Systematic studies of the side effects of<unk>  are lacking. However, its side effects are assumed to be identical to those of estradiol and other estradiol esters. The side effects of<unk>  are partially dependent on sex. Common or frequent (>10%) side effects are considered to include headache, abdominal pain, nausea, rash, pruritus, loss of libido, erectile dysfunction, breast tenderness, gynecomastia, feminization, demasculinization, infertility, and vaginal bleeding or spotting. Side effects that occur occasionally or uncommonly (0.1–1%) include sodium and water retention, edema, hypersensitivity, breast tension, depression, dizziness, visual disturbances, palpitations, dyspepsia, erythema nodosum, urticaria, and chest pain. All other side effects of<unk>  are considered to be rare. The rare (<0.1%) side effects of<unk>  are considered to include weight gain, impaired glucose tolerance, mood changes (elation or depression), nervousness, tiredness, headache, migraine, intolerance of contact lenses, hypertension, thrombosis, thrombophlebitis, thromboembolism, heart failure, myocardial infarction, vomiting, bloating, cholestatic jaundice, cholelithiasis, transient increases in transaminases and bilirubin, erythema multiforme, hyperpigmentation, muscle cramps, dysmenorrhea, vaginal discharge, premenstrual-like symptoms, breast enlargement, testicular atrophy, allergic reactions (e.g., urticaria, bronchial asthma, anaphylactic shock) due to mepivacaine, and injection site reactions (e.g., pain, sterile abscesses, inflammatory infiltrates). As thromboembolic and other cardiovascular complications are associated mainly with synthetic oral estrogens like ethinylestradiol and diethylstilbestrol, they occur much less often with parenteral bioidentical forms of estrogen like<unk> . Cardiovascular effects<unk>  produces minimal undesirable effects on coagulation factors and is thought to increase the risk of blood clots little or not at all. This is in spite of the fact that estradiol levels can reach high concentrations of as much as 700 pg/mL with high-dose (320 mg/month)<unk>  therapy. It is also in contrast to oral synthetic estrogens such as diethylstilbestrol and ethinylestradiol, which produce marked increases in coagulation factors and high rates of blood clots at the high doses used to achieve castrate levels of testosterone in prostate cancer. The difference between the two types of therapies is due to the bioidentical and parenteral nature of<unk>  and its minimal influence on liver protein synthesis.<unk>  might actually reduce the risk of blood clots, due to decreases in levels of certain procoagulatory proteins. Although<unk>  does not increase the hepatic production or levels of procoagulatory factors, it has been found to significantly decrease levels of the anticoagulatory antithrombin III, which may indicate a potential risk of thromboembolic and cardiovascular complications. On the other hand,<unk>  significantly increases levels of HDL cholesterol and significantly decreases levels of LDL cholesterol, changes which are thought to protect against coronary artery disease. It appears that<unk>  may have beneficial effects on cardiovascular health at lower dosages (e.g., 160 mg/day) due to its beneficial effects on HDL and LDL cholesterol levels, but these are overshadowed at higher dosages (e.g., 240 mg/day) due to unfavorable dose-dependent effects on hemostasis, namely antithrombin III levels. Small early pilot studies of<unk>  for prostate cancer in men found no cardiovascular toxicity with the therapy. A dosage of<unk>  of 160 mg/month specifically does not appear to increase the risk of cardiovascular complications. In fact, potential beneficial effects on cardiovascular mortality have been observed at this dosage. However,<unk>  at a higher dosage of 240 mg/month has subsequently been found in large studies to significantly increase cardiovascular morbidity relative to GnRH modulators and orchiectomy in men treated with it for prostate cancer. The increase in cardiovascular morbidity with<unk>  therapy is due to an increase in non-fatal cardiovascular events, including ischemic heart disease and heart decompensation, specifically heart failure. Conversely,<unk>  has not been found to significantly increase cardiovascular mortality relative to GnRH modulators and orchiectomy. Moreover, numerically more patients with preexisting cardiovascular disease were randomized to the<unk>  group in one large study (17.1% vs. 14.5%; significance not reported), and this may have contributed to the increased incidence of cardiovascular morbidity observed with<unk> . In any case, some studies have found that the increased cardiovascular morbidity with<unk>  is confined mainly to the first one or two years of therapy, whereas one study found consistently increased cardiovascular morbidity across three years of therapy. A longitudinal risk analysis that projected over 10 years suggested that the cardiovascular risks of<unk>  may be reversed with long-term treatment and that the therapy may eventually result in significantly decreased cardiovascular risk relative to GnRH modulators and orchiectomy, although this has not been confirmed. The cardiovascular toxicity of<unk>  is far less than that of oral synthetic estrogens like diethylstilbestrol and ethinylestradiol, which increase the risk of venous and arterial thromboembolism, consequently increase the risk of transient ischemic attack, cerebrovascular accident (stroke), and myocardial infarction (heart attack), and result in substantial increases in cardiovascular mortality. It is thought that the relatively minimal cardiovascular toxicity of parenteral forms of estradiol, like<unk>  and high-dose transdermal estradiol patches, is due to their absence of effect on hepatic coagulation factors.
Polyestradiol phosphate
Polyestriol phosphate
Progestogen ester
Androgen ester
Progestogen 
Progestogen
Estradiol sulfate
Estrogen ester