Indications
PO, IM, Topical, Transdermal: Replacement of estrogen
(HRT) to diminish moderate to severe vasomotor
symptoms of menopause and of various estrogen
deficiency states including: Female hypogonadism,
Ovariectomy, Primary ovarian failure. Treatment and
prevention of postmenopausal osteoporosis (not vaginal
dose forms). PO: Inoperable metastatic postmenopausal
breast or prostate carcinoma. Vag: Management
of atrophic vaginitis that may occur with menopause
(low dose), bothersome systemic symptoms of menopause
(higher dose). Concurrent use of progestin is
recommended during cyclical therapy to decrease the
risk of endometrial carcinoma in patients with an intact
uterus.
Action
Estrogens promote growth and development of female
sex organs and the maintenance of secondary sex characteristics
in women. Metabolic effects include reduced
blood cholesterol, protein synthesis, and sodium and
water retention. Therapeutic Effects: Restoration
of hormonal balance in various deficiency states, including
menopause. Treatment of hormone-sensitive
tumors.
Pharmacokinetics
Absorption: Well absorbed after oral administration.
Readily absorbed through skin and mucous membranes.
Distribution: Widely distributed. Crosses the placenta
and enters breast milk.
Metabolism and Excretion: Mostly metabolized
by the liver and other tissues. Enterohepatic recirculation
occurs, and more absorption may occur from the
GI tract.
Half-life: Gel: 36 hr.
TIME/ACTION PROFILE (estrogenic effects)
ROUTE ONSET PEAK DURATION
PO unknown unknown unknown
IM unknown unknown unknown
TD unknown unknown 3–4 days (Estraderm),
7
days (Climara)
Topical unknown unknown unknown
Vaginal ring unknown unknown 90 days
Vaginal tablet unknown unknown 3–4 days
Contraindications/Precautions
Contraindicated in: History of anaphylaxis or angioedema
to estradiol; Thromboembolic disease (e.g.,
DVT, PE, MI, stroke); Protein C, protein S, or antithrombin
deficiency or other thrombophilic disorder;
History of breast cancer; History of estrogen-dependent
cancer; Hepatic impairment; Undiagnosed vaginal
bleeding; OB: Positive evidence of fetal risk.
Use Cautiously in: Underlying cardiovascular disease;
Severe hepatic or renal disease; Mayqthe risk of
endometrial carcinoma; History of porphyria; History of
hereditary angioedema; Lactation: Usually compatible
with breast feeding (AAP).
Adverse Reactions/Side Effects
CNS: headache, dizziness, lethargy. EENT: intolerance
to contact lenses, worsening of myopia or astigmatism.
CV: MI, THROMBOEMBOLISM, edema, hypertension.
GI: nausea, weight changes, anorexia,qappetite,
jaundice, vomiting. GU: women—amenorrhea, dysmenorrhea,
breakthrough bleeding, cervical erosions,
loss of libido, vaginal candidiasis; men, erectile dysfunction,
testicular atrophy Derm: oily skin, acne, pigmentation,
urticaria. Endo: gynecomastia (men), hyperglycemia.
F and E: hypercalcemia, sodium and
water retention. MS: leg cramps. Misc: breast tenderness.
Interactions
Drug-Drug: May alter requirement for warfarin,
oral hypoglycemic agents, or insulins. Barbiturates
or rifampin maypeffectiveness. Smokingq
risk of adverse CV reactions.
Route/Dosage
Estrogens should be used in the lowest doses for the
shortest period of time consistent with desired therapeutic
outcome.
Symptoms of Menopause, Atrophic Vaginitis,
Female Hypogonadism, Ovarian
Failure/Osteoporosis
PO (Adults): 0.45–2 mg daily or in a cycle.
IM (Adults): 1–5 mg monthly (estradiol cypionate)
or 10–20 mg (estradiol valerate) monthly.
Topical Emulsion (Estrasorb) (Adults): Apply two
1.74-g pouches (4.35 mg estradiol) daily.
Gel (Adults): Apply contents of one packet (Divigel) or
one actuation from pump (EstroGel, Elestrin) daily.
Spray EvaMist (Adults): 1 spray daily, may beqto 2–
3 sprays daily.
Transdermal (Adults): Alora—25–50–mcg/24-hr
transdermal patch applied twice weekly. Estraderm—
50–mcg/24-hr transdermal patch applied twice
weekly. Climara—25-mcg/24-hr transdermal patch
applied weekly. Vivelle-Dot—25–50–mcg/24-hr
transdermal patch applied twice weekly. Menostar—
14-mcg/24-hr transdermal patch applied q 7 days. Progestin
may be administered for 10–14 days of each
mo. Minivelle—37.5–mcg/24–hr transdermal patch applied twice weekly (for treatment of vasomotor symptoms);
25–mcg/24–hr transdermal patch applied
twice weekly (for prevention of postmenopausal osteoporosis).
Vag (Adults): Cream—2–4 g (0.2–0.4 mg estradiol)
daily for 1–2 wk, thenpto 1–2 g/day for 1–2
wk; then maintenance dose of 1 g 1–3 times weekly for
3 wk, then off for 1 wk; then repeat cycle once vaginal
mucosa has been restored; Vaginal ring (Estring)—
2-mg (releases 7.5 mcg estradiol/24 hr) q 3 mo; Vaginal
ring (Femring)—12.4 mg (releases 50 mcg estradiol/
24 hr) q 3 mo or 24.8 mg (releases 100 mcg
estradiol/24 hr) q 3 mo (Femring requires concurrent
progesterone); Vaginal insert—1 tablet once daily for
2 wk, then twice weekly.
Postmenopausal Breast Carcinoma
PO (Adults): 10 mg 3 times daily.
Prostate Carcinoma
PO (Adults): 1–2 mg 3 times daily.
IM (Adults): 30 mg q 1–2 wk (estradiol valerate).
Availability (generic available)
Tablets: 0.5 mg, 1 mg, 2 mg. Cost: Generic—0.5 mg
$10.83/100, 1 mg $10.83/100, 2 mg $10.83/100. Injection
(valerate in oil): 10 mg/mL, 20 mg/mL, 40
mg/mL. Injection (cypionate in oil): 5 mg/mL. Topical
emulsion: 4.35 mg/1.74-g pouch. Cost: $1.36/
pouch. Topical gel packet (Divigel): 0.25 mg/
packet, 0.5 mg/packet, 1 mg/packet. Cost: All strengths
$3.45/pkt. Topical gel pump (Elestrin): 0.52 mg/
actuation. Cost: Elestrin (0.52 mg/actuation)—
$89.44/26 g. Topical gel pump (Estrogel): 0.75 mg/
actuation. Cost: EstroGel (0.75 mg/actuation)—
$103.80/50 g. Transdermal spray: 1.53 mg/spray.
Cost: $108.76/9 mL. Transdermal system: 14 mcg/
24-hr release rate, 25 mcg/24-hr release rate, 37.5
mcg/24-hr release rate, 50 mcg/24-hr release rate, 60
mcg/24-hr release rate, 75 mcg/24-hr release rate, 100
mcg/24-hr release rate. Cost: 14 mcg/24 hr $221.46/
4, 25 mcg/24 hr $88.40/4, 37.5 mcg/24 hr $88.40/4,
50 mcg/24 hr $88.40/4, 60 mcg/24 hr $88.40/4, 75
mcg/24 hr $88.40/4, 100 mcg/24 hr $88.40/4. Vaginal
cream: 0.01%. Cost: $165.70/43 g. Vaginal ring
(Estring): 2 mg (releases 7.5 mcg/day over 90 days).
Cost: $252.72/1 ring. Vaginal ring (Femring): 12.4
mg (releases 50 mcg/day over 90 days), 24.8 mg (releases
100 mcg/day over 90 days). Cost: 50 mcg/day
$248.98/1 ring, 100 mcg/day $259.58/1 ring. Vaginal
insert: 10 mcg. Cost: $97.05/8. In combination
with: norethindrone (Combipatch). See Appendix B.
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