A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer.

Role of androgen excess in the development of estrogen receptor-positive and estrogen receptor-negative breast cancer.

The androgen-excess theory posits a central role of androgens in promoting breast cancer development. At first glance, this appears to contradict the currently accepted central role of estrogens in this process, but as we will show, the apparent contradiction is not a real one. In the present article, we review the mechanisms by which androgen excess may stimulate cancer growth in different subsets of estrogen receptor-positive and estrogen receptor-negative tumors.

Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone.

Studies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks).

Relationship of endogenous levels of sex hormones to cognition and depression in frail, elderly women.

Neuropsychological evaluations and sex hormone assays for 188 elderly, female nursing home residents (mean age: 87.8 years; standard deviation: 7.0 years) revealed inverse relationships for dehydroepiandrosterone (DHEA) blood levels and cognition scores based on the Mini-Mental State Exam and the Test for Severe Impairment, as well as for scores of the Immediate Recall, Copy, and Recognition tests of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised (WMS-R; VR).