Chpt 33 Menopause – Flashcards
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What is the definition of menopause?
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Cessation of menses for 12 months due to the loss of ovarian activity.
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What is the definition of perimenopause?
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The period of time immediately before and after menopause ending prior to completion of 12 months after the last menstrual period.
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Approximately how long is the perimenopausal period?
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Four years.
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What is the definition of the climacteric?
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The transition from the reproductive stages of life to the postmenopausal years, a period marked by waning ovarian function—this includes perimenopause and menopause.
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What is the mean age for menopause?
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51.4 years.
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What percentage of their lifetime will most women spend in postmenopausal life?
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30%. Given a life expectancy of 75 years and a median age of 51 for menopause.
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How much of the female population in the United States is currently postmenopausal?
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20%. This is increasing because life expectancy is also increasing.
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What causes earlier menopause?
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Smoking, low weight, some women who had hysterectomies, malnourishment, living at high altitudes, mosaic Turner's, and genetic predisposition. Age of menarche, race, family history, and parity do not influence age of menopause.
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How much earlier does menopause occur in smokers?
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About 2 years.
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What percentage of women will undergo premature menopause (before age 40)?
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1%.
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What percentage of women will undergo late menopause (after age 55)?
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5%.
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What percentage of women will undergo early menopause (between ages 40 and 45)?
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5%.
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What is the weight of the postmenopausal ovary?
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5 g.
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What histological changes occur in the ovary with menopause?
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Lack of follicles and a prominent stroma.
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What are the common changes associated with estrogen depletion?
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Menstrual cycle changes, cardiovascular disease, osteoporosis, genitourinary atrophy, vasomotor psychological, and sexual symptoms
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What happens to the menstrual cycle with age?
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Initially, the follicular phase and cycle decreases and then increases prior to menopause, and luteal phase defects may occur.
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What happens to gonadotropin levels in the premenopausal years?
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Follicle-stimulating hormone (FSH) increases (as a result of decreased inhibin production from granulosa cells) and luteinizing hormone (LH) remains the same.
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Why cannot FSH levels be suppressed in menopause?
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Inhibin production from granulosa cells is lost. Inhibin normally suppresses FSH levels prior to menopause. Inhibin is the hormone that starts to decline first in the climacteric.
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What FSH values are indicative of menopause?
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Levels >35 IU/L, but may vary based on laboratory.
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What are the expected changes in gonadotropin levels after menopause?
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FSH increases 10- to 20-fold and LH increases 3-fold, reaching a maximum 1 to 3 years after menopause.
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Which hormones decline as a result of menopause?
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Estrogen, androstenedione, and progesterone.
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Which hormones decline as a result of age?
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Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and testosterone.
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What is the level of DHEA-S in a 70-year-old compared with peak levels in a 25-year-old?
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10% to 20% of peak.
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Where is most of the postmenopausal androstenedione produced?
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The adrenal gland.
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How much estradiol (E2) is produced each day in postmenopausal women?
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6 μg/day, decreased from 80 to 500 μg/day in reproductive age women.
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How much estrone (E1) is produced each day in postmenopausal women?
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40 μg/day, decreased from 80 to 300 μg/day in reproductive age women.
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What is the circulating estradiol (E2) level in women after menopause?
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10 to 20 pg/mL (40 to 70 pmol/L).
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What is the primary source of estrogen in postmenopausal women?
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Peripheral conversion of adrenal and ovarian androgens by extraglandular aromatase in adipose.
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What is the predominant estrogen of the postmenopausal woman?
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Estrone (E1).
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What is the biological potency of estrone compared with estradiol?
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It is only one third as potent as estradiol.
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What happens to progesterone production in menopause?
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Progesterone is no longer produced.
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What hormone is secreted more by the postmenopausal ovary than the premenopausal ovary?
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Testosterone; prior to menopause the ovary contributes 25% of circulating testosterone and in menopause the ovary contributes 40% of circulating testosterone.
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Why does the postmenopausal ovary produce more testosterone than the premenopausal ovary?
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Elevated gonadotropins stimulate the stromal tissue to secrete testosterone.
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Although the ovary produces increased testosterone in menopause, why is the total amount of testosterone not increased?
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Androstenedione is reduced, adrenal testosterone is reduced, and sex hormone binding globulin (SHBG) levels are reduced.
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Does serum testosterone change over the menopausal transition?
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No.
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What is the cause of mild hirsutism in menopause?
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Increased free androgen to estrogen ratio as a result of decreased SHBG and estrogen.
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What increases aromatization of androgens to estrogens?
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Age and weight. Aromatase activity increases twofold in the perimenopausal period and adipose tissue is a rich source of aromatase.
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In which tissues has aromatase been identified?
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Liver, fat, muscle, and certain hypothalamic nuclei
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What is the leading cause of death for women?
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Heart disease, followed by malignancies, cerebrovascular disease, and motor vehicle accidents.
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How many deaths are attributed to cardiovascular disease in women over 50?
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>50%.
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What is the risk of heart disease after menopause compared with premenopause?
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Twice the risk.
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What are the risk factors for cardiovascular disease?
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Hypertension, smoking, diabetes, hypercholesterolemia, obesity, and family history.
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Does the onset of heart disease occur at the same age in men as it does in women?
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No. Typically the onset of heart disease occurs 10 years later in women. Similarly, myocardial infarction and sudden death typically occur 20 years later in women than in men.
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What cholesterol fraction is associated with atherosclerosis in women?
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High-density lipoprotein (HDL) is more closely associated than low-density lipoprotein (LDL).
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How important are triglycerides in predicting coronary risk?
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Triglycerides are uniquely predictive in older women, especially at levels above 400 mg/dL.
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What contributes to cardioprotection in women?
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Higher HDLs, 10 mg/dL higher than in men, an effect of estrogen.
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What are the changes in cholesterol fractions at the age of menopause?
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HDL decreases, LDL increases, and the average cholesterol increases to levels higher than in men.
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What is estrogen's effect upon lipids and lipoproteins?
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It increases HDL and decreases total cholesterol and LDL.
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What lipoprotein-independent mechanisms of estrogen may protect against cardiovascular disease?
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Vasodilatation, decreased platelet aggregation, decreased smooth muscle cell proliferation of arterial vessels, direct inotropic actions on the heart, antioxidant activity, favorable impact on clotting mechanisms, inhibition of intimal thickening, inhibition of macrophage foam cell formation, improved glucose metabolism, and decreased insulin levels.
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Are estrogen and progesterone receptors present in the vascular tree?
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Yes. In the endothelium and smooth muscles of arterial vessels.
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How does estrogen exert a cardioprotective effect through the vasculature?
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Vasodilatation and decreased peripheral resistance.
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How does estrogen exert cardioprotection via endothelium-dependent mechanisms?
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Augmentation of nitric oxide and prostacyclin leading to vasodilation and decreased platelet aggregation.
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What direct effects does estrogen have on the heart?
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Increases left ventricular diastolic filling and stroke volume, delaying age-related decreases in compliance.
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What effect does acute administration of estradiol have on myocardial ischemia in women with coronary artery disease?
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Signs of ischemia on electrocardiograms are delayed and exercise tolerance is increased.
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How does estrogen decrease LDL levels?
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It increases hepatic LDL catabolism and increases LDL receptors.
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How does estrogen increase HDL levels?
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It inhibits hepatic lipase activity.
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How does estrogen replacement therapy exert an antioxidant cardioprotective effect?
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It inhibits LDL oxidation and resultant endothelial vasospasm.
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What other antioxidants may decrease the risk of coronary artery disease?
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Vitamin E and β-carotene (the prohormone of vitamin A).
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What effect does estrogen have on body fat distribution?
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It prevents the tendency to increase central body fat with aging.
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What is the relationship between truncal adiposity and coronary heart disease?
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An increased waist to hip circumference ratio is associated with an increased risk of coronary heart disease. Truncal adiposity is associated with an androgenic state, hypertension, insulin resistance, hyperinsulinemia, and an atherogenic lipid profile, all risk factors for coronary heart disease.
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What lipid profiles are correlated with women who have a central body fat distribution?
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Positive correlation with increases in total cholesterol, triglycerides, and LDL and negatively correlated with HDL.
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What effect does oral estrogen have on diabetes?
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The Nurses Health Study documented a 20% decreased risk of noninsulin dependent diabetes in current users of estrogen.
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Does postmenopausal estrogen replacement therapy adversely affect hypertension?
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No.
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What did the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial demonstrate regarding hormone replacement therapy (HRT) and cardiovascular disease risk factors?
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Estrogen as well as estrogen progestin combinations had a favorable impact on cardiovascular risk factors, an increase in HDL, a decrease in LDL, as well as prevention of the age-related increase in fibrinogen.
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In the PEPI trial, which progesterone combined with conjugated equine estrogen had the most favorable effect on HDL?
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Cyclic micronized progesterone resulted in a significantly greater increase in HDL than either sequential or cyclic medroxyprogesterone acetate.
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What did the Women's Health Initiative (WHI) show regarding cardiovascular risk of HRT?
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An increase in coronary events with Prempro and no significant difference with Premarin.
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What is osteoporosis?
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A progressive, systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue, leading to an increase in bone fragility and susceptibility to fracture (World Health Organization).
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In what type of bone is resorption more prevalent?
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Trabecular bone, which is the predominant type of bone in the spine, because it is most sensitive to changes in estrogen levels.
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What is the role of osteoclasts?
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They absorb and remove osseous tissue, forming lacuna.
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What is the role of osteoblasts?
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They deposit the osseous matrix called osteoid (B is for build).
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At what age does bone loss begin on most women?
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In the spine (trabecular bone), bone loss typically begins at age 20. However, the femur, which is made up of cortical bone, maximum density is typically in the late 20s.
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At what age does bone resorption exceed formation?
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40, by about 0.5%.
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After menopause, what is the percentage of bone loss per year?
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5% per year in trabecular bone, 1% per year total bone loss.
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What is the most important factor associated with bone loss?
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Age.
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What are the other risk factors for osteoporosis?
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Family history, early menopause (younger than 45), Caucasian or Asian race, low body weight, smoking, excessive alcohol use, sedentary lifestyle, low calcium intake, low vitamin D intake, poor health, impaired vision, natural menopause, surgical menopause, glucocorticoids, and caffeine intake.
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What medications are associated with bone loss?
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Corticosteroids, thyroid hormone, anticonvulsants, and heparin.
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What mechanisms contribute to osteoporosis?
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Menopause, thyrotoxicosis, glucocorticoid excess, hyperparathyroidism, multiple myeloma, leukemia or lymphoma, alcoholism, long-term heparin therapy, immobilization, and metastatic cancer.
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What preventive measures can be taken for osteoporosis early in life?
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Improved calcium intake, diet, weight-bearing exercise, avoidance of alcohol and smoking, and maintenance of normal menstrual cycles.
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What is the most common site of fractures in menopause?
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Vertebral fractures, they account for 50% of all fractures. 25% of women over age 70 will experience vertebral fractures.
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What is the expected loss in height as a result of vertebral fractures in untreated postmenopausal women?
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2.5 inches (6.4 cm).
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What percentage of patients will die within 1 year after hip fracture?
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20%, due to complications of prolonged immobilization.
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How does estrogen therapy help maintain bone mass?
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A direct effect on osteoblasts, improved intestinal absorption of calcium, and decreased renal excretion of calcium.
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What is the total calcium requirement to minimize bone loss in postmenopausal women not taking estrogen replacement?
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1500 mg.
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What is the total calcium requirement to minimize bone loss in women on estrogen replacement therapy?
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1200 mg.
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In addition to calcium, in women over the age of 70, what other supplementation should be included for osteoporosis fracture prevention?
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Vitamin D 800 IU, especially if in Northern latitudes.
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Does skim milk have less calcium than whole milk?
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No. Since calcium is water-soluble skim milk has more calcium than whole milk.
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What disease process can be unmasked with high calcium supplementation?
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Asymptomatic hyperparathyroidism.
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What other agents are known to reduce bone resorption?
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Calcitonin, fluoride, androgens and bisphosphonates (etidronate disodium, risedronate, alendronate), SERMS (selective estrogen receptor modulators such as raloxifene).
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Why is not calcitonin more widely used for osteoporosis?
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It is expensive and must be administered parenterally or nasally, and it is effective only against vertebral fracture reduction.
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How often are vertebral compression fractures asymptomatic?
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60% to 66% of the time.
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How many osteoporotic fractures occur each year in the United States?
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Approximately 1.3 million.
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How many of these are vertebral fractures?
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About 50%. Hip fractures account for another 25%.
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What percentage of Caucasian women will experience a hip fracture?
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20%.
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What percentage of bone is resting at any one time?
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88.
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What percentage of bone is remodeling (forming or resorbing) at any one time?
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12.
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What percentage of bone mass is formed in a young woman between the ages of 13 and 16?
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Almost 50.
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When does bone loss accelerate?
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After menopause, and the rapid loss continues for about 5 years. Accelerated bone loss has also been observed in women 2 to 3 years prior to the cessation of menstruation; the rate of bone loss was correlated to an elevation of FSH and bone turnover markers.
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What percentage of bone mass is lost in this time?
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20.
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Are osteoporotic fractures more common than heart attack, stroke, and breast cancer combined?
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Yes.
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What percentage increase in mortality is seen after hip fracture?
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24.
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What percentage of hip fracture survivors are incapacitated for an extended time?
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50.
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In women who have a vertebral fracture, what percentage will have another fracture within a year?
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19%. After one vertebral fracture, there is a fivefold increased risk of a second vertebral fracture and almost a twofold increased risk of a hip fracture.
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Does a hip fracture increase the risk of a second hip fracture?
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Yes.
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Which is more common, a fall causing a hip fracture or a fracture causing a fall?
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A fall causing a fracture is much more common.
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What are the secondary causes of osteoporosis?
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Low vitamin D intake, low calcium intake, irritable bowel syndrome, diabetes malabsorption syndromes, hyperparathyroidism, hyperthyroidism, malnutrition, liver disease, glucocorticoids, heparin, rheumatoid arthritis, and osteoarthritis.
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Who should have tests for bone mineral density (BMD) (DXA scan)?
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All women 65 years or older without risk factors. All postmenopausal women younger than 65 with risk factors. All postmenopausal women younger than 65 with a history of fracture. All postmenopausal women considering therapy for osteoporosis. All women on estrogen/progestogen therapy for a prolonged period (National Osteoporosis Foundation Guidelines).
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How is osteoporosis diagnosed? What is the most accurate technique available for measuring bone density?
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Using dual energy absorptiometry (DXA) measuring the hip and lumbar spine (central DXA). This is the most accurate technique available for measuring bone density. DXA scans are reported using a T score.
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What hip areas are routinely assessed for BMD using a DXA scan?
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The femoral neck, trochanter, Ward's triangle, and intertrochanter.
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What areas are most reproducible on DXA?
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A-P spine and femoral neck.
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What is the ideal screening interval for DXA?
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Every 2 years.
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Can a peripheral DXA (heel, finger, wrist) be used to diagnose osteoporosis?
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No. These are used to screen for osteoporosis. The diagnosis is made by central DXA.
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Can a peripheral DXA be used to predict fracture risk?
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Yes (NORA trial).
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What is the T score?
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A measurement of BMD that indicates the number of standard deviations above or below the average peak bone mass in a young woman.
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What does the T score indicate?
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A T score of -1.0 is one standard deviation below peak bone mass, and represents about a 10% loss in bone mass at the site measured.
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What is the Z score?
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This number indicates the number of standard deviations from average bone mass compared with a population the same age. If there is a significant variance, one should look for secondary causes of osteoporosis.
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Does the T score correlate with fracture risk?
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Yes. For each T score below normal the risk of fracture doubles at that site. (A T score of -1.0 doubles the fracture risk compared with a T score of 0.0.)
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How does age relate to fracture risk and T score?
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As age increases fracture risk increases at the same T score.
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Does the T score fully explain the fracture risk at one particular site?
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No. There are other characteristics that impact bone strength that are difficult to measure.
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What is the Fracture Risk Assessment tool (FRAX)?
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An online tool developed by the World Health Organization to predict an individual's 10-year fracture risk. It can be used with or without a bone mineral density result. It is used to help guide in treatment decisions.
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What impacts bone strength?
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Bone quality, bone turnover, and microarchitecture.
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Can you see a normal T score at one site and osteoporosis at another site in the same patient?
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Yes.
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What T score is considered normal?
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Above -1.0 (WHO).
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What T scores suggest low bone mass, or osteopenia?
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Between -1.0 and -2.5.
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What T score represents osteoporosis?
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Less than -2.5.
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What is severe osteoporosis?
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A T score of -2.5 or below with a previous fracture.
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When should treatment be started for osteoporosis?
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When the T score at the A-P spine or hip is -2.0 or lower without risk factors, or -1.5 or lower with risk factors (NOF Guidelines).
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What are biochemical markers of bone formation?
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Bone-specific alkaline phosphatase and osteocalcin.
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What are the biochemical markers for bone resorption?
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Pyridinoline, N-telopeptides, and c-telopeptides.
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Are biochemical markers usually used in individual patients to help diagnose osteoporosis?
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No. They are used more in research in large groups of patients to evaluate how effective a drug is regarding its effect on bone.
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What therapies are currently available to treat osteoporosis?
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Alendronate, risedronate, and ibandronate, which are bisphosphonates. Raloxifene, a SERM. Calcitonin nasal spray. These are all antiresorptive agents—less bone resorbed by osteoclasts. Another medication is teriparatide, a form of parathyroid hormone (PTH)—functions as an anabolic agent.
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What therapy is presently used only to prevent osteoporosis?
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Estrogen-progestin therapy.
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In the WHI trial, what effect did estrogen plus progestin have on fracture risk?
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There was a reduction in fractures of the spine and hip in patients who took estrogen plus progestin compared with placebo.
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Is it necessary to supplement an osteoporosis therapy drug with calcium and vitamin D to obtain maximal fracture protection?
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Yes.
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How important is it for a patient at risk of osteoporosis to exercise, specifically walking and upper body strengthening?
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Extremely important. This reduces the risk of falling and thus reduces the risk of fracture.
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Is long-term steroid use a risk factor for osteoporosis?
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Yes.
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How soon after starting steroids does one see significant bone loss?
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3 months.
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What percentage of patients taking prednisone 7.5 mg or greater develop an osteoporotic fracture?
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50.
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Can lower doses of steroids also increase risk of fracture?
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Yes.
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Does age or gender impact fracture risk if a person is on steroids?
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No.
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How do steroids affect bone?
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They cause a toxic effect on osteoblasts, which shortens their lifespan. Calcium absorption is blocked through the intestine. Calcium is also lost by the kidney, decreasing serum calcium. This causes PTH to be secreted, thereby increasing bone resorption.
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How soon after treatment is started should a repeat DXA be done?
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1 to 2 years. The sensitivity of DXA is such that it would take this long to see a meaningful change. One exception is a patient on steroids. In this situation, the DXA can be done as early as 6 months.
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What change would you expect to see after 1 to 2 years of treatment?
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The DXA should show stabilization or improvement in BMD.
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What if there is a significant loss (>4-5%) at 2 years?
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Check the Z score. If it is lower than expected, evaluate for secondary causes of osteoporosis.
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What logical steps can be suggested to a patient to prevent falls?
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Safeguard the home by removing electrical wires from the floor. Remove throw rugs. Improve lighting. Evaluate the patient's vision. Treat urinary incontinence—fewer nighttime awakenings and decrease urine leakage onto floor.
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Can smoking one pack per day throughout adulthood reduce bone density by as much as 10% by menopause?
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Yes.
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What percentage of patients with hip fractures have histological evidence of osteomalacia, the classic manifestation of vitamin D deficiency?
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30%.
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What is the largest source of dietary vitamin D?
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Milk.
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What genitourinary tissues are estrogen sensitive?
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The vagina, vulva, urethra, and trigone of the bladder.
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What vaginal symptoms are related to atrophy?
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Dryness, dyspareunia, and recurrent atrophic vaginitis.
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What causes dyspareunia in aging women?
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Decreased vaginal lubrication and elasticity.
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Is vaginal estrogen therapy more effective than moisturizers and lubricants?
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Yes.
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How much greater is the potency of vaginal conjugated estrogens than that of oral conjugate estrogens?
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Four times greater.
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What is the most common vulvar symptom of menopause relieved with estrogen replacement?
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Burning and pruritis secondary to atrophy.
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Pruritis is also the presenting complaint of vulvar dystrophies. What percentage of vulvar dystrophies are squamous cell carcinomas?
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5% on initial exam, another 5% may develop squamous cell carcinomas within 3-5 years after hypertrophic vulvar dystrophy is diagnosed.
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What is the most common cause of postmenopausal bleeding?
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Endometrial atrophy.
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Why does vaginitis increase during the postmenopausal years?
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Due to estrogen deficiency, the vaginal pH increases from 3.5-4.5 to 6.0-8.0, predisposing to colonization of bacterial pathogens.
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What cervical changes are associated with menopause?
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Stenosis, atrophy, erosion, and ulcers.
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What changes occur in the squamocolumnar junction and transformation zone?
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They migrate up into the endocervical canal.
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What urethral conditions can develop as a result of estrogen deficiency?
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Ectropion (urethral caruncle), diverticula, and urethrocoele.
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What is the most common problem in menopause related to urethral changes?
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Urethral syndrome, consisting of burning, frequency, hesitancy, nocturia, and urgency associated with sterile urine cultures.
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How is the urethral syndrome treated?
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Estrogen therapy.
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What urinary symptoms are associated with atrophy?
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Dysuria, urgency, and recurrent urinary tract infections.
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Does bacteriuria increase in menopause?
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Yes. The incidence of bacteriuria increases from 4% in reproductive age women to 7-10% in postmenopausal women. This is due to thinning of the urothelium, which predisposes to ascending infections, particularly with intercourse.
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Is urinary stress incontinence related to estrogen deficiency?
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Yes. Urethral shortening and decreased urethral closing pressures associated with atrophy may contribute to urinary incontinence.
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Can urge incontinence be treated with estrogen therapy?
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Yes.
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Can estrogen therapy improve urinary stress incontinence?
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There is conflicting data, but the best available evidence suggests estrogen therapy is not effective.
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What is the best initial therapy for urinary stress incontinence?
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Kegel exercises.
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What other treatments exist for urinary stress incontinence?
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Duloxetine (SNRI), collagen injections, and surgery
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What is a hot flash?
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Sudden onset of warmth and reddening of the skin beginning in the head spreading to the neck and chest, sometimes concluded by profuse perspiration, lasting a few seconds to several minutes. It is often accompanied by palpations and feelings of anxiety.
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What percentage of women experience hot flashes?
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75% to 85%.
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What is the physiology of the hot flash?
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It originates in the hypothalamus and represents thermoregulatory instability in response to estrogen fluctuation.
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How long do hot flashes typically continue?
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Typically 1 to 2 years, usually 5 years at most. The incidence of flashes is 80% at 1 year and 20% at 5 years.
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What physiologic changes are associated with the hot flash?
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An LH surge, an increase in body surface temperature, and skin conductance followed by a decline in core body temperature.
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What's the frequency of hot flashes?
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Usually several times a day. Can range from 1 to 2 daily to 1 per hour.
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Are hot flashes more common at night?
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Yes.
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What effect do "night sweats" (hot flashes at night) have?
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Interruption of sleep patterns and thus a decline in sleep quality and length.
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How does estrogen exert its effects on improving "quality of life" in postmenopausal women?
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Alleviation of hot flashes and improved quality of sleep leading to improved mood, memory, and quality of life.
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What alternatives to estrogen are partially effective in treating hot flashes?
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Clonidine, medroxyprogesterone acetate, methyldopa, SSRIs, gabapentin, and black cohosh.
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What alternatives to estrogen are ineffective in treating hot flashes?
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Bellergal, propranolol, vitamin E, and soy extracts.
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What alternatives to estrogen are currently recommended for the treatment of hot flashes?
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">Transdermal clonidine 100 μg weekly, Effexor 37.5 to 75 mg qd, and black cohosh.
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Are there any safety data on black cohosh?
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Yes. For use up to 6 months.
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What is the first diagnostic test recommended for postmenopausal bleeding if the uterus is normal?
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Endometrial biopsy.
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In the perimenopausal period, after exclusion of gynecological causes of dysfunctional uterine bleeding (DUB), what endocrine gland should be evaluated?
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The thyroid gland.
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What endometrial thickness on ultrasound requires biopsy in postmenopausal women?
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4 mm.
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How do you treat simple hyperplasia in perimenopause?
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Monthly oral progestin therapy, repeat biopsy in 6 months, if hyperplasia persists, D&C.
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How effective is monthly progestin therapy in treating simple hyperplasia?
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95% to 98% of the time.
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What is the incidence of endometrial hyperplasia after 1 year of unopposed estrogen (conjugated estrogen 0.625 mg or its equivalent)?
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20% incidence of hyperplasia, predominantly simple hyperplasia.
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When DUB in perimenopause is diagnosed, what are the treatment options?
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Observation, oral contraceptives, and progestational agents.
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What is the incidence of adenomatous or atypical hyperplasia in unopposed estrogen users?
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10% per year.
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What percentage of atypical endometrial hyperplasia will progress to cancer within 1 year?
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20% to 25%.
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What is the time required for endometrial hyperplasia to progress to cancer?
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5 years.
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What is the risk of endometrial cancer in postmenopausal women not on HRT?
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4 per 1000 (0.4%).
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What is the risk of endometrial cancer in postmenopausal women with abnormal uterine bleeding?
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20%.
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How much higher is the risk of endometrial cancer in patients on unopposed estrogen compared with the general population?
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2 to 10 times higher, depending on dose and duration of exposure.
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How long does the risk of endometrial cancer persist after discontinuation of estrogen?
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10 years.
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What characteristics of endometrial adenocarcinoma are present in patients on estrogen therapy?
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Most lesions are low grade and early stage, and associated with better survival.
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What is the 5-year survival rate in women whose uterine cancer was diagnosed while they were taking estrogen replacement therapy?
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95%.
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How does progesterone counter effect estrogen on endometrial growth?
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It decreases estrogen receptors, induces enzymatic conversion of estradiol to an excreted conjugate, estrone sulfate, and suppresses estrogen-induced oncogene transcription.
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What are the top three types of cancer diagnosed in women?
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Breast cancer. Lung cancer. Colorectal cancer. In men—Prostate (1), lung (2), and colorectal (3).
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What is the leading cause of cancer deaths in women?
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Lung cancer. Breast cancer is second.
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What is the leading gynecologic cancer in women?
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Endometrial cancer.
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What is the leading cause of gynecologic cancer deaths in women?
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Ovarian cancer.
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Is there an increased risk of breast cancer associated with estrogen replacement therapy?
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There may be a slightly increased risk of breast cancer especially with long duration of use (5 or more years in users of continuous combined therapy).
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Do estrogen users have improved breast cancer survival?
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Yes. This is probably as a result of earlier diagnosis but this is controversial after the results of the WHI.
question
Does estrogen use affect breast cancer tumor differentiation?
answer
Yes. Women on estrogen develop better differentiated tumors.
question
What is the diagnosis of an adnexal mass in menopause?
answer
Cancer, until proven otherwise.
question
What type of adnexal mass may be managed conservatively, with serial ultrasounds?
answer
Clear fluid filled cysts without septations, <5 cm.
question
What is the risk of breast and ovarian cancer in BRCA carriers?
answer
50% to 80% and 40% to 60%, respectively.
question
Is the risk of breast cancer increased in all postmenopausal hormone users?
answer
Not according to WHI: not in users of Premarin.
question
What is the recommended screening for colon cancer?
answer
Colonoscopy in women over the age of 50 every 10 years. Alternatives are yearly Hemoccults with sigmoidoscopy or barium enema every 5 years.
question
Who should be offered genetic screening for BRCA mutation?
answer
Women with a history of a first-degree relative with premenopausal breast cancer or a family history of several women with breast and/or ovarian cancer or women with premenopausal breast or ovarian cancer.
question
What can be recommended for BRCA protection for mutation-positive women?
answer
Prophylactic oophorectomy in the late 40s or use of oral contraceptive pill for long term.
question
Is oophorectomy 100% protective in these women?
answer
No. About 2% to 3% of women get primary peritoneal cancer.
question
What dosages of the following estrogens are equivalent to conjugated estrogens 0.625mg?
answer
Oral micronized estradiol - 1mg Transcutaneous 17 beta-estradiol - 0.05mg Estrone sulfate - 0.625mg Esterified estrogen - 0..625mg
question
What type of estrogens is present int he following medications?
answer
Premarin - conjugated estrogens Transdermal patch; Estrace - Estradiol Ogen - Estropipate Estratab - Esterified estrogens
question
What are conjugated estrogens?
answer
Estrone, Equilin, and 17 α-dihydroequilin; they have hydrophilic side groups attached to them, such as sulfate.
question
What is the daily dose of norethindrone equivalent to 2.5 mg medroxyprogesterone acetate?
answer
0.35 mg.
question
Can intravaginal estrogen be absorbed and have systemic effects?
answer
Yes. Atrophic mucosa absorbs estrogen readily. If the patient has a uterus, she needs progesterone therapy as well.
question
Is there an intravaginal estrogen therapy that is not systemically absorbed?
answer
Yes. Vagifem (vaginal estradiol) as well as vaginal estrogen ring.
question
What herbs contain estrogen-like compounds?
answer
Ginseng, black cohosh, and red clover.
question
What is the sequential method of hormone replacement administration?
answer
Estrogen on days 1 to 25 or 1 to 30 and medroxyprogesterone acetate 5 mg or norethindrone 0.5 mg for 13 days of estrogen administration per month.
question
What is the recommended dose of micronized progesterone for sequential therapy?
answer
200 mg for 14 days every month.
question
What is the continuous combined method of HRT?
answer
Daily estrogen and daily progestins, either medroxyprogesterone 2.5 mg, norethindrone 0.35 mg, or 100 to 200 mg micronized progesterone.
question
What concentration differences of estrogen exist in the portal system versus the periphery after oral estrogen administration?
answer
The estrogen concentration is four to five times higher in the portal system.
question
Does the first pass effect occur for transdermal estrogen administration?
answer
No.
question
What are some of the adverse symptoms associated with the dose of progesterone in sequential HRT?
answer
Withdrawal bleeding, breast tenderness, bloating, fluid retention, and depression.
question
What percentage of women on sequential hormone replacement will have progestin withdrawal bleeding?
answer
80% to 90%.
question
What percentage of women will experience breakthrough bleeding on continuous HRT?
answer
40% to 60% in the first 6 months and 20% after 1 year.
question
What is the origin of breakthrough bleeding in continuous HRT?
answer
Progestational dominance resulting in an atrophic endometrium.
question
What evaluation should be performed for breakthrough bleeding in patients on continuous therapy?
answer
Observation for the first 6 months, then consider endometrial biopsy, or hysteroscopy and D&C to rule out fibroids and polyps.
question
What are some conservative treatment alternatives to overcome breakthrough bleeding on continuous HRT?
answer
Observation, sequential therapy, or a progestin intrauterine device (IUD). A progestin IUD will suppress the endometrium.
question
Is the addition of progestin required in women on estrogen replacement who undergo endometrial ablation?
answer
Yes.
question
What are some causes of chronic estrogen exposure predisposing patients to a higher risk of endometrial changes?
answer
Obesity, DUB, anovulation and infertility, hirsutism, high alcohol intake, hepatic disease, diabetes, and hypothyroidism.
question
When should endometrial biopsies be performed prior to initiating HRT?
answer
Patients at high risk of endometrial changes associated with chronic estrogen exposure and a history of previous unopposed estrogen therapy, or patients with abnormal bleeding.
question
When is an endometrial biopsy recommended when breakthrough bleeding occurs on HRT?
answer
Women who have used unopposed estrogen in the past, an endometrial thickness >5 mm, or after 1 year of amenorrhea on HRT.
question
How should women who take unopposed estrogen be followed?
answer
Endometrial sampling or vaginal probe ultrasound yearly.
question
Why is the estrogen progesterone combination sometimes recommended in hysterectomized women with endometriosis?
answer
Adenocarcinoma has occurred in patients with endometriosis on unopposed estrogen.
question
What are some of the potential benefits of androgen replacement?
answer
Improved well-being and sexual behavior.
question
What negative effects does testosterone replacement therapy have?
answer
Hirsutism and adverse effects on lipids.
question
Patients with what stage of endometrial cancer can safely take estrogen replacement therapy?
answer
Stage 1 grade 1, and low-grade adenocarcinoma.
question
What conditions are not contraindications for HRT?
answer
Controlled hypertension, diabetes, and varicose veins.
question
Does estrogen replacement therapy promote fibroid tumor growth?
answer
No.
question
What gynecological malignancies are not contraindications to HRT?
answer
Ovarian, cervical, and vulvar.
question
What effect does estrogen therapy have on colorectal cancer?
answer
It significantly decreases the risk of colorectal cancer.
question
Does estrogen therapy improve visual acuity?
answer
Yes. Possibly due to the beneficial effect on lacrimal fluid and protection against lens opacities.
question
What effect does estrogen therapy have on oral complaints common in menopause?
answer
It relieves oral discomfort, burning, bad taste, and dryness. It also decreases gingival inflammation, bleeding, and tooth loss.
question
What effect does estrogen therapy have on skin?
answer
It prevents the age-related declines in skin collagen and thickness.
question
What effect does estrogen therapy have on muscle strength?
answer
It prevents the age-related decline in handgrip strength.
question
What are contraindications to estrogen therapy?
answer
Estrogen sensitive-cancers, chronically impaired liver function, undiagnosed genital bleeding, history of stroke, DVT or PE, neuro-ophthalmologic vascular disease, and known or suspected pregnancy.
question
What disorders may be aggravated by estrogen?
answer
Seizure disorders, familial hyperlipidemias (high triglycerides), and migraine headaches.
question
What effect does estrogen alone or in combination with progestin have on clotting factors in menopause?
answer
It prevents menopause-related increases in clotting factors (fibrinogen, factor VII, and plasminogen activator inhibitor) and does not alter antithrombin.
question
When is a history of venous thromboembolism not a contraindication to estrogen therapy?
answer
A thromboembolic event related to trauma.
question
Is there an increased risk of gallbladder disease with estrogen therapy?
answer
Estrogen therapy may increase the risk of gallbladder disease by 1.5- to 2.0-fold.
question
How is estrogen believed to induce cholelithiesis?
answer
Estrogen alters bile salts leading to stone formation.
question
What effect does oral estrogen replacement have on triglyceride levels?
answer
It increases triglyceride levels.
question
What route of estrogen administration does not affect triglycerides?
answer
Transdermal.
question
What complications can be precipitated by estrogen administration in women with elevated triglycerides?
answer
Pancreatitis and severe hypertriglyceridemia.
question
How should estrogen be administered to women with triglyceride levels between 250 and 750 mg/dL?
answer
A nonoral route of estrogen with careful surveillance of triglyceride levels.
question
How quickly do triglyceride levels increase after estrogen replacement administration?
answer
Triglycerides increase quickly and can be measured between 2 and 4 weeks.
question
What triglyceride levels are an absolute contraindication to estrogen therapy?
answer
>750 mg/dL.
question
What effect does estrogen have on Alzheimer disease?
answer
According to the NHS, Alzheimer disease is less frequent among HRT users, and cognitive function in affected individuals is improved; however, in WHI dementia is more frequent in HRT and ET users entering the study over age 65 although the difference is not statistically significant.
