estradiol

es-tra-DYE-ole

Therapeutic Classification: hormones

Pharmacologic Classification: estrogens

IM:

REMS

PO:
Replacement of estrogen 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.
Management of:
- Atrophic vaginitis due to menopause,
- Moderate to severe dyspareunia due to menopause.

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.

Absorption: Well absorbed after oral administration. Readily absorbed through skin and mucous membranes.

Distribution: Widely distributed to tissues.

Metabolism/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.

(estrogenic effects)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	unknown
IM	unknown	unknown	unknown
Transdermal	unknown	unknown	3–4 days (Estraderm), 7 days (Climara)
Topical	unknown	unknown	unknown
Vaginal insert	unknown	unknown	3–4 days
Vaginal ring	unknown	unknown	90 days

Contraindicated in:

History of anaphylaxis or angioedema to estradiol;
Thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, 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: Pregnancy.

Use Cautiously in:

Underlying cardiovascular disease;
Severe renal impairment;
History of porphyria;
History of hereditary angioedema;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

CV: edema, hypertension, MI, THROMBOEMBOLISM

Derm: oily skin, acne, pigmentation, urticaria

EENT: intolerance to contact lenses, worsening of myopia or astigmatism

Endo: gynecomastia (men), hyperglycemia

F and E: hypercalcemia, sodium and water retention

GI: nausea, weight changes, anorexia, jaundice, vomiting

GU:

women

amenorrhea, dysmenorrhea, breakthrough bleeding, cervical erosions, loss of libido, vaginal candidiasis;,

men

erectile dysfunction, testicular atrophy.

Metab: ↑appetite

MS: leg cramps

Neuro: headache, dementia, dizziness, lethargy, STROKE

Misc: breast tenderness, MALIGNANCY (BREAST, ENDOMETRIAL, OVARIAN)

Drug-drug:

May alter requirement for warfarin, oral hypoglycemic agents, or insulins.
Barbiturates or rifampin may ↓ effectiveness.
Smoking↑ risk of adverse CV reactions.

Estrogens should be used in the lowest doses for the shortest period of time consistent with desired therapeutic outcome. Concurrent use of progestin is recommended during cyclical therapy to decrease the risk of endometrial carcinoma in patients with an intact uterus.

Symptoms of Menopause, Atrophic Vaginitis, Moderate to Severe Dyspareunia, Female Hypogonadism, Ovarian Failure/Osteoporosis

PO (Adults ): 0.45–2 mg once daily or in a cycle.
IM (Adults ): 1–5 mg monthly (estradiol cypionate) or 10–20 mg (estradiol valerate) monthly.
Gel
(Adults ): Apply contents of one packet (Divigel) or one actuation from pump (EstroGel, Elestrin) once daily.
Spray EvaMist
(Adults ): 1 spray once daily, may be ↑ to 2–3 sprays once daily.
Transdermal (Adults ): 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 every 7 days. Progestin may be administered for 10–14 days of each mo. Dotti, Lyllana, or 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).
(Adults ): Cream: 2–4 g (0.2–0.4 mg estradiol) once daily for 1–2 wk, then ↓ to 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) every 3 mo; Vaginal ring (Femring): 12.4 mg (releases 50 mcg estradiol/24 hr) every 3 mo or 24.8 mg (releases 100 mcg estradiol/24 hr) every 3 mo (Femring requires concurrent progesterone); Vaginal insert (Vagifem, Yuvafem, or Imvexxy): 1 insert once daily for 2 wk, then 1 insert twice weekly.

Postmenopausal Breast Cancer

PO (Adults ): 10 mg 3 times daily.

Prostate Cancer

PO (Adults ): 1–2 mg 3 times daily.
IM (Adults ): 30 mg every 1–2 wk (estradiol valerate).

(Generic available)

Estradiol

Tablets: 0.5 mg; 1 mg; 2 mg
In combination with: dienogest (Natazia); drospirenone (Angeliq); elagolix/norethindrone (Oriahnn); norethindrone (Activella, Amabelz, Mimvey); norgestimate (Prefest); progesterone (Bijuva); relugolix/norethindrone (Myfembree). See Appendix [not included in this PDA edition].

Estradiol Cypionate

Injection (in oil): 5 mg/mL

Estradiol Transdermal Preparations

Gel packet (Divigel): 0.25 mg/pkt; 0.5 mg/pkt; 0.75 mg/pkt; 1 mg/pkt; 1.25 mg/pkt
Gel pump (Elestrin): 0.52 mg/actuation
Gel pump (Estrogel): 0.75 mg/actuation
Transdermal patch: 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
Spray: 1.53 mg/spray
In combination with: levonorgestrel (Climara Pro); norethindrone (Combipatch). See Appendix [not included in this PDA edition].

Estradiol Vaginal Preparations

Vaginal cream: 0.01%
Vaginal tablet (Vagifem or Yuvafem): 10 mcg
Vaginal insert (Imvexxy): 4 mcg; 10 mcg
Vaginal ring (Estring): 2 mg (releases 7.5 mcg/day over 90 days)
Vaginal ring (Femring): 12.4 mg (releases 50 mcg/day over 90 days); 24.8 mg (releases 100 mcg/day over 90 days)

Estradiol Valerate

Injection (in oil): 10 mg/mL; 20 mg/mL; 40 mg/mL

Assess BP before and periodically during therapy.
Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain.
Menopause: Assess frequency and severity of vasomotor symptoms.

Lab Test Considerations:

May cause ↑ HDL and triglycerides and ↓ serum LDL and total cholesterol concentrations.
- May cause ↑ serum glucose, sodium, cortisol, prolactin, prothrombin, and factor VII, VIII, IX, and X levels. May ↓ serum folate, pyridoxine, antithrombin III, and urine pregnanediol concentrations.
- Monitor hepatic function before and periodically during therapy.
- May cause false interpretations of thyroid function tests, false ↑ in norepinephrine platelet-induced aggregability, and false ↓ in metyrapone tests.
- May cause hypercalcemia in patients with metastatic bone lesions.

PO: Administer with or immediately after food to reduce nausea.
Manufacturer provides applicator with cream. Dose is marked on the applicator. Wash applicator with mild soap and warm water after each use.
When switching from PO form, begin transdermal therapy 1 wk after the last dose or when symptoms reappear.
Apply Divigel individual-use once-daily packets of quick drying gel to an area measuring 5 inches by 7 inches (size of 2 palm prints) on the thigh. Do not wash area for at least 1 hr after gel has dried.
- Start with 1 pump daily and apply Elestrin to skin of upper arm to shoulder in a thin layer.
- Before first use of Estrogel, remove large canister cover and fully depress pump 5 times. Discard unused gel by rinsing down the sink or placing it in the household trash. After priming, pump is ready to use. Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder.
- Spray EvaMist on inside of forearm at the same time each day. Do not massage or rub the spray into the skin. Allow to dry for 2 min before dressing and at least 1 hr before washing. Never spray EvaMist around breast or vagina. Do not use more than 56 doses, even if fluid remains in pump.
IM: Injection has oil base. Roll syringe to ensure even dispersion. Administer deep IM. Avoid IV administration.

Instruct patient on correct method of administration. Instruct patient to take medication as directed. Take missed doses as soon as remembered as long as it is not just before next dose. If a dose of EvaMist is missed, apply if more than 12 hr before next dose; if less than 12 hr, omit dose and return to regular schedule. Do not double doses.
- Explain dose schedule and maintenance routine. Discontinuing medication suddenly may cause withdrawal bleeding.
- If nausea becomes a problem, advise patient that eating solid food often provides relief.
- Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet, weight gain), thromboembolic disorders (pain, swelling, tenderness in extremities, headache, chest pain, blurred vision), mental depression, or hepatic dysfunction (yellowed skin or eyes, pruritus, dark urine, light-colored stools) to health care professional.
- Advise patient to notify health care professional of medication regimen before treatment or surgery.
- Caution patient that cigarette smoking during estrogen therapy may cause increased risk of serious side effects, especially for women over age 35.
- Caution patient to use sunscreen and protective clothing to prevent increased pigmentation.
- Advise patient treated for osteoporosis that exercise has been found to arrest and reverse bone loss. Patient should discuss any exercise limitations with health care professional before beginning program.
- Inform patient that estrogens should not be used to decrease risk of cardiovascular disease. Estrogens may increase risk of cardiovascular disease (MI, stroke), dementia, and breast cancer.
- Instruct females of reproductive potential to stop taking medication and notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
- Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; Papanicolaou smears every 6–12 mo; and mammogram every 12 mo or as directed. Health care professional will evaluate possibility of discontinuing medication every 3–6 mo. If on continuous (not cyclical) therapy or without concurrent progestins, endometrial biopsy may be recommended, if uterus is intact.
Instruct patient in the correct use of applicator. Patient should remain recumbent for at least 30 min after administration. May use sanitary napkin to protect clothing, but do not use tampon. If a dose is missed, do not use the missed dose, but return to regular dosing schedule.
- Instruct patient to use applicator provided with vaginal tablet. Insert as high up in the vagina as comfortable, without using force.
Vaginal Ring: Instruct patient to press ring into an oval and insert into the upper third of the vaginal vault. Exact position is not critical. Once ring is inserted, patient should not feel anything. If discomfort is felt, ring is probably not in far enough; gently push farther into vagina. Leave in place continuously for 90 days. Ring does not interfere with sexual intercourse. If straining at defecation makes ring move to lower vagina, push up with finger. If expelled totally, rinse ring with lukewarm water and reinsert. To remove, hook a finger through the ring and pull it out.
Instruct patient to wash and dry hands first. Apply disc to intact skin on hairless portion of abdomen (do not apply to breasts or waistline). Apply patch to lower abdomen or buttocks. Press disc/patch for 10 sec to ensure contact with skin (especially around edges). Avoid areas where clothing may rub disc loose. Change site with each administration to prevent skin irritation. Do not reuse site for 1 wk; disc may be reapplied if it falls off.
Advise patient referred for MRI test to discuss patch with referring health care professional and MRI facility to determine if removal of patch is necessary prior to test and for directions for replacing patch.
Evamist: Caution patient to make sure children are not exposed to Evamist and do not come into contact with any skin area where the drug was applied. Women who cannot avoid contact with children should wear a garment with long sleeves to cover the application site.

Resolution of menopausal vasomotor symptoms.
Decreased vaginal and vulvar itching, inflammation, or dryness associated with menopause.
Normalization of estrogen levels in patients with ovariectomy or hypogonadism.
Control of the spread of advanced metastatic breast or prostate cancer.
Prevention of osteoporosis.

estradiol cypionate: Depo-Estradiol,

estradiol tablets: Estrace,

estradiol transdermal gel: Divigel, Elestrin, EstroGel,

estradiol transdermal spray: EvaMist,

estradiol transdermal system : ~~Alora,~~ Climara, Dotti, ~~Estraderm,~~ Lyllana, Menostar, Minivelle, Vivelle-Dot,

estradiol vaginal cream: Estrace,

estradiol vaginal insert: Imvexxy,

estradiol vaginal ring: Estring, Femring,

estradiol vaginal tablet: Vagifem, Yuvafem,

estradiol valerate: Delestrogen

estradiol transdermal system : Estradot, Oesclim

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆