Publications

BACKGROUND

The recent publication of clinical trial results has led to a dramatic shift in the evidence about postmenopausal hormone therapy.

OBJECTIVE

To examine whether the publication of clinical trial results, specifically the Heart and Estrogen/progestin Replacement Study (HERS) in 1998 and the Women's Health Initiative (WHI) in 2002, has influenced the use of hormone therapy among postmenopausal women.

DESIGN

Observational cohort (1997 to 2003).

SETTING

San Francisco Mammography Registry, San Francisco, California.

PARTICIPANTS

Postmenopausal women between the ages of 50 and 74 years without a personal history of breast cancer who underwent mammography (151862 mammograms).

MEASUREMENTS

Self-reported current use of hormone therapy.

RESULTS

Among menopausal women who had mammography, it was estimated that 41% were currently using hormone therapy in 1997. Before the publication of HERS, the use of hormone therapy was increasing at a rate of 1% (95% CI, 0% to 2%) per quarter. After the publication of HERS, use decreased by 1% (CI, -3% to 0%) per quarter. In contrast, the publication of the WHI in 2002 was associated with a more substantial decline in the use of hormone therapy of 18% (CI, -21% to -16%) per quarter. Similar associations were observed for most subgroups of women, including women older than 65 years of age; women with a previous hysterectomy; and women who described their race or ethnicity as white, African American, Latina, Chinese, or Filipina.

CONCLUSIONS

The release of the HERS data was temporally associated with a modest decline in the use of hormone therapy. In contrast, the release of the principal findings from the WHI was associated with a more substantial decline in use by postmenopausal women. The reason for the differences in decline may relate to the fact that the WHI results were widely publicized or were more applicable to most postmenopausal women because the WHI study was performed in healthy women.

Nitric oxide generation from porcine kidney slices is assessed using a new planar NO-selective amperometric sensor. The planar shape of the sensor allows for direct NO measurements near the surface (10 microm) of renal tissue slices in real time. Renal NO production may be modulated by the addition of L-arginine, arginine homopolymers (R2, R6, R10), and protamine, all of which can potentially transport across cellular membranes and provide a substrate for nitric oxide synthase within kidney parenchyma. Real-time amperometric measurements demonstrate that most L-arginine species can translocate across the cell membrane and rapidly increase NO production. However, no increase in NO generation is observed when the dimer of L-arginine (R2) is added to the solution bathing the tissue, suggesting that this species cannot permeate cell membranes. The degree of enhancement in NO generation observed for L-arginine and the larger peptides depends on the structure and follows the following sequence: R10 (decamer) > protamine > R6 (hexamer) > L-arginine. Protamine and the R10 decamer, especially, induce the largest increases in NO generation owing to their apparent rapid translocation into cells and subsequent cleavage by proteases to create high intracellular levels of L-arginine. The effect of sensor size (for sensor dimensions of 0.15- and 1-mm outer diameters) on the measured surface NO levels is also examined. The larger sensor traps more NO but hinders access of the L-arginine species to the tissue area between the flat distal plane of the sensor and the surface of the kidney slice. The use of such NO-generating peptides may be important in numerous biological systems that depend on NO production, such as ischemia-reperfusion injury and thrombogenesis.