THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

15. Women's Health - Andrea S. Franks, PharmD, BCPS

15-1. Postmenopausal Hormone Replacement Therapy

Introduction

Menopause is the permanent cessation of menses resulting from diminishing ovarian follicular function. It is defined as 12 consecutive months of amenorrhea. Median age of onset in the United States is 51 years of age (range 40-55). Physiologic changes and symptoms of menopause may present up to 8 years prior to cessation of menses.

Perimenopause, also called the menopausal transition, is the time before menopause and the first year following menopause. Ovarian function and production of estrogen decline during this time, and menstrual cycles may be irregular.

Clinical Presentation

• Cessation of menses for at least 12 consecutive months

• Symptoms of perimenopause related to declining estrogen:

• Anovulation

• Dysfunctional uterine bleeding

• Extended menstrual cycle intervals

• Oligomenorrhea

• Symptoms of menopause directly related to lack of estrogen:

• Vaginal dryness and vulvar or vaginal atrophy

• Vasomotor symptoms (night sweats, hot flashes)

• Symptoms associated with menopause, but without a proven link to estrogen deficiency:

• Arthralgia

• Depression

• Insomnia

• Migraines

• Mood swings

• Myalgia

• Urinary frequency

• Cognitive changes (memory, concentration)

Pathophysiology

• Loss of ovarian follicular activity results in endocrine, biologic, and clinical changes.

• Ovarian production of estradiol and progesterone diminishes.

• Follicle-stimulating hormone and luteinizing hormone concentrations increase.

• Primary estrogen available is now estrone (which is converted peripherally from androstenedione and is less potent), not estradiol.

Treatment Principles

• Women with an intact uterus must be treated with estrogen plus progestin to reduce the risk of endometrial hyperplasia and endometrial cancer.

• Women who have had a hysterectomy are treated with unopposed estrogen.

• Hormone replacement therapy (HRT) should be initiated on an individual basis with careful consideration of the risks and benefits.

• Contraindications to estrogen replacement therapy (ERT) are

• Abnormal, undiagnosed genital bleeding

• Known, suspected, or history of breast cancer

• History of deep-vein thrombosis or pulmonary embolism

• Estrogen-dependent neoplasia

• Pregnancy

• Stroke or myocardial infarction in the past year

• Liver dysfunction or disease

Drug Therapy

Table 15-1 provides an overview of selected HRT products.

Estrogen and progestin

Mechanism of action

ERT is used alone (if no uterus) or in combination with progestin to replace diminished levels of endogenous hormones.

Combined estrogen-progestin therapy (EPT) includes progestin to prevent endometrial hyperplasia and cancer.

Patient instructions and counseling

• Side effects of estrogen may be diminished by starting with a low dose and may be alleviated by changing products. Most side effects improve with time.

• Side effects of progestin may be alleviated or diminished by changing products or changing from a continuous to a cyclic regimen.

• Patients should be instructed to immediately report any unusual vaginal bleeding.

• Patients should be instructed to contact their physician promptly if any of the following events occur:

• Abdominal tenderness, pain, or swelling

• Coughing up of blood

• Disturbances of vision or speech

• Dizziness or fainting

• Lumps in the breast

• Numbness or weakness in an arm or leg

• Severe vomiting or headache

• Sharp chest pain or shortness of breath

• Sharp pain in the calves

Adverse drug events

Increased risks for venous thromboembolism, stroke, coronary heart disease, and breast cancer were identified in the Women's Health Initiative (WHI) trial with postmenopausal women receiving estrogen and estrogen plus progestin products. The beneficial effects included reductions in fractures and colorectal cancer. Both ERT and EPT should be used at the lowest doses and for the shortest possible time period for women who are experiencing moderate to severe vasomotor symptoms or vulvovaginal atrophy. Consider topical estrogen.

The following adverse effects are most common with estrogen:

• Breast tenderness

• Heavy or irregular bleeding

• Headache

• Nausea

The following adverse effects are most common with progestin:

• Depression

• Headache

• Irritability

Drug-drug and drug-disease interactions

Estrogen may exacerbate illness in the following disease states:

• Depression

• Hypertriglyceridemia (avoid by using transdermal product)

• Thyroid disorder (patients may require an increased dose of thyroid supplement)

• Impaired hepatic function (poor metabolism of estrogens)

• Cardiovascular disorders (coronary heart disease and venous thromboembolism risk may be increased with estrogens)

• Cholelithiasis

• Gastroesophageal reflux disease

Interaction may result in decreased pharmacologic effect of estrogens:

• Cytochrome P450 (CYP450) 3A4 inducers:

• Barbiturates

• Carbamazepine

• Rifampin

• St. John's wort

• Phenytoin

Interaction may result in increased pharmacologic effect of estrogens:

• CYP450 3A4 inhibitors:

• Azole antifungales

• Macrolide antibiotics

• Ritonavir

Parameters to monitor

Laboratory monitoring is not recommended. Patients should be monitored for symptom improvement, adverse effects, and appropriate health maintenance (e.g., through annual mammograms).

[Table 15-1. Selected Hormone Replacement Therapy Products]

Androgens (testosterone)

Mechanism of action

Androgens are the precursor hormones to estrogen production by the ovaries and peripheral sites. Ovarian testosterone production declines with menopause.

Androgens act at androgen receptor sites or exhibit action following conversion to estrogen. Androgen replacement improves deficiency-related symptoms (i.e., decreased sexual desire, decreased energy, diminished well-being).

Patient instructions and counseling

• Testosterone therapy should be administered only to postmenopausal women who are receiving concurrent estrogen therapy.

• The following are relative contraindications to testosterone therapy:

• Androgenic alopecia

• Hirsutism

• Moderate to severe acne

Adverse drug events

• Fluid retention

• Decreased high-density lipoprotein and triglycerides

• Hepatic dysfunction

• Hepatocellular carcinoma (prolonged use of high doses)

Parameters to monitor

Laboratory monitoring is not recommended.

Nondrug Therapy

Phytoestrogens

• Phytoestrogens are plant compounds (isoflavones, lignans, coumestans).

• Food sources of phytoestrogens include soy (milk, edamame, tofu); flaxseed; and alfalfa sprouts.

• Some studies have shown improvement in vaginal symptoms.

• Phytoestrogens may decrease loss of bone mineral density.

• No evidence supports improvement in other symptoms of menopause (i.e., hot flashes, depression, anxiety, headache, myalgia).

• Phytoestrogens may have beneficial effects on lipids, weight, blood pressure.

15-2. Contraception

Introduction

Contraception is the prevention of pregnancy by one of two methods:

• Preventing implantation of the fertilized ovum in the endometrium

• Inhibiting contact of sperm with mature ovum

Prescription Contraceptive Options

Oral contraceptives

• Estrogen plus progestin (combined oral contraceptive)

• Progestin only (minipill)

• Appropriate for use in breast-feeding women

• Less efficacious than combined oral contraceptives

• Free of cardiovascular risks associated with estrogen-containing products

• Long-term injectable or implanted products: progestin only

• Estrogens and progestins used in prescription contraceptives (

Table 15-2):

• Estrogens:

• Ethinyl estradiol

• Mestranol

• Progestins:

• Desogestrel

• Norgestrel; levonorgestrel

• Ethynodiol diacetate

• Norethindrone, norethindrone acetate, norethynodrel

• Drospirenone: progestin with progestogenic, anti-androgenic, and antimineralocorticoid activity

Drug Therapy

Mechanism of action

Estrogens prevent development of a dominant follicle by suppression of follicle-stimulating hormone. They do not block ovulation.

Progestin blocks ovulation. It contributes to the production of thick and impermeable cervical mucus. It also contributes to involution and atrophy of the endometrium.

Patient instructions and counseling

• Efficacy is high but depends on appropriate use and adherence.

• Oral contraceptives do not prevent the transmission of sexually transmitted diseases.

• Patients should be educated on warning signs of important complications:

• Severe abdominal pain

• Severe chest pain, shortness of breath, coughing up of blood

[Table 15-2. Prescription Contraceptive Products]

• Severe headache

• Eye problems (i.e., blurred vision, flashing lights, or blindness)

• Severe leg pain in the calf or thigh

• Patients should be advised to expect changes in characteristics of the menstrual cycle.

• Use of a backup contraceptive method is advised if more than one dose is missed per cycle.

Adverse drug events

The World Health Organization (WHO) suggests refraining from prescribing combined oral contraceptives to women with the following diagnoses:

• Breast cancer

• Deep-vein thrombosis or pulmonary embolism

• Cerebrovascular disease or coronary artery disease

• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease

• Migraine headaches

• Uncontrolled hypertension (≥ 160/90 mm Hg)

• Breast-feeding women (< 6 weeks postpartum)

• Liver disease

• Pregnancy

• Surgery with prolonged immobilization or any surgery on the legs

• Age > 35 years and currently smoking (≥ 15 cigarettes a day)

• Hypercoagulable states (e.g., factor V Leiden, protein C or S deficiency)

For these medical conditions, use of progestin-only oral contraceptives, depot medroxyprogesterone acetate, or an intrauterine device may be an appropriate contraceptive choice.

The most common adverse drug events are

• Nausea and vomiting (usually resolves within 3 months)

• Breakthrough bleeding, spotting, amenorrhea, and altered menstrual flow

• Melasma

• Headache or migraine

• Weight change or edema

Serious but less common effects are venous thrombosis, pulmonary embolism, myocardial infarction, coronary thrombosis, arterial thromboembolism, and cerebral thrombosis.

Potential hormonal effects are associated with an imbalance in estrogen and progestin (

Table 15-3).

Drug-drug and drug-disease interactions

Interaction with the following drugs may result in decreased pharmacologic effect of oral contraceptives:

[Table 15-3. Potential Hormonal Effects Associated with an Imbalance in Estrogen or Progestin]

• Ampicillin, griseofulvin, sulfonamides, tetracycline

• Anticonvulsants (barbiturates, carbamazepine, felbamate, phenytoin, topiramate)

• Some antiretroviral medications (e.g., nevirapine, lopinavir + ritonavir)

• Rifampin

Interaction with these drugs may result in increased plasma levels of oral contraceptives:

• Atorvastatin

• Vitamin C

• CYP450 3A4 inhibitors

Interaction with the following drugs may result in decreased pharmacologic effect of the interacting drug:

• Anticoagulants (estrogens have a procoagulant effect)

• Some benzodiazepines (e.g., lorazepam, oxazepam, temazepam)

• Methyldopa

• Phenytoin

Interaction with the following may result in increased pharmacologic effect of interacting drug:

• Tricyclic antidepressants

• Benzodiazepine tranquilizers (other than the benzodiazepines previously listed)

• β-blockers

• Theophylline

Parameters to monitor

Patients must monitor themselves for warning signs of serious complications previously listed. Laboratory monitoring is not recommended with use of oral contraceptives.

Nondrug Therapy

Nondrug therapy includes use of the following:

• Condoms

• Diaphragms

• Intrauterine devices

• Spermicides

15-3. Osteoporosis

Introduction

Osteoporosis is characterized by low bone mineral density and deterioration of bone tissue, increasing fragility of bone, and subsequent risk of fracture.

Types of Osteoporosis

• Primary

• Type I: Postmenopausal (most common and the focus of this chapter)

• Type II: Age related

• Secondary

• Drug induced

• Medical conditions

Diagnostic Criteria

Dual-energy x-ray absorptiometry (DEXA) scans are used to diagnosis osteoporosis. T scores are used to guide diagnosis and decision to treat osteoporosis. The WHO classification of bone mass is based on T scores:

• Osteopenia: T score -1.0 to -2.5 standard deviations below the young adult mean

• Osteoporosis: T score below -2.5 standard deviations below the young adult mean

Risk factors for osteoporosis are as follows:

• Advanced age

• Amenorrhea

• Cigarette smoking

• Current low bone mass

• Late menarche or early menopause

• Ethnicity (Caucasian or Asian)

• Excessive alcohol use

• Family history of osteoporosis or history of fracture in a primary relative

• Female

• History of fracture over the age of 50

• Inactive lifestyle

• Long-term use of corticosteroids or anticonvulsants

• Low lifetime calcium intake

• Low testosterone levels in men (hypogonadism)

• Thin or small frame

• Vitamin D deficiency

Medical conditions associated with increased risk of osteoporosis are as follows:

• Acquired immune deficiency syndrome (AIDS)

• Cushing's disease

• Eating disorders

• Hyperthyroidism

• Hyperparathyroidism

• Inflammatory bowel disease

• Insulin-dependent diabetes mellitus

• Lymphoma and leukemia

• Malabsorption syndromes

• Rheumatoid arthritis

• Chronic kidney disease

• Chronic obstructive pulmonary disease

The following drugs are associated with an increased risk of osteoporosis:

• Anticonvulsants (phenobarbital, phenytoin)

• Cytotoxic drugs

• Glucocorticoids

• Immunosuppressants

• Lithium

• Long-term heparin use

• Depot medroxyprogesterone

• Supraphysiologic thyroxine doses

• Tamoxifen (premenopausal)

• Aromatase inhibitors

The American Association of Clinical Endocrinologists and the National Osteoporosis Foundation recommend that all women 65 years of age and older be screened for osteoporosis. In addition, postmenopausal women less than 65 years of age with a family history of osteoporosis or clinical risk factors and women with a fracture history unrelated to trauma should be screened.

Clinical Presentation

• Shortened stature

• Vertebra, hip, or forearm fracture

• Kyphosis

• Lordosis

• Bone pain (especially back pain, which could indicate vertebral compression fracture)

Pathophysiology

There are two types of bone: trabecular (i.e., vertebrae, wrist and ankle, and ends of long bones, which are the most susceptible to fracture) and cortical. Osteoblasts (formation) and osteoclasts (destruction) create a constant state of bone remodeling.

Bone formation exceeds destruction during childhood. Peak bone mass is reached around age 25-35; then bone density begins to decline:

• A 3% to 4% decline per decade in men

• A 8% to 12% decline per decade in women 10 years after menopause

Following menopause (postmenopausal osteoporosis), estrogen production declines and osteoclastic activity increases.

Treatment Principles

Adequate calcium and vitamin D intake through diet or supplementation is recommended for everyone (calcium 1,000-1,500 mg daily plus 400-1,000 IU [international units] vitamin D daily) (

Table 15-4).

Lifestyle modifications are recommended, including weight-bearing exercise, smoking cessation, limited alcohol intake, dietary calcium, and vitamin D.

Prescription drug therapy should be initiated on an individual basis, considering risk factors, bone mineral density, fracture history, and concomitant diseases and medications.

Initiation of Treatment

The National Osteoporosis Foundation recommends initiation of therapy in the following situations:

• History of vertebral or hip fracture

• T score below -2.5 (osteoporosis)

• T score -1 to -2.5 (osteopenia) with

• Secondary causes (steroids, immobility)

• History of other fractures

• 10-year probability of hip fracture ≥ 3% or 10-year probability of any major fracture ≥ 20% based on the U.S.-adapted WHO algorithm (Fracture Risk Assessment Tool, or FRAX)

[Table 15-4. Select Calcium Supplement Products]

Drug Therapy

Calcium and vitamin D

Mechanism of action

Calcium is necessary to improve bone mass. It is absorbed through the gastrointestinal (GI) tract, stored in the bone, and made available when calcium levels become low.

Vitamin D facilitates absorption and regulation of calcium levels.

Patient instructions and counseling

• Approximately 500 mg of calcium can be absorbed from the GI tract at a time; separate doses appropriately to achieve a dose of 1,000-1,500 mg per day.

• Calcium carbonate contains the highest level of elemental calcium; take with food to facilitate absorption.

• Calcium citrate products may be administered without regard to meals.

Adverse drug events

The most common adverse drug events are as follows:

• GI upset (nausea, vomiting, cramping, flatulence, especially with carbonate)

• Headache

• Hypophosphatemia and hypercalcemia

• Nephrolithiasis

Drug-drug and drug-disease interactions

Concomitant administration may decrease the bioavailability of fluoroquinolones, tetracyclines, and levothyroxine.

Parameters to monitor

Laboratory monitoring is not recommended.

Bisphosphonates

Table 15-5 provides summary information about bisphosphonates.

Mechanism of action

Bisphosphonates bind to bone (hydroxyapatite) and incorporate into bone to increase and stabilize bone mass. They inhibit osteoclasts and have a very long half-life in the bone.

[Table 15-5. Antiresorptive Agents]

Patient instructions and counseling

• Bisphosphonates must be taken with a full glass of water (8 oz) 30-60 minutes prior to the first meal of the day and 30-60 minutes before any other medications.

• Remain in an upright position for at least 30 minutes following ingestion.

• Take medication on a regularly scheduled basis.

• Compliance may be increased by extended dosing intervals (weekly, monthly, quarterly); however, studies demonstrated antifracture benefits with daily dosing.

Adverse drug events

The most common adverse drug events are GI related: abdominal pain, dyspepsia, constipation, diarrhea, flatulence, nausea, gastritis, esophageal ulceration (if not taken appropriately). Rarely, patients experience osteonecrosis of the jaw (mostly in cancer patients on intravenous bisphosphonates) or myalgia, arthralgia, or flu-like symptoms (especially with intravenous [IV] zoledronic acid)

Drug-drug and drug-disease interactions

Interaction may result in decreased pharmacologic effect of bisphosphonates such as calcium supplements and antacids. Separate administration by 1 hour.

Interaction may result in increased pharmacologic effect of bisphosphonates such as ranitidine. IV ranitidine may double bioavailability of alendronate.

Interaction may result in increased toxicity of interacting drugs such as aspirin. Alendronate > 10 mg daily may increase risk of upper GI side effects of aspirin.

Parameters to monitor

Laboratory monitoring is not recommended.

Estrogen replacement therapy

ERT has a beneficial effect on bone mineral density and fracture risk, but the risks of long-term therapy appear to outweigh that benefit. ERT should be used at the lowest effective dose for the shortest duration in women experiencing vasomotor symptoms or vulvovaginal atrophy.

Estrogen agonist-antagonist (selective estrogen receptor modulator): raloxifene (Evista)

Mechanism of action

Raloxifene is an estrogen receptor agonist in the bone. It decreases resorption of bone and overall bone turnover. It acts as an antagonist in breast tissue.

Patient instructions and counseling

• This medication may be taken without regard to food.

• Concomitant use with estrogen therapy is not recommended.

• This medication will not treat symptoms of menopause such as hot flashes and may aggravate them.

• In the event of prolonged immobilization, discontinue raloxifene 3 days prior to and during the immobile period when possible.

Adverse drug events

The most common adverse drug events are as follows:

• Cardiovascular: Hot flashes, chest pain, syncope

• GI: Nausea, diarrhea, vomiting

• Musculoskeletal: Arthralgia, myalgia, nocturnal leg cramps

• Central nervous system (CNS): Insomnia, neuralgia

• Skin: Rash, sweating

• Thrombotic: deep-vein thrombosis, pulmonary embolism

Drug-drug and drug-disease interactions

For the following drugs, interaction may result in decreased pharmacologic effect of raloxifene:

• Ampicillin: Peak levels are reduced by 28% and overall absorption is reduced by 14%. Coadministration is not contraindicated because of maintained systemic exposure and elimination.

• Cholestyramine: Absorption and enterohepatic cycling are reduced. Do not administer together.

In the case of warfarin, interaction may result in decreased pharmacologic effect of the interacting drug. Prothrombin time may decrease up to 10%. Patients with history of venous thromboembolism should not be on raloxifene.

Parameters to monitor

Laboratory monitoring is not recommended.

Calcitonin (Miacalcin, Fortical)

Mechanism of action

Calcitonin participates in the regulation of calcium and bone metabolism. It inhibits bone resorption by binding to osteoclast receptors.

Patient instructions and counseling

• If this medication is administered as an injection, it should be given in the upper arm, thigh, or buttocks.

• Proper education regarding administration of the injection and the nasal spray preparation is necessary.

• Patient should be advised that if a shot is missed, it should be administered as soon as possible, but not if it is almost time for the next dose.

• Store the nasal spray in the refrigerator until time for use. Warm the spray to room temperature prior to first use and then store at room temperature.

Adverse drug events

The most common adverse drug events are as follows:

• Skin: Facial flushing and hand flushing (most common overall)

• GI: Nausea, diarrhea, vomiting, abdominal pain

• Taste disorder: Salty taste

• Genitourinary: Nocturia, urinary frequency

• Nasal (with nasal spray): Rhinitis, nasal dryness, irritation, itching, congestion

• Ophthalmic: Blurred vision, abnormal lacrimation

Drug-drug and drug-disease interactions

In the case of lithium, interaction may result in decreased pharmacologic effect of interacting drug. Concomitant administration may decrease lithium levels.

Salmon calcitonin should be avoided in patients with a true allergy to seafood.

Parameters to monitor

Laboratory monitoring is not recommended.

Parathyroid hormone: teriparatide (Forteo)

Mechanism of action

Teriparatide increases the rate of bone formation by stimulating osteoblasts, thereby increasing bone mass density and decreasing fracture risk.

Because of limited long-term safety data (< 2 years) and risks of osteosarcoma in animal models, this medication is recommended for use only in men and women at high risk of fracture.

Patient instructions and counseling

Patients should be educated regarding appropriate use of the prefilled pen delivery device, storage (refrigerator), and adverse effects (orthostasis with first dose).

Adverse drug events

The most common adverse drug events are as follows:

• Musculoskeletal: Pain, arthralgia

• CNS: Paresthesias

• GI: Nausea, diarrhea, abdominal cramps

• Taste disorder: Metallic taste

• Skin: Injection pain, urticaria

Drug-drug and drug-disease interactions

No drug-drug or drug-disease interactions are known; however, teriparatide is contraindicated in patients who are at increased risk of osteosarcoma, including those who have received radiation to the bone, adolescents or young adults with open epiphyses, and individuals with Paget's disease.

Parameters to monitor

Laboratory monitoring is not recommended.

Nondrug Therapy

Nondrug therapies include

• Weight-bearing exercise

• Smoking cessation

• Limited alcohol consumption

• Calcium-rich diet

• Strategies to reduce the risk of falls

15-4. Key Points

Postmenopausal Hormone Replacement Therapy

Postmenopausal HRT must be selected on an individual basis taking into account the risks and benefits, concomitant diseases, and medications. Important patient parameters to consider include menopause symptoms, risk of coronary artery disease, risk of osteoporosis, risk of breast cancer, and risk of thromboembolism.

The primary indication for initiating HRT is to relieve vasomotor and other menopause symptoms to improve quality of life. Hormone replacement therapy is not recommended for use in the primary prevention of any other disease states.

Hormone replacement therapy should be used at the lowest effective dose and for the shortest duration possible. Estrogen plus progestin therapy is indicated in patients with a uterus. Estrogen alone is indicated in women who no longer have a uterus.

Contraceptives

Oral contraceptives are highly effective and safe when used properly according to the manufacturer's recommended dose and administration. Selection of prescription contraceptives requires careful consideration of patient medical history, lifestyle, compliance, and preference.

In addition to the contraceptive benefit of these products, other menstrual-related health problems may be resolved or lessened (e.g., menstrual pain, irregular menses, headache, and spotting).

Changes in dose or product are often necessary to achieve an appropriate balance of estrogen and progestin that minimizes undesirable adverse effects associated with deficiencies or excess amounts of the hormones.

Patients must be educated to report immediately the onset of severe abdominal pain, severe chest pain, shortness of breath, severe headache, visual disturbances, or severe pain in the leg or calf.

Osteoporosis

Women should be counseled about the following preventive measures:

• Adequate calcium consumption, using dietary supplements if dietary sources are not adequate

• Adequate vitamin D consumption (400-1,000 IU daily) and the natural sources of this nutrient

• Regular weight-bearing and muscle-strengthening exercises to reduce falls and prevent fractures

• Smoking cessation

• Moderation of alcohol intake

• Fall prevention strategies

Bone mineral density testing should be recommended to all postmenopausal women 65 years of age or older and for postmenopausal women younger than 65 years who have one or more risk factors for osteoporosis.

Therapy must be selected on an individual basis considering risks and benefits, concomitant diseases, and medications.

Appropriate calcium and vitamin D intake is an important component of prevention and treatment. If they are not obtained in the diet, supplementation is recommended for all individuals, especially patients receiving prescription therapy for osteoporosis.

Bisphosphonates are first-line pharmacologic options for osteoporosis prevention and treatment. They must be taken with a full glass of water 30-60 minutes prior to the first meal of the day or any other medications. The patient must remain upright for at least 30 minutes after taking a dose.

Estrogen replacement therapy is not approved for the treatment of osteoporosis and should not be initiated for this reason. It is approved for prevention of osteoporosis, but should be used only short term for women who are experiencing vasomotor or vaginal atrophy symptoms.

15-5. Questions

1.

A. J. is a 35-year-old premenopausal woman who is concerned about her family history of osteoporosis. She does not eat dairy products because she is lactose intolerant. Her recent bone mineral density screening revealed a T score of 1.0. Select the appropriate therapy recommendation from the choices below.

A. Daily estrogen replacement therapy

B. Daily calcium and vitamin D supplementation

C. Daily combined estrogen and progestin replacement therapy

D. Daily teriparatide injections

E. Daily calcitonin nasal spray

 

2.

The pharmacist receives a prescription for Fosamax 70 mg daily for prevention of osteoporosis with instructions to the patient to take with food and remain upright for at least 30 minutes following ingestion. From the choices below, identify the errors in this prescription.

A. The dose of Fosamax should be 35 mg weekly for prevention.

B. Fosamax should be taken at least 30 minutes prior to a meal; it should not be taken with food.

C. Patients should lie down for 1 hour following administration of Fosamax.

D. Choices B and C are correct.

E. Choices A and B are correct.

 

3.

What is the recommended dosage range of daily calcium intake for an adult?

A. 200-400 mg

B. 250-500 mg

C. 300-600 mg

D. 500-1,000 mg

E. 1,000-1,500 mg

 

4.

Which of the following agents is considered first-line therapy for postmenopausal osteoporosis?

A. Alendronate

B. Calcitonin

C. Prempro

D. Denosumab

E. Teriparatide

 

5.

Which of the following products is available in an injectable and nasal spray dosage form?

A. Raloxifene

B. Alendronate

C. Teriparatide

D. Calcitonin

E. Prempro

 

6.

Which of the following drugs does not increase the risk of osteoporosis?

A. Anticonvulsants

B. Tamoxifen

C. Glucocorticoids

D. Estrogen

E. Depo-Provera

 

7.

What is the recommended dose of raloxifene in the prevention and treatment of postmenopausal osteoporosis?

A. 10 mg daily

B. 15 mg daily

C. 40 mg daily

D. 60 mg daily

E. 120 mg daily

 

8.

S. T. is a 32-year-old woman who wants to begin using a prescription contraceptive product. She is a new mother and would like to know if any products are safe for use during breast-feeding. S. T. states that she is not interested in using a device intravaginally and experiences irritation and inflammation with condom use. Which of the following product(s) would be an appropriate choice for S. T.?

A. Ortho Tri-Cyclen

B. Micronor

C. Depo-Provera

D. A or B

E. B or C

 

9.

T. H. is a 27-year-old woman currently taking Nordette oral contraceptive pills. She presents to your pharmacy with a prescription of ampicillin 500 mg qid for 1 week. Which of the following choices describes appropriate action taken by the pharmacist?

A. Call the physician and request a change to amoxicillin to avoid a drug interaction between Nordette and ampicillin.

B. Dispense the ampicillin and counsel T. H. on the appropriate administration and duration of therapy for the antibiotic.

C. Dispense the ampicillin and counsel T. H. regarding the potential for ampicillin to interfere with the efficacy of Nordette. Instruct T. H. to use a backup method of contraception until her next menstrual period begins.

D. Refuse to fill the ampicillin prescription, and counsel T. H. that she should never take antibiotics while she is on oral contraceptives.

 

10.

Which of the following oral contraceptives is a biphasic product?

A. Ortho Tri-Cyclen

B. Ortho-Novum 10/11

C. Ortho-Novum 1/35

D. Yasmin

E. Seasonale

 

11.

Which of the following products is a progestin-only oral contraceptive?

A. Nordette

B. Ortho Tri-Cyclen

C. Nor-QD

D. Demulen 1/50

E. Necon 1/35

 

12.

A 26-year-old female who is recently initiated on a combination hormonal oral contraceptive complains of late-cycle breakthrough bleeding. Which of the following is she most likely experiencing?

A. Too much estrogen

B. Too little estrogen

C. Too much progestin

D. Too little progestin

E. Too much androgen

 

13.

What is the highest dose of estrogen (ethinyl estradiol) offered in an oral contraceptive?

A. 25 mcg

B. 30 mcg

C. 35 mcg

D. 40 mcg

E. 50 mcg

 

14.

A progestin-only oral contraceptive would be preferable over a combination oral contraceptive in all of the following cases except

A. a one pack per day smoker over 35 years old.

B. a patient with fibrocystic breast changes.

C. a lactating woman.

D. a patient with a history of thromboembolic disease.

 

15.

A. J. is a 55-year-old woman who presents to your pharmacy with a prescription for Premarin 0.625 mg daily. She has an intact uterus and has been recently diagnosed with menopause. Which of the following statements describes the appropriate action to be taken by the pharmacist?

A. Refuse to fill the prescription and recommend a phytoestrogen supplement.

B. Call the physician and confirm that the patient has an intact uterus and recommend a product containing estrogen plus progestin.

C. Fill the prescription and counsel the patient regarding administration instructions and potential adverse effects.

D. None of the above.

 

16.

Which of the following factors is a contraindication to the use of hormone replacement therapy in postmenopausal women?

A. Diabetes

B. Basal cell skin cancer

C. Thromboembolic disease

D. Depression

E. Obesity

 

17.

From the choices below, select the most common side effect(s) associated with estrogen replacement.

A. Breast tenderness

B. Depression

C. Nausea

D. Brittle fingernails

E. A and C

 

18.

The Women's Health Initiative study was terminated because HRT increased the risk of all of the following conditions except

A. breast cancer.

B. stroke.

C. cardiovascular disease.

D. uterine cancer.

E. pulmonary embolism.

 

19.

Which of the following product dosing regimens is correct?

A. Climara Transdermal: apply to skin once daily.

B. Vagifem: 1 tablet vaginally once daily for 2 weeks; then 1 tablet vaginally twice weekly.

C. Estring: insert ring intravaginally once daily at bedtime.

D. Premarin tablets: 0.625-2.5 mg tid.

E. Premarin vaginal cream: 20-40 g vaginally once daily.

 

20.

Which of the following drug interactions may result in increased pharmacologic effect of estrogen?

A. Macrolide antibiotics

B. Itraconazole

C. Ketoconazole

D. A and C

E. A, B, and C

 

15-6. Answers

1.

B. A. J. has neither osteopenia nor osteoporosis with a T score of 1.0. At this point, preventive therapy is appropriate, with adequate calcium and vitamin D intake. Prescription therapy is not indicated at this time.

 

2.

E. The appropriate use of Fosamax (alendronate sodium) for prevention of osteoporosis includes a 35 mg weekly or 5 mg daily dose. The 70 mg weekly dose is for treatment of osteoporosis. The medication should be taken with a full glass of water at least 30 minutes prior to ingesting food or other beverages. Patients should remain in the upright position for at least 30 minutes following ingestion of Fosamax.

 

3.

E. According to the National Osteoporosis Foundation, adults < 50 years of age require 1,000 mg daily, and those 50 and older should have 1,200 mg daily. The recommended dosage range of daily calcium intake for an adult is 1,000-1,500 mg.

 

4.

A. Bisphosphonates are first-line therapy for osteoporosis because data demonstrates that they reduce the risk of fracture.

 

5.

D. Injectable and nasal spray dosage forms of calcitonin are available. Teriparatide is available as an injection only. Prempro, raloxifene, and alendronate are available only in oral dosage forms.

 

6.

D. Estrogen decreases rather than increases the risk of osteoporosis.

 

7.

D. The approved and recommended dose of raloxifene is 60 mg once daily.

 

8.

E. Micronor is a progestin-only (minipill) oral contraceptive and is considered compatible with breast-feeding. Depo-Provera is an injectable progestin-only contraceptive option that is considered safe and appropriate for women who desire to breast-feed because it does not affect milk production or adversely affect infant development. Ortho Tri-Cyclen is a combined oral contraceptive that may decrease the quantity of breast milk available and may adversely affect the infant.

 

9.

C. Ampicillin may interact with combined oral contraceptives. Although clinical studies have not consistently demonstrated an interaction, more than 25 case reports of unintended pregnancies have been attributed to concomitant use of ampicillin and oral contraceptives. Concomitant administration of ampicillin, as well as other antibiotics, may decrease the effectiveness of combined oral contraceptives, resulting in pregnancy. The American Medical Association recommends that women be counseled about the potential risk of antibiotics decreasing efficacy of oral contraceptives. If the patient desires, the pharmacist should recommend a backup method of contraception until menses occurs.

 

10.

B. Ortho-Novum 10/11 is a biphasic oral contraceptive.

 

11.

C. Nor-QD is a progestin-only oral contraceptive.

 

12.

D. Too little progestin may result in breakthrough bleeding late in the menstrual cycle. She should be changed to a product with a higher progestin content.

 

13.

E. The highest dose of estrogen (ethinyl estradiol) offered in an oral contraceptive is 50 mcg.

 

14.

B. Fibrocystic breast changes are not a contraindication to using combined oral contraceptives.

 

15.

B. Unopposed estrogen is not recommended in women with an intact uterus because of an increased risk of endometrial hyperplasia and endometrial cancer. Women with an intact uterus should receive a product containing estrogen plus progestin.

 

16.

C. Thromboembolic disease is a definite contraindication to the use of hormone replacement therapy in postmenopausal women.

 

17.

E. Breast tenderness and nausea are the most common side effects associated with estrogen replacement.

 

18.

D. The WHI study was not terminated because of an increased risk of uterine cancer.

 

19.

B. Vagifem dosage is 1 tablet vaginally once daily for 2 weeks; then 1 tablet vaginally twice weekly.

 

20.

E. Macrolide antibiotics, itraconazole, and ketoconazole may result in increased pharmacologic effect of estrogen by inhibiting CYP450 3A4.

 

15-7. References

Postmenopausal Hormone Replacement Therapy

Kalantaridou SN, Davis SR, Calis KA. Hormone replacement therapy in women. In: Dipiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill; 2008:1351-68.

Klasco RK, ed. DRUGDEX® System (electronic version). Greenwood Village, Colo.: Thomson Micromedex.

Loose DS, Stancel GM. Estrogens and progestins. In: Brunton LL, ed. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill; 2006:1541-71.

North American Menopause Society. Estrogen and progestogen use in postmenopausal women: July 2008 position statement of the North American Menopause Society. Menopause. 2008;15:584-602. Available at: www.menopause.org.

O'Mara NB, Tom WC. Estrogen-containing hormone replacement products for postmenopausal women. Pharmacist's Letter. 2008;24(12):240407.

O'Neil CK. Health issues in older women. In: Dunsworth T, Richadrson M, Chant C, et al., eds. Pharmacotherapy Self-Assessment Program. 6th ed. Book 7: Women's and Men's Health. Lenexa, Kans.: American College of Clinical Pharmacy, 2008;143-57.

Parent-Stevens L, Sagraves R. Gynecologic and other disorders of women. In: Koda-Kimble MA, Young LY, eds. Applied Therapeutics: The Clinical Use of Drugs. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:48-28 to 48-44.

Warren MP. A comparative review of the risks and benefits of hormone replacement therapy regimens. Am J Obstet Gynecol. 2004;190:1141-67.

Contraception

Allen J, Cupp M. Hormonal contraception. Pharmacist's Letter. 2007;23(12):231207.

American College of Obstetricians and Gynecologists. The use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol. 2006;107(6):1453-72.

Dickerson LM, Shrader SP, Diaz VA. Contraception. In: Dipiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill; 2008:1313-27.

Hardman JL. Contraception. In: Koda-Kimble MA, Young LY, eds. Applied Therapeutics: The Clinical Use of Drugs. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:45-1 to 45-26.

Klasco RK, ed. DRUGDEX® System (electronic version). Greenwood Village, Colo.: Thomson Micromedex.

Osteoporosis

Klasco RK, ed. DRUGDEX® System (electronic version). Greenwood Village, Colo.: Thomson Micromedex.

MacLaughlin EJ, Raehl CL. ASHP therapeutic position statement on the prevention and treatment of osteoporosis in adults. Am J Health-Syst Pharm. 2008;65:343-57.

National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis, 2008. Available at: www.nof.org/professionals/Clinicians_Guide.htm.

O'Connell MB, Vondracek SF. Osteoporosis and other metabolic bone diseases. In: Dipiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill; 2008:1483-504.