estradiol

Estradiol is a prescription medication prescribed to treat the symptoms of menopause, prevent of bone fractures (osteoporosis), painful uterine bleeding, vaginal pain, dryness, and atrophy associated with menopause. Estradiol is also prescribed for the treatment of breast cancer, and some cases of prostate cancer.

• Estrogen is one of the major female hormones, the other one being progesterone.
• Estrogens occur in nature in several chemical forms. In women with active menstrual cycles, the ovaries produce between 70 and 500 micrograms of estradiol daily. This is converted to estrone and to a lesser extent estriol. After menopause, estrone made in the adrenal glands is the most active circulating estrogen.
• Estrogens cause the growth and development of female sex organs and maintain sex characteristics, including underarm and pubic hair and the shape of body contours and skeleton. Estrogens also increase secretions from the cervix and the growth of the inner lining of the uterus (endometrium). Estrogens reduce LDL-cholesterol ("bad" cholesterol) and increase HDL-cholesterol ("good" cholesterol) concentrations in the blood.
• Estrogens, when taken alone or in combination with progestin (progesterone), have been shown to reduce the risk of hip fracture due to osteoporosis by 25%.

• Among the most common endocrine side effects are:
  • break-through bleeding or spotting,
  • loss of periods or excessively prolonged periods,
  • breast pain,
  • breast enlargement, and
  • changes in sexuality (increase or decrease in libido).
• Abdominal pain may indicate the development of gallstones or occasionally hepatitis.
• Migraine headaches have been associated with estrogen therapy.
• Estrogens can cause sodium and fluid retention leading to edema.
• Melasma, tan or brown patches, may develop on the forehead, cheeks, or temples. These may persist even after the estrogen is stopped.
• Conjugated estrogens may cause an increase in the curvature of the cornea. Patients with contact lenses may develop intolerance to their lenses.
• Blood clots are an occasional but serious adverse effect and are dose-related. (The higher the dose of estradiol, the more likely blood clots are to form.) Cigarette smokers are at a higher risk for clots, and, therefore, patients requiring estrogen therapy are strongly encouraged to quit smoking.
• Estrogens can increase the risk of endometrial cancer. This risk may be decreased if estrogens are combined with progestin.
• Some people also have a higher chance of developing breast cancer while taking estrogens. Sometimes people who have breast cancer when they are taking estrogens may have increased calcium in the blood. If this happens, the estrogen should be stopped.

• The dose of estradiol can vary depending on the condition that is being treated.
• Estradiol tablets are given daily or they can be prescribed to be taken in a cyclic regimen, wherein estradiol is given daily for 3 weeks followed by 1 week of no medication, after which the cycle resumes.
• The tablets can also be given more than once a day for some conditions. The topical gel or the topical emulsions are applied to the skin daily at the same time.
• The vaginal ring is inserted in the vagina and left without removal for 3 months at a time.
• The intramuscular dose and the frequency it is given can differ depending on the product.
• The adhesive part of patches should be applied to a dry, hairless, clean part of the trunk, but not on the breasts. It should not be placed on irritated or damaged skin. Sites of application should be rotated, with at least one week between repeated applications to any one site. The patch should be applied immediately after removing the protective layer, and pressure should be applied to the patch when it is attached for about 10 seconds.

• Estrogens can inhibit the metabolism of cyclosporine, resulting in increased cyclosporine blood levels. Such increased blood levels can result in kidney and/or liver damage. If this combination cannot be avoided, cyclosporine concentrations can be monitored, and the dose of cyclosporine can be adjusted to assure that its blood levels are not elevated.
• Estrogens appear to increase the risk of liver disease in patients receiving dantrolene through an unknown mechanism. Women over 35 years of age and those with a history of liver disease are especially at risk. Estrogens increase the liver's ability to manufacture clotting factors. Because of this, patients receiving warfarin need to be monitored for loss of anticoagulant (blood thinning) effect if estrogen is added when warfarin is already being taken.
• Rifampin, barbiturates, carbamazepine (Tegretol), griseofulvin, phenytoin (Dilantin), primidone and St. John's wort preparations can all increase the elimination of estrogen by enhancing the liver's ability to metabolize it. Concurrent use may result in reduction of the beneficial effects of estrogens. On the other hand, drugs such as erythromycin, clarithromycin, ketoconazole (Nizoral, Extina, Xolegel, Kuric), itraconazole (Sporanox), ritonavir (Norvir) and grapefruit juice can decrease the liver's ability to metabolize and eliminate estrogens and may increase the side effects of estrogen.
• Estrogens may increase the levels and effects of exogenous corticosteroids (corticosteroids used as drugs that are not produced by the body), ropinirole (Requip, Requip XL), tipranavir (Aptivus) and medications that contain theophylline (Elixophyllin, Theo-24, Theochron).
• Estrogens may reduce the levels and the effects of anastrozole (Arimidex), aripiprazole (Abilify), axitinib (Inlyta), hyaluronidase (Amphadase, Hylenex, Vitrase), saxagliptin (Onglyza), somatropin (Genotropin, Humatrope, Norditropen Flexpro etc.), ibrutinib (Imbruvica), and ursodiol (Actigall, Urso 250, Urso Forte).
• Estrogen levels and effects may be decreased by dabrafenib (Tafinlar), deferasirox (Exjade), peginterferon Alfa-2b (Peg-Intron, Peg-Intron Redipen, Peg-Intron Redipen Pak 4 and Sylatron), P-glycoprotein inducers, tocilizumab (Actemra) and herbs that belong to a class of medications called CYP3A4 inducers. herbs with contents similar to estrogens may increase the side effects of estrogens.
• Estrogen levels and effects may be increased by dehydroepiandrosterone, P-glycoprotein inhibitors, nonsteroidal anti-inflammatory drugs called COX-2 inhibitors such as celecoxib (Celebrex) and ascorbic acid (vitamin C).

• Estrogens should not be used during pregnancy due to an increased risk of fetal abnormalities.
• Estrogens are secreted in milk and cause unpredictable effects in the infant. Estrogens generally should not be used by women if they are breastfeeding.

What preparations of estradiol are available?

Estradiol is available in several forms.

• Tablets, micronized: 0.5mg, 1mg, 2mg;
• Vaginal cream: 0.01%;
• Continuous release skin patch: 14 mcg/day, 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.1 mg/day, 0.06 mg/day, 0.075 mg/day;
• Topical emulsion: 4.35 mg/1.74 g; Topical Gel: 0.25 mg/0.25 g, 0.5 mg/0.5 g, 1 mg/g;
• Intramuscular oil: 5 mg/mL, 10 mg/mL, 20 mg/mL, 40 mg/mL; Vaginal Ring: 0.05 mg/24 hr, 0.1 mg/24 hr.

How should I keep estradiol stored?

• All forms of estradiol should be stored between 15 C (59 F) and 30 C (86 F).