Gynecology_Novak

Gynecology_Novak. Intermediate density lipoproteins (IDL) consist of cholesterol esters, which are posthepatic remnants derived from dietary sources. Metabolites of IDL are transient lipoproteins measured only in certain pathologic conditions. Low-density lipoprotein (LDL) is mainly composed of the cholesterol ester and is associated with B-100 apoprotein. LDL cholesterol is approximately 60% to 70% of total cholesterol. Elevated levels of LDL cholesterol are associated with increased myocardial infarction in women older than 65 years of age. There is a structural class called LDL (a ) that is associated with myocardial infarction. High-density lipoprotein (HDL) is composed of cholesterol esters with apoproteins A-I and A-II. These particles are 20% to 30% of total cholesterol and are the most dense.


Gynecology_Novak

Gynecology_Novak. High-density lipoprotein (HDL) is composed of cholesterol esters with apoproteins A-I and A-II. These particles are 20% to 30% of total cholesterol and are the most dense. Metabolism Cholesterol metabolism is divided into two pathways: (i) the exogenous pathway derived from dietary sources, and (ii) the endogenous pathway or the lipid transport pathway. Individuals vary in their ability to metabolize cholesterol, with patients classified as normals, hyporesponders, and hyperresponders (29). Hyporesponders may be given cholesterol-loaded diets with no effect on serum cholesterol measurements. Hyperresponders, in contrast, have high serum cholesterol levels, regardless of dietary intake. Explanations for these differences are well described in animal models, but not in humans.


Gynecology_Novak

Gynecology_Novak. When a meal is eaten, cholesterol is transported as dietary fat. The average daily American diet contains approximately 100 g of triglyceride and approximately 1 g of cholesterol. Triglycerides are found in the core lipoprotein particles and are removed through the capillary endothelium and the chylomicron. Theories suggest that hypo-and hyperresponses to dietary cholesterol may occur secondary to the liver’s ability to recognize and metabolize apoprotein E. In the animal model, populations with large numbers of liver receptors for apoprotein E easily metabolize cholesterol and are labeled hyporesponders. Individuals with a reduced number of apoprotein E receptors are unable to metabolize cholesterol as readily, which increases the number of lipid particles. These individuals are considered hyperresponders. Despite dietary cholesterol modification, these individuals continue to have high serum cholesterol levels.


Gynecology_Novak

Gynecology_Novak. After metabolic degradation of dietary chylomicrons, apoprotein substitution occurs and liver metabolism of cholesterol esters begins. Lipid transport is now in the endogenous pathway. Carbohydrates are synthesized to fatty acids and esterified with glycerol to form triglycerides. These newly formed triglycerides are not of dietary origin and are placed in the core of VLDL. These particles are relatively large and carry five to ten times more triglyceride than cholesterol esters with apoprotein B-100. Hypertriglyceridemia is an independent risk factor for cardiovascular disease. The relationship between hypertriglyceridemia and cardiovascular disease is well known but poorly defined.


Gynecology_Novak

Gynecology_Novak. VLDL particles are transported to tissue capillaries, where they are broken down to usable fuels, monoglycerides, and fatty acids. After metabolic enzymatic degradation in the peripheral tissues, IDL remains and is either catabolized in the liver by binding to LDL receptors or modified in the peripheral tissues. As noted previously, they are associated with apoprotein E receptors, the liver recognition receptors. The LDL cholesterol, or the so-called high-risk cholesterol, is found in high circulating levels. Despite the negative connotation of LDL in cardiovascular disease, it is a very important cellular metabolite and precursor for adrenocortical cells, lymphocytes, and renal cells. The liver uses LDL for synthesis of bile acids and free cholesterol, which is secreted into the bile. In the normal human, 70% to 80% of LDL is removed from the plasma each day and secreted in the bile by utilization of the LDL receptor pathway.


Gynecology_Novak

Gynecology_Novak. The final metabolic pathway is the transformation of HDL cholesterol in extrahepatic tissue. HDL cholesterol carries the plasma enzyme lecithin cholesterol acyltransferase (LCAT). LCAT allows HDL cholesterol to resynthesize lipids to VLDL cholesterol and recycle the lipid cascade. HDL cholesterol acts as a “scavenger” and therefore reverses the deposit of cholesterol into tissues. There is good evidence that HDL cholesterol is responsible for the reversal of atherosclerotic changes in vessels, hence the term “good cholesterol” (27).


Gynecology_Novak

Gynecology_Novak. Hyperlipoproteinemia When cholesterol is measured, various fractions are reported. Plasma cholesterol or total cholesterol consists of cholesterol and unesterified cholesterol fractions. If triglycerides are analyzed in conjunction with cholesterol, then assumptions can be made concerning which metabolic pathway may be abnormal. Elevation of both total cholesterol and triglycerides signifies a problem with chylomicrons and VLDL synthesis. If the triglyceride-to-cholesterol ratio is greater than 5:1, the predominant fractions are chylomicrons and VLDL. A triglycerides-to-cholesterol ratio less than 5:1 signifies a problem in the VLDL and LDL fractions.


Gynecology_Novak

Gynecology_Novak. Hyperlipoproteinemias are defined by establishing a “normal population” and then setting various limits at the 10th and 90th percentiles. Standards for women set the 80th percentile for cholesterol at 240 mg/dL and the 50th percentile at 200 mg/dL (Table 9.8). A diet low in animal fat and high in vegetable and fiber consumption helps control the level of cholesterol (27–29). Plasma elevations of chylomicrons, LDL, VLDL, various remnants of IDL, and VLDL are classified by the elevated fraction. Table 9.8 Initial Classification Based on the Total Cholesterol, LDL, HDL, and Triglyceride Levels LDL, low-density lipoprotein; HDL, high density lipoprotein. Adapted from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486–2497.


Gynecology_Novak

Gynecology_Novak. There are multiple causes of variation in cholesterol measurements (30,31). Major sources of variation within individuals include diet, obesity, smoking, ethanol intake, and the effects of exercise. Other clinical conditions that affect cholesterol measurements include hypothyroidism, diabetes, acute or recent myocardial infarction, and recent weight changes. Measurements can be altered by fasting, position of the patient while the sample is drawn, the use and duration of venous occlusion, various anticoagulants, and the storage and shipping conditions. Intrapersonal variation is well described. If multiple samples are taken within a given day, weekly and monthly variations can be as high as 6%. At least two specimens should be taken 1 month apart and should be collected in the same dietary state in order for a lipid value to be considered accurate.


Gynecology_Novak

Gynecology_Novak. Age and gender contribute to variations in total cholesterol measurements. Before age 50, women have lower lipid values than men, after which age the level in women is higher than in men. This finding may be modified by exogenous oral conjugated estrogens. Seasonal variation also occurs, with lipid samples in December or January being found to be approximately 2.5% higher than those measured in June or July. The effect of diet and obesity is well established. Weight reduction in an obese individual affects the triglyceride level, which may decrease as much as 40%. Total cholesterol and LDL decrease less than 10% with diet; however, HDL increases approximately 10%. Weight gain negates any benefit from prior weight loss. Accuracy of lipid measurements depends on the stability of the patient’s weight.


Gynecology_Novak

Gynecology_Novak. Alcohol and cigarette smoking are well-known modifiers of cholesterol. Moderate sustained alcohol intake increases HDL and decreases LDL; there is a complementary increase in triglycerides. Alcohol has a protective effect when taken in moderation (defined as approximately 2 alcoholic drinks [2 ounces of absolute alcohol] per day), but this effect is negated in higher quantities. The increase in HDL is in the HDL3 fraction, which is important in the scavenger mechanism of removing LDL. Smoking has the opposite effect, increasing LDL and triglyceride levels and decreasing HDL. HDL3 decreases with cigarette smoking. The critical number of cigarettes smoked is 15 to 20 per day, regardless of gender, and a variation in the number smoked will affect results. Caffeine has a mixed effect on lipoprotein measurements and should be avoided for 12 hours before blood collection. Exercise is an important variable in the overall risk management of heart disease.


Gynecology_Novak

Gynecology_Novak. Exercise is an important variable in the overall risk management of heart disease. Moderate levels of exercise are as important in overall cardiovascular health as control of hypertension and cessation of cigarette smoking. Strenuous exercise lowers the concentrations of triglycerides and LDL and increases HDL in the serum. Because of these acute blood changes, vigorous exercise should be avoided within 12 hours of drawing the blood for testing. Certain disease states and medications affect cholesterol measurements. Use of diuretics and propranolol increases triglycerides and decreases HDL. Diuretics may increase total cholesterol levels. Diabetes, especially in the presence of poor control, may be associated with very high levels of triglycerides and LDL and decreased levels of HDL. This may explain why these individuals are prone to cardiovascular diseases. Patients with diabetes under tight control have improved lipoprotein profiles.


Gynecology_Novak

Gynecology_Novak. Pregnancy is associated with decreased total cholesterol in the first trimester and continuous increases of all fractions over the second and third trimesters (32). The LDL and triglyceride concentrations are the lipoproteins most affected by pregnancy. Patients with hypothyroidism have increased levels of total cholesterol and LDL.


Gynecology_Novak

Gynecology_Novak. Patients with hypothyroidism have increased levels of total cholesterol and LDL. Because of the diurnal variation of blood triglycerides, blood samples should be collected in the morning after a 12-hour fast. Excessive quantities of water should not be consumed before blood is drawn. After 2 minutes of venous occlusion, serum cholesterol levels can increase 2% to 5%. Therefore, the sample used for cholesterol testing should be collected first if multiple blood samples are required. One of the most important aspects of overall standardization of lipoprotein measurements is the laboratory used. It may be worthwhile to consult a clinical pathologist to determine if the laboratory complies with Centers for Disease Control and Prevention (CDC) standards for cholesterol and lipoprotein measurements.


Gynecology_Novak

Gynecology_Novak. When hyperlipidemia is confirmed on at least two separate occasions, secondary causes should be diagnosed or excluded by taking a detailed medical and drug history, measuring serum creatinine and fasting glucose levels, and testing thyroid and liver function. Causes of secondary dyslipidemia include diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and use of medications such as progestins, anabolic steroids, and corticosteroids. Therapeutic lifestyle changes should be initiated in all patients to reduce their risk of coronary heart disease: 1. Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg per day) 2. Therapeutic options for enhancing LDL lowering, such as plant stanols/sterols (2 g per day) and increased viscous (soluble) fiber (10–25 g per day) 3. 4.


Gynecology_Novak

Gynecology_Novak. Therapeutic options for enhancing LDL lowering, such as plant stanols/sterols (2 g per day) and increased viscous (soluble) fiber (10–25 g per day) 3. 4. LDL ≥190 mg/dL Drug therapy Lifestyle LDL >100 mg/dL CHD or CHD risk equivalents Lifestyle Check total cholesterol, HDL, LDL and triglycerides in 5 years changes Drug therapy Drug therapy Lifestyle changes CHD or CHD risk equivalents? No Yes no CHD or CHD risk factors and no changes 0–1 Risk factor and equivalents* 2 or more risk CHD or CHD risk equivalents LDL ≥160 mg/dL LDL ≥130 mg/dL No


Gynecology_Novak

Gynecology_Novak. Figure 9.4 Treatment decisions based on the LDL cholesterol. LDL, low-density lipoprotein; HDL, high-density lipoprotein. *Coronary heart disease (CHD) risk equivalents: Diabetes or other forms of atherosclerotic disease like peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease. (Adapted from The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program [NCEP] Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486–2497.)


Gynecology_Novak

Gynecology_Novak. Figure 9.4 is a suggested algorithm for cholesterol control based on LDL levels. Cholesterol fat-lowering diet books abound in most bookstores and allow the patient to choose a diet she will best follow. The role of exercise and cigarette cessation should be stressed to all patients. Patients with a family history of cardiovascular disease (history of premature coronary artery problems and strokes) should be tested and started on conservative programs in their 20s. After 3 to 6 months, if the LDL remains above 160 mg/dL with zero to one risk factor or above 130 mg/dL with two or more risk factors, then medical therapy should be initiated. Any woman with coronary heart disease or equivalents such as diabetes or other forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) should initiate lifestyle changes if her LDL is 100 mg/dL or more and drug therapy if her LDL is 130 mg/dL or more. Anyone with an LDL 190


Gynecology_Novak

Gynecology_Novak. aortic aneurysm, and symptomatic carotid artery disease) should initiate lifestyle changes if her LDL is 100 mg/dL or more and drug therapy if her LDL is 130 mg/dL or more. Anyone with an LDL 190 mg/dL or higher should be considered for drug therapy (33).


Gynecology_Novak

Gynecology_Novak. The bile acid-binding resins cholestyramine and colestipol were the mainstay of therapy. Their usefulness is limited by side effects such as constipation, bloating, nausea, and heartburn, and by their tendency to interfere with the absorption of other drugs. Nicotinic acid (500 mg three times daily) decreases triglycerides, LDL, and lipoprotein (a ) and increases HDL more than any other drug. Flushing, pruritus, gastrointestinal distress, and, rarely, hepatotoxicity are a few of the adverse effects of nicotinic acid. Starting at a low dose and pretreating with aspirin 325 mg or ibuprofen 200 mg can minimize the facial ﬂushing. Fibric acid derivatives like clofibrate and gemfibrozil are used to lower triglycerides and increase HDL but may increase LDL in some patients. The HMG-CoA (3-hydroxy-3methyl-glutaryl-coenzyme A) reductase inhibitors (statins) include atorvastatin, ﬂuvastatin, lovastatin, pravastatin, and simvastatin. These medicines inhibit HMG-CoA reductase, the enzyme that


Gynecology_Novak

Gynecology_Novak. A) reductase inhibitors (statins) include atorvastatin, ﬂuvastatin, lovastatin, pravastatin, and simvastatin. These medicines inhibit HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in cholesterol synthesis. Several clinical trials showed that pravastatin, simvastatin, and lovastatin have a beneficial effect in cardiovascular disease. Statins are better tolerated than other lipid-lowering drugs, but reported side effects include severe myalgias, muscle weakness with increases in creatine phosphokinase, and, rarely, rhabdomyolysis, leading to renal failure.


Gynecology_Novak

Gynecology_Novak. Diabetes mellitus (DM) is a chronic disorder of altered carbohydrate, protein, and fat metabolism resulting from a deficiency in the secretion or function of insulin. The disease is defined by the presence of either fasting hyperglycemia or elevated plasma glucose levels based on an oral glucose tolerance testing (OGTT). The major complications of DM are primarily vascular and metabolic. The prevalence of DM is higher in women and certain ethnic groups, although a background rate in the general population is 6.29%, which has increased threefold in 15 years (34). Risk factors for DM are: 1. 2. 3. A family history of diabetes 4. 5. 6. HDL cholesterol less than or equal to 35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL 7. History of gestational diabetes or delivery of a baby weighing more than 9 pounds


Gynecology_Novak

Gynecology_Novak. HDL cholesterol less than or equal to 35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL 7. History of gestational diabetes or delivery of a baby weighing more than 9 pounds Major complications of DM include blindness, renal disease, gangrene of an extremity, heart disease, and stroke. Diabetes is one of the four major risk factors for cardiovascular disease. Classification In January 1999, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus published a report revising the system that was in use since 1979 (35,36). The goal of the revision was to provide guidelines for nomenclature and testing that might reduce diagnostic confusion and improve patient well-being (Table 9.9). The terms insulin dependent diabetes mellitus (IDDM) and noninsulin dependent diabetes mellitus (NIDDM) were replaced by the terms type 1 and type 2 diabetes mellitus.


Gynecology_Novak

Gynecology_Novak. Type 1 Diabetes Mellitus With type 1 diabetes, the major metabolic disturbance is the absence of insulin from the destruction of beta cells in the pancreas. Insulin is necessary for glucose metabolism and cellular respiration. When insulin is absent, ketosis results. The cause of type 1 diabetes is unknown; data suggest an autoimmune association from either a viral infection or toxic components in the environment. Studies in the past decade showed a correlation between many autoimmune diseases and the human leukocyte antigens (HLA).


Gynecology_Novak

Gynecology_Novak. Insulin-sensitive tissues (muscle, liver, and fat) fail to metabolize glucose efficiently in the absence of insulin. In uncontrolled type 1 diabetes, an excess of counter-regulatory hormones (cortisol, catecholamines, and glucagon) contributes to further metabolic dysfunction. In the absence of adequate amounts of insulin, increasing breakdown products of muscle (amino acid proteolysis), fat (fatty acid lipolysis), and glycogen (glucose glycogenolysis) are recognized. There is an increase in glucose production from noncarbohydrate precursors as a result of gluconeogenesis and ketogenesis in the liver. Without prompt treatment, severe metabolic decompensation (i.e., diabetic ketoacidosis) will occur and may lead to death.


Gynecology_Novak

Gynecology_Novak. Type 2 Diabetes Mellitus Type 2 diabetes mellitus is a heterogeneous form of diabetes that commonly occurs in older age groups (>40 years) and more frequently has a familial tendency than type 1 diabetes. This form of diabetes mellitus accounts for approximately 90% to 95% of those with diabetes. The presence of risk factors strongly inﬂuences the development of type 2 diabetes in susceptible populations. Risk factors for type 2 diabetes include ethnicity, obesity, family history of DM, sedentary lifestyle, impaired glucose tolerance, upper-body adiposity, and a history of gestational diabetes and hyperinsulinemia. In contrast to an absence of insulin that occurs with type 1 diabetes, in type 2 diabetes the altered metabolism of insulin results in insulin resistance. This condition is characterized by Table 9.9 Classification of Diabetes Mellitus 1. Type 1 diabetes Characterized by pancreatic destruction leading to insulin deficiency A. Idiopathic


Gynecology_Novak

Gynecology_Novak. Table 9.9 Classification of Diabetes Mellitus 1. Type 1 diabetes Characterized by pancreatic destruction leading to insulin deficiency A. Idiopathic B. Immune mediated 2. Type 2 diabetes A combination of insulin resistance and some degree of inadequate insulin secretion 3. Other types of diabetes: A. Impaired glucose tolerance (IGT) B. Endocrinopathies (Cushing’s, acromegaly, pheochromocytoma, hyperaldosteronism) C. Drug-or chemical-induced D. Diseases of the exocrine pancreas (pancreatitis, neoplasia) E. Infections F. Genetic defects of beta-cell function and insulin action G. Gestational diabetes mellitus Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4–S42.


Gynecology_Novak

Gynecology_Novak. impaired glucose uptake in target tissues. A compensatory increase in insulin secretion results, causing higher-than-normal circulating insulin levels (36). Obesity is present in 85% of affected patients. The cause of type 2 diabetes is unknown, but defects in both the secretion and action of insulin are suspected. Many patients diagnosed with type 2 diabetes at an early age eventually exhaust endogenous pancreatic insulin and require injected insulin. When under severe stress, such as infection or surgery, they may develop diabetic ketoacidosis or a hyperglycemic hyperosmolar nonketotic state. Diagnosis Three methods are available to diagnose diabetes mellitus in nonpregnant women: 1. A single fasting blood glucose greater than or equal to 126 mg/dL on two separate occasions 2. A random blood glucose equal to or above 200 mg/dL in an individual with classic signs and symptoms of diabetes (polydipsia, polyuria, polyphagia, and weight loss) 3.


Gynecology_Novak

Gynecology_Novak. A random blood glucose equal to or above 200 mg/dL in an individual with classic signs and symptoms of diabetes (polydipsia, polyuria, polyphagia, and weight loss) 3. A 2-hour OGTT greater than or equal to 200 mg/dL (fasting sample, 60-, and 120-minute samples) after a 75-g load of glucose. A 2-hour OGTT should not be performed if the first two criteria are present. Diagnostic criterion for impaired glucose intolerance (IGT) is a fasting glucose greater than or equal to 100 mg/dL but less than 126 mg/dL (36). A 2-hour OGTT should be performed under the following conditions: 1. A 10-hour fast should precede morning testing. 2. The patient should sit throughout the procedure. Assessment of Glycemic Control 3. No smoking is permitted during the test interval. 4. Caffeinated beverages should not be consumed. 5. More than 150 g of carbohydrates should be ingested for 3 days before the test. 6. No drugs should be taken before the test.


Gynecology_Novak

Gynecology_Novak. 4. Caffeinated beverages should not be consumed. 5. More than 150 g of carbohydrates should be ingested for 3 days before the test. 6. No drugs should be taken before the test. 7. The patient should not be bedridden or under stress. Patients who should be considered for diabetes testing are: All individuals 45 years of age or older (repeat at 3-year intervals) Persons with classic signs and symptoms of diabetes (i.e., polyuria, polydipsia, polyphagia, and weight loss) Ethnic groups at high risk (Pacific Islanders, Native Americans, African Americans,


Gynecology_Novak

Gynecology_Novak. Persons with classic signs and symptoms of diabetes (i.e., polyuria, polydipsia, polyphagia, and weight loss) Ethnic groups at high risk (Pacific Islanders, Native Americans, African Americans, Hispanic Americans, and Asian Americans) Obesity (body mass index >27 kg/m2) History of a first-degree relative with diabetes Women with gestational diabetes or who have delivered a baby weighing more than 9 pounds Individuals with hypertension (blood pressure >140/90 mm Hg) An HDL cholesterol level less than or equal to 35 mg/dL or triglyceride level greater than or equal to 250 mg/dL Presence of impaired glucose tolerance on previous testing


Gynecology_Novak

Gynecology_Novak. The only acceptable method for assessment of glycemic control is determination of blood glucose by direct enzyme analysis, not by measurement of urine values, which do not correlate. Glucometers with memory storage made home glucose monitoring more reliable. Physician treatment guidelines are in Table 9.10 and patient guidelines in Table 9.11. In a 10 multicenters’ study, the diabetes control and complication trial (DCCT), performed under the auspices of the National Institutes of Health, showed a marked reduction (40%–50%) in complications of neuropathy, retinopathy, and nephropathy when patients with type 1 diabetes received intensive therapy (accomplished by a team approach) as compared with those who received standard therapy.


Gynecology_Novak

Gynecology_Novak. Oral Hypoglycemic Agents Oral hypoglycemic agents are recommended for many type 2 diabetic patients. The first oral hypoglycemic agents introduced were first-and second-generation sulfonylureas. Other classes of drugs that have different effects in patients with type 2 diabetes—such as biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and insulin secretagogues—were introduced. The mode of action of sulfonylureas is based on two different mechanisms: (i) enhanced insulin secretion from the pancreas, and (ii) an extrapancreatic effect that is poorly understood. Endogenous insulin secretion (as measured by C-peptide) is necessary for oral hypoglycemic agents to work. If the fasting blood glucose on an adequate diabetic diet is greater than 250 mg/dL, there is little effect. Frequent evaluation to monitor control (every 3 to 4 months) is important. If glucose levels cannot be controlled with oral hypoglycemic agents (i.e., sulfonylureas) or other


Gynecology_Novak

Gynecology_Novak. Table 9.10 Physician Guidelines in the Therapy of Diabetes Mellitus Establish diagnosis and classify type of diabetes mellitus (DM). The oral glucose tolerance test (OGTT) is not recommended for routine clinical use because of its higher cost, time requirement, and limited reproducibility. Initiate diabetes education classes to learn blood glucose monitoring and diabetes medications; to learn signs, symptoms, and complications; and to learn how to manage sick days. Place patient on ADA diet with appropriate caloric, sodium, and lipid restrictions. Establish cardiac risk factors, kidney function (serum creatinine, urine for microalbuminuria). If neuropathy is present, refer to a neurologist. Establish extent of fundoscopic lesion (refer to ophthalmologist as needed). Check feet and toenails at least once a year and refer to a foot specialist. Use finger-stick blood glucose for daily diabetic control. Follow chronic glycemic control by HgA1c every 2 to 3 months in the office.


Gynecology_Novak

Gynecology_Novak. Use finger-stick blood glucose for daily diabetic control. Follow chronic glycemic control by HgA1c every 2 to 3 months in the office. Initial general health evaluation should consist of a complete history and physical examination and the following laboratory tests: CBC with differential, chemistry profile, lipid profile, urinalysis, thyroid function tests, urine for microalbuminuria, and ECG (baseline at age 40 or older, repeat yearly). Oral hypoglycemic agents like the sulfonylureas may be considered if fasting blood glucose does not decline or increase and if the patient has diabetes for fewer than 10 years, does not have severe hepatic or renal disease, and is not pregnant or allergic to sulfa drugs. While on oral hypoglycemic agents, check the HgA1C every 3 months and at least two times a year if stable. If the HgA1C is <7% or the postprandial glucose is <200 mg/dL, omit the oral hypoglycemic agents, place on diet alone, and follow every 3 months.


Gynecology_Novak

Gynecology_Novak. If the HgA1C is <7% or the postprandial glucose is <200 mg/dL, omit the oral hypoglycemic agents, place on diet alone, and follow every 3 months. If the fasting serum glucose is >200 mg/dL consistently or the HgA1C is more than 10%, consider starting insulin and referring the patient to an internist. Administer the ﬂu vaccine every fall and the pneumococcal vaccine every 6 years. ADA, American Diabetic Association; HgA1c, hemoglobin A1C; CBC, complete blood count; ECG, electrocardiogram. Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4–S42. Table 9.11 Patient Guidelines for Treatment of Type 2 Diabetes Initiate an ADA reducing diet (50% CHO, 30% fat, 20% protein, high fiber) with three meals a day. Maintain ideal body weight or to reduce weight by 5% to 15% in 3 months if obese.


Gynecology_Novak

Gynecology_Novak. Initiate an ADA reducing diet (50% CHO, 30% fat, 20% protein, high fiber) with three meals a day. Maintain ideal body weight or to reduce weight by 5% to 15% in 3 months if obese. Modify risk factors (smoking, exercise, fat intake). Check fasting blood glucose by finger stick daily for 2 months. If FBS declines, no other therapy is needed. If FBG does not decline or increases, use of an oral hypoglycemic agent may be considered. ADA, American Diabetic Association; CHO, carbohydrate; FBS, fasting blood glucose. Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4–S42. medicines (i.e., metformin, a biguanide), insulin therapy should be initiated and referral should be considered because of the increased rate of complications.


Gynecology_Novak

Gynecology_Novak. Thyroid disorders are more common in women and some families, although the exact rate of inheritance is unknown (38,39). In geriatric populations, the incidence may be as high as 5% (40). The laboratory diagnosis of thyroid disease can be difficult because of altered hormonal states such as pregnancy and exogenous hormones. Thyroid hormones act in target tissues by binding to nuclear receptors, which induce change in gene expression. Extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3) takes place in target tissue. T3 binds the nuclear receptor with higher affinity than T4, which makes T3 more biologically active. Pituitary thyroid stimulating hormone (TSH) and hypothalamic thyrotropin-releasing hormone (TRH) regulate hormone production and thyroid growth by normal feedback physiology. Thyroid-stimulating immunoglobulins (TSI), once known as a long-acting thyroid stimulator (LATS), bind to the TSH receptor, which results in hyperthyroid Graves disease.


Gynecology_Novak

Gynecology_Novak. More than 99% of circulating T4 and T3 concentrations are bound by plasma proteins, predominately to thyroxine-binding globulin (TBG), and the remaining 1% of thyroid hormones are free. Free levels of thyroid hormones remain constant despite physiologic or pharmacologic alterations. Regardless of total serum protein levels, active thyroid hormone remains stable. In healthy women, transitions from puberty to menopause do not alter free thyroid hormone concentrations. Excess endogenous or exogenous sources of estrogen increase TBG plasma concentration by decreasing hepatic clearance. Androgens (especially testosterone) and corticosteroids have the opposite effect by increasing hepatic TBG clearance.


Gynecology_Novak

Gynecology_Novak. Thyroid function tests may be misleading in women receiving exogenous sources of estrogen because of altered binding characteristics. In euthyroid individuals, elevations of thyroid hormone concentrations arise from three mechanisms: (i) increased protein binding because of altered albumin and estrogen states, (ii) decreased peripheral conversion of T4 to T3,or (iii) congenital tissue resistance to thyroid hormones, which is rare. Postmenopausal hormonal therapy and pregnancy alter laboratory findings and complicate interpretation of thyroid function studies. Most laboratories compensate by reporting a free T4 level that mathematically corrects for physiologic alterations. If questions arise, a clinical pathologist should be consulted.


Gynecology_Novak

Gynecology_Novak. Hypothyroidism Overt hypothyroidism occurs in 2% of women, and at least an additional 5% develop sub-clinical hypothyroidism. This is another disease that disproportionally impacts women five-to eightfold more commonly than men. This is especially true in the elderly, in whom many of the signs and symptoms are subtle. The principal cause of hypothyroidism is autoimmune thyroiditis (Hashimoto’s thyroiditis). A familial predisposition is observed in many cases, but the specific genetic or environmental trigger is unknown. The incidence of autoimmune thyroiditis increases with age, affecting up to 15% of women older than 65 years. Many have subclinical hypothyroidism, which is defined as an elevated serum TSH concentration with a normal serum free T4 level. It is uncertain whether treatment will improve quality of life in otherwise healthy patients who have subclinical hypothyroidism (41,42). Chronic autoimmune thyroiditis (Hashimoto’s) is the more common cause of hypothyroidism in


Gynecology_Novak

Gynecology_Novak. will improve quality of life in otherwise healthy patients who have subclinical hypothyroidism (41,42). Chronic autoimmune thyroiditis (Hashimoto’s) is the more common cause of hypothyroidism in countries without iodine deficiency. In this process one has both cellular and antibody-mediated destruction of the thyroid, which can result in either a goiter or atrophic thyroid. Autoimmune thyroiditis may be associated with other endocrine (e.g., type 1 diabetes, primary ovarian failure, adrenal insufficiency, and hypoparathyroidism) and nonendocrine (e.g., vitiligo and pernicious anemia) disorders (43). When autoimmune diseases are present, there should be a high degree of suspicion for concurrent thyroid disorders. With postpartum thyroiditis there will be a hyperthyroid phase followed by a hypothyroid phase that can last for months. Iatrogenic causes of hypothyroidism occur after surgical removal or radioactive iodine therapy for hyperthyroidism (Graves) or thyroid cancer. Radiation was


Gynecology_Novak

Gynecology_Novak. phase that can last for months. Iatrogenic causes of hypothyroidism occur after surgical removal or radioactive iodine therapy for hyperthyroidism (Graves) or thyroid cancer. Radiation was used to treat acne and other dermatologic disorders 45 years ago; patients undergoing such treatment have an increased risk of thyroid cancer and require close monitoring. Although worldwide iodine deficiency goiter is the most common form of hypothyroidism, this is uncommon in North America given the iodine supplementation in salt as well as other dietary sources. Hypothyroidism rarely occurs secondary to pituitary or hypothalamic diseases from TSH or TRH deficiency, but this must be considered if symptoms occur after neurosurgical procedures.


Gynecology_Novak

Gynecology_Novak. Clinical Features Manifestations of hypothyroidism include a broad range of signs and symptoms: fatigue, lethargy, cold intolerance, nightmares, dry skin, hair loss, constipation, periorbital carotene deposition (causing a yellow discoloration), carpal tunnel syndrome, weight gain (usually less than 5–10 kg), depression, irritability, hyperlipidemia, and impaired memory. Menstrual dysfunction is common, either as menorrhagia or amenorrhea. Infertility may arise from anovulation, but exogenous thyroid hormone is not useful for anovulatory euthyroid women. The finding of hyperlipidemia may be the first indication of hypothyroidism, especially the presence of high triglycerides. Empirical use of thyroid extract should be discouraged.


Gynecology_Novak

Gynecology_Novak. Hypothyroidism is not a cause of premenstrual syndrome (PMS), but worsening PMS may be a subtle manifestation of hypothyroidism (44). Hypothyroidism may cause precocious or delayed puberty. Hyperprolactinemia and galactorrhea are unusual manifestations of hypothyroidism; however, assessment of thyroid function should be considered. To distinguish primary hypothyroidism from a prolactin-secreting pituitary adenoma, TSH levels should be assessed in women who have amenorrhea, galactorrhea, and hyperprolactinemia. Diagnosis Recommendations for screening for thyroid disorders in women range from every 5 years starting at age 35 in women (American Thyroid Association), to age 50 (American College of Physicians), to periodically in older women (American Academy of Family Physicians and American Association of Clinical Endocrinologist), to evidence is insufficient to recommend for or against screening (United States Preventive Services Task Force) (45–49).


Gynecology_Novak

Gynecology_Novak. Suspected hypothyroidism should always be confirmed with laboratory studies. Primary hypothyroidism is characterized by the combination of an elevated serum TSH with a low serum free T4 level. Autoimmune thyroiditis can be confirmed by the presence of serum antithyroid peroxidase (formerly referred to as antimicrosomal) antibodies. An elevated TSH with a normal free T4 level implies subclinical hypothyroidism. Central hypothyroidism, although rare, is distinguished by a low or low-normal serum free T4 level with either a low or inappropriate normal serum TSH concentration.


Gynecology_Novak

Gynecology_Novak. Therapy Synthetic L-thyroxine (T4) is the treatment of choice for hypothyroidism and is available as generic levothyroxine. There is debate about the value of replacing thyroxine in the subclinical hypothyroidism patient. Such replacement did not result in improved survival, decreased cardiovascular morbidity, or improve quality of life (44). The mode of action is by conversion of T4 to T3 in peripheral tissues. Levothyroxine should be taken on an empty stomach. Absorption may be poor when taken in combination with aluminum hydroxide (common in antacids), cholestyramine, ferrous sulfate, or fatty meals. The usual T4 requirement is weight related (approximately 1.6 μg/kg) but decreases for the elderly. Normal daily dosage is 0.1 to 0.15 mg but should be adjusted to maintain TSH levels within the normal range. TSH levels should be checked in 6 weeks and when dosages or brands are changed.


Gynecology_Novak

Gynecology_Novak. In the early 1980s, many clinicians thought that increasing the serum T4 to mildly elevated levels would enhance conversion of T4 to T3. Subsequent data proved that even a mild increase of T4 was associated with cortical bone loss and atrial fibrillation, particularly in older women (44). A low initial T4 dose (0.025 mg per day) should be initiated in the elderly or patients with known or suspected coronary artery disease. Rapid replacement may worsen angina and in some cases induce myocardial infarction.


Gynecology_Novak

Gynecology_Novak. Hyperthyroidism Hyperthyroidism affects 2% of women during their lifetime, most often during their childbearing years and impacts women fivefold more commonly than men. Graves disease represents the most common disorder; it is associated with orbital inﬂammation, causing the classic exophthalmus associated with the disease and a characteristic dermopathy, pretibial myxedema. It is an autoimmune disorder caused by TSH reception antibodies that stimulate gland growth and hormone synthesis. The etiology of Graves disease in genetically susceptible women is unknown. Autonomously functioning benign thyroid neoplasias are less common causes of hyperthyroidism and are associated with toxic adenomas and toxic multinodular goiter. Transient thyrotoxicosis may be the result of unregulated glandular release of thyroid hormone in postpartum (painless, silent, or lymphocytic) thyroiditis and subacute (painful) thyroiditis. Other rare causes of thyroid overactivity include human chorionic


Gynecology_Novak

Gynecology_Novak. glandular release of thyroid hormone in postpartum (painless, silent, or lymphocytic) thyroiditis and subacute (painful) thyroiditis. Other rare causes of thyroid overactivity include human chorionic gonadotropin–secreting choriocarcinoma, TSH-secreting pituitary adenoma, and struma ovarii. Factitious ingestion or iatrogenic overprescribing should be considered in patients with eating disorders.


Gynecology_Novak

Gynecology_Novak. Clinical Features Symptoms of thyrotoxicosis include fatigue, diarrhea, heat intolerance, palpitations, dyspnea, nervousness, and weight loss. In young patients there may be paradoxical weight gain from an increased appetite. Thyrotoxicosis may cause vomiting in pregnant women, which may be confused with hyperemesis gravidarum (50). Tachycardia, lid lag, tremor, proximal muscle weakness, and warm moist skin are classic physical findings. The most dramatic physical changes are ophthalmologic and include lid retraction, periorbital edema, and proptosis. These eye findings occur in less than one-third of women. In elderly adults, symptoms are often more subtle, with presentations of unexplained weight loss, atrial fibrillation, or new onset angina pectoris. Menstrual abnormalities span from regular menses to light ﬂow to anovulatory menses and associated infertility. Goiter is common in younger women with Graves disease, but may be absent in older women. Toxic nodular goiter is


Gynecology_Novak

Gynecology_Novak. from regular menses to light ﬂow to anovulatory menses and associated infertility. Goiter is common in younger women with Graves disease, but may be absent in older women. Toxic nodular goiter is associated with nonhomogeneous glandular enlargement, whereas in subacute thyroiditis the gland is tender, hard, and enlarged.


Gynecology_Novak

Gynecology_Novak. Diagnosis Most thyrotoxic patients have elevated total and free T4 and T3 concentrations (measured by radioimmune assay). In thyrotoxicosis, serum TSH concentrations are virtually undetectable, even with very sensitive assays (sensitivity measured to 0.1 units). Sensitive serum TSH measurements may aid in the diagnosis of hyperthyroidism. Radioiodine uptake scans are useful in the differential diagnosis of established hyperthyroidism. Scans with homogeneous uptake of radioactive iodine are suggestive of Graves disease, whereas heterogeneous tracer uptake is suggestive of a diagnosis of toxic nodular goiter. Thyroiditis and medication-induced thyrotoxicosis have diminished glandular radioisotope concentration.


Gynecology_Novak

Gynecology_Novak. Therapy Antithyroid medications, either propylthiouracil (PTU 50–300 mg every 6–8 hours) or methimazole (10–30 mg per day) are used for initial therapy. After metabolic control is achieved, definitive therapy is obtained by thyroid ablation with radioiodine, which results in permanent hypothyroidism. Both antithyroid drugs block thyroid hormone biosynthesis and may have additional immunosuppressive effects on the gland. The primary difference in oral medications is that PTU partially inhibits extrathyroidal T4-to-T3 conversion, whereas methimazole does not. Methimazole has a longer half-life and permits single daily dosing, which may encourage compliance. Euthyroidism is typically restored in 3 to 10 weeks, and treatment with oral antithyroid agents is continued for 6 to 24 months, unless total ablation with radioiodine or surgical resection is performed. Surgery is less popular because it is invasive and may result in inadvertent parathyroid removal, which commits the patient to


Gynecology_Novak

Gynecology_Novak. total ablation with radioiodine or surgical resection is performed. Surgery is less popular because it is invasive and may result in inadvertent parathyroid removal, which commits the patient to lifelong calcium therapy.


Gynecology_Novak

Gynecology_Novak. The relapse rate with oral antithyroid medications is 50% over a lifetime. Lifelong follow-up is important when medical therapy is used solely because of the high relapse rate. Both medications have infrequent (5%) minor side effects, which include fever, rash, or arthralgias. Major toxicity (e.g., hepatitis, vasculitis, and agranulocytosis) occurs in less than 1%. Agranulocytosis cannot be predicted by periodic complete blood counts; therefore, patients who have a sore throat or fever should stop taking the medication and call their physician immediately. Therapy with iodine-131 provides a permanent cure of hyperthyroidism in 90% of patients.


Gynecology_Novak

Gynecology_Novak. Therapy with iodine-131 provides a permanent cure of hyperthyroidism in 90% of patients. The principal drawback to radioactive iodine therapy is the high rate of postablative hypothyroidism, which occurs in at least 50% of patients immediately after therapy, with additional cases developing at a rate of 2% to 3% per year. Based on the assumption that hypothyroidism will develop, these patients should be given lifetime thyroid replacement therapy. Beta-adrenergic blocking agents such as propranolol or atenolol are useful adjunctive therapy for control of sympathomimetic symptoms such as tachycardia (51). An additional benefit of beta-blockers is the blocking of peripheral conversion of T4 to T3. In rare cases of thyroid storm, PTU, beta-blockers, glucocorticoids, and high-dose iodine preparations (intravenous sodium iodide) should be administered immediately, and referral to an intensive care unit is advisable.


Gynecology_Novak

Gynecology_Novak. Thyroid Nodules and Thyroid nodules are common and found on physical examination in up to 5% of patients. Cancer Nodules may be demonstrated on ultrasound in approximately 50% of 60-year-olds. The vast majority of nodules when discovered are asymptomatic and benign; however, malignancy and hyperthyroidism must be excluded (52). Ultrasound-guided fine-needle aspiration is recommended in the presence of the following factors: history of radiation to the head, neck, or upper chest; family history of thyroid cancer; ultrasound findings suggestive of malignancy; or a nodule larger than 1.5 cm in diameter (53).


Gynecology_Novak

Gynecology_Novak. Thyroid function tests should be performed before fine-needle aspiration and, if results are abnormal, the underlying disease should be treated. Because most nodules are “cold” on scanning, it is more cost-effective to proceed with tissue sampling rather than scanning. Needle biopsy provides a diagnosis in 95% of cases; in the 5% of patients in whom the diagnosis cannot be established, excisional biopsy is necessary. Only 20% of excisional biopsies of an “indeterminate aspiration” are found to be malignant (54). Lesions that are confirmed malignant on biopsy should be treated with extirpative surgery, and benign nodules should be palpated every 6 to 12 months. Thyroxine suppressive therapy for benign nodules is not recommended (53).


Gynecology_Novak

Gynecology_Novak. Papillary thyroid carcinoma is the most common malignancy, found in 75% of thyroid cancers. For unclear reasons the incidence of papillary cancer increased by almost threefold in the past 30 years, from 2.7 to 7.7 per 100,000 people (55). This may represent the more ready diagnosis of smaller cancers. The majority of cancers are found incidentally during routine examinations. Risk factors include a history of radiation exposure during childhood and family history. Signs include rapid growth of neck mass, new onset hoarseness, or vocal cord paralysis. In the setting of rapid growth, fixed nodule, new onset hoarseness, or the presence of lymphadenopathy, it is important to be sure a fine-needle aspiration is done. Thyroidectomy is the primary treatment with radioactive iodine and TSH suppression with thyroxine. Patients younger than 50 years of age with a primary tumor of less than 4 cm at presentation, even with associated cervical lymph node metastasis, are usually cured. In the


Gynecology_Novak

Gynecology_Novak. with thyroxine. Patients younger than 50 years of age with a primary tumor of less than 4 cm at presentation, even with associated cervical lymph node metastasis, are usually cured. In the elderly, anaplastic tumors have a poor prognosis and progress rapidly despite therapy.


Gynecology_Novak

Gynecology_Novak. Follicular thyroid cancer is the second most common thyroid cancer, comprising up to 10% of cases. These tend to occur in an older population with peak ages of 40 to 60. It has a threefold greater prevalence in women than men. This form of cancer tends to have vascular invasion, frequently with distant metastases. The prognosis tends to be less favorable with this form of cancer than with papillary cancers, although women do have a better prognosis than men.


Gynecology_Novak

Gynecology_Novak. Irritable bowel syndrome (IBS) is a common problem, affecting about 10% to 15% of the population, with women being twice as likely to have the diagnosis (56). Given that its primary symptom is typically crampy chronic abdominal pain, IBS is often in the differential diagnosis for patients with chronic pelvic pain. Stress and certain foods will often trigger the pain, and defecation often will provide some relief from the pain. Other gastrointestinal symptoms include diarrhea and constipation, gastroesophageal reﬂux disease, nausea, bloating, and ﬂatulence. What makes this a more difficult diagnosis is the spectrum of additional symptoms, including dysmenorrhea, dyspareunia, fibromyalgia complaints, urinary symptoms of frequency and urgency, and even sexual dysfunction.


Gynecology_Novak

Gynecology_Novak. This spectrum of symptoms renders diagnosis difficult and led to a consensus group that created the Rome criteria in 1992, revised in 2005 (57). The resulting Rome III criteria are: recurrent abdominal pain or discomfort for at least 3 days per month for 3 months associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in the appearance of the stool IBS should be a diagnosis of exclusion with consideration initially given to other causes for the dominant symptom. If that is diarrhea, considerations of lactose intolerance, infectious etiology, malabsorption, or celiac disease should be entertained. Symptoms that result in weight loss, rectal bleeding, anemia, or that are noctural or progressive could indicate something other than IBS unless proven otherwise.


Gynecology_Novak

Gynecology_Novak. A basic workup might include complete blood count and chemistries. Evaluation of diarrhea, if that is the dominant symptom, should potentially include stool cultures if infectious etiology is suspected or 24-hour stool collection (if osmotic) of secretory diarrhea is suspected. Flexible sigmoidoscopy is not done routinely unless needed to rule out inﬂammatory conditions or malignancy in families with Lynch syndrome. Initiate dietary reviews for lactose intolerance or gluten sensitivity.


Gynecology_Novak

Gynecology_Novak. Management General management of IBS can be extremely difficult. Often, the first step is to reassure the patient that this is a functional disease and is not related to cancer or malignancy, assuming those were eliminated by history and examination. Many individuals have some underlying concerns that diagnostic testing needs to be performed or that something is being missed. Constant reassurance is an important aspect of management. The patient needs to be an active participant in her care and understand the chronic nature of the disease. A symptom diary for several weeks may show a link between various foods and stressors that may be modifiable. Some individuals are able to link various stressors in their lives to symptoms while others will not have identifiable causes. Common triggers include stress, anxiety, medication (antibiotics, antacids), menstrual cycles, abusive relationships, certain foods (lactose, sorbitol), and travel. Patients should be counseled about dietary


Gynecology_Novak

Gynecology_Novak. include stress, anxiety, medication (antibiotics, antacids), menstrual cycles, abusive relationships, certain foods (lactose, sorbitol), and travel. Patients should be counseled about dietary interventions, including increasing dietary fiber, decreasing total fat intake, and avoiding foods that trigger symptoms. Stool softeners are recommended for individuals with hard stools, and bulk aiding agents may be helpful for those individuals with constipation. The overuse of laxatives is to be discouraged. Good bowel habits should be discussed. Patients with poor habits should set aside a quiet time every day to attempt defecation. Many individuals get into a habit of ignoring stooling symptoms, leading to further problems with lower gastrointestinal disease.


Gynecology_Novak

Gynecology_Novak. Antidiarrheal agents, specifically loperamide or diphenoxylate, are often useful in patients with mild disease. The goal is to reduce the number of bowel movements and help to relieve rectal urgency. Anticholinergics including hyoscyamine and dicyclomine hydrochloride often are helpful. Powder opium, an antidiarrheal, combined with an antispasmodic (belladonna alkaloid), is another option for refractory disease. Antispasmodic agents have anticholinergic agents as the primary ingredient, and compliance may be a problem because side effects include dry mouth, visual disturbances, and constipation. These agents can precipitate toxic megacolon, which may result in severe colitis. Toxic megacolon is a medical and potential surgical emergency, in some cases requiring colectomy. Even though these patients may be extremely difficult to treat, judicious use of symptom-based pharmacologic approaches, reassurance, and patient insight may be helpful. The quality of life for some individuals with


Gynecology_Novak

Gynecology_Novak. patients may be extremely difficult to treat, judicious use of symptom-based pharmacologic approaches, reassurance, and patient insight may be helpful. The quality of life for some individuals with IBS is extremely compromised, requiring intense counseling. It may be difficult to treat them in a busy primary care practice. Those with a concurrent psychiatric disease, such as depression, will often benefit from psychiatric consultation and pharmacologic treatment of the underlying disease in the overall management.


Gynecology_Novak

Gynecology_Novak. Individuals with chronic, debilitating irritable bowel syndrome should be referred to a gastroenterologist. Any suspicion of organic disease with systemic changes, including weight loss and bloody diarrhea, should be considered for referral. Studies suggest a relationship between IBS symptoms and an imbalance of central nervous system neurotransmitters related to stress in the environment (58,59). Serotonins (5hydroxytryptamine or 5-HT) are important in the development of gut disorders. Only 5% of total body serotonin is found in the central nervous system, while 95% is found in the gastrointestinal tract. Other neurotransmitters associated with gastrointestinal disorders include calcitonin, neurotensin, substance P, nitric oxide, vasoactive intestinal peptide, and acetylcholine. These neurotransmitters function at the level of the bowel and the central nervous system.


Gynecology_Novak

Gynecology_Novak. Several compounds were studied that interact with serotonin receptors in the bowel (5 HT-3 and 5 HT-4). The 5-HT-3 antagonist, alosetron, was introduced to treat patients with diarrhea. Patients with other symptoms, including alternating diarrhea and constipation, and individuals with primary constipation received the drug, resulting in severe constipation in approximately one-third of patients. There were reports of ischemic colitis with the use of this drug. Although the drug was withdrawn for a time period, the U.S. Food and Drug Administration allowed its reintroduction. Tegaserod is a 5-HT-4 receptor (serotonin receptor) agonist that is approved for short-term use in patients with constipation. It has gastrointestinal stimulatory effects facilitated by intercolonergic transmission as its primary mode of action. There are many 5-HT drugs under development that will be introduced over the next 2 to 5 years.


Gynecology_Novak

Gynecology_Novak. The term gastroesophageal reﬂex disease (GERD) is a commonly used label for many forms of indigestion and heartburn. The American College of Gastroenterology defines it as symptoms or mucosal damage produced by the abnormal reﬂux of gastric contents into the esophagus (60). The term “abnormal” is key because some reﬂux is physiologic, usually occurring postprandial and typically being asymptomatic. Given the variation in definition, its prevalence is hard to determine, but it is clear that GERD is more common in the Western world. Symptoms of GERD include heartburn (burning sensation in the retrosternal area) commonly postprandial, regurgitation gastric contents into mouth, dysphagia from esophageal inﬂammation, and chest pain that can be confused as angina. Dysphagia that is progressive is concerning for Barrett’s metaplasia or adenocarcinoma and merits an endoscopic evaluation (61).


Gynecology_Novak

Gynecology_Novak. Treatment of GERD is multifaceted with lifestyle modification and use of antacids and over-the-counter H2 receptor antagonists or proton pump inhibitors (PPI). Lifestyle modifications include smoking cessation, avoidance of eating late in the evening, avoidance of being supine after eating, weight loss, avoidance of tight clothing, and restriction of alcohol use. Dietary modifications are helpful but should not be draconian, which will ensure noncompliance. Key foods to try to minimize are fatty foods, chocolate, peppermint, and excessive alcohol. The patient can monitor her own symptoms for the foods that are most problematic for her.


Gynecology_Novak

Gynecology_Novak. Medications that reduce acid secretions are best and include H2 blockers or proton pump inhibitors. They do not prevent the reﬂux but decrease the damage done by the acid when reﬂuxed. Medication needs to be titrated to the severity of the symptoms. H2 blockers commonly work well for acute pain but in placebo-controlled studies in chronic cases without resolution of heartburn after the common 6-week course, it was found that patients on PPI do better. Maintenance therapy is recommended for patients who have rapid recurrence of symptoms (in less than 2–3 months) after they stop their medication. Otherwise patients can be managed with episodic treatments. The linkage of Helicobacter pylori infections and GERD is poorly understood but seems to be mediated through increased gastric acid secretion. Treatment can initially worsen GERD and may not improve it (62). Benefits and risks should be discussed with the patient prior to testing and treating for H. pylori. The management of GERD


Gynecology_Novak

Gynecology_Novak. secretion. Treatment can initially worsen GERD and may not improve it (62). Benefits and risks should be discussed with the patient prior to testing and treating for H. pylori. The management of GERD during pregnancy is similar to the treatment in the nonpregnant patient.


Gynecology_Novak

Gynecology_Novak. Carpal tunnel syndrome (CTS) is the cluster of symptoms brought on by compression in the carpal tunnel of the median nerve. These are paresthesia, pain, and weakness. The symptoms are commonly worse at night and may wake the patient from sleep. It is thought women may be more likely to present with complaints of CTS because of their small wrists, repetitive motion injury at work (typing, holding telephone, and reading), and pregnancy with increased edema. The pain and paresthesia can be located in the wrist or hand or can be in the forearm. The weakness may cause a patient to have difficulty opening jars, lifting a plate, turning a doorknob, or holding a glass.


Gynecology_Novak

Gynecology_Novak. A detailed history is very diagnostic but the use of a couple simple tests can help to confirm it (63). The most common one is the Phalen maneuver, in which the patient ﬂexes her palms at the wrist as close to 90 degrees as possible. Then with the dorsal portion of the hands touching and the arms parallel to the ﬂoor, the patient presses the ﬂexed hands against each other for approximately 1 minute. This should reproduce her symptoms along the median nerve. The Tinel test involves percussion over the top of the carpal tunnel where the median nerve travels. A positive test is when the percussion reproduces the pain and paresthesia. Additional testing such as nerve conduction studies should be reserved for patients who do not respond to conservative management or have significant muscle weakness.


Gynecology_Novak

Gynecology_Novak. Treatment involves lifestyle modification to decrease repetitive motion injuries or prolonged marked ﬂexion at the wrist. A carpal tunnel brace can be very helpful in maintaining adequate extension at the wrist, thereby “opening” the tunnel and reducing compression on the medial nerve. Only if these strategies do not work is a surgical intervention indicated. Mitral Valve Prolapse Syndrome, Dysautonomia, and Postural Orthostatic Tachycardia Syndrome


Gynecology_Novak

Gynecology_Novak. The terms mitral valve prolapse syndrome (MVPS), dysautonomia, and postural orthostatic tachycardia syndrome (POTS) all refer to a syndrome in which the patient has problems with palpitations, hypotension, syncope, dyspnea, panic/anxiety disorder, numbness, hyperﬂexible joints, pectus excavatum, and gastric emptying disorders. Initially patients (typically fivefold times more likely to be women) who presented with these symptoms were thought to be somatizing their anxiety disorder. It is now accepted that it is a syndrome that appears to involve the autonomic nervous system (64). This often will present first in early adolescence with gradual worsening of the symptoms. The patients are very slender in build and lose weight to a low body mass index over a number of months as the syndrome evolves. This weight loss is the probable cause of the secondary amenorrhea that prompts these women to seek gynecologic care. The symptoms are not clearly explained by the degree of mitral valve


Gynecology_Novak

Gynecology_Novak. evolves. This weight loss is the probable cause of the secondary amenorrhea that prompts these women to seek gynecologic care. The symptoms are not clearly explained by the degree of mitral valve prolapse, so many feel MVPS is a marker for individuals at risk for this complex of symptoms. Increased sympathetic activity is the common pathway for most of the proposed mechanisms for POTS or MVPS. There appears to be a genetic component, with over 10% of patients reporting the diagnosis in family members with orthostatic intolerance (65,66).


Gynecology_Novak

Gynecology_Novak. A tilt table test is often key to the diagnosis. Treatment focuses on the symptoms and maintaining intravascular volume by encouraging oral intake of water and salts (67). Physical fitness with aerobic exercises to increase muscle mass and reduce dependent pooling of blood; avoidance of smoking, caffeine, and alcohol; and limiting simple carbohydrates will minimize symptoms over time. Additional medications, including adrenoreceptor agonists, acetylcholinesterase inhibitor, mineralocorticoid agonist, beta-blockers, and selective serotonin reuptake inhibitors, may be necessary. Because this is a multifaceted disease, it may be best to refer the patient during the acute phase to a physician who is experienced with this syndrome. 1. Piccirillo JR. Acute bacterial sinusitis. N Eng J Med 2004;351:902– 910. 2. Williams JN, Simel DL. Does this patient have sinusitis?: Diagnosing acute sinusitis by history and physical examination. JAMA 1993;270:1242–1246. 3.


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Gynecology_Novak. 2. Williams JN, Simel DL. Does this patient have sinusitis?: Diagnosing acute sinusitis by history and physical examination. JAMA 1993;270:1242–1246. 3. Hirschmann JV. Antibiotics for common respiratory tract infections. Arch Intern Med 2002;162:256–264. 4. Zalmanovici TA, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database Syst Rev 2009;4:CD005149. 5. Dolor RJ, Witsell DL, Hellkamp AS, et al. Comparison of cefuroxime with or without intranasal ﬂuticasone for the treatment of rhinosinusitis. JAMA 2001;286:3097–3105. 6. Ahovuo-Saloranta A, Borisenko OV, Kovanen N, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev 2008;2:CD000243. 7. Kassel JC, King D, Spurling GKP, et al. Saline nasal irrigation for acute upper respiratory tract infections. Cochrane Database Syst Rev 2010;3:CD0068921. 8. Smith SM, Fahay T, Smucny J, et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2004;4:CD000245. 9.


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Gynecology_Novak. 8. Smith SM, Fahay T, Smucny J, et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2004;4:CD000245. 9. Nolan TE, Hankins GDV. Adult respiratory distress. In: Pastorek J, ed. Infectious disease in obstetrics and gynecology. Rockville, MD: Aspen Publications, 1994:197–206. 10. Niederman MS, Mandell LA, Bass JB, et al. American Thoracic Society guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy and prevention. Am J Respir Crit Care Med 2001;163:1730– 1754. 11. Halm EA, Teirstein AS. Management of community acquired pneumonia. N Engl J Med 2002;347:2039–2045. 12. Bjerre LM, Verheij TJM, Kochen MM. Antibiotics for community-acquired pneumonia in adult outpatients. Cochrane Database Syst Rev 2009;4:CD002109. 13.


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Gynecology_Novak. 12. Bjerre LM, Verheij TJM, Kochen MM. Antibiotics for community-acquired pneumonia in adult outpatients. Cochrane Database Syst Rev 2009;4:CD002109. 13. Centers for Disease Control and Prevention. Prevention and control of inﬂuenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbid Mortal Wkly Rep 2000;49[RR3]:1–38. 14. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII). JAMA 2003;289:2560– 2572. 15. Powrie RO. A 30-year-old woman with chronic hypertension trying to conceive. JAMA 2007;298:1548–1559. 16. Roccella EJ, Lenfant C. Regional and racial differences among stroke victims in the United States. Clin Cardiol 1989;12:IV4–IV8. 17. Moorman PG, Hames CG, Tyroler HA. Socioeconomic status and morbidity and mortality in hypertensive blacks. Cardiovasc Clin 1991;21(3):179–194. 18.


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Gynecology_Novak. 17. Moorman PG, Hames CG, Tyroler HA. Socioeconomic status and morbidity and mortality in hypertensive blacks. Cardiovasc Clin 1991;21(3):179–194. 18. Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database Syst Rev 2009;3: CD004349. 19. American Society of Hypertension. Recommendations for routine blood pressure measurement by indirect cuff sphygmomanometry. Am J Hypertens 1992;5:207–209. 20. The National High Blood Pressure Education Program Working Group Report on Ambulatory Blood Pressure Monitoring. Arch Intern Med 1990;150:2270–2280. 21. Appel lJ, Brands MW, Daniels SR, et al. Dietary approaches to prevent and treat hypertension: a scientific statement form the American Heart Association. Hypertension 2006;47:296. 22. Selby JV, Friedman GD, Quensenberry CP Jr. Precursors of essential hypertension: the role of body fat distribution pattern. Am J Epidemiol 1989;129:43–53. 23.


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Gynecology_Novak. 22. Selby JV, Friedman GD, Quensenberry CP Jr. Precursors of essential hypertension: the role of body fat distribution pattern. Am J Epidemiol 1989;129:43–53. 23. Whelton PK, Appel LJ, Espeland, MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA 1998;279:839. 24. Beyer FR, Dickinson HO, Nicolson D, et al. Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev 2006;3: CD004805. 25. Wright JM, Musini VM. First line drugs for hypertension. Cochrane Database Syst Rev 2009;3:CD001841. 26. Freis ED. Critique of the clinical importance of diuretic-induced hypokalemia and elevated cholesterol level. Arch Intern Med 1989; 149:2640–2648. 27. Brunner E, Rees K, Ward K, et al. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev 2007;4:CD 002128.


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Gynecology_Novak. 27. Brunner E, Rees K, Ward K, et al. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev 2007;4:CD 002128. 28. Hooper L, Summerbell CD, Higgins JPT, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev 2001;3:CD002137. 29. Katan MB, Beynen AC. Characteristics of human hypo-and hyper-responders to dietary cholesterol. Am J Epidemiol 1987;125:387–399. 30. Naughton MJ, Luepker RV, Strickland D. The accuracy of portable cholesterol analyzers in public screening programs. JAMA 1990;263:1213–1217. 31. Irwig L, Glaszious P, Wilson A, et al. Estimating an individual’s true cholesterol level and response to intervention. JAMA 1991;266:1678– 1685. 32. van Stiphout WAHJ, Hofman A, de Bruijn AM. Serum lipids in young women before, during, and after pregnancy. Am J Epidemiol 1987;126:922–928. 33.


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Gynecology_Novak. 32. van Stiphout WAHJ, Hofman A, de Bruijn AM. Serum lipids in young women before, during, and after pregnancy. Am J Epidemiol 1987;126:922–928. 33. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497. 34. Centers for Disease Control and Prevention. Diabetes surveillance 2007. Washington DC: U.S. Department of Health and Human Services, Public Health Service, 2007. 35. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4–S42. 36. Professional Practice Committee. American Diabetes Association: clinical practice recommendations 2005. Diabetes Care 2005;28:S4– S42. 37.


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Gynecology_Novak. 36. Professional Practice Committee. American Diabetes Association: clinical practice recommendations 2005. Diabetes Care 2005;28:S4– S42. 37. Wood PD, Stefanick ML, Williams PT, et al. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N Engl J Med 1991;325:461–466. 38. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7:481–493. 39. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin Endocrinol 1995;43:55–68. 40. Helfand M, Crapo LM. Screening for thyroid disease. Ann Intern Med 1990;112:840–849. 41. Helfand M. Screening for subclincal thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:128–141. 42.


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Gynecology_Novak. 41. Helfand M. Screening for subclincal thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:128–141. 42. Villar HCCE, Saconato H, Valente O, et al. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007;3:CD003419. 43. Volp´eR. Autoimmunity causing thyroid dysfunction. Endocrinol Metab Clin North Am 1991;20:565–587. 44. Schmidt PJ, Grover GN, Roy-Byrne PP, et al. Thyroid function in women with premenstrual syndrome. J Clin Endocrinol Metab 1993;76:671–674. 45. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. [erratum appears in Arch Intern Med 2001 Jan 22;161(2):284]. Arch Intern Med 2000;160(11):1573–1575. 46. American College of Physicians. Clinical guideline, part 1. Screening for thyroid disease. Ann Intern Med 1998;129(2):141–143. 47.


Gynecology_Novak

Gynecology_Novak. 46. American College of Physicians. Clinical guideline, part 1. Screening for thyroid disease. Ann Intern Med 1998;129(2):141–143. 47. American Academy of Family Physicians. Summary of Policy Recommendations for Periodic Health Examinations. Leawood, KS: American Academy of Family Physicians; 2002. 48. American Association of Clinical Endocrinologists. 2002 clinical guidelines for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002;8:457–467. 49. US Preventative Services Task Force. Screening for thyroid disease: recommendation statement. Ann Intern Med 2004;140: 125–127. 50. Mori M, Amino N, Tamaki H, et al. Morning sickness and thyroid function in normal pregnancy. Obstet Gynecol 1988;72:355–359. 51. Zonszein J, Santangelo RP, Mackin JF, et al. Propranolol therapy in thyrotoxicosis. AmJMed 1979;66:411–416. 52. Hegedus L. The thyroid nodule. N Engl J Med 2004;351:1764–1771. 53.


Gynecology_Novak

Gynecology_Novak. 51. Zonszein J, Santangelo RP, Mackin JF, et al. Propranolol therapy in thyrotoxicosis. AmJMed 1979;66:411–416. 52. Hegedus L. The thyroid nodule. N Engl J Med 2004;351:1764–1771. 53. Tan GH, Gharib H. Management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226–231. 54. McHenry CR, Walfish PG, Rosen IB. Non-diagnostic fine needle aspiration biopsy: a dilemma in management of nodular thyroid disease. Am Surg 1993;59:415–419. 55. Howlader N, Noone AM, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975–2008, National Cancer Institute. Bethesda, MD. Available online at: http://seer.cancer.gov/csr/1975 2008/. 56. Hungin AP, Whorwell PJ, Tack J, et al. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther 2003;17:643–650. 57.


Gynecology_Novak

Gynecology_Novak. 56. Hungin AP, Whorwell PJ, Tack J, et al. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther 2003;17:643–650. 57. Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. 2010. Available online at: http://www. romecriteria.org/assets/pdf/19 RomeIII apA 885–898.pdf. 58. Monnikes H, Schmidt BG, Tache Y. Psychological stress-induced accelerated colonic transit in rats involves hypothalamic corticotropinreleasing factor. Gastroenterology 1993;104;716–723. 59. Heymann-Monnikes I, Arnold R, Florin I, et al. The combination of medical treatment plus multicomponent behavioral therapy is superior to medical treatment alone in the therapy of irritable bowel syndrome. Am J Gastroenterol 2000;95:981–994. 60. Devault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reﬂux disease. Am J Gastroenterol 2005;100:190. 61.


Gynecology_Novak

Gynecology_Novak. 60. Devault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reﬂux disease. Am J Gastroenterol 2005;100:190. 61. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reﬂux disease. Gastroenterology 2008;135:1383. 62. Moayyedi P, Soo S, Deeks JJ, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006;2:CD002096. 63. MacDermid JC, Wessel J. Clinical diagnosis of carpal tunnel syndrome: a systematic review. J Hand Ther 2004;17:309. 64. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral valve prolapsed. N Engl J Med 1999;341:1. 65. Jacob G, Biaggioni I. Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am J MedSci 1999;317:88. 66. Jacob G, Costa F, Shannon JR, et al. The neuropathic postural tachycardia syndrome. N Engl J Med 2000;343:1008. 67.


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Gynecology_Novak. 66. Jacob G, Costa F, Shannon JR, et al. The neuropathic postural tachycardia syndrome. N Engl J Med 2000;343:1008. 67. Raj SR, Biaggioni I, Yambure PC, et al. Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia syndrome. Circulation 2005;111:1574. Phillip G. Stubblefield Danielle M. Roncari The most common methods of contraception used in the United States are sterilization, oral contraceptives, and condoms, in that order. Latex condoms and other barriers reduce the risk of sexually transmitted diseases (STDs) and cervical cancer. The two intrauterine devices (IUDs) available in the United States, the copper T380A (ParaGard) and the levonorgestrel T (Mirena), are as effective as tubal sterilization and are associated with a long-term risk of pelvic infection that is no greater than that in the general population.


Gynecology_Novak

Gynecology_Novak. The combination estrogen–progestin oral contraceptive, patch, and vaginal ring all provide excellent contraception when used correctly but all increase the risk of venous thrombosis and thromboembolism. Present low-dose estrogen–progestin combinations do not increase the risk of heart attack among nonsmokers younger than age 35 years who have no other risks for vascular disease. Oral contraceptives do not increase the risk of breast cancer. Use of progestin-only injectable and implant hormonal contraceptives results in very low pregnancy rates without the estrogen-associated risk of thrombosis. Hormonal contraceptives provide extensive contraceptive and noncontraceptive health benefits, including reduced risk for endometrial and ovarian cancer.


Gynecology_Novak

Gynecology_Novak. Hormonal contraceptives provide extensive contraceptive and noncontraceptive health benefits, including reduced risk for endometrial and ovarian cancer. Levonorgestrel 1.5 mg (Plan B) and ulipristal acetate are the most effective hormonal means of emergency contraception. Efficacy is greatest within 24 hours of intercourse but remains high at 5 days. The copper T380A IUD inserted 5 days after intercourse is even more effective than hormonal methods. Long-acting reversible contraceptive (LARC) methods include injectable progestins, subdermal progestin implants, and copper-or levonorgestrel-releasing intrauterine devices. These offer pregnancy rates comparable to sterilization and are among the safest methods. Safe, long-term contraception is provided with laparoscopy and bipolar electrocautery application to three adjacent sites on each tube, the Silastic band, or the Filshie clip.


Gynecology_Novak

Gynecology_Novak. Safe, long-term contraception is provided with laparoscopy and bipolar electrocautery application to three adjacent sites on each tube, the Silastic band, or the Filshie clip. Hysteroscopic sterilization techniques provide highly effective permanent contraception for women without the use of general anesthesia or abdominal incision. Vasectomy provides highly effective, low-cost sterilization for men and is associated with neither heart disease nor prostate cancer. Abortion mortality rates fell rapidly with legalization; currently, the overall mortality risk is less than 1 per 100,000, well below the maternal mortality rate of 12.7 per 100,000 live births. The risk of abortion mortality increases with gestational age, from 0.1 per 100,000 at 8 weeks or less. Even at 16 to 20 weeks abortion is safer than continuing pregnancy.


Gynecology_Novak

Gynecology_Novak. The risk of abortion mortality increases with gestational age, from 0.1 per 100,000 at 8 weeks or less. Even at 16 to 20 weeks abortion is safer than continuing pregnancy. The history of contraception is a long one, dating to ancient times. The voluntary control of fertility is especially important in modern society (1). A woman who expects to have no more than one or two children spends most of her reproductive years trying to avoid pregnancy. Effective control of reproduction is essential to a woman’s ability to accomplish her individual goals. From a larger perspective, the rapid growth of the human population in this century threatens the survival of all. At present rates, the population of the world will double in 66 years, and that of the United States will double in 75 years (2). For the individual and for the planet, reproductive health requires careful use of effective means to prevent both pregnancy and sexually transmitted disease (STD) (3).


Gynecology_Novak

Gynecology_Novak. Table 10.1 Number of Women Aged 15–44 Years, and Percentage Currently Using Contraception Methods According to Age at Interview, United States 2006–2008a aWomen could list up to four current methods. The method shown above was the most effective method used. bIncludes diaphragm (with or without jelly or cream), emergency contraception, female condom, foam, cervical cap, Today™ sponge, suppository or insert, jelly or cream (without diaphragm), and other methods. From Vital and Health Statistics. Use of contraception in the United States 1982–2008. National Survey of Family Growth. Series 23. Number 29. May 2010, Tables 6 and 14.


Gynecology_Novak

Gynecology_Novak. Figure 10.1 Abortion rate*, ratio+, and percentage of total abortions by age group of women who obtained abortion, United States, 2006§. *Number of abortions per 1,000 women aged 15–44 years. +Number of abortions per 1,000 live births. §Data from 48 reporting areas, excludes California, Florida, Louisiana, and New Hampshire. (From Pazol K, Gamble SB, Parker WY, et al. Abortion surveillance—United States 2005. MMWR Surveil Sum 2009;58(SS08):35 [Figure 2].


Gynecology_Novak

Gynecology_Novak. From puberty until menopause, women are faced with concerns about childbearing or its avoidance: the only options are sexual abstinence, contraception, or pregnancy. The contraceptive choices made by couples in the United States in 2008 are shown in Table 10.1 (4). Oral contraceptives (OCs) were the first choice among women, used by 17.3%. Female sterilization was the second choice, used by 16.7%. With the addition of the 6.1% of couples relying on male sterilization, 22.8% of couples were relying on sterilization, making this the first choice of couples. Condoms were third choice, used by 10%. OC use declines with age, and the rate of sterilization increases. Twenty percent of women under 25 who use contraceptives use OCs and only 0.7% is sterilized. Of women aged 35 to 44 using contraception 17.3% uses OCs and 33.8% is sterilized, as is 13.9% of their consorts (Table 10.1). About 10% of women use more than one method of contraception. Although use of contraception is high, a


Gynecology_Novak

Gynecology_Novak. 17.3% uses OCs and 33.8% is sterilized, as is 13.9% of their consorts (Table 10.1). About 10% of women use more than one method of contraception. Although use of contraception is high, a significant proportion of sexually active couples (7.4%) does not use contraception, and each year, 2 of every 100 women aged 15 to 44 years have an induced abortion (4,5). Abortion is an obvious indicator of unplanned pregnancy. Abortion ratios by age group indicate that the use of abortion is greatest for the youngest women and least for women in their late 20s and early 30s who are most likely to continue pregnancies (Fig. 10.1). Use of abortion increases from the late 30s on. Young women are much more likely to experience unplanned pregnancy because they are more fertile than older women and because they are more likely to have intercourse without contraception. The effect of age on pregnancy rates with different contraceptive methods is shown in Figure 10.2.


Gynecology_Novak

Gynecology_Novak. Factors affecting whether pregnancy will occur include the fecundity of both partners, the timing of intercourse in relation to the time of ovulation, the method of contraception used, the intrinsic effectiveness of the contraceptive method, and the correct use of the method. It is impossible to assess the effectiveness of a contraceptive method in isolation from the other factors. The best way to assess effectiveness is long-term evaluation of a group of sexually active women using a particular method for a specified period to observe how frequently pregnancy occurs. A pregnancy rate per 100 women per year can be calculated using the Pearl formula (dividing the number of pregnancies by the total number of months contributed by all couples, and then multiplying the quotient by 1,200). With most methods, pregnancy rates decrease with time as the more fertile or less careful couples become pregnant and drop out of the calculations.


Gynecology_Novak

Gynecology_Novak. Figure 10.2 Percentage of women experiencing an accidental pregnancy, in the first 2 years of use, according to method, combined 1988 and 1995 National Survey of Family Growth. (From Ranjit N, Bankole A, Forrest JD, et al. Contraception failure in the first two years of use: differences across socioeconomic subgroups. Fam Plann Perspect 2001;33:25 [Table 6.]). More accurate information is provided by the life-table method. This method calculates the probability of pregnancy in successive months, which are then added over a given interval. Problems relate to which pregnancies are counted: those occurring among all couples or those in women the investigators deem to have used the method correctly. Because of this complexity, rates of pregnancy with different methods are best calculated by reporting two different rates derived from multiple studies (i.e., the lowest rate and the usual rate), as shown in Table 10.2.


Gynecology_Novak

Gynecology_Novak. Safety Some contraceptive methods have associated health risks; areas of concern are listed in Table 10.3. All of the methods are safer than the alternative (pregnancy with birth), with the possible exception of estrogen-containing hormonal contraceptives (pills, patches and ring) used by women older than 35 years of age who smoke (6). Most methods provide noncontraceptive health benefits in addition to contraception. Oral contraceptives reduce the risk of ovarian and endometrial cancers and ectopic pregnancy. Barrier methods provide some protection against STDs including HIV, cervical cancer, and tubal infertility. Table 10.2 Percentage of Women Experiencing a Contraceptive Failure During the First Year of Use and the Percentage Continuing Use at the End of the First Year Women Experiencing Women Accidental Pregnancy within Continuing Use the First Year of Use (%) at 1 Year (%) Combined pill and progestin-only pill 8 0.3 68 Patch (Evra™) 8 0.3 68 NuvaRing 8 0.3 68


Gynecology_Novak

Gynecology_Novak. Women Experiencing Women Accidental Pregnancy within Continuing Use the First Year of Use (%) at 1 Year (%) Combined pill and progestin-only pill 8 0.3 68 Patch (Evra™) 8 0.3 68 NuvaRing 8 0.3 68 ParaGard™(Copper T380A) 0.8 0.6 78 Myrena (levonorgestrel T) 0.1 0.1 81 DepoProvera 3 0.3 70 Lunelle 3 0.05 56 Norplanta and Norplant II 0.05 0.05 84 Implanon™ 0.05 0.05 84 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 aCumulative 5-year pregnancy rate for pliable tubing, divided by 5. From Hatcher RA, Trussell J, Stewart F, et al. Contraceptive technology. 18th ed. New York: Ardent Media, 2004:226, with permission.


Gynecology_Novak

Gynecology_Novak. present methods of contraception are assigned to one of four categories of suitability of use by women with more than 60 characteristics or conditions. The categories are: 1. A condition for which there is no restriction for the use of the contraceptive method; 2. A condition for which the advantages of using the method generally outweigh the theoretical or proven risks; Table 10.3 Overview of Contraceptive Methods HIV, human immunodeficiency virus; IUD, intrauterine device; PID, pelvic inﬂammatory disease; MI, myocardial infarction; DMPA, depomedroxyprogesterone acetate; STDs, sexually transmitted diseases. 3. A condition for which the theoretical or proven risks usually outweigh the advantages of using method; 4. A condition that represents an unacceptable health risk if the contraceptive method is used.


Gynecology_Novak

Gynecology_Novak. A condition that represents an unacceptable health risk if the contraceptive method is used. Cost Some methods, such as intrauterine devices (IUDs) and subdermal implants, require an initial high investment but provide prolonged protection for a low annual cost. A complex cost analysis based on the cost of the method plus the cost of pregnancy if the method fails concludes that sterilization and the long-acting methods are the least expensive over the long term (8) (Table 10.4). Table 10.4 Cost per Patient per Year of Contraceptive Methods a For every $1.00 spent on vasectomy, the amount shown would be spent on the method indicated. From Ashraf T, Arnold SB, Maxfield M. Cost effectiveness of levonorgestrel subdermal implants: comparison with other contraceptive methods available in the United States. J Reprod Med 1994;39:791–798, with permission.


Gynecology_Novak

Gynecology_Novak. Several contraceptive methods are as effective as sterilization, but are completely reversible. All have the important advantage of being “forgettable,” that is, little is required of the user after the method is begun, very much in contrast to methods like the condom that must be used with each act of intercourse, or the OC, which must be taken daily. These forgettable methods have pregnancy rates in typical use of less than 2 per 100 woman-years, are effective for at least 3 months without attention from the user, and are among the safest methods. They include the injectable progestins, depomedroxyprogesterone acetate (DMPA) and norethindrone enanthate, the etonogestrel and levonorgestrel subdermal implants, copper-bearing intrauterine devices such as the copper T380A and the levonorgestrel-releasing intrauterine system (9,10).


Gynecology_Novak

Gynecology_Novak. Coitus Interruptus Coitus interruptus is withdrawal of the penis from the vagina before ejaculation. This method, along with induced abortion and late marriage, is believed to account for most of the decline in fertility of preindustrial Europe (11). Coitus interruptus remains a very important means of fertility control in many countries. Eighty-five million couples are estimated to use the method worldwide, yet it has received little recent formal study. This method has obvious advantages: immediate availability and no cost. The penis must be completely withdrawn both from the vagina and from the external genitalia. Pregnancy has occurred from ejaculation on the female external genitalia without penetration. Coitus interruptus reduces transmission of human immunodeficiency virus (HIV) in mutually monogamous couples (12). Theoretically, some reduction of risk from other STDs would be expected, but this phenomenon apparently was not studied. Efficacy is estimated to range from 4


Gynecology_Novak

Gynecology_Novak. in mutually monogamous couples (12). Theoretically, some reduction of risk from other STDs would be expected, but this phenomenon apparently was not studied. Efficacy is estimated to range from 4 pregnancies per 100 women in the first year with perfect use to 27 per 100 with typical use (Table 10.2). Jones and colleagues offer a modern review of this practice and conclude that it likely is as effective as the condom (13).


Gynecology_Novak

Gynecology_Novak. Breastfeeding Breastfeeding can be used as a form of contraception and can be effective depending on individual variables. The use of contraception during lactation should take into consideration the women’s needs and the need to maintain lactation.


Gynecology_Novak

Gynecology_Novak. Ovulation is suppressed during lactation. The suckling of the infant elevates prolactin levels and reduces gonadotropin-releasing hormone (GnRH) from the hypothalamus, reducing luteinizing hormone (LH) release and thus inhibiting follicular maturation (14). Even with continued nursing, ovulation eventually returns but is unlikely before 6 months, especially if the woman is amenorrheic and is fully breastfeeding with no supplemental foods given to the infant (15). For maximum contraceptive reliability, feeding intervals should not exceed 4 hours during the day and 6 hours at night, and supplemental feeding should not exceed 5% to 10% of the total amount of feeding (16). Six-month pregnancy rates of 0.45% to 2.45% are reported for couples relying solely on this method (17). To prevent pregnancy, another method of contraception should be used from 6 months after birth or sooner if menstruation resumes. Breastfeeding reduces the mother’s lifetime risk of breast cancer (18).


Gynecology_Novak

Gynecology_Novak. Use of combination estrogen–progestin hormonal methods (OCs, the patch, and the ring) is generally not advised during lactation because they reduce the amount and quality of breast milk. Combination hormonal methods can be used after 6 weeks, once milk production is established. Progestin-only OCs, implants, and injectable contraception do not affect milk quality or quantity (16). Labeling of the U.S. Food and Drug Administration (FDA) and guidelines from the American College of Obstetricians and Gynecologists suggest that progestinonly OCs can be started 2 to 3 days postpartum, whereas depot medroxyprogesterone acetate (Depo Provera) injections or implants can begin at 6 weeks (19). These recommendations are not based on any observed adverse effect of early administration, and many maternity programs begin injectable contraception with progestin at the time of hospital discharge. Barrier methods, spermicides, and the copper T380A intrauterine device (IUD) (ParaGard) are good options


Gynecology_Novak

Gynecology_Novak. programs begin injectable contraception with progestin at the time of hospital discharge. Barrier methods, spermicides, and the copper T380A intrauterine device (IUD) (ParaGard) are good options for nursing mothers. Because levonorgestrel implants have no adverse effect on breastfeeding, none should be expected from the levonorgestrel T IUD, which releases levonorgestrel but produces lower blood levels than the implants.


Gynecology_Novak

Gynecology_Novak. Fertility Awareness Periodic abstinence, described as “natural contraception” or “fertility awareness,” requires avoiding intercourse during the fertile period around the time of ovulation. A variety of methods are used: the calendar method, the mucous method (Billings or ovulation method), and the symptothermal method, which is a combination of the first two methods. With the mucous method, the woman attempts to predict the fertile period by feeling the cervical mucus with her fingers. Under estrogen inﬂuence, the mucus increases in quantity and becomes progressively more slippery and elastic until a peak day is reached. The mucus then becomes scant and dry under the inﬂuence of progesterone until onset of the next menses. Intercourse may be allowed during the “dry days” immediately after menses until mucus is detected. Thereafter, the couple must abstain until the fourth day after the “peak” day.


Gynecology_Novak

Gynecology_Novak. In the symptothermal method, the first day of abstinence is predicted either from the calendar, by subtracting 21 from the length of the shortest menstrual cycle in the preceding 6 months, or the first day mucus is detected, whichever comes first. The end of the fertile period is predicted by use of basal body temperature. The woman takes her temperature every morning and resumes intercourse 3 days after the thermal shift, the rise in body temperature that signals that the corpus luteum is producing progesterone and that ovulation occurred. The postovulatory method is a variation in which the couple has intercourse only after ovulation is detected.


Gynecology_Novak

Gynecology_Novak. A system of hormone monitoring designed to better define the fertile period involves placement of disposable test sticks in a small battery-powered device to detect urinary estrone-3 glucuronide and LH. Changes in these hormones reliably predict the fertile period. These devices (Persona™ and Clearblue Easy Fertility Monitor™) can serve as aids both to becoming pregnant and to avoiding it (20). Persona™ is marketed in Europe for contraception. It is reported to have a correct use effectiveness of 94% in avoiding pregnancy. Clearblue Easy™ (CEFM) is approved in the United States as an aid to becoming pregnant but is used off label to avoid pregnancy. Exact effectiveness rates are not known. The CEFM is used in the Marquette method, which combines observation of cervical mucus changes with the CEFM results. A correct use pregnancy rate of 2% and a typical use pregnancy rate of 12% were reported (21).


Gynecology_Novak

Gynecology_Novak. The ovulation method was evaluated by the World Health Organization in a five-country study. Women who successfully completed three monthly cycles of teaching were enrolled in a 13-cycle efficacy study. There was a 3.1% probability of pregnancy in 1 year for the small proportion of couples who used the method perfectly and 86.4% probability of pregnancy for the rest (22). A review of 15 national surveys from developing countries estimated a 12-month gross failure rate of 24 pregnancies per 100 (23). Conceptions resulting from intercourse remote from the time of ovulation more often lead to spontaneous abortion than conceptions from midcycle intercourse (24). Malformations are not more common (18).