ANDROGENSAND ESTROGENS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Depo-Testadiol ²
• Estratest ¹
• Estratest H.S. ¹
• Valertest No. 1 ²

In Canada?

• Climacteron ²

Category

• Androgen-estrogen
• This monograph includes information on the following: ?Estrogens, Esterified, and Methyltestosterone; Testosterone and Estradiol

Description

Androgensand estrogens (AN-droe-jensand ESS-troe-jens) are hormones. Estrogens are produced bythe body in greater amounts in females. They are necessary for normal sexualdevelopment of the female and for regulation of the menstrual cycle duringthe childbearing years. Androgens are produced by the body in greater amountsin males. However, androgens are also present in females in small amounts.

The ovaries and adrenal glands begin to produce less of these hormonesafter menopause. This combination product is prescribed to make up for thislower production of hormones. This may relieve signs of menopause, such ashot flashes and unusual sweating, chills, faintness, or dizziness.

Androgens and estrogens may also be used for other conditions as determinedby your doctor.

There is no medical evidence to support the belief that the use of estrogens(contained in this combination medicine) will keep the patient feeling young,keep the skin soft, or delay the appearance of wrinkles. Nor has it been proventhat the use of estrogens during the menopause will relieve emotional andnervous symptoms, unless these symptoms are caused by other menopausal symptoms,such as hot flashes.

A paper called ?Information for the Patient?should be given to you with your prescription. Read this carefully.Also, before you use an androgen and estrogen product, you and your doctorshould discuss the good that it will do as well as the risks of using it.

This medicine is available only with your doctor's prescription, in thefollowing dosage forms:

Oral
• Estrogens, Esterified, and Methyltestosterone
  • Tablets (U.S.)

Parenteral
• Testosterone and Estradiol
  • Injection (U.S. and Canada)

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 androgen and estrogencombination products, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to androgens, anabolic steroids, or estrogens. Also tellyour health care professional if you are allergic to any other substances,such as foods, preservatives, or dyes.

Pregnancy?Estrogens (contained in this combination medicine)are not recommended for use during pregnancy, since some estrogens have beenshown to cause serious birth defects in humans. Some daughters of women whotook diethylstilbestrol (DES) during pregnancy have developed reproductive(genital) tract problems and, rarely, cancer of the vagina and/or uterinecervix when they reached childbearing age. Some sons of women who took DESduring pregnancy have developed urinary-genital tract problems.

Androgens (contained in this combination medicine) should not be used duringpregnancy because they may cause male-like changes in a female baby.

Breast-feeding?Use of this medicine is not recommended in nursingmothers. Estrogens pass into the breast milk and their possible effect onthe baby is not known. It is not known if androgens pass into breast milk.However, androgens may cause unwanted effects in nursing babies such as tooearly sexual development in males or male-like changes in females.

Older adults?This medicine has been tested and has not been shownto cause different side effects or problems in older women than it does inyounger females.

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 takingan androgen and estrogen combination product, it is especially important thatyour health care professional know if you are taking any of the following:

• Acetaminophen (e.g., Tylenol) (with long-term, high-dose use) or
• Amiodarone (e.g., Cordarone) or
• Anabolic steroids (nandrolone [e.g., Anabolin], oxandrolone [e.g.,Anavar], oxymetholone [e.g., Anadrol], stanozolol [e.g., Winstrol]) or
• Anti-infectives by mouth or by injection (medicine for infection)or
• Antithyroid agents (medicine for overactive thyroid) or
• Carbamazepine (e.g., Tegretol) or
• Carmustine (e.g., BiCNU) or
• Chloroquine (e.g., Aralen) or
• Dantrolene (e.g., Dantrium) or
• Daunorubicin (e.g., Cerubidine) or
• Disulfiram (e.g., Antabuse) or
• Divalproex (e.g., Depakote) or
• Etretinate (e.g., Tegison) or
• Gold salts (medicine for arthritis) or
• Hydroxychloroquine (e.g., Plaquenil) or
• Mercaptopurine (e.g., Purinethol) or
• Methotrexate (e.g., Mexate) or
• Methyldopa (e.g., Aldomet) or
• Naltrexone (e.g., Trexan) (with long-term, high-dose use) or
• Phenothiazines (acetophenazine [e.g., Tindal], chlorpromazine [e.g.,Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil],perphenazine [e.g., Trilafon], prochlorperazine [e.g., Compazine], promazine[e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril],trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine[e.g., Temaril]) or
• Phenytoin (e.g., Dilantin) or
• Plicamycin (e.g., Mithracin) or
• Valproic acid (e.g., Depakene)?Androgens, estrogens, and allof these medicines can cause liver damage. Your doctor may want you to haveextra blood tests that tell about your liver, while you are taking any ofthese medicines with an androgen and estrogen combination product.

• Anticoagulants (blood thinners)?Androgens can cause an increasedeffect of blood thinners, which could lead to uncontrolled or excessive bleeding

• Cyclosporine (e.g., Sandimmune)?Estrogens can increase thechances of toxic effects to the kidney or liver from cyclosporine becauseestrogens can interfere with the body's ability to get the cyclosporine outof the bloodstream as it normally would

Other medical problems?The presence of other medicalproblems may affect the use of androgen and estrogen combination products.Make sure you tell your doctor if you have any other medical problems, especially:

• Blood clots (or history of during previous estrogen therapy)?Estrogensmay worsen blood clots or cause new clots to form

• Breast cancer (active or suspected)?Estrogens may cause growthof the tumor

• Changes in vaginal bleeding of unknown causes?Some irregularvaginal bleeding is a sign that the lining of the uterus is growing too muchor is a sign of cancer of the uterus lining; estrogens may make these conditionsworse

• Type 2 diabetes mellitus?Androgens can decreaseblood sugar levels

• Edema (swelling of feet or lower legs caused by retaining [keeping]too much body water) or
• Heart or circulation disease or
• Kidney disease or
• Liver disease?Androgens can worsen these conditions becauseandrogens cause the body to retain extra fluid (keep too much body water).Also, heart or circulation disease can be worsened by androgens because androgensmay increase blood cholesterol levels

• Endometriosis?Estrogens may worsen endometriosis by causinggrowth of endometriosis implants

• Fibroid tumors of the uterus?Estrogens may cause fibroid tumorsto increase in size

• Gallbladder disease or gallstones (or history of)?There isno clear evidence as to whether estrogens increase the risk of gallbladderdisease or gallstones

• Jaundice (or history of during pregnancy)?Estrogens use mayworsen or cause jaundice in these patients

• Liver disease?Toxic drug effects may occur in patients withliver disease because the body is not able to get this medicine out of thebloodstream as it normally would

• Porphyria?Estrogens can worsen porphyria

Proper Use of This Medicine

For patientstaking any of the androgen and estrogen products by mouth:

• Take this medicine only as directed by your doctor.Do not take more of it and do not take it for a longer time than your doctorordered.
• Try to take the medicine at the same time each day to reduce thepossibility of side effects and to allow it to work better.
• 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.

The number of tablets that you take depends on the strength of the medicine.Also, the number of doses you take each day, the timeallowed between doses, and the length of time you take the medicine dependon the medical problem for which you are taking combinations of androgen andestrogen.

For esterified estrogens and methyltestosterone
• For oral dosage form (tablets):
  • For treatment of certain signs of menopause, such as hot flashesand unusual sweating, chills, faintness, or dizziness:
    • Adults?0.625 to 2.5 mg of esterified estrogens and 1.25 to5 mg of methyltestosterone once a day for twenty-one days. Stop the medicinefor seven days, then repeat the twenty-one day cycle.

For testosterone cypionate and estradiol cypionate
• For injection dosage form:
  • For treatment of certain signs of menopause, such as hot flashesand unusual sweating, chills, faintness, or dizziness:
    • Adults?50 milligrams (mg) of testosterone cypionate and 2 mgof estradiol cypionate injected into a muscle once every four weeks.

For testosterone enanthate and estradiol valerate
• For injection dosage form:
  • For treatment of certain signs of menopause, such as hot flashesand unusual sweating, chills, faintness, or dizziness:
    • Adults?90 milligrams (mg) of testosterone enanthate and 4 mgof estradiol valerate injected into a muscle once every four weeks.

For testosterone enanthate benzilic acid hydrazone, estradiol dienanthate,and estradiol benzoate
• For injection dosage form:
  • For treatment of bone loss (osteoporosis) or certain signs of menopause,such as hot flashes and unusual sweating, chills, faintness, or dizziness:
    • Adults?150 milligrams (mg) of testosterone enanthate benzilicacid hydrazone, 7.5 mg of estradiol dienanthate, and 1 mg of estradiol benzoateinjected into a muscle once every four to eight weeks or less.

Missed dose?If you miss a dose of this medicine and your dosingschedule is:

• One dose a day?Take the missed dose as soon as possible. However,if you do not remember it until the next day, skip the missed dose and goback to your regular dosing schedule. Do not double doses.
• More than one dose a day?Take the missed dose as soon as possible.However, if it is almost time for your next dose, skip the missed dose andgo back to your regular dosing schedule. Do not double doses.

If you have any questions about this, check with your doctor.

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.
• Keep the injectable form of this medicine from freezing.
• 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 6 to 12 months, but many doctorsrequire them more often.

It is not yet known whether the use of estrogen increases the risk of breastcancer in women. Therefore, it is very important that you regularly checkyour breasts for any unusual lumps or discharge. You should also have a mammogram(x-ray picture of the breasts) done if your doctor recommends it.

In some patients using estrogens, tenderness, swelling, or bleeding ofthe gums may occur. Brushing and flossing your teeth carefully and regularlyand massaging your gums may help prevent this. See your dentist regularlyto have your teeth cleaned. Check with your medical doctor or dentist if youhave any questions about how to take care of your teeth and gums, or if younotice any tenderness, swelling, or bleeding of your gums.

For diabetic patients:

• This medicine may affect blood sugar levels. If you notice a changein the results of your blood or urine sugar tests or if you have any questions,check with your doctor.

If you think that you may have become pregnant, checkwith your doctor immediately. Continued use of this medicine duringpregnancy may cause birth defects or future health problems in the child.

In studies with oral contraceptives (birth control pills) containing estrogens,cigarette smoking during the use of estrogens was shown to cause an increasedrisk of serious side effects affecting the heart or blood circulation, suchas dangerous blood clots, heart attack, or stroke. The risk increased as theamount of smoking and the age of the smoker increased. Women aged 35 and overwere at greatest risk when they smoked while using oral contraceptives containingestrogens. It is not known if this risk exists with the use of androgens andestrogens for symptoms of menopause. However, smoking may make estrogens lesseffective.

Do not give this medicine to anyone else. Your doctor has prescribed itspecifically for you after studying your health record and the results ofyour physical examination. Androgens and estrogens may be dangerous for somepeople because of differences in their health and body chemistry.

Side Effects of This Medicine

Discuss these possible effectswith your doctor:

• Tumors of the liver, liver cancer, and peliosis hepatis (a form ofliver disease) have occurred during long-term, high-dose therapy with androgens.Although these effects are rare, they can be very serious and may cause death.
• When androgens are used in women, especially in high doses, male-likechanges may occur, such as hoarseness or deepening of the voice, unnaturalhair growth, or unusual hair loss. Most of these changes will go away if themedicine is stopped as soon as the changes are noticed. However, some changes,such as voice changes, may not go away.
• The prolonged use of estrogens has been reported to increase therisk of endometrial cancer (cancer of the uterus lining) in women after menopause.The risk seems to increase as the dose and the length of use increase. Whenestrogens are used in low doses for less than one 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.
• 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.

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Check with your doctorimmediately if any of the following side effects occur:

Less common

Yellow eyes or skin

Rare

Uncontrolled jerky muscle movements; vomiting of blood (with long-term use or high doses)

Also, check with your doctoras soon as possible if any of the following side effects occur:

More common

Acne or oily skin (severe); breast painor tenderness; changes in vaginal bleeding (spotting,breakthrough bleeding, prolonged or heavier bleeding, or complete stoppageof bleeding); enlarged clitoris; enlargement or decrease in size of breasts; hoarsenessor deepening of voice; swelling of feet or lowerlegs; unnatural hair growth; unusual hair loss; weight gain (rapid)

Less common or rare

Confusion; dizziness; flushing or redness of skin; headaches (frequentor continuing); hives (especially at place of injection); shortness of breath (unexplained); skin rash, hives, or itching; unusualbleeding; unusual tiredness or drowsiness

With long-term use or high doses

Black, tarry, or light-colored stools; dark-colored urine; general feeling of discomfortor illness (continuing); hives (frequent or continuing); loss of appetite (continuing); lump in, or discharge from breast; nausea (severe); pain, swelling, or tenderness in stomach or upperabdomen (continuing); purple- or red-colored spotson body or inside the mouth or nose; sore throator fever (continuing); unpleasant breath odor (continuing); vomiting (severe)

Other side effects may occurthat usually do not need medical attention. These side effects may go awayduring treatment as your body adjusts to the medicine. However, check withyour doctor if any of the following side effects continue or are bothersome:

More common

Bloating of abdomen or stomach; crampsof abdomen or stomach; loss of appetite (temporary); nausea (mild); stomachpain (mild); unusual increase in sexual desire; vomiting (mild)

Less common

Constipation; diarrhea (mild); dizziness (mild); headaches (mild); infection, redness, pain, or other irritation at place of injection; migraine headaches; problemsin wearing contact lenses; trouble in sleeping

Also, many women who are taking a progestin (anothertype of female hormone) with this medicine will begin to have monthly vaginalbleeding again, similar to menstrual periods. This effect will continue foras long as this medicine is used. However, monthly bleeding will not occurin women who have had the uterus removed by surgery (total hysterectomy).

Other side effects not listed above may also occur insome patients. If you notice any other effects, check with your doctor.