mass. Although the proximal ra- tor, divided by the chance of this outcome among dius and ulna and the six middle metacarpal of a similar group without this suspect factor. both hands have been used, the mid-shaft of the Reliability second metacarpal is the usual measurement site. The reproducibility of results over repeated mea- Radius surements, and relates to the lack of random error The bone on the outer or thumb side of the fore- over these repeated measurements. Reliability is arm. The distal radius is the end of the radius a prerequisite to validity. bone adjacent to the wrist. The proximal radius is the end of the radius adjacent to the elbow. Retrospective study An epidemiologic study in which data that are al- Random allocation ready available are analyzed to test a hypothesis In a randomized clinical trial, allocation of indi- (e.g., inferences about exposure to a possible viduals to treatment groups such that each individ- causal factor are derived from data on subjects ual has an equal probability of being assigned to who already have the disease in question, any group. compared to other subjects who do not have the Randomized clinical trial (RCT) (also disease). called randomized controlled clinical Risk factor trial or controlled clinical trial) An aspect of personal behavior or lifestyle, an en- In epidemiology, a clinical trial of a prophylactic, vironmental exposure, or an inborn or inheritance diagnostic, or therapeutic agent, device, regimen, characteristic, which on the basis of epidemiolog- procedure, etc. in which human (or animal) sub- ic evidence is known to be associated with health jects are randomly allocated into groups, usually related conditions considered important to pre- called “the experimental group” (in which sub- vent. jects receive the treatment being studied) and “the control group” (in which subjects do not receive Route of administration the treatment being studied), and outcomes are In pharmacology, refers to the means by which a compared. drug is administered: namely intravenous (in- Recall bias jected into the bloodstream), inhalation (through Bias caused by differences in abilities of two the lungs), oral (through ingestion), and dermal groups to remember exposure to suspected caus- (through the skin). ative factors. Secondary preventions Recency An intervention that strives to shorten the course Time since last exposure to a suspected causative of an illness by early identification and rapid inter- factor. vention. Regression analysis Selection bias A statistical procedure for determining the best A distortion in the estimate of effect resulting approximation of the relationship between vari- from the manner in which subjects are selected for ables. Multiple regression analysis is a method for a study population. Appendix K Abbreviations and Glossary 227

Sensitivity by the sum of true-negatives plus false-positives). The percentage of all those who actually have the Compare sensitivity. condition being tested who are currently identi- Statistically significant fied as positive by the test. The likelihood that an observed association is not Sensitivity analysis due to chance. See P value. In cost-effectiveness and cost-benefit analysis, an Steroid hormone analysis of the effect of changes in key assump- Any of numerous hormones characterized by ste- tions or uncertainties on the findings and outcome roid structure (i.e., four carbon rings interlocked of the overall study. to forma hydrogenated cyclopentophenanthrene- Serum lipid profiles ring system). Steroid hormones include the sex A quantitative representation of the level of serum hormones estrogen, progestin, and androgen; they lipids. also include cortisone and adrenocortical hormones. Serum triglycerides Esters formed from glycerol and one to three fatty Steroids acids; fats and oils are triglycerides. Any of a class of compounds characterized by a polycyclic structure like that of the sterols and that Significance level usually include the sterols (e.g., cholesterol) and The significance level, or “p” value, is the proba- vitamin D, as well as many other naturally occur- bility of concluding that a relative risk is different ring compounds (e.g., bile acids). from 1.0 when it is not. By convention, a difference in risk is said to be statistically significant if Stratification there is less than a five percent chance of making In randomized clinical trials, the categorization of this type of error (i.e., p < 0.05). The significance individuals for the purpose of adjusting the groups can also be expressed as a confidence interval. to take into account unequal distribution of characteristics of prognostic importance. Stratifica- Single photon absorptiometry (SPA) tion may be used during patient allocation, A bone densitometry technique that employs a creating subgroups within which individuals are sealed source of radioactive material that emits a randomized to treatments; or stratification maybe single energy radiation (photon), and a detector applied during data analysis to statistically adjust that measures the amount of photons transmitted for differences between the groups. through bone and soft tissue. The radius and calcareous can be measured with this device. Stress incontinence See urinary stress incontinence. Single photon x-ray absorptiometry (SXA) Stroke A bone densitometry technique similar to SPA but Loss of sensation, movement, or function caused using an x-ray source rather than a radioactive by a sudden interruption of the blood supply or a source. Both the radius and calcareous can be leakage of blood in the brain. This can be caused measured with this device. by heart failure, blockage of arteries (cerebral thrombosis or cerebral embolism), or hemorrhage Specificity in the brain. One measure of the validity (or accuracy) of a diagnostic or screening test: the percentage of all Subcutaneous those who do not have the condition being tested Beneath the skin. or who are correctly identified as negative by the Subgroup analysis test. Operationally, it is the number of negative A separate analysis performed on a subgroup of test results divided by the number of patients that the population being studied to identify important actually have the disease (true-negatives divided differences in risk. Such differences in risk maybe 228 Cost Effectiveness of Screening for Osteoporosis

due to interactions of the purported causative fac- artery or vein, causing thrombophlebitis or deep tor with other risk factors for the disease. vein thrombosis. Factors contributing to thrombosis include atherosclerosis, an increase in coag- Surgical menopause Menopause following the surgical removal of the ulation factors, or a deficiency of anticlotting ovaries. factors in the blood. Symptomatology Total cumulative exposure The combined symptoms of a disease. The total dose, which is related both to the level and to the duration of exposure. For example, for Synthetic calcitonin estrogen replacement therapy, total dose is related A synthetically produced/manufactured form of to how much and for how long the estrogen is the hormone calcitonin, a 32 amino acid polypep- given. tide, one of the three calcium regulating hormones found in humans. The FDA has granted qualified Trabecular bone approval for both natural and synthetic calcitonin See cancellous bone. for the treatment but not the prevention of osteo- Transdermal porosis. Through the skin. Synthetic estrogen Transmenopausal A synthetically produced/manufactured estrogen Occurring across the time period of the meno- product. pause. Systemic circulation Treatment group Channels through which nutrient fluids of the In a randomized clinical trial, the group receiving body flow: often restricted to the vessels convey- the treatment being evaluated for safety and effi- ing blood. cacy. Also known as the experimental group. See Testosterone randomized clinical trial (RCT). An androgen or steroid hormone secreted by the interstitial cells of the testes, which functions in Tumor the induction and maintenance of male secondary A new growth of tissue in which the multiplica- sex characteristics and affects sperm production; tion of cells is uncontrolled and progressive. Also testosterone and its cypionate, enanthate, and pro- called neoplasm. pionate esters are used in palliative therapy in in- Ultrasound operable carcinoma of the female breast and Predictor of fracture risk using sound velocity and certain gynecologic conditions. sound attenuation to measure both bone mass and Thromboembolitic disease altered bone architecture. Disease related to blood vessel obstruction. Unopposed estrogen Thrombosis Estrogen used alone, without a progestin. Also The abnormal development of a blood clot known as estrogen replacement therapy (ERT). (thrombus) inside an intact blood vessel, which Unopposed progestin can be life-threatening if it obstructs the blood Progestin used alone. Progestins alone have been supply to the brain (leading to stroke), heart (lead- used to relieve menopausal symptoms. ing to myocardial infarction), the lungs (leading to pulmonary embolism), or other organs (leading to Urinary bladder tissue damage or loss of function); the presence of The hollow, muscular organ that collects urine such clots also raises the risk that part of the clot from the ureters and stores it until the urine is dis- (an embolus) may break off and travel to a distant charged through the urethra during urination. Appendix K Abbreviations and Glossary 229

Urinary incontinence Vagina An involuntary loss of urine sufficient in quantity The canal in the female, from the vulva to the cer- and/or frequency to be a social or health problem. vix uteri, that receives the penis in copulation and Urinary stress incontinence is the birth canal. Involuntary escape of urine due to strain on the Vaginal atrophy orifice of the bladder, as in coughing or sneezing. The wasting or diminution in size of the vagina. Vaginismus Urodynamics A process that evaluates characteristics of the Painful, involuntary contraction or spasm of the muscles around the outer third of the vagina, inter- urine stream and the pelvic musculature, and the fering with sexual intercourse. activity of the bladder. Validity Uterine prolapse A measure of the extent to which an observed situ- Descension of the uterus down into the vagina, ation reflects the “true” situation. caused by weakening of the support ligaments and muscles that hold the uterus in place. Vertebra In the human body, any of the 33 bones of the spi- Uterus nal column, comprising the 7 cervical, 12 thorac- The hollow muscular organ in the female in which ic, 5 lumbar, 5 sacral, and 4 coccygeal vertebrae. the fertilized ovum normally becomes embedded Withdrawal bleeding and in which the developing embryo and fetus are Bleeding, associated with hormone replacement nourished. Its cavity opens into the vagina below therapy, caused by the sloughing of the endome- and into a fallopian tube on either side. trium due to withdrawal of estrogen stimulation.

*U.S. G.P. O. : 1995-387-789:47402