Preparations
Preparations for HT are listed in Tables 61.2, 61.3, and 61.4.
Dosing may be oral, transdermal, or intravaginal. The oral estrogens employed most often are conjugated equine estrogens [Premarin] (prepared by extraction from pregnant mares’ urine), estradiol [Estrace], and estropipate. For transdermal therapy, estradiol is the only estrogen employed, formulated in patches, gels, a spray, and an emulsion. Oral estrogen/progestin combina-tions include conjugated equine estrogens/medroxyprogesterone acetate [Prempro, Premphase], estradiol/norethindrone acetate [Activella], and ethinyl estradiol/norethindrone [Femhrt]. Com-bination estrogen/progestin patches are estradiol/norethindrone [CombiPatch] and estradiol/levonorgestrel [Climara Pro].
Intravaginal products—formulated as tablets, creams, and rings—are used primarily to manage symptoms of urogenital atrophy.
Dosing Schedules
Every woman undergoing systemic HT receives an estrogen, and every woman with a uterus also receives a progestin to
CHAPTER 61 Estrogens and Progestins: Basic Pharmacology and Noncontraceptive Applications
Generic Name Brand Name Strength (mcg absorbed/day) Application
ESTROGENS Transdermal Patches
Estradiol Menostar 14 Once weekly
Climara 25, 37.5, 50, 60, 75, 100 Once weekly
Alora 25, 50, 75, 100 Twice weekly
Estradot 25, 37.5, 50, 75, 100 Twice weekly
Oesclim 25, 37.5, 50, 75, 100 Twice weekly
Vivelle-Dot 25, 37.5, 50, 75, 100 Twice weekly
Estraderm 50, 100 Twice weekly
Topical Emulsion
Estradiol hemihydrate Estrasorb 50 Once daily
Transdermal Spray
Estradiol Evamist 1.53–4.6 mg is applieda Once daily
Topical Gel
Estradiol EstroGel 0.75 mg is applieda Once daily
Elestrin 0.52 or 1.04 mg is applieda Once daily
Divigel 0.25, 0.5, or 1 mg is applieda Once daily
ESTROGEN/PROGESTIN COMBINATIONS Transdermal Patches
Estradiol/norethindrone CombiPatch 50/140, 50/250 Twice weekly
Estradiol/levonorgestrel Climara Pro 45/15 Once weekly
TABLE 61.4 ■ Transdermal Drugs for Menopausal Hormone Therapy
aApplication of this dose produces blood levels of estrogen and estrone similar to those seen in the follicular phase of the ovulatory cycle.
aProgestins are used to counteract the effects of estrogen on the uterus. The progestins listed can be used when the regimen calls for taking estrogen and progestin separately, rather than using a combination product. In estrogen/progestin regimens, the estrogen is taken daily, and the progestin is taken daily or intermittently (e.g., 14 days on, 14 days off).
bBazedoxifene is an estrogen antagonist/SERM that acts to reduce excessive growth of the uterine lining that can occur with the estrogen component.
Generic Name Brand Name Usual Dosage
ESTROGEN/PROGESTIN COMBINATIONSa
Conjugated estrogens/medroxyprogesterone acetate Prempro 0.3/1.5, 0.45/1.5, 0.625/2.5, or 0.625/5 mg daily Conjugated estrogens/medroxyprogesterone acetate Premphase Days 1–14: 0.625 mg estrogen (alone) daily
Days 15–28: 0.625/5 mg estrogen/progesterone daily
Estradiol/drospirenone Angeliq 0.5/0.25 or 1/0.5 mg daily
Estradiol/norethindrone acetate Activella 0.5/0.1 or 1/0.5 mg daily
Estradiol/norgestimate Prefest 1 mg estradiol every day; 0.09 mg norgestimate in a repeating
cycle of 3 days on and 3 days off
Ethinyl estradiol/norethindrone Femhrt 2.5 mcg/0.5 mg or 5 mcg/1 mg daily
OTHER ESTROGEN COMBINATIONS
Esterified estrogens/methyltestosterone Covaryx 1.25 mg/2.5 mg daily
Esterified estrogens/methyltestosterone Covaryx HS 0.625/1.25 mg daily
Conjugated estrogens/bazedoxifeneb Duavee 0.45 mg/20 mg twice daily
TABLE 61.3 ■ Oral Drugs for Menopausal Hormone Therapy—cont’d
KEY POINTS
■ Estradiol is the principal endogenous estrogen.
■ Progesterone is the principal endogenous progestational hormone.
■ The first half of the 28-day menstrual cycle is called the follicular phase. The second half is called the luteal phase.
■ During the follicular phase, estrogens produced by maturing ovarian follicles cause proliferation of the endometrium.
■ During the luteal phase, progesterone produced by the corpus luteum causes the endometrium to become more vascular and the endometrial glands to secrete glycogen.
■ Toward the end of the menstrual cycle, progesterone levels decline, causing breakdown of the endometrium, which results in menstrual bleeding.
■ In addition to their role in the menstrual cycle, estrogens are required for the growth and maturation of the uterus, vagina, fallopian tubes, and breasts. Estrogens also control pigmentation of the nipples and genitalia.
■ Estrogens suppress bone mineral resorption, and thereby have a positive effect on bone mass.
■ Estrogens raise levels of HDL cholesterol and reduce levels of LDL cholesterol. These actions partially explain the low incidence of coronary heart disease in premenopausal women.
■ Nausea is the most common adverse effect of exogenous oral estrogens.
■ Prolonged use of estrogens alone is associated with an increased risk for endometrial hyperplasia and endometrial carcinoma. However, when estrogens are used in combina-tion with a progestin, there is little or no risk for this cancer.
■ Estrogens are potentially teratogenic. Research has shown that high dose exposure can affect testicular development in the developing male fetus, leading to eventual infertil-ity. Follow-up studies of women who inadvertently took estrogen (as a component in combined oral contraceptives) early during an undiagnosed pregnancy did not identify subsequent abnormalities in their offspring.
■ Symptoms of menopause result from a decline in ovarian production of estrogen.
■ Menopausal hormone therapy (HT), formerly known as hormone replacement therapy (HRT), has three approved indications: suppression of vasomotor symptoms, prevention of urogenital atrophy, and prevention of bone loss and osteoporosis.
■ Hormone therapy is not approved for cardiovascular protec-tion, and should not be used for this purpose.
■ The Women’s Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS)—two large,
randomized, placebo-controlled trials—have given us the most statistically valid data to date on the benefits and risks of HT; however, problems related to the advanced age of subjects, high doses of HT, and prolonged regimens resulted in findings that do not reflect optimal recommendations.
■ When the Endocrine Society extrapolated findings from research that reflected women younger than 60, HT was found to have far fewer adverse effects and life-promoting benefits.
■ We have two basic regimens for HT: estrogen alone (ET) and estrogen combined with a progestin (EPT). The purpose of the estrogen is to manage symptoms caused by estrogen loss. The progestin is present to counteract the adverse effects that unopposed estrogen has on the endometrium.
In women who no longer have a uterus, the progestin is omitted.
■ The major risks of HT are CHD, MI, DVT, pulmonary embolism, stroke, breast cancer, gallbladder disease, and dementia. Ovarian cancer and lung cancer are also a concern.
■ Risk factors associated with HT depend on the regimen and the age of the user. An extrapolation of findings from the WHI by the Endocrine Society found that for women ages 50 to 59, HT resulted in 5 to 5.3 fewer deaths per 1000 women. The risk for adverse events increases with increasing age.
■ The benefits of using HT short term to reduce vasomotor symptoms generally outweigh the risks, especially in younger women. To keep risk low, women should use the smallest effective dose for the shortest time needed.
■ The benefits of using HT short term to manage urogenital symptoms probably outweigh the risks. If this is the only reason for HT, a topical estrogen should be considered.
■ For protection against osteoporosis, HT must be taken long term. When HT is discontinued, 12% of bone mass is lost. Because of the risks associated with prolonged HT, alternative therapies are preferred.
■ Premenstrual disorder (PMD) consists of a constellation of psychologic and physical symptoms that develop in the luteal phase of the menstrual cycle and resolve with menses.
■ SSRIs are the most effective drugs known for PMD. In addition to relieving psychologic symptoms, they often reduce physical symptoms (e.g., breast tenderness, bloating, headache).
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counteract the stimulant effects of estrogen on the endometrium.
Several dosing schedules may be employed. Estrogen and progestin are commonly administered continuously, thereby eliminating monthly bleeding. An alternative is to give estrogen continuously but give the progestin cyclically (e.g., on calendar days 15 through 28). However, cyclic progestin has the dis-advantage of promoting monthly bleeding, which may explain why most women prefer continuous dosing.
Vaginal estrogens can be given continuously for 1 to 2 weeks, followed by dosing 1 to 3 times per week, titrating the dosing schedule based on symptoms. Estring remains in the vagina for 3 months, after which it is removed and replaced with a new ring.
CHAPTER 61 Estrogens and Progestins: Basic Pharmacology and Noncontraceptive Applications
Summary of Major Nursing Implications
aESTROGENS Conjugated estrogens
Conjugated estrogens, synthetic Estradiol
Estradiol acetate Estropipate Ethinyl estradiol
Preadministration Assessment Therapeutic Goal
Estrogens are used primarily for contraception (see Chapter 62) and for menopausal HT, but only to prevent osteoporosis, suppress vasomotor symptoms, and manage symptoms related to vulvar and vaginal atrophy. Indications unrelated to HT are female hypogonadism, prostate cancer, and dysfunctional uterine bleeding.
Baseline Data
Assessment should include a breast examination, pelvic examination, lipid profile, mammography, and blood pressure measurement. If the indication for HT is vasomotor symptoms, menopause should be verified by a serum FSH level.
Identifying High-Risk Patients
Estrogens are contraindicated for patients with estrogen-dependent cancers, undiagnosed abnormal vaginal bleeding, active thrombophlebitis or thromboembolic disorders, or a history of estrogen-associated thrombophlebitis, thrombosis, or thromboembolic disorders. In addition, estrogens are contraindicated during pregnancy—not because they are especially harmful, but because there is no indication for use in pregnancy.
Implementation: Administration Routes
Oral, IM, IV, transdermal, and intravaginal.
Administration
Transdermal Patch. Give the patient the following instructions for using estradiol transdermal patches:
• Apply to an area of clean, dry intact skin on the abdomen or some other region of the trunk (but not the breasts or waistline) by pressing the patch firmly in place for 10 seconds.
• If the patch falls off, reapply the same patch or, if necessary, apply a new patch.
• Remove the old patch and apply a new patch once or twice weekly according to the product specifications.
• Rotate the application site such that the same site is not used more than once each week.
Transdermal Emulsion. Instruct the patient to apply the emulsion each morning to the top of both thighs and the back of both calves.
Transdermal Gel. Instruct the patient to apply the gel once daily after showering to one arm, from the shoulder to the wrist.
Transdermal Spray. Instruct the patient to apply 1, 2, or 3 sprays once daily to the inner forearm, and then let it dry at least 2 minutes before dressing and at least 30 minutes before washing.
Intravaginal Cream. Instruct the patient to apply estrogen cream high into the vagina, usually at bedtime, using the applicator provided.
Intravaginal Ring. Instruct the patient to insert the ring as deeply as possible and to leave it in place for 3 months, after which it should be removed, and then replaced with a new ring if indicated.
Intravaginal Tablet. Inform patients that dosing consists of 1 tablet daily for 2 weeks, followed by 1 tablet twice a week thereafter. Instruct patients to insert each tablet as far as comfortably possible using the applicator supplied.
Dosing Schedules for Hormone Therapy
Women with an intact uterus should receive estrogen plus progestin, whereas women who have had a hysterectomy should use estrogen alone. In both cases, dosing with oral estrogen is done daily. With estrogen plus progestin, the progestin component may be given daily or cyclically 10 days per month.
Ongoing Evaluation and Interventions Monitoring Summary
The patient should receive a yearly follow-up breast and pelvic examination.
Minimizing Adverse Effects
Nausea. Nausea is common early in treatment but diminishes with time. Inform the patient that nausea can be reduced by taking estrogens with food and by dosing at night.
Endometrial Hyperplasia and Cancer. Menopausal HT with estrogen alone increases the risk for endometrial carci-noma. Adding a progestin lowers this risk to the pretreatment level. Instruct the patient to notify the prescriber if persistent or recurrent vaginal bleeding develops so that the possibility of endometrial carcinoma can be evaluated.
Breast Cancer. Estrogen, combined with a progestin, produces a small increase in the risk for breast cancer in postmenopausal women. To minimize risk, remind patients of the need to receive periodic mammograms. Estrogen alone may increase breast cancer risk, but only when HT is started after menopause onset. Among younger women, estrogen alone may actually protect against breast cancer.
Ovarian Cancer. In postmenopausal women, giving ET or EPT may pose a small risk for ovarian cancer. Advise women using ET or EPT to undergo periodic evaluation for ovarian cancer.
Lung Cancer. Menopausal EPT, but not ET, may increase the risk for lung cancer. Advise women using EPT to undergo periodic evaluation for lung cancer.
Cardiovascular Events. Estrogen plus a progestin increases the risk for CHD, MI, DVT, pulmonary embolism, and stroke. For women over the age of 60, therapy with
Continued
aPatient education information is highlighted as blue text.
estrogen alone carries the same risks. For women ages 50 to 59, therapy with estrogen alone increases the risk for DVT, pulmonary embolism, and stroke, but may protect against CHD and MI. To reduce cardiovascular risk, advise women to avoid smoking, perform regular exercise, decrease intake of saturated fats, and take appropriate drugs to treat hyperten-sion, diabetes, and high cholesterol.
Effects Resembling Those Caused by Oral Contra-ceptives. Use of estrogens for noncontraceptive purposes can produce adverse effects similar to those caused by oral contraceptives (e.g., abnormal vaginal bleeding, hyperten-sion, benign hepatic adenoma, reduced glucose tolerance).
Nursing implications regarding these effects are summarized in Chapter 62.
Minimizing Adverse Interactions. The interactions of estrogens are probably similar to those seen with oral contraceptives. Implications regarding these interactions are summarized in Chapter 62.
PROGESTINS Drospirenone
Hydroxyprogesterone caproate Levonorgestrel
Medroxyprogesterone acetate Megestrol acetate
Norethindrone Norethindrone acetate Norgestimate
Norgestrel Progesterone
Preadministration Assessment Therapeutic Goal
Progestins are used for contraception (see Chapter 62) and to counteract endometrial hyperplasia that could be caused by unopposed estrogen during HT. Other uses include
dysfunctional uterine bleeding, amenorrhea, endometriosis, and support of pregnancy in women with corpus luteum deficiency. Progestins are also used in IVF cycles and to prevent prematurity in women at high risk for preterm birth.
Baseline Data
The physical examination should include breast and pelvic examinations. A pregnancy examination is warranted for premenopausal women.
Identifying High-Risk Patients
Progestins are contraindicated in the presence of undiagnosed abnormal vaginal bleeding. Relative contraindications include active thrombophlebitis or a history of thromboembolic disorders, active liver disease, and carcinoma of the breast.
Implementation: Administration Routes
Oral, IM, transdermal, intravaginal.
Administration
Advise patients to take oral progestins with food if GI upset occurs.
Ongoing Evaluation and Interventions Minimizing Adverse Effects
Gynecologic Effects. Progestins can cause breakthrough bleeding, spotting, and amenorrhea. Inform patients about potential side effects. Instruct the patient to report any persistent or recurrent vaginal bleeding.
Teratogenic Effects. High-dose therapy during the first 4 months of pregnancy has been associated with an increased incidence of birth defects (limb reductions, heart defects, masculinization of the female fetus). Accordingly, use of progestins during early pregnancy is not recommended.
Summary of Major Nursing Implications
a—cont’d
C H A P T E R
62 Birth Control
Effectiveness of Birth Control Methods, p. 753