Estradiol adverse effects

Of 206 postmenopausal women who took the oral combination of estradiol valerate plus norethisterone (5) eight withdrew because of bleeding during year 1 during years 2 and 3 there were no withdrawals because of bleeding. By the end of year 3, 133 patients had completed the study. There were serious adverse effects in 24, but there was no definite relation to therapy. The numbers of adverse events reported each year by the patients who completed the study are shown in Table 1. The authors concluded that this combination was effective in the majority of patients and was well tolerated. 

Estrogens Diethylstilbestrol Estradiol Others Advanced, inoperable breast cancer in selected men and postmenopausal women advanced, inoperable prostate cancer in men Cardiovascular complications [including stroke and heart attack-espe-cially in men] many other adverse effects [see Chapter 30]... 

Tamoxifen is a competitive partial agonist inhibitor of estradiol at the estrogen receptor and is extensively used in the palliative treatment of advanced breast cancer in postmenopausal women. It is a nonsteroidal agent (see structure below) that is given orally. Peak plasma levels are reached in a few hours. Tamoxifen has an initial half-life of 7-14 hours in the circulation and is predominantly excreted by the liver. It is used in doses of 10-20 mg twice daily. Hot flushes and nausea and vomiting occur in 25% of patients, and many other minor adverse effects are observed. Studies of patients treated with tamoxifen as adjuvant therapy for early breast cancer have shown a 35% decrease in contralateral breast cancer. However, adjuvant therapy extended beyond 5 years in patients with breast cancer has shown no further improvement in outcome. Toremifene is a structurally similar compound with very similar properties, indications, and toxicities. 

Adverse effects These are primarily related to CNS and Gl disturbances. They include impaired concentration, dizziness, ataxia, diplopia, somnolence, nervousness, and confusion, as well as nausea and weight loss. Renal stones have been reported in 1.5 percent of patients. Topiramate is teratogenic in animals, and should be avoided during pregnancy. Inducers of drug metabolism such as phenytoin and carbamazepine decrease topiramate serum concentrations by approximately 50 percent. Topiramate decreases ethinyl estradiol concentrations of oral contraceptive preparations, and individuals should supplement the amount of ethinyl estradiol. 

OESTROGENS -ESTRADIOL, POSSIBLY ETHINYLESTRADIOL GRAPEFRUIT JUICE t efficacy and t adverse effects of oestrogens Oral administration only, t bioavailability and 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal cytochrome CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Monitor for t side-effects... 

Another variant on hormone replacement therapy involves using aU three types of sex steroid in parallel, starting from the argument that during the fertile period all three are sjmthesized by the ovary (7). A natural version of this therapy uses estradiol, testosterone (with or without dehydroepiandrosterone), and progesterone in an appropriate pharmaceutical form (for example micro-nized), so that absorption is attained without the need for 17-substitution. This approach naturally avoids some of the undesirable effects of the synthetic steroids, and has been stated to improve menopausal depression and anxiety. However, the adverse effects of all three types of component can be experienced. 

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