Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17b (E2; subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 lg/mL) or E2 on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast.

Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17β (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women.

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Thirty patients with primary cardiac compression due to constrictive pericarditis, lax effusion, or cardiac tamponade and an additional seven patients with spurious evidence of cardiac compression or with pericardial effusion playing an unimportant role in the circulatory disorder were studied. Rather stringently defined physical findings were sought which might allow discrimination between cardiac disorders. The following conclusions are drawn from the results. 1. Constrictive pericarditis is associated with venous and auscultatory phenomena which do not allow separation from other forms of heart disease causing congestive heart failure. Kussmaul's sign is present in less than 40%; pulsus paradoxus as classically defined is rare. 2. In lax pericardial effusion, Kussmaul's sign and Friedreich's sign, along with third heart sounds, are not present. Pulsus paradoxus is inconstant with tranquil breathing but is regularly induced by deep inspiration. There is inspiratory decrease in venous pressure and pericardial pressure. Cardiac index is normal and venous pressure is less than 12 mm Hg. Circulatory distress is not apparent. 3. Tamponade induces signs of circulatory distress and is regularly characterized by pulsus paradoxus but Friedreich's sign, a third heart sound, as well as Kussmaul's venous sign, are absent. The venous pressure exceeds 12 mm Hg. There is an inspiratory decrease in venous pressure and pericardial pressure. The low cardiac index is usually relieved by tap. When aortic stenosis is present, respiratory variation in left ventricular systolic pressure may not be reflected by clinical pulsus paradoxus. 4. Spurious signs of cardiac compression may be due to (1) respiratory disease, (2) severe myocardial disease and incidental effusion, or (3) obesity. In the respiratory disease pulsus paradoxus, normal cardiac index, low venous pressure, and venous and pericardial-pressure decrease with inspiration are present. The second group does not show pulsus paradoxus and the elevated venous pressure, diastolic dip, and third heart sounds are due to heart failure. Obesity may cause pulsus paradoxus and increased peripheral venous pressure, which does not reflect central venous pressure. These findings seem related to inspiratory collapse of extrathoracic vessels.

Lead is a widely spread environmental pollutant known to affect both male and female reproductive systems in humans and experimental animals and causes infertility and other adverse effects. The present paper investigated the effects of prenatal exposure to lead on different parameters of estrogen stimulation in the uterus of the prepubertal rat. In prenatally and perinatally exposed rats, estrogen-induced endometrial eosinophilia, endometrial stroma edema, and eosinophil migration towards the endometrium, and uterine luminal epithelial hypertrophy are enhanced while several other responses to estrogen appear unchanged. These effects may contribute to decrease in fertility following prenatal exposure to lead. The striking difference between most of these effects of prenatal exposure and the previously reported effects of chronic exposure to lead suggests that prenatal exposure to lead may neutralize the effects of chronic exposure to lead, providing partial protection of cell function against the adverse effects of chronic exposure to lead. We propose that the mechanism involved, named imprinting or cell programming, persisted through evolution as a nongenetic adaptive mechanism to provide protection against long-term environmental variations that otherwise may cause the extinction of species not displaying this kind of adaptation.