Female Sex Hormones- Estrogen Drugs

Name of the Estrogen Drugs

1. Estradiol
2. Estrogens- Conjugated
3. Estrogens- Esterified
4. Estropipate

Therapeutic Action

• The most potent endogenous female sex hormone responsible for estrogen effects on the body.
• Affect the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• Responsible for the proliferation of the endometrial lining and are known to compete with androgens for receptor sites.
• The loss of estrogen is responsible for the signs and symptoms of menopause in the uterus, vagina, breasts, and cervix.

Mechanism of action:

Binds to nuclear receptors in responsive tissues (such as female genital organs, breasts, and pituitary gland), enhancing DNA, RNA, and protein synthesis. In androgen-dependent prostate cancer, competes for androgen receptor sites, inhibiting androgen activity. Also decreases pituitary release of follicle-stimulating hormone and luteinizing hormone

Indications:

• Treatment of moderate to severe vasomotor symptoms associated with menopause
• Vulvar and vaginal atrophy associated with menopause
• Hypoestrogenism (due to castration, hypogonadism, primary ovarian failure)
• Metastatic breast cancer (palliation) in men and postmenopausal women
• Advanced prostate cancer (palliation)
• Prevention of osteoporosis in postmenopausal women.

Contraindications & Cautions:

• Hypersensitivity to estradiol
• Angioedema
• Hepatic dysfunction or disease
• Undiagnosed abnormal vaginal bleeding
• Active or history of arterial thrombosis
• Estrogen-dependent cancer (known, suspected, or history of)
• Known or suspected breast cancer (except for pts being treated for metastatic disease),
• Pregnancy
• Thrombophlebitis or thromboembolic disorders (current or history of)
• Known protein C, protein S, antithrombin deficiency or other known thrombophilic disorder.

Cautions: ​

Renal insufficiency, diabetes mellitus, endometriosis severe hypocalcemia, hyperlipidemias, asthma, epilepsy, migraines, SLE, hypertension, hypothyroidism, history of jaundice due to past estrogen use or pregnancy, cardiovascular disease, obesity, porphyria, severe hypocalcaemia.​

​Metabolism and Half- Life:

Well absorbed from GI tract. Widely distributed. Protein binding: 50%–80%.

Metabolized in liver. Primarily excreted in urine. Half-life: Unknown

Drug Interactions:

• CYP3A4 inducers (e.g., carbamazepine, rifampin) may decrease concentration/effects.
• CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir) may increase concentration/effect.
• May decrease therapeutic effect of anastrozole, exemestane.
• May increase serum glucose, calcium, HDL, triglycerides.
• May decrease serum cholesterol, LDL.
• May affect Meta-pyrone testing, thyroid function tests.

Side- Effects:

Frequent:

Anorexia, nausea, swelling of breasts, peripheral edema marked by swollen ankles and feet.

Transdermal: Skin irritation, redness.

Occasional:

Vomiting (esp. with high doses), headache (may be severe), intolerance to contact lenses, hypertension, glucose intolerance, brown spots on exposed skin.

Vaginal: Local irritation, vaginal discharge, changes in vaginal bleeding (spotting, breakthrough, prolonged bleeding).

Rare:

Chorea (involuntary movements), hirsutism (abnormal hairiness), loss of scalp hair, depression.

Prolonged administration increases risk of gallbladder disease, thromboembolic disease, breast/ cervical/ vaginal/ endometrial/ hepatic carcinoma. Cholestatic jaundice occurs rarely

Nursing Considerations

Baseline assessment

• Assess frequency/severity of vasomotor symptoms.
• Question medical history as listed in Precautions.
• Question for possibility of pregnancy (contraindicated).

Intervention/evaluation

• Monitor B/P, weight, serum calcium, glucose, LFT.
• Monitor for loss of vision, sudden onset of proptosis, diplopia, migraine, thromboembolic disorders.
• Monitor vital signs and cardiovascular status, especially for hypertension, thromboembolism, and MI.
• Be aware that a few cases of ring adherence to the vaginal wall have occurred, which may require evaluation of wall ulceration and erosion.
• In diabetic patient, monitor blood glucose level and watch for signs and symptoms of hyperglycaemia.

Patient/family teaching

• Limit alcohol, caffeine.
• Avoid grapefruit products.
• Immediately report sudden headache, vomiting, disturbance of vision/speech, numbness/weakness of extremities, chest pain, calf pain, shortness of breath, severe abdominal pain, mental depression, unusual bleeding.
• Avoid smoking.
• Report abnormal vaginal bleeding.
• Never place patch on breast or waistline.
• Instruct patient to place transdermal patch on clean, dry skin area.
• Teach proper technique for use of vaginal tablet, ring, or cream, as appropriate.
• Tell patient drug may cause loss of libido (in women) or erectile dysfunction (in men). Encourage patient to discuss these issues with prescriber.
• Teach patient to recognize and immediately report signs and symptoms of thromboembolism.
• Caution patient not to take drug if she is or plans to become pregnant.
• Advise patient that drug may worsen near sightedness or astigmatism and make contact lenses uncomfortable.

Mechanism of Action

Increase the rate of DNA and RNA synthesis in the cells of female reproductive organs, hypothalamus, pituitary glands, and other target organs. In the hypothalamus, estrogens reduce the release of gonadotropin-releasing hormone, which decreases pituitary release of follicle-stimulating hormone and luteinizing hormone.

In women, these hormones are required for normal genitourinary and other essential body functions. At the cellular level, estrogens increase cervical secretions, cause endometrial cell proliferation, and increase uterine tone. Estrogen replacement helps maintain genitourinary function and reduce vasomotor symptoms when estrogen production declines from menopause, surgical removal of ovaries, or other estrogen deficiency. Estrogen also helps prevent osteoporosis by keeping bone resorption from exceeding bone formation.

In men, estrogens inhibit pituitary secretion of luteinizing hormone and decrease testicular secretion of testosterone.

These actions may decrease prostate tumor growth and lower the level of prostate-specific antigen.

Metabolism and half- life:

• Readily absorbed from gastrointestinal (GI) tract
• Onset: 2-4 weeks (PO-menopause)
• Metabolized in liver to inactive sulfates and glucuronides
• Metabolites: Estradiol, estrone, estriol
• Excretion: Mainly in urine as conjugates with small amount of unchanged drug; most estrogens are also excreted in bile and undergo enterohepatic recycling.

Drug interactions:

• Corticosteroids: enhanced corticosteroid effects
• CYP450 inducers (such as barbiturates, rifampin): decreased estrogen efficacy
• Hypoglycaemics, warfarin: altered requirement for these drugs
• Phenytoin: loss of seizure control
• Tricyclic antidepressants: reduced antidepressant effects
• Antithrombin III, folate, low-density lipoproteins, pyridoxine, total cholesterol, urine pregnanediol: decreased values
• Thyroid function tests: false interpretation
• Caffeine: increased caffeine blood level
• Smoking: increased risk of adverse cardiovascular reactions

Side- Effects:

• CNS: headache, dizziness, lethargy, depression, asthenia, paraesthesia, syncope, cerebrovascular accident (CVA), seizures
• CV: hypertension, chest pain, myocardial infarction (MI), thromboembolism
• EENT: contact lens intolerance, worsening of myopia or astigmatism, otitis media, sinusitis, rhinitis, pharyngitis
• GI: nausea, vomiting, diarrhea, abdominal cramps, bloating, enlarged abdomen, dyspepsia, flatulence, gastritis, gastroenteritis, haemorrhoids, colitis, gallbladder disease, anorexia, pancreatitis
• GU: urinary incontinence, dysuria, urinary tract infection, amenorrhea, dysmenorrhea, endometrial hyperplasia, vaginal candidiasis, leukorrhea, vaginal hemorrhage, genital eruptions, gynecomastia, breast tenderness, breast enlargement or secretion, reduced libido, erectile dysfunction, testicular atrophy, increased risk of breast cancer, endometrial cancer, haemolytic uremic syndrome
• Hepatic: cholestatic jaundice, hepatic adenoma
• Metabolic: hyperglycaemia, hypercalcemia, sodium and fluid retention, reduced carbohydrate tolerance
• Musculoskeletal: leg cramps, back pain, skeletal pain
• Respiratory: upper respiratory tract infection, bronchitis, pulmonary embolism
• Skin: acne, oily skin, pigmentation changes, urticaria, pruritus, erythema nodosum, haemorrhagic eruption, skin hypertrophy, hirsutism, alopecia, erythema multiforme
• Other: edema, weight changes, increased appetite, hypersensitivity reaction, angioedema

Nursing Considerations

• Monitor liver function test results and assess abdomen for enlarged liver.
• Evaluate patient for breast tenderness and swelling. As needed, give analgesics and apply cool compresses.
• Monitor fluid intake and output, and weigh patient daily.
• Know that drug increases risk of thromboembolism, CVA, and MI.
• Be aware that exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema.
• Check serum phosphatase level in patients with prostate cancer.
• Monitor calcium, glucose, and folic acid levels.
• Evaluate bone density annually
• Use conjugated estrogens cautiously in patients with severe hypocalcemia because a sudden increase in serum calcium level may cause adverse reactions.
• Reconstitute conjugated estrogens with normal saline solution, dextrose, or invert sugar solution and use within a few hours.
• Discard solution that contains precipitate.
• Monitor serum calcium level to detect severe hypercalcemia in patients with bone metastasis from breast cancer.
• Watch for elevated liver function test results because estrogen and progestins may worsen such conditions as acute intermittent or variegate hepatic porphyria.
• Assess hypertensive patients for increases in blood pressure because estrogens may cause fluid retention.
• Monitor patients with asthma, diabetes mellitus, endometriosis, heart disease, lupus erythematosus, migraine headaches, renal disease, or seizure disorder for worsening of these conditions.
• If patient takes warfarin, assess PT for loss of anticoagulant effects because estrogens increase production of clotting factors and promote platelet aggregation.
• Expect to stop drug during periods of immobilization, 4 weeks before elective surgery, and if jaundice develops.
• Expect to stop estrogen combination therapy in any woman who develops signs or symptoms of cancer; cardiovascular disease, such as MI, pulmonary embolism, venous thrombosis, or stroke; or dementia.
• Check triglyceride level routinely because, in hypertriglyceridemia, estrogen therapy may increase triglycerides enough to cause pancreatitis and other complications.
• If patient takes thyroid hormone replacement therapy, monitor her for increased signs and symptoms of hypothyroidism because estrogen may increase thyroid binding globulin level, which may make the patient’s current dose of thyroid hormone insufficient.
• Estrogen may worsen mood disorders, including depression. Monitor patient for depression, fatigue, insomnia, or mood changes.

Patient/ Family Teaching:

• Teach patient to recognize and report signs and symptoms of thromboembolism.
• Caution patient not to take drug if she is or plans to become pregnant.
• Explain the risks of estrogen therapy, including increased risk of breast, endometrial, or ovarian cancer; cardiovascular disease; dementia; and gallbladder disease.
• Instruct patient how to use vaginal cream and to cleanse plunger by removing it from barrel and washing it with mild soap and warm water after each use.
• Urge patient to immediately report breakthrough bleeding to prescriber.
• Instruct patient to perform monthly breast self-examination and to comply with all prescribed follow-up examinations.
• Warn female patient that long-term use may increase risk of dementia, heart disease, stroke, gallbladder disease, and breast or endometrial cancer.
• Inform patient that estrogen vaginal cream may alter effectiveness of condoms, diaphragms, or cervical caps made of latex or rubber.

Mechanism of Action:

Bind to nuclear receptors in responsive tissues (such as female genital organs, breasts, and pituitary gland), enhancing DNA, RNA, and protein synthesis. In androgen-dependent prostate cancer, compete for androgen receptor sites, inhibiting androgen activity. Also decrease pituitary release of follicle stimulating hormone and luteinizing hormone.

Indications:

• Moderate to severe vasomotor symptoms or atrophic vaginitis
• Female hypogonadism
• Inoperable/ Palliative treatment of prostate cancer
• Selected breast cancers (inoperable, progressing)
• Prevention of osteoporosis
• Menopause, Atrophic Vaginitis, Kraurosis Vulvae
• Female Castration/Primary Ovarian Failure

Contraindications & Cautions:

• Hypersensitivity to drug or its components
• Thromboembolic disease (current or previous)
• Undiagnosed vaginal bleeding
• Breast and reproductive cancers (except metastatic disease)
• Estrogen-dependent neoplasms
• Pregnancy

Use cautiously in:

cardiovascular disease, severe hepatic or renal disease, asthma, bone disease, migraines, seizures, breast nodules,

fibrocystic breasts, family history of breast or genital tract cancer, breastfeeding patients.

Metabolism and Half- Life:

• Protein Bound: 50-80%
• Metabolism: Principally and rapidly in liver and undergoes extensive first-pass metabolism to less active products such as estriol; kidneys, gonads, and muscle tissues may be involved in metabolism to some extent
• Metabolites: Estriol
• Excretion: Mainly in urine as conjugates with small amount of unchanged drug, most estrogens are also excreted in bile and undergo enterohepatic recycling.

Drug Interactions:

• Corticosteroids: enhanced corticosteroid effects
• CYP450 inducers (such as barbiturates, rifampin): decreased estrogen efficacy
• Hypoglycemics, warfarin: altered requirement for these drugs
• Phenytoin: loss of seizure control
• Tricyclic antidepressants: reduced antidepressant effect
• Antithrombin III, folate, low-density lipoproteins, pyridoxine, total cholesterol, urine pregnanediol: decreased values
• Thyroid function tests: false interpretation
• Caffeine: increased caffeine blood level
• Smoking: increased risk of adverse cardiovascular reactions

Side- Effects:

• CNS: headache, dizziness, lethargy, depression, asthenia, paresthesia, syncope, increased risk of cerebrovascular accident (CVA), seizures
• CV: hypertension, chest pain,myocardial infarction (MI), thromboembolism
• EENT: contact lens intolerance, worsening of myopia or astigmatism, otitis media, sinusitis, rhinitis, pharyngitis
• GI: nausea, vomiting, diarrhea, dyspepsia, flatulence, gastritis, gastroenteritis, enlarged abdomen, hemorrhoids, colitis, gallbladder disease, anorexia, pancreatitis
• GU: urinary incontinence, dysuria, amenorrhea, dysmenorrhea, endometrial hyperplasia, urinary tract infection, leukorrhea, vaginal discomfort or pain, vaginal haemorrhage, genital eruptions, gynecomastia, breast tenderness, breast enlargement or secretion, reduced libido, erectile dysfunction, testicular atrophy, increased risk of breast cancer, endometrial cancer, hemolytic uremic syndrome
• Hepatic: cholestatic jaundice, hepatic adenoma
• Metabolic: hyperglycaemia, hypercalcemia, sodium and fluid retention, reduced carbohydrate tolerance
• Musculoskeletal: leg cramps, back pain, skeletal pain
• Respiratory: upper respiratory tract infection, bronchitis, pulmonary embolism
• Skin: acne, increased pigmentation, urticaria, pruritus, erythema nodosum, haemorrhagic eruption, alopecia, hirsutism
• Other: increased appetite, weight changes, edema, flulike symptoms, hypersensitivity reactions

Nursing Considerations

• Monitor fluid intake and output, and weigh patient daily.
• Evaluate patient for breast tenderness and swelling. As needed, administer analgesics and apply cool compresses.
• Know that drug increases risk of thromboembolism, CVA, and MI.
• Monitor liver function test results and assess abdomen for enlarged liver.
• Check serum phosphatase level in patients with prostate cancer and adjust dosage as appropriate.
• Monitor calcium, glucose, and folic acid levels.

Patient/ Family teaching

• Teach patient to recognize and immediately report signs and symptoms of thromboembolism.
• Caution patient not to take drug if she is or plans to become pregnant.
• Teach patient how to perform breast self-examination. Emphasize importance of monthly checks.
• Tell patient to report breakthrough vaginal bleeding.
• Mention that drug may cause contact lens intolerance. Advise patient to report vision changes.
• Inform male patient that drug may cause gynecomastia.

Mechanism of Action:

Semisynthetic conjugate of estrone with piperazine; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of LH and FSH from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues

Indications:

• Menopause
• Ovarian failure
• Osteoporosis, prevention
• Vasomotor symptoms associated with menopause
• Treatment of female hypogonadism due to castration, or primary ovarian failure
• Menopausal atrophic vaginitis (vaginal cream) daily

Contraindications & Cautions:

• Documented hypersensitivity
• Active or history of breast cancer
• Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
• Estrogen-dependent neoplasia, liver disease, liver tumors
• Undiagnosed abnormal vaginal bleeding
• Uncontrolled hypertension
• Diabetes mellitus with vascular involvement
• Jaundice with prior oral contraceptive use

Cautions

Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, elderly, hepatic/renal impairment, uterine leiomyomata, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, ovarian cancer, exacerbation of endometriosis or other conditions, smoking and >35 years old, SLE, depression.

Drug Interactions:

• Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count;
• Inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.
• Inducers of CYP3A4 such as St. John’s Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
• Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.

Side- Effects:

• Peripheral edema
• Depression
• Headache
• Melasma
• Bloating
• Nausea & vomiting
• Breast enlargement & tenderness
• Amenorrhea
• Breakthrough bleeding
• Spotting
• Weight changes
• Corneal curvation change

Nursing Considerations

• Monitor fluid intake and output, and weigh patient daily.
• Evaluate patient for breast tenderness and swelling. As needed, administer analgesics and apply cool compresses.
• Monitor liver function test results and assess abdomen for enlarged liver.
• Know that drug increases risk of thromboembolism, CVA, and MI
• Check serum phosphatase level in patients with prostate cancer and adjust dosage as appropriate.
• Monitor calcium, glucose, and folic acid levels.
• Do not use estrogens with or without progestins to prevent heart disease, heart attacks or strokes.

Patient/ Family teaching

• Caution patient not to take drug if she is or plans to become pregnant.
• Teach patient how to perform breast self-examination. Emphasize importance of monthly checks.
• Tell patient to report breakthrough vaginal bleeding.
• Mention that drug may cause contact lens intolerance. Advise patient to report vision changes.
• Using estropipate can increase your risk of blood clots, stroke, heart attack, or cancer of the breast, uterus, or ovaries. Estropipate should not be used to prevent heart disease, stroke, or dementia.

REFERENCES

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