estradiol/progesterone

Estradiol: Represents the primary estrogen secreted prior to menopause. Modulates the pituitary secretion of the gonadotropins, luteinizing hormone, and follicle-stimulating hormone, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Progesterone: opposes the action of estrogen by ↓ estrogen receptor levels, ↑ the metabolism of estrogen to less active metabolites, or blunting the response to estrogen at the cellular level.

Therapeutic effects:

Reduction in frequency and severity of moderate to severe vasomotor symptoms.

Pharmacokinetics ⬆ ⬇

Estradiol

Absorption: Absorption subject to first-pass metabolism.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver; also undergo enterohepatic recirculation via conjugation in the liver; primarily excreted in urine.

Half-Life: 26 hr.

Progesterone

Absorption: Absorption subject to first-pass metabolism.

Distribution: Unknown

Protein Binding: 96–99%.

Metabolism/Excretion: Primarily metabolized by the liver; excreted in urine and bile.

Half-Life: 10 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Estradiol PO	unknown	5 hr	unknown
Progesterone PO	unknown	3 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

History of anaphylaxis or angioedema to estradiol or progesterone;
Undiagnosed abnormal genital bleeding;
History of breast cancer;
History of estrogen-dependent cancer;
Thromboembolic disease (e.g., deep vein thrombosis [DVT], pulmonary embolism [PE], MI, stroke);
Protein C, protein S, or antithrombin deficiency or other thrombophilic disorder;
Hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Long-term use (more than 4–5 yr); may ↑ risk of MI, stroke, invasive breast cancer, PE, DVT, and dementia in postmenopausal women;
Underlying cardiovascular disease;
Hypothyroidism;
Renal impairment;
History of hereditary angioedema;
Asthma, diabetes, seizure disorders, migraine, porphyria, or systemic lupus erythematosus (↑ risk of exacerbation);
Hypoparathyroidism (↑ risk of hypocalcemia).

Adv. Reactions/Side Effects ⬆ ⬇

CV: DVT, hypertension, MI, peripheral edema

EENT: retinal thrombosis

Endo: hypothyroidism

F and E: hypercalcemia, hypocalcemia

GI: cholelithiasis

GU: pelvic pain, vaginal bleeding, vaginal discharge

Metab: hypertriglyceridemia

Neuro: dementia, headache, STROKE

Resp: PE

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

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, erythromycin, itraconazole, ketoconazole, or ritonavir may ↑ levels and risk of toxicity.
Strong CYP3A4 inducers, including carbamazepine, phenobarbital, and rifampin may ↓ levels and effectiveness.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness.

Grapefruit juice may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

PO (Adults ): One capsule (estradiol 1 mg/progesterone 100 mg) each evening with food.

Availability ⬆ ⬇

(Generic available)

Capsules: estradiol 1 mg/progesterone 100 mg

Assessment ⬆ ⬇

Assess frequency and severity of vasomotor symptoms periodically during therapy.
Assess BP and weight before and periodically during therapy.

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.

Implementation ⬆ ⬇

Limit to lowest effective dose and for shortest duration. Reevaluate postmenopausal women periodically to determine if therapy is still necessary.
If feasible, discontinue estradiol/progesterone at least 4–6 wk before surgeries with an increased risk of thromboembolism, or during periods of prolonged immobilization.
PO: Administer each evening with food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Advise patient to avoid drinking grapefruit juice during therapy. Take missed doses as soon as remembered, but not within 2 hr of next dose. Do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Inform patient that estrogens should not be used to decrease risk of cardiovascular disease. Estrogens may increase risk of cardiovascular disease, breast cancer, and dementia.
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), depression, hepatic dysfunction (yellowed skin or eyes, pruritus, dark urine, light-colored stools), new breast lumps, or abnormal vaginal bleeding to health care professional.
Caution patient that cigarette smoking during estrogen therapy may increase risk of serious side effects, especially for women over age 35.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort.
Rep: May cause fetal harm. Instruct patient to stop taking medication and notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
Emphasize importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; Papanicolaou (Pap) 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇