Side Effects of Estratest (esterified estrogens and methyltestosterone)

Estratest(esterified estrogens and methyltestosterone) is a combination of female sex hormones and a form of the male hormone testosterone used to treatsymptoms of menopausesuch ashot flashes, andvaginal dryness, burning, and irritation.

Estrogens, when taken alone or in combination with a progestin, have been shown to reduce the risk forhip fracturedue toosteoporosisas well as the risk ofheart attackandstroke.

Esterified estrogensare used for numerous medical situations. Estrogens cause growth and development of female sex organs and the maintain sex characteristics, including growth of underarm and pubic hair and shaping of body contours and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium). Estrogens reduce LDL-cholesterol("bad" cholesterol) and increaseHDL-cholesterol ("good" cholesterol) concentrations.

Testosterone is the major male sex hormone responsible for many male sexual characteristics, but women also produce small amounts of testosterone. Followingmenopause, a woman's production of testosterone decreases.

When testosterone in the form ofmethyltestosteroneis added to estrogens, there may be a further alleviation of thehot flashesseen aftermenopause, and there also may be an improvement in a woman's sexual function. The brand name Estratest is discontinued.

Common side effects of Estratest include

• breakthrough bleeding orspotting,
• loss of periods,
• excessively prolonged periods,
• breast pain,
• breast enlargement,
• changes in sex drive,
• acne, and
• the growth of facial hair.

Serious side effects of Estratest include

• gallstones,
• hepatitis,
• migraineheadaches, and
• fluid retention (swelling of the lower legs),
• enlargement of the clitoris,
• reduction in breast size, and
• deepening of the voice.

Melasma(tan or brown patches) may develop on the forehead, cheeks, or temples.

Esterified estrogens may cause an increase in the curvature of thecornea, and patients withcontact lensesmay develop intolerance to their lenses.

Drug interactionsof Estratest includewarfarin, because esterified estrogens increase theliver's ability to manufacture proteins that are required for blood to clot.

• Patients receiving warfarin, which reduces clotting by inhibiting the production of proteins required for clotting, should receive clotting tests if an estrogen is added to their treatment.
• Rifampin,barbiturates,carbamazepine,griseofulvin,phenytoin, andprimidone可以增加消除酯化estroge吗ns by enhancing the liver's ability to metabolize it.
• Use of thesedrugsmay result in a reduction of the beneficial effects of esterified estrogens.
• Conversely, drugs such aserythromycin,ketoconazole,itraconazole, andritonavirmay reduce the elimination of esterified estrogens by the liver and lead to increased levels of estrogens in the blood.
• Grapefruit juice also may increase levels of esterified estrogens by increasing the absorption of estrogens from the intestine. Increased levels of estrogens in the blood may result in more estrogen-related side effects.
• Methyltestosterone can increase the effects of warfarin, increasing the risk of bleeding.
• Taking methyltestosterone andimipraminetogether has led toparanoiain a few patients.
• Methyltestosterone can increase blood concentrations ofcyclosporine, which can increase the risk of kidney damage.

Both methyltestosterone and estrogens should not be used duringpregnancydue to an increased risk of fetal abnormalities.

Estrogens are secreted in milk and cause unpredictable effects in the infant. They should not be used duringbreastfeeding.

For side effects, please read the esterified estrogens article.

Important side effects of methyltestosterone can have masculinizing effects in women, including:

• the development ofacne,
• growth of facial hair,
• enlargement of the clitoris,
• reduction in breast size, and
• deepening of the voice.

If treatment is discontinued when these symptoms first appear, they usually diminish or disappear; however, prolonged treatment can cause irreversible masculinizing effects.

Becauseclinical trialsare conducted under widely varying conditions, adverse reaction rates observed in theclinical trialsof a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Theadverse reactioninformation from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related todrug useand for approximating rates.

Associated with Estrogens

The following additional adverse reactions have been reported withestrogenand/orprogestintherapy.

• Genitourinary System:Changes invaginal bleedingpattern andabnormalwithdrawal bleeding or flow; breakthrough bleeding; spotting;dysmenorrhea, increase in size of uterine leiomyomata;vaginitis, including vaginalcandidiasis;change in amount ofcervicalsecretion; changes in cervical ectropion;ovariancancer;endometrial hyperplasia;endometrial cancer;cystitis-likesyndrome.
• Breasts:Tenderness; enlargement;pain,nipple discharge,galactorrhea;fibrocystic breast changes;breast cancer.
• Cardiovascular:Deep andsuperficialvenousthrombosis;pulmonary embolism;thrombophlebitis;myocardial infarction;stroke;增加官网地址bwin.
• Gastrointestinal:Nausea;vomiting;abdominalcramps;bloating;cholestaticjaundice;increased incidence ofgallbladder disease;pancreatitis, enlargement ofhepatichemangiomas.
• Skin:Chloasma ormelasmathat may persist when drug is discontinued;erythema multiforme;erythema nodosum;hemorrhagiceruption; loss ofscalphair;hirsutism;pruritus,rash.
• Eyes:Retinalvascularthrombosis, steepening ofcornealcurvature, intolerance to contact lenses.
• Central Nervous System:Headache,migraine,dizziness;mentaldepression;chorea;nervousness; mood disturbances; irritability;exacerbationofepilepsy,dementia.
• Miscellaneous:Increase or decrease in weight; reducedcarbohydratetolerance; aggravation ofporphyria;edema;arthralgias;legcramps; changes inlibido;urticaria,angioedema, anaphylactoid/anaphylactic reactions;hypocalcemia;exacerbation ofasthma;increasedtriglycerides.

Associated with Methyltestosterone

Endocrine and Urogenital

• Female:The most common side effects ofandrogentherapy areamenorrheaand othermenstrualirregularities, inhibition ofgonadotropinsecretion, and virilization, including deepening of the voice andclitoralenlargement. The latter usually is not reversible after androgens are discontinued. When administered to apregnantwoman, androgens cause virilization of externalgenitaliaof the female fetus.
• Skin and Appendages:Hirsutism, male pattern ofbaldness, andacne.
• Fluid andElectrolyteDisturbances:Retention ofsodium,chloride, water,potassium,calcium, and inorganic phosphates.
• Gastrointestinal:Nausea, cholestaticjaundice, alterations inliverfunction test, rarely hepatocellular neoplasms, andpeliosis hepatis.
• Hematologic:Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitantanticoagulanttherapy, andpolycythemia.
• Central Nervous System:Increased ordecreased libido,headache,anxiety,depression, and generalizedparesthesia.
• Metabolic:Increasedserumcholesterol.
• Miscellaneous:Inflammationandpainat the site ofintramuscularinjection orsubcutaneousimplantationoftestosteronecontaining pellets, stomatitis with buccal preparations, and rarely anaphylactoid reactions.

Drug/Laboratory Test Interactions (Estrogens)

1. Acceleratedprothrombin time, partial thromboplastin time, andplateletaggregation time; increasedplatelet count;increased factors II, VIIantigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels offibrinogenand fibrinogen activity; increased plasminogen antigen and activity.
2. Increased thyroid-binding globulin (TBG) levels leading to increased circulating totalthyroid hormonelevels as measured by protein-boundiodine(PBI), T4 levels (by column or byradioimmunoassay) or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients onthyroidreplacement therapy may require higher doses of thyroidhormone.
3. Other bindingproteinsmay be elevated in serum (i.e.,corticosteroidbinding globulin (CBG), sex hormone binding globulin (SHBG)) leading to increased total circulatingcorticosteroidsand sex steroids, respectively. Free hormone concentrations may be decreased. Otherplasmaproteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
4. Increased plasmaHDLand HDL2 cholesterol subfraction concentrations, reducedLDLcholesterol concentration, increasedtriglycerideslevels.
5. Impaired glucose tolerance.
6. Reduced response tometyraponetest.

Drug Interactions (Androgens)

• Anticoagulants:C-17 substituted derivatives of testosterone, such as methandrostenolone, have been reported to decrease theanticoagulantrequirements of patients receiving oral anticoagulants. Patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped.
• Oxyphenbutazone:Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
• Insulin:In diabetic patients, the metabolic effects of androgens may decreaseblood glucoseand insulin requirements.

Drug/Laboratory Test Interferences (Androgens)

• Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased T4 serum levels and increased resin uptake of T3 and T4.
• Freethyroid hormone水平仍保持d, however, and there is no clinical evidence of thyroiddysfunction.

Carcinogenesis, Mutagenesis, Impairment of Fertility (Estrogens)

• Long-term continuous administration of estrogen, with and without progestin, in women with and without auterus, has shown an increased risk of
  • endometrial cancer,
  • breast cancer, and
  • ovarian cancer.
• Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the
  • breast,
  • uterus,
  • cervix,
  • vagina,
  • testis, and
  • liver.