A phase I trial of CGS 16949A: a new aromatase inhibitor

Article Abstract:

Normal and cancerous breast tissue may be influenced by estrogens, and some breast cancer therapy is oriented towards the suppression of this response. In postmenopausal women, or women who have had their ovaries removed, the major source of estrogen is the enzymatic conversion of androstenedione to estrone in peripheral tissue. This conversion is accomplished by a multicomponent enzyme complex called aromatase. Over two-thirds of breast cancers have been shown to have aromatase activity. CGS 16949A is an experimental imidazole derivative which has aromatase inhibitory activity. The drug was used in the treatment of 16 postmenopausal women with measurable metastatic breast cancer. None of the 16 women had tumors which were conclusively negative for the estrogen receptor, a cell surface protein thought to mediate the effects of estrogen on the cell. The CGS 16949A was tolerated well by the patients with only minor side effects. Levels of estrone, estradiol, and estrone sulfate circulating in the blood fell to 53 to 72 percent of the normal levels in these patients. Two patients achieved a partial response resulting from the treatment; these responses lasted 5 and 15 months. Seven patients stabilized, and the disease continued to progress in the remaining seven patients. The response of these patients, all of whom had widespread metastatic disease, seemed encouraging. Further studies will determine the optimal dosage of CGS 16949A for metastatic breast cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Case studies, Breast cancer, Cancer, Chemotherapy, Cancer endocrinology

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Evidence of heterogeneous mechanisms in lipoprotein lipid alterations in hyperandrogenic women

Article Abstract:

Women who become hyperandrogenic develop an excess of male sex hormones, and tend to have higher blood levels of lipids (fats) and lower levels of high-density lipoprotein (HDL) cholesterol, which are associated with an increased risk for cardiovascular disease. Higher blood levels of insulin have also been found. There are numerous causes of hyperandrogenism. To determine the relationship between androgen excess and blood lipid alterations, 51 women with hirsutism (hairiness indicative of androgen excess) caused by different disorders were evaluated. The results suggest that androgens such as testosterone influence lipoproteins and lipids independently of insulin level, body weight, or waist/hip ratio (a predictor of circulatory system disease). Insulin levels independently correlated with blood levels of triglyceride (fat) but not HDL cholesterol. When this analysis was considered for women divided into subgroups according to cause of androgen excess, only those with polycystic ovarian syndrome had the same significant correlations between androgen and lipid levels. However, each group had low levels of HDL cholesterol and high levels of triglycerides. The results suggest that varying hormonal changes contribute to the observed effects on blood lipids. The study suggests that women with hyperandrogenism, often signalled by hirsutism, are at higher risk of coronary artery disease due to alterations in insulin and lipid handling. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Lipid metabolism, Androgens, Stein-Leventhal syndrome, Polycystic ovary syndrome

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Thyroid dysfunction in elderly hospitalized patients: effect of age and severity of illness

Article Abstract:

Elderly patients commonly have thyroid dysfunction, even in the absence of symptoms. However, it is sometimes difficult to ascertain how much decline in thyroid function is a normal consequence of aging and how much is pathological. To determine the prevalence of thyroid dysfunction among elderly hospitalized patients, 190 patients aged 60 years and older were tested. Only 27 percent had normal values for all aspects of thyroid function. Triiodothyronine, a thyroid hormone often abbreviated T3, was reduced in 125 patients. Although the age of the patient was a significant determinant of T3 levels, statistical regression analysis showed that the greatest contributing factor to T3 levels was the severity of illness. Since only 34 percent of the patients tested had normal T3 levels, it is clear that undiagnosed thyroid dysfunction is common among the elderly. The fact that in many cases the thyroid dysfunction was not reflected in clinical symptoms suggests that thyroid testing should be routine for elderly hospitalized patients. The results also support previous findings that elevation of thyroid stimulating hormone (TSH) and reduction of thyroxine (T4) are probably indicators of generally reduced thyroid function and do not occur as a specific result of illness, whereas reduced levels of T3 are more suggestive of a disease process. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Abnormalities, Measurement, Demographic aspects, Hypothyroidism, Thyroid hormones, Thyroxine, Thyroid gland, Thyroid gland function tests, Thyroid function tests

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