ESTROGENS AND PROGESTINS (OVARIAN HORMONE THERAPY) (Systemic)

Some commonly used brand names are:

In the U.S.?

• Activella ³
• femhrt ²
• Ortho-Prefest ¹

Other commonly used names are:

• Ethinylestradiol [Ethinyl estradiol]
• Ethinyloestradiol [Ethinyl estradiol]
• Norethindrone [Norethisterone]

Category

• Estrogen-progestin?17 beta-Estradiol and norgestimate tablets; Ethinyl estradiol and norethindrone tablets; Estradiol and norethindrone tablets
• Ovarian hormone therapy agent?17 beta-Estradioland norgestimate tablets; Ethinyl estradioland norethindrone tablets; Estradiol andnorethindrone tablets
• Osteoporosisprophylactic?17 beta-Estradiol and norgestimatetablets; Ethinyl estradiol and norethindronetablets

Description

Estrogens (ES-troe-jenz)and progestins (pro-GEST-ins) are female hormones.They are produced by the body and are necessary for the normal sexual developmentof the female and for the regulation of the menstrual cycle during the childbearingyears.

The ovaries begin to produce less estrogen after menopause (the changeof life). This medicine is prescribed to make up for the lower amount of estrogen.Estrogens help relieve signs of menopause, such as hot flashes and unusualsweating, chills, faintness, or dizziness. Progestins help to regulate theeffects of estrogens.

Estrogens are prescribed for several reasons:

• to provide additional hormone when the body does not produce enoughof its own, such as during menopause. They can also help to relieve a genitalskin condition called vaginal or vulvar atrophy.
• to help prevent weakening of bones (osteoporosis) in women past menopause.

Estrogens may also be used for other conditions as determined by your doctor.

There is no medical evidence to support thebelief that the use of estrogens will keep the patient feeling young, keepthe skin soft, or delay the appearance of wrinkles. Nor has it been proventhat the use of estrogens during menopause will relieve emotional and nervoussymptoms, unless these symptoms are caused by other menopausal symptoms, suchas hot flashes or hot flushes.

Estrogens and progestins are available only with your doctor's prescription,in the following dosage forms:

Oral
• 17 beta-estradiol and norgestimate
  • Tablets (U.S.)
• Ethinyl estradiol and norethindrone
  • Tablets (U.S.)
• Estradiol and norethindrone
  • Tablets (U.S.)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For estrogens and progestins,the following should be considered:

Allergies?Tell your doctor if you have ever had any unusualor allergic reaction to estrogens or progestins. Also tell your health careprofessional if you are allergic to any other substances, such as foods, preservatives,or dyes

Pregnancy?Estrogens and progestins are not recommended foruse during pregnancy or right after giving birth. Becoming pregnant or maintaininga pregnancy is not likely to occur around the time of menopause.

Breast-feeding?Estrogens and progestins pass into the breastmilk and can change the content or lower the amount of breast milk. Use ofthis medicine is not recommended in nursing mothers.

Older adults?Many medicines have not been studied specificallyin older people. Therefore, it may not be known whether they work exactlythe same way they do in younger adults or if they cause different side effectsor problems in older people. There is no specific information comparing useof estrogens and progestins in the elderly with use in other age groups.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takingestrogens and progestins, it is especially important that your health careprofessional know if you are taking any of the following:

• Cyclosporine (e.g., Sandimmune)?Estrogens can prevent cyclosporine'sremoval from the body; this can lead to kidney or liver problems caused bytoo much cyclosporine

Other medical problems?The presence of other medicalproblems may affect the use of estrogens and progestins. Make sure you tellyour doctor if you have any other medical problems, especially:

• Asthma or
• Calcium, too much or too little in blood or
• Diabetes mellitus (sugar diabetes)
• Epilepsy (seizures) or
• Heart problems or
• Kidney problems or
• Liver tumors, benign or
• Lupus erythematosus, systemic or
• Migraine headaches or
• Porphyria?Estrogens may worsen these conditions.

• Blood clotting problems (or history of during previous estrogen therapy)?Estrogensusually are not used until blood clotting problems stop; using estrogens isnot a problem for most patients without a history of blood clotting problemsdue to estrogen use

• Breast cancer or
• Bone cancer or
• Cancer of the uterus or
• Fibroid tumors of the uterus?Estrogens may interfere with thetreatment of breast or bone cancer or worsen cancer of the uterus when theseconditions are present

• Changes in genital or vaginal bleeding of unknown causes?Useof estrogens may delay diagnosis or worsen condition. The reason for the bleedingshould be determined before estrogens are used

• Endometriosis or
• Gallbladder disease or gallstones (or history of) or
• High cholesterol or triglycerides (or history of) or
• Liver disease or
• Pancreatitis (inflammation of pancreas)?Estrogens may worsenthese conditions; while estrogens can improve blood cholesterol, they mayworsen blood triglycerides for some people

• Hypothyroid (too little thyroid hormone)?Dose of thyroid medicinemay need to be increased.

• Vision changes, sudden onset including
• Bulging eyes or
• Double vision or
• Migraine headache or
• Vision loss, partial or complete?Estrogens may cause theseproblems. Tell your doctor if you have had any of these problems, especiallywhile taking estrogen or oral contraceptives (?birth control pills?).

Proper Use of This Medicine

Estrogensand progestins usually come with patient information or directions. Read themcarefully before taking this medicine.

Take this medicine only as directed by your doctor.Do not take more of it and do not take or use it for a longer time than yourdoctor ordered. Try to take the medicine at the same time each dayto reduce the possibility of side effects and to allow it to work better.

For patients taking estrogens and progestins by mouth:

• Nausea may occur during the first few weeks after you start takingestrogens. This effect usually disappears with continued use. If the nauseais bothersome, it can usually be prevented or reduced by taking each dosewith food or immediately after food.

Dosing?The dose of these medicines will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of these medicines. If your dose isdifferent, do not change it unless your doctor tells you to do so.

For 17 beta-estradiol and norgestimate
• For oral dosage forms (tablets)
  • For treating a genital skin condition (vaginal or vulvar atrophy),or vasomotor symptoms of menopause:
    • Adults?Oral, 1 mg estradiol for three days followed by 1 mgof estradiol combined with 0.09 mg of norgestimate for three days. The regimenis repeated continuously without interruption.
  • To prevent loss of bone (osteoporosis):
    • Adults?Oral, 1 mg estradiol for three days followed by 1mgof estradiol combined with 0.09 mg of norgestimate for three days. The regimenis repeated continuously without interruption.

For ethinyl estradiol and norethindrone
• For oral dosage forms (tablets)
  • For treating vasomotor symptoms of menopause:
    • Adults?Oral, 2.5 mcg (0.025 mg) ethinyl estradiol and 0.5 mgnorethindrone once daily.
  • To prevent loss of bone (osteoporosis):
    • Adults?Oral, 2.5 mcg (0.025 mg) ethinyl estradiol and 0.5 mgnorethindrone once daily.

For estradiol and norethindrone
• For oral dosage forms (tablets)
  • For treating vasomotor symptoms of menopause or treatment of vaginalor vulvar atrophy:
    • Adults?Oral, 1 mg estradiol and 0.5 mg norethindrone once daily.
  • To prevent loss of bone (osteoporosis):
    • Adults?Oral, 1 mg estradiol and 0.5 mg norethindrone once daily.

Missed dose?If you miss a dose of this medicine, take itas soon as possible. However, if it is almost time for your next dose, skipthe missed dose and take only your next regularly scheduled dose. Do not doubledoses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom medicine cabinet because the heat ormoisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It is very important that your doctor check your progress atregular visits to make sure this medicine does not cause unwanted effects. These visits will usually be every year, but some doctors requirethem more often.

It is not yet known whether the use of estrogens increasesthe risk of breast cancer in women. Therefore,it is very important that you regularly check your breasts for any unusuallumps or discharge. Report any problems to your doctor. You shouldalso have a mammogram (x-ray pictures of the breasts) done if your doctorrecommends it. Because breast cancer has occurred in men taking estrogens,regular breast self-exams and exams by your doctor for any unusual lumps ordischarge should be done.

Tell the doctor in charge that you are taking this medicine before havingany laboratory test because some results may be affected.

Side Effects of This Medicine

Womenrarely have severe side effects from taking estrogens to replace estrogen.Discuss these possible effects with your doctor:

• The prolonged use of estrogens has been reported to increase therisk of endometrial cancer (cancer of the lining of the uterus) in women aftermenopause. This risk seems to increase as the dose and the length of use increase.When estrogens are used in low doses for less than 1 year, there is less risk.The risk is also reduced if a progestin (another female hormone) is addedto, or replaces part of, your estrogen dose. If the uterus has been removedby surgery (total hysterectomy), there is no risk of endometrial cancer, andno need to take an estrogen and progestin combination.
• It is not yet known whether the use of estrogens increases the riskof breast cancer in women. Although some large studies show an increased risk,most studies and information gathered to date do not support this idea.

Check with your doctor as soon as possible if any of the following sideeffects occur:

More common

Breast pain or tenderness; dizzinessor light-headedness; headache; swelling of feet and lower legs; rapid weight gain; vaginal bleeding

Rare

Breast lumps; change in vaginal discharge; discharge from nipple; nausea and vomiting; pains in stomach, side, or abdomen; pain or feeling of pressure in pelvis; yellow eyes or skin; severe or suddenheadache; sudden loss of coordination; pains in chest, groin, or leg, especially calf; sudden and unexplained shortness of breath; sudden slurred speech; sudden vision changes; weakness or numbness in arm or leg

Other side effects mayoccur that usually do not need medical attention. These side effects may goaway during treatment as your body adjusts to the medicine. However, checkwith your doctor if any of the following side effects continue or are bothersome:

More common

Back pain; dizziness; general feeling of tiredness; bloating or gas; flu-like symptoms; mental depression; muscle aches; nausea?takingtablet with food may decrease; vaginitis

Other side effects not listed abovemay also occur in some patients. If you notice any other effects, check withyour doctor.