Estradiol topical

Vasomotor symptoms due to menopause, vulvar and vaginal atrophy due to menopause

Topical Prep Moderate to severe vasomotor symptoms due to menopause, moderate to severe symptoms of vulvar and vaginal atrophy due to menopause Topical gel 0.06% Metered-dose pump: Daily administration of EstroGel 0.06% 1.25 g per day (1 pump depression) to the arm Gel: 1 pump depression of EstroGel 0.06% delivers 1.25 g of gel containing 0.75 mg estradiol

Before using the canister for the first time, it must be primed. Remove the large canister cover, and fully depress the pump 5 times. Discard the unused gel by thoroughly rinsing down the sink or placing it in the household trash. After priming, the pump is ready to use. The recommended area of application is the arm. Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder

Undiagnosed abnormal genital bleeding Breast cancer or a history of breast cancer Estrogen-dependent neoplasia Active DVT, PE, or history of these conditions Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions Known anaphylactic reaction, angioedema, or hypersensitivity to Estradiol Hepatic impairment or disease Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Endometrial Cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in nonusers, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestogen to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Breast Cancer The WHI substudy of daily CE (0.625 mg)-alone provided information about breast cancer in estrogen-alone users. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0.8]) compared to placebo. After a mean follow-up of 5.6 years, the WHI substudy of daily Ce (0.625 mg) plus MPA (2.5 mg) reported an increased risk of invasive breast cancer in women who took daily CE plus MPA compared to placebo. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase

Not Classi Pregnancy Risk Summary Estradiol is not indicated for use in pregnancy. There are no data with the use of Estradiol in pregnant women, however, epidemiologic studies and meta-analysis have not found an increased risk of genital or non-genital birth defects (including cardiac anomalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Lactation Estrogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breastfeeding is well established. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Estradiol and any potential adverse effects on the breastfed child from Estradiol or from the underlying maternal condition.

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John’s wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogen and may result in adverse reactions.

The most common adverse reactions with Estradiol (>5 percent) are: headache, flatulence, and breast pain. Increased risks of stroke and DVT are reported with estrogen-alone therapy. Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Immediately discontinue estrogen with or without progestogen if any of these occur or are suspected. An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. After a mean follow-up of 5.6 years, the WHI substudy of daily Ce (0.625 mg) plus MPA (2.5 mg) reported an increased risk of invasive breast cancer in women who took daily CE plus MPA compared to placebo. The CE plus MPA substudy of WHI reported that estrogen plus progestin increased the risk of ovarian cancer.

Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, 2 estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.