Drug information of Estropipate
Estrone sulfate (as estropipate) is a form of estrogen. It has several uses such as: alleviate symptoms of menopause as hormone replacement therapy, treatment some types of infertility, treatment of some conditions leading to underdevelopment of female sexual characteristics, treatment of vaginal atrophy, treatment of some types of breast cancer (particularly in men and postmenopausal women), treatment of prostate cancer and prevention of osteoporosis.
Mechanism of effect
Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.
Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Half-Life: IM: 1.5-5 hr
Bioavailability: Readily absorbed through GI tract, skin, mucous membrane
Protein bound: 50-80%
Metabolism: Undergoes rapid and extensive first-pass metabolism in liver to less active products such as estriol; kidneys, gonads, and muscle tissues may be involved in metabolism to some extent
Excretion: Mainly in urine as conjugates with small amount of unchanged drug, most estrogens are also excreted in bile and undergo enterohepatic recycling
0.75-6 mg PO qDay; taper at 3-6 month intervals
Cream: 2-4 g intravaginal 3 weeks on, 1 week off
1.5-9 mg PO qDay for 3 weeks, then off for 8 days; repeat if necessary
0.75 mg PO qDay for 25 days, then off for 6 days; repeat
Safety & efficacy not established
Drug contraindicationspulmonary embolism , Uncontrolled hypertension , active thrombophlebitis or thromboembolic disorder
Diabetes mellitus with vascular involvement Jaundice with prior oral contraceptive use thrombogenic valvular disease
InteractionsDalteparin , Tinzaparin , Erythromycin , Enoxaparin , Rifampin , Cimetidine , Heparin , Warfarin , Antithrombin III , Antithrombin alfa , Apalutamide , fondaparinux , Phenindione , Bivalirudin , Argatroban , Lepirudin , Idelalisib , ospemifene , Carbamazepine , Ketoconazole , Clarithromycin , Rifabutin , Quinidine , Nefazodone , Calcitriol (topical)
Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, elderly, hepatic/renal impairment, uterine leiomyomata, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, ovarian cancer, exacerbation of endometriosis or other conditions, smoking and >35 years old, SLE, depression
Fluid retention may exacerbate asthma, epilepsy, migraines, & cardiac or renal dysfunction
Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery.
Hypercalcemia may occur in patients with breast cancer and bone metastases
Increased risk of endometrial and ovarian cancer in postmenopausal women
Long-term postmenopausal estrogen treatment has been associated with increased risk of breast cancer, MI, stroke, DVT, PE, and dementia
May increase risk of thromboembolic disorders, may need to increase anticoagulant dose when administering concomitantly with anticoagulants
Black Box Warnings
Estrogens increase risk of endometrial cancer
- Close clinical surveillance of all women taking estrogens is important
- Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding
- Estrogens with and without progestins should not be used to prevent cardiovascular disease
- Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 yr) during 5.6 yr of treatment with daily PO conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) compared with placebo
- Estrogens alone: A substudy of the WHI Study reported increased risk for stroke and DVT in postmenopausal women (aged 50-79 yr) during 6.8 yr of treatment with oral conjugated estrogens (0.625 mg/day) alone compared with placebo
- Increased Dementia risks
- Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks
Points of recommendation
Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.
Estropipate may increase your risk of developing a condition that may lead to uterine cancer. Your doctor may prescribe a progestin to help lower this risk. Report any unusual vaginal bleeding right away.
Your doctor should check your progress on a regular basis to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using estropipate.
If you need major surgery or will be on long-term bed rest, you may need to stop using estropipate for a short time. Any doctor or surgeon who treats you should know that you are using estropipate.
Store this medication at room temperature away from moisture and heat.
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using estropipate.
Grapefruit may interact with estropipate and lead to unwanted side effects. Avoid the use of grapefruit products.