estrogens esterified (Estrogens, Esterified, Menest)
Dosing and uses of Estrogens, Esterified, Menest (estrogens esterified)
Adult dosage forms and strengths
tablet
- 0.3mg
- 0.625mg
- 1.25mg
- 2.5mg
Menopause, Atrophic Vaginitis, Kraurosis Vulvae
0.3-1.25 mg PO qDay (3 weeks on, 1 week off)
Female Hypogonadism
2.5-7.5 mg PO qDay in divided doses (20 days on, 10 days off)
Female Castration/Primary Ovarian Failure
1.25 mg PO qDay in cyclic regimen
Breast Cancer
10 mg PO q8hr for 3 months (minimum)
Prostate Cancer
1.25-2.5 mg PO q8hr
Other Indications & Uses
Vasomotor symptoms associated with menopause
Palliative treatment of metastatic inoperable breast cancer in men & postmenopausal women
Palliative treatment of prostate cancer
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
Menopause, atrophic vaginitis, kraurosis vulvae
0.3-1.25 mg PO qDay (3 weeks on, 1 week off)
Breast cancer
10 mg PO q8hr for 3 months (minimum)
Prostate cancer
1.25-2.5 mg PO q8hr
Estrogens, Esterified, Menest (estrogens esterified) adverse (side) effects
Frequency not defined
Common
- Edema, peripheral edema
- Headache
- Melasma
- Breast enlargement, breast tenderness
- Bloating
- Nausea
- Vomiting
Less common
- Depression
- Amenorrhea
- Breakthrough bleeding
- Spotting
- Weight changes
- Corneal curvation change
Warnings
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
- There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses
Cardiovascular risks
- 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 year) during 5.6 yr of treatment w/ daily PO conjugated estrogens (CE 0.625 mg) combined w/ 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 year of treatment with oral conjugated estrogens (0.625 mg/day) alone compared with placebo
Dementia risks
- Estrogens with and without progestins should not be used to prevent dementia
- Women's Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 4 yr of treatment with daily CE 0.625 mg combined w/ MPA 2.5 mg, compared with placebo
- Estrogens alone: A substudy of the WHIMS reported an increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 5.2 yr of treatment with conjugated estrogens 0.625 mg alone compared with placebo
- Unknown whether these findings apply to younger postmenopausal women
Dose & duration
- In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations & dosage forms of estrogens & progestins
- Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose & for shortest duration consistent w/ treatment goals and individual risks
Contraindications
Documented hypersensitivity
Active or history of breast cancer
Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
Estrogen-dependent neoplasia, liver disease, liver tumors
Uncontrolled hypertension
Diabetes mellitus with vascular involvement
Jaundice with prior oral contraceptive use
Undiagnosed abnormal genital bleeding
Cautions
Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, liver impairment, uterine leiomyomata, smoking, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, hypothyroidism, ovarian cancer, exacerbation of endometriosis or other conditions
Conditions exacerbated by fluid retention (asthma, epilepsy, migraine etc)
Hypercalcemia may occur in patients with breast cancer and bone metastases
Long-term postmenopausal estrogen treatment has been associated with an increased risk of breast cancer, MI, stroke, DVT, PE, and dementia
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
Concomitant warfarin, oral anticoagulants: estrogens increase risk of thromboembolic disorders; may need to increase anticoagulant dose
Pregnancy and lactation
Pregnancy category: X
Lactation: Controversial; estrogens are excreted into breast milk in small quantities, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Estrogens, Esterified, Menest (estrogens esterified)
Mechanism of action
Mixture of sodium salts and sulfate esters of estrogenic substances, principally estrone sodium sulfate; reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increase synthesis of DNA, RNA, and various proteins in target tissues
Pharmacokinetics
Protein Bound: 50-80%
Metabolism: Principally and rapidly in liver and undergoes extensive first-pass metabolism to less active products such as estriol; kidneys, gonads, and muscle tissues may be involved in metabolism to some extent
Metabolites: EstrioL
Excretion: Mainly in urine as conjugates with small amount of unchanged drug, most estrogens are also excreted in bile and undergo enterohepatic recycling
