al pharmacology, clinical studies . ) in the ce/mpa substudy of whi, an increased risk of coronary heart disease (chd) events (defined as nonfatal myocardial infarction and chd death) was observed in women receiving ce/mpa compared to women receiving placebo (37 versus 30 per 10,000 women-years). the increase in risk was observed in year 1 and persisted. in the same substudy of whi, an increased risk of stroke was observed in women receiving ce/mpa compared to women receiving placebo (29 versus 21 per 10,000 women-years). the increase in risk was observed after the first year and persisted. in postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years) a controlled clinical trial of secondary prevention of cardiovascular disease (heart and estrogen/progestin replacement study; hers) treatment with ce/mpa (0.625 mg/2.5 mg per day) demonstrated no cardiovascular benefit. during an average follow-up of 4.1 years, treatment with ce/mpa did not reduce the overall rate of chd events in postmenopausal women with established coronary heart disease. there were more chd events in the ce/mpa-treated group than in the placebo group in year 1, but not during the subsequent years. two thousand three hundred and twenty one women from the original hers trial agreed to participate in an open-label extension of hers, hers ii. average follow-up in hers ii was an additional 2.7 years, for a total of 6.8 years overall. rates of chd events were comparable among women in the ce/mpa group and the placebo group in hers, hers ii, and overall. large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis. venous thromboembolism (vte.): in the women’s health initiative (whi) study, an increase in vte was observed in women receiving ce compared to placebo. the ce-only substudy has concluded. the impact of those results are under review. (see clinical pharmacology, clinical studies . ) in the ce/mpa substudy of whi, a 2-fold greater rate of vte, including deep venous thrombosis and pulmonary embolism, was observed in women receiving ce/mpa compared to women receiving placebo. the rate of vte was 34 per 10,000 women-years in the ce/mpa group compared to 16 per 10,000 women-years in the placebo group. the increase in vte risk was observed during the first year and persisted. if feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. malignant neoplasms endometrial cancer: the use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. the reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. most studies show no significant increased risk associated with use of estrogens for less than one year. the greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. clinical surveillance of all women taking estrogen/progestin combinations is important. adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. there is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. breast cancer: the use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer. the most important randomized clinical trial providing information about this issue is the women’s health initiative (whi) substudy of ce/mpa. (see clinical pharmacology, clinical studies . ) the results from observational studies are generally consistent with those of the whi clinical trial and report no significant variation in the risk of breast cancer among different estrogens or progestins, doses, or routes of administration. the ce/mpa substudy of whi reported an increased risk of breast cancer in women who took ce/mpa for a mean follow-up of 5.6 years. observational studies have also reported an increased risk for estrogen/progestin combination therapy, and a smaller increased risk for estrogen alone therapy, after several years of use. in the whi trial and from observational studies, the excess risk increased with duration of use. from observational studies, the risk appeared to return to baseline in about five years after stopping treatment. in addition, observational studies suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen/progestin combination therapy as compared to estrogen alone therapy. in the ce/mpa substudy, 26% of the women reported prior use of estrogen alone and/or estrogen/progestin combination hormone therapy. after a mean follow-up of 5.6 years during the clinical trial, the overall relative risk of invasive breast cancer was 1.24 (95% confidence interval 1.01-1.54), and the overall absolute risk was 41 versus 33 cases per 10,000 women-years, for ce/mpa compared with placebo. among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for ce/mpa compared with placebo. among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for ce/mpa compared with placebo. in the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the ce/mpa group compared with the placebo group. metastatic disease was rare with no apparent difference between the two groups. other prognostic factors such as histologic subtype, grade and hormone receptor status did not differ between the groups. the use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. all women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. in addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. dementia in the women’s health initiative memory study (whims), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. after an average follow-up of 4 years, 40 women being treated with ce/mpa (1.8%, n = 2,229) and 21 women in the placebo group (0.9%, n = 2,303) received diagnoses of probable dementia. the relative risk for ce/mpa versus placebo was 2.05 (95% confidence interval 1.21 – 3.48), and was similar for women with and without histories of menopausal hormone use before whims. the absolute risk of probable dementia for ce/mpa versus placebo was 45 versus 22 cases per 10,000 women-years, and the absolute excess risk for ce/mpa was 23 cases per 10,000 women-years. it is unknown whether these findings apply to younger postmenopausal women. (see clinical pharmacology, clinical studies and precautions, geriatric use . ) the estrogen alone substudy of the women’s health initiative memory study has concluded. it is unknown whether these findings apply to estrogen alone. gallbladder disease a 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. glucose tolerance a worsening of glucose tolerance has been observed in a significant percentage of patients on estrogen-containing oral contraceptives. for this reason, diabetic patients should be carefully observed while receiving estrogens. hypercalcemia estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. if hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level. visual abnormalities retinal vascular thrombosis has been reported in patients receiving estrogens. discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. if examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued. warnings associated with methyltestosterone in patients with breast cancer, androgen therapy may cause hypercalcemia by stimulating osteolysis. in this case the drug should be discontinued. prolonged use of high doses of androgens has been associated with the development of peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma. [see precautions – carcinogenesis (androgens) .] peliosis hepatis can be a life-threatening or fatal complication. cholestatic hepatitis and jaundice occur with 17-alpha-alkylandrogens at a relatively low dose. if cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, the androgen should be discontinued and the etiology should be determined. drug-induced jaundice is reversible when the medication is discontinued. edema with or without heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. in addition to discontinuation of the drug, diuretic therapy may be required.

alone. the lowest dose that will control symptoms should be chosen and medication should be discontinued as promptly as possible. administration should be cyclic (e.g., three weeks on and one week off). attempts to discontinue or taper medication should be made at three- to six month intervals. usual dosage range: 1 tablet of esterified estrogens and methyltestosterone tablets or 1 to 2 tablets of esterified estrogens and methyltestosterone tablets h.s. daily as recommended by the physician. treated patients with an intact uterus should be monitored closely for signs of endometrial cancer and appropriate diagnostic measures should be taken to rule out malignancy in the event of persistent or recurring abnormal vaginal bleeding.

a, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer; cystitis-like syndrome. breasts: tenderness; enlargement; pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer. cardiovascular: deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure. gastrointestinal: nausea; vomiting; abdominal cramps; bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis, enlargement of hepatic hemangiomas. skin: chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash. eyes: retinal vascular thrombosis, steepening of corneal curvature, intolerance to contact lenses. central nervous system: headache, migraine, dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia. miscellaneous: increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides. associated with methyltestosterone endocrine and urogenital female: the most common side effects of androgen therapy are amenorrhea and other menstrual irregularities, inhibition of gonadotropin secretion, and virilization, including deepening of the voice and clitoral enlargement. the latter usually is not reversible after androgens are discontinued. when administered to a pregnant woman, androgens cause virilization of external genitalia of the female fetus. skin and appendages: hirsutism, male pattern of baldness, and acne. fluid and electrolyte disturbances: retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates. gastrointestinal: nausea, cholestatic jaundice, alterations in liver function test, rarely hepatocellular neoplasms, and peliosis hepatis. (see warnings .) hematologic: suppression of clotting factors ii, v, vii, and x, bleeding in patients on concomitant anticoagulant therapy, and polycythemia. central nervous system: increased or decreased libido, headache, anxiety, depression, and generalized paresthesia. metabolic: increased serum cholesterol. miscellaneous: inflammation and pain at the site of intramuscular injection or subcutaneous implantation of testosterone containing pellets, stomatitis with buccal preparations, and rarely anaphylactoid reactions.

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 follicle stimulating hormone (fsh), through a negative feedback mechanism. estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. estrogen pharmacokinetics distribution the distribution of exogenous estrogens is similar to that of endogenous estrogens. estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. estrogens circulate in the blood largely bound to sex hormone binding globulin (shbg) and albumin. metabolism exogenous estrogens are metabolized in the same manner as endogenous estrogens. circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. these transformations take place mainly in the liver. estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. in postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. excretion estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates. drug interactions 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 preparations (hypericum perforatum), 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 estrogens and may result in side effects. clinical studies women’s health initiative studies the women’s health initiative (whi) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (ce) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (mpa) per day compared to placebo in the prevention of certain chronic diseases. the primary endpoint was the incidence of coronary heart disease (chd) (nonfatal myocardial infarction and chd death), with invasive breast cancer as the primary adverse outcome studied. a “global index” included the earliest occurrence of chd, invasive breast cancer, stroke, pulmonary embolism (pe), endometrial cancer, colorectal cancer, hip fracture, or death due to other cause. the study did not evaluate the effects of ce or ce/mpa on menopausal symptoms. the ce-only substudy has concluded. the impact of those results are under review. the ce/mpa substudy was stopped early because, according to the predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the “global index.” results of the ce/mpa substudy, which included 16,608 women (average age of 63 years, range 50 to 79; 83.9% white, 6.5% black, 5.5% hispanic), after an average follow-up of 5.2 years are presented in table 1 below. a adapted from jama , 2002; 288:321-333 b includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer c a subset of the events was combined in a “global index,” defined as the earliest occurrence of chd events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes d not included in global index * nominal confidence intervals unadjusted for multiple looks and multiple comparisons for those outcomes included in the “global index,” the absolute excess risks per 10,000 women-years in the group treated with ce/mpa were 7 more chd events, 8 more strokes, 8 more pes, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. the absolute excess risk of events included in the “global index” was 19 per 10,000 women-years. there was no difference between the groups in terms of all-cause mortality. (see boxed warnings , warnings , and precautions . ) women’s health initiative memory study the women’s health initiative memory study (whims), a substudy of whi, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of ce/mpa (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate) on the incidence of probable dementia (primary outcome) compared with placebo. after an average follow-up of 4 years, 40 women in the estrogen/progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. the relative risk of probable dementia in the hormone therapy group was 2.05 (95% ci, 1.21 to 3.48) compared to placebo. differences between groups became apparent in the first year of treatment. it is unknown whether these findings apply to younger postmenopausal women. (see boxed warnings and warnings, dementia . ) androgens: endogenous androgens are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. these effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as beard, pubic, chest, and axillary hair, laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. drugs in this class also cause retention of nitrogen, sodium, potassium, phosphorus, and decreased urinary excretion of calcium. androgens have been reported to increase protein anabolism and decrease protein catabolism. nitrogen balance is improved only when there is sufficient intake of calories and protein. androgens are responsible for the growth spurt of adolescence and for the eventual termination of linear growth which is brought about by fusion of the epiphyseal growth centers. in children, exogenous androgens accelerate linear growth rates, but may cause a disproportionate advancement in bone maturation. use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating factor. androgen pharmacokinetics testosterone given orally is metabolized by the gut and 44 percent is cleared by the liver in the first pass. oral doses as high as 400 mg per day are needed to achieve clinically effective blood levels for full replacement therapy. the synthetic androgens (methyltestosterone and fluoxymesterone) are less extensively metabolized by the liver and have longer half-lives. they are more suitable than testosterone for oral administration. testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life. about 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in the feces, mostly in the unconjugated form. inactivation of testosterone occurs primarily in the liver. testosterone is metabolized to various 17-keto steroids through two different pathways. there are considerable variations of the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. in many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, which binds to cytosol receptor proteins. the steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action. ab03b87f-figure-02

� to 30°c (59° to 86°f). [ see usp controlled room temperature.] manufactured by: eci pharmaceuticals fort lauderdale, fl 33309

n of cancer of the uterus (womb). your healthcare provider should check any unusual vaginal bleeding to find out the cause. • do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes.using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots. using estrogens with progestins may increase your risk of dementia. you and your healthcare provider should talk regularly about whether you still need treatment with esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. what are esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s.? esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. are medicines that contain estrogen and androgen hormones. what are esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. used for? esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. are used after menopause to: • reduce moderate to severe hot flashes. estrogens are hormones made by a woman’s ovaries. the ovaries normally stop making estrogens when a woman is between 45 to 55 years old. this drop in body estrogen levels causes the “change of life” or menopause (the end of monthly menstrual periods). sometimes, both ovaries are removed during an operation before natural menopause takes place. the sudden drop in estrogen levels causes “surgical menopause.” when the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating (“hot flashes” or “hot flushes”). in some women, the symptoms are mild, and they will not need estrogens. in other women, symptoms can be more severe. you and your healthcare provider should talk regularly about whether you still need treatment with esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. • treat moderate to severe dryness, itching, and burning in and around the vagina. you and your healthcare provider should talk regularly about whether you still need treatment with esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. to control these problems. if you use esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. only to treat your dryness, itching, and burning in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you. who should not take esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s.? do not start taking esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. if you: • have unusual vaginal bleeding. • currently have or have had certain cancers. estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. if you have or had cancer, talk with your healthcare provider about whether you should take esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. • had a stroke or heart attack in the past year. • currently have or have had blood clots. • currently have or have had liver problems. • are allergic to esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. or any of their ingredients. see the end of this leaflet for a list of ingredients in esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. • think you may be pregnant. tell your healthcare provider: • if you are breastfeeding. the hormones in esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. can pass into your milk. • about all of your medical problems. your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. • about all the medicines you take. this includes prescription and nonprescription medicines, vitamins, and herbal supplements. some medicines may affect how esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. work. esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. may also affect how your other medicines work. • if you are going to have surgery or will be on bed rest. you may need to stop taking estrogens. how should i take esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s.? estrogens should be used at the lowest dose possible for your treatment only as long as needed. the lowest effective dose of esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. has not been determined. you and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. what are the possible side effects of estrogens? less common but serious side effects include: • breast cancer • cancer of the uterus • stroke • heart attack • blood clots • dementia • gallbladder disease • ovarian cancer these are some of the warning signs of serious side effects: • breast lumps • unusual vaginal bleeding • dizziness and faintness • changes in speech • severe headaches • chest pain • shortness of breath • pains in your legs • changes in vision • vomiting call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you. common side effects include: • headache • breast pain • irregular vaginal bleeding or spotting • stomach/abdominal cramps, bloating • nausea and vomiting • hair loss other side effects include: • high blood pressure • liver problems • high blood sugar • fluid retention • enlargement of benign tumors of the uterus (“fibroids”) • vaginal yeast infection these are not all the possible side effects of esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. for more information, ask your healthcare provider or pharmacist. what can i do to lower my chance of a serious side effect with esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s.? • talk with your healthcare provider regularly about whether you should continue taking esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. • if you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you. • see your healthcare provider right away if you get vaginal bleeding while taking esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. • have a breast exam and mammogram (breast x-ray) every year unless your healthcare provider tells you something else. if members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often. • if you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. ask your healthcare provider for ways to lower your chances for getting heart disease. general information about safe and effective use of esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. do not take esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. for conditions for which it was not prescribed. do not give esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. to other people, even if they have the same symptoms you have. it may harm them. keep esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. out of the reach of children. this leaflet provides a summary of the most important information about esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. if you would like more information, talk with your healthcare provider or pharmacist. you can ask for information about esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. that is written for health professionals. questions or comments? call 1-888-514-4727. what are the ingredients in esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s.? esterified estrogens and methyltestosterone tablets. each light green, oval-shaped, biconvex tablet debossed with "640" on one side and scripted "e" on other side contains the following active ingredients: 1.25 mg of esterified estrogens, usp and 2.5 mg of methyltestosterone, usp. esterified estrogens and methyltestosterone tablets h.s. “half strength”. each dark green, oval-shaped, biconvex tablet debossed with "639" on one side and scripted "e" on other side contains the following active ingredients: 0.625 mg of esterified estrogens, usp and 1.25 mg of methyltestosterone, usp. esterified estrogens and methyltestosterone tablets and esterified estrogens and methyltestosterone tablets h.s. contain the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, d&c yellow #10, fd&c blue #1, fd&c blue #2, fd&c yellow # 6, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium bicarbonate, sodium citrate, talc, and titanium dioxide. store at 20° to 25°c (68° to 77°f); excursions permitted to 15° to 30°c (59° to 86°f). [ see usp controlled room temperature.] manufactured by: eci pharmaceuticals fort lauderdale, fl 33309 iss. 09/20