17 β Estradiol
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.
Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women with a history of endometriosis may need a progestogen.Use estrogen-alone, or in combination with a progestogen at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary.Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause: Estradiol 0.06% 1.25 g per day is the single approved dose for the treatment of moderate to severe vasomotor symptoms due to menopause. The lowest effective dose of Estradiol 0.06% for this indication has not been determined. 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.Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause: Estradiol 0.06% 1.25 g per day is the single approved dose for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. The lowest effective dose of Estradiol 0.06% for this indication has not been determined. When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, first consider the use of topical vaginal products. 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.
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.
Estradiol is contraindicated in women with any of the following conditions:Undiagnosed abnormal genital bleedingBreast cancer or a history of breast cancerEstrogen-dependent neoplasiaActive DVT, PE, or history of these conditionsActive arterial thromboembolic disease (for example, stroke or MI), or a history of these conditionsKnown anaphylactic reaction, angioedema, or hypersensitivity to EstradiolHepatic impairment or diseaseProtein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Estradiol is not indicated for use in pregnancy. There are no data with the use of EstroGel 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.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 breast- feeding is well established. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for EstroGel and any potential adverse effects on the breastfed child from EstroGel or from the underlying maternal condition.
{'Indications': 'Treatment of Moderate to Severe-Vasomotor Symptoms due to Menopause.Symptoms of Vulvar and Vaginal Atrophy due to Menopause.'}