estradiols

(ess tra dye' ole)

estradiol
Oral:
Estrace, Gynodiol
Transdermal system:
Alora, Climara, Esclim, Estraderm, Vivelle, Vivelle Dot
Topical vaginal cream:
Estrace
Vaginal ring:
Estring
Topical emulsion:
Estrasorb

estradiol cypionate
Injection in oil:
Depo-Estradiol

estradiol hemihydrate
Vaginal tablet:
Vagifem

estradiol valerate
Injection in oil:
Delestrogen

Pregnancy Category X

Drug classes
Hormone
Estrogen

Therapeutic actions
Estradiol is the most potent endogenous female sex hormone. Estrogens are important in
the development of the female reproductive system and secondary sex characteristics;
affect the release of pituitary gonadotropins; cause capillary dilatation, fluid retention,
protein anabolism and thin cervical mucus; conserve calcium and phosphorus and
encourage bone formation; inhibit ovulation and prevent postpartum breast discomfort.
They are responsible for the proliferation of the endometrium; absence or decline of
estrogen produces signs and symptoms of menopause on the uterus, vagina, breasts,
cervix; relief in androgen-dependent prostatic carcinoma is attributable to competition
with androgens for receptor sites, decreasing the influence of androgens.
Indications
• Topical emulsion, all forms: Palliation of moderate to severe vasomotor
symptoms, atrophic vaginitis or kraurosis vulvae associated with menopause
• Estradiol oral, transdermal, ring, vaginal tablets, estradiol valerate: Prevention of
postmenopausal osteoporosis
• Estradiol oral, transdermal, estradiol cypionate, valerate: Treatment of female
hypogonadism, female castration, primary ovarian failure
• Estradiol oral, estradiol valerate: Palliation of inoperable prostatic cancer
• Estradiol oral: Palliation of inoperable, progressing breast cancer
• Prevention of osteoporosis

Contraindications and cautions

• Contraindicated with allergy to estrogens, allergy to tartrazine (in 2-mg oral
tablets), breast cancer (with exceptions), estrogen-dependent neoplasm,
undiagnosed abnormal genital bleeding, active or past history of thrombophlebitis
or thromboembolic disorders (potential serious fetal defects; women of
childbearing age should be advised of risks and birth control measures suggested).
• Use cautiously with metabolic bone disease, renal insufficiency, CHF, lactation.

Available forms
Transdermal—release rates of 0.025, 0.0375, 0.05, 0.075, 0.1 mg/24 hr; tablets—0.5, 1,
2 mg; injection—5, 10, 20, 40 mg/mL; vaginal cream—0.1 mg; vaginal ring—2 mg;
vaginal tablet—25 mcg; topical emulsion—0.1 mg

Dosages
ADULTS
• Moderate to severe vasomotor symptoms, atrophic vaginitis, kraurosis vulvae
associated with menopause: 1–2 mg/day PO. Adjust dose to control symptoms.
Cyclic therapy (3 wk on/1 wk off) is recommended, especially in women who
have not had a hysterectomy. 1–5 mg estradiol cypionate in oil IM every 3–4 wk.
10–20 mg estradiol valerate in oil IM, every 4 wk. 0.025–0.05-mg system applied
to the skin weekly or twice weekly. If oral estrogens have been used, start
transdermal system 1 wk after withdrawal of oral form. Given on a cyclic
schedule (3 wk on/1wk off). Attempt to taper or discontinue medication every 3–6
mo.
• Female hypogonadism, female castration, primary ovarian failure: 1–2 mg/day
PO. Adjust dose to control symptoms. Cyclic therapy (3 wk on/1 wk off) is
recommended. 1.5–2 mg estradiol cypionate in oil IM at monthly intervals. 10–
20 mg estradiol valerate in oil IM every 4 wk. 0.05-mg system applied to skin
twice weekly as above.
Vaginal
• Vaginal cream: 2–4 g intravaginally daily for 1–2 wk, then reduce to one-half
dosage for similar period followed by maintenance doses of 1 g 1–3 times/wk
thereafter. Discontinue or taper at 3- to 6-mo intervals.
• Vaginal ring: Insert one ring high into vagina. Replace every 90 days.
 • Vaginal tablet: 1 tablet inserted vaginally daily for 2 wk; then twice weekly.
Oral
• Prostatic cancer (inoperable): 1–2 mg PO tid. Administer long-term. 30 mg or
more estradiol valerate in oil IM every 1–2 wk.
• Breast cancer (inoperable, progressing): 10 mg tid PO for at least 3 mo.
• Prevention of postpartum breast engorgement: 10–25 mg estradiol valerate in oil
IM as a single injection at the end of the first stage of labor.
• Osteoporosis prevention: 0.5 mg/day PO given cyclically—23 days on, 5 days
rest—starting as soon after menopause as possible or 0.05 mg/24 hr applied to
skin once or twice weekly.
PEDIATRIC PATIENTS
Not recommended due to effect on the growth of the long bones.

Pharmacokinetics
Route Onset Peak
Oral Slow Days

Metabolism: Hepatic; T1/2: Not known

Distribution: Crosses placenta; enters breast milk
Excretion: Urine

Adverse effects
• CNS: Steepening of the corneal curvature with a resultant change in visual acuity
and intolerance to contact lenses, headache, migraine, dizziness, mental
depression, chorea, seizures
• CV: Increased blood pressure, thromboembolic and thrombotic disease
• Dermatologic: Photosensitivity, peripheral edema, chloasma, erythema nodosum
or multiforme, hemorrhagic eruption, loss of scalp hair, hirsutism, urticaria,
dermatitis
• GI: Gallbladder disease (in postmenopausal women), hepatic adenoma, nausea,
vomiting, abdominal cramps, bloating, cholestatic jaundice, colitis, acute
pancreatitis
• GU: Increased risk of postmenopausal endometrial cancer, breakthrough
bleeding, change in menstrual flow, dysmenorrhea, premenstrual-like syndrome,
amenorrhea, vaginal candidiasis, cystitis-like syndrome, endometrial cystic
hyperplasia
• Hematologic: Hypercalcemia, decreased glucose tolerance
• Local: Pain at injection site, sterile abscess, postinjection flare
• Other: Weight changes, reduced carbohydrate tolerance, aggravation of
porphyria, edema, changes in libido, breast tenderness
Topical vaginal cream
Systemic absorption may cause uterine bleeding in menopausal women and may cause
serious bleeding of remaining endometrial foci in sterilized women with endometriosis.

Interactions
Drug-drug
• Increased therapeutic and toxic effects of corticosteroids
• Decreased serum levels of estradiol with drugs that enhance hepatic metabolism
of the drug—barbiturates, phenytoin, rifampin
Drug-lab test
• Increased prothrombin and factors VII, VIII, IX, and X; thyroid-binding globulin
with increased PBI, T4, increased uptake of free T3 resin (free T4 is unaltered),
serum triglycerides and phospholipid concentration
• Decreased antithrombin III, pregnanediol excretion, response to metyrapone test,
serum folate concentration
• Impaired glucose tolerance

Nursing considerations
Assessment
• History: Allergy to estrogens, tartrazine; breast cancer, estrogen-dependent
neoplasm; undiagnosed abnormal genital bleeding; active or previous
thrombophlebitis or thromboembolic disorders; pregnancy; lactation; metabolic
bone disease; renal insufficiency; CHF
• Physical: Skin color, lesions, edema; breast exam; injection site; orientation,
affect, reflexes; P, auscultation, BP, peripheral perfusion; R, adventitious sounds;
bowel sounds, liver evaluation, abdominal exam; pelvic exam; serum calcium,
phosphorus; liver and renal function tests; Pap smear; glucose tolerance test

Interventions
• Arrange for pretreatment and periodic (at least annual) history and physical,
which should include BP, breasts, abdomen, pelvic organs, and a Pap smear.
• Caution patient of the risks of estrogen use, the need to prevent pregnancy during
treatment, for frequent medical follow-up, and for periodic rests from drug
treatment.
• Administer cyclically for short-term only when treating postmenopausal
conditions because of the risk of endometrial neoplasm; taper to the lowest
effective dose, and provide a drug-free week each month.
• Apply transdermal system to a clean, dry area of skin on the trunk of the body,
preferably the abdomen; do not apply to breasts; rotate the site at least 1 wk
between applications; avoid the waistline because clothing may rub the system
off; apply immediately after opening and compress for about 10 sec to attach.
• Insert vaginal ring as deeply as possible into upper one-third of vagina. Ring will
remain in place for 3 months. Then, remove and evaluate need for continued
therapy. If a ring falls out during 3 mo, rinse with warm water and reinsert.
• Arrange for the concomitant use of progestin therapy during long-term estrogen
therapy; this will mimic normal physiologic cycling and allow for a cyclic uterine
bleeding that may decrease the risk of endometrial cancer. Women without a
uterus do not need progestin.
• Administer parenteral preparations by deep IM injection only. Monitor injection
sites and rotate with each injection to decrease development of abscesses.
Teaching points
• Use this drug in cycles or short term; prepare a calendar of drug days, rest days,
and drug-free periods.
• Apply transdermal system and vaginal cream properly; insert vaginal tablet as
high into the vagina as is comfortable.
• Insert vaginal ring high in vagina; it should remain in place for 3 months. If it
falls out before that time, rinse with warm water and reinsert.
• Potentially serious side effects include cancers, blood clots, liver problems; it is
very important to have periodic medical exams throughout therapy.
• This drug cannot be given to pregnant women because of serious toxic effects to
the baby.
• These side effects may occur: Nausea, vomiting, bloating; headache, dizziness,
mental depression (use caution if driving or performing tasks that require
alertness); sensitivity to sunlight (use a sunscreen and wear protective clothing);
rash, loss of scalp hair, darkening of the skin on the face; changes in menstrual
patterns.
• Report pain in the groin or calves of the legs, chest pain or sudden shortness of
breath, abnormal vaginal bleeding, lumps in the breast, sudden severe headache,
dizziness or fainting, changes in vision or speech, weakness or numbness in the
arm or leg, severe abdominal pain, yellowing of the skin or eyes, severe mental
depression, pain at injection site.

Adverse effects in Italic are most common; those in Bold are life-threatening.