Histology of leiomyomata in patients treated with leuprolide acetate.

This study examined the histologic changes associated with administration of leuprolide acetate, a gonadotropin-releasing hormone agonist, in leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (+/- 3 years), race, and uterine size (+/- 2 weeks) with untreated controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined "blinded" by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis). A matched case-control analysis was conducted for each morphologic characteristic. Cellularity, hyalinization, and fibrosis were graded as 1(+) versus 2(+); all other characteristics were graded as present or absent. The analysis showed that leuprolide acetate-treated leiomyomata had significantly increased hyalinization (p < 0.005) and decreased cellularity (p < 0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p < 0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having > 30% reduction in tumor size) more frequently had thickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.

Maternal-fetal transfer of ionized serum magnesium during the stress of labor and delivery: a human study.

OBJECTIVE: The purpose of this study was to compare levels and fractions of ionized magnesium in maternal venous serum with those in umbilical venous and arterial serum and to determine whether the maternal levels and fractions change during the stress of labor. METHODS: Utilizing an ion-selective electrode, we determined levels and fractions of ionized magnesium (IMg2+) and levels of ionized calcium (ICa2+) in the maternal venous serum (MVS) of 12 parturients on admission and at the end of labor, as well as in the umbilical venous (UVS) and umbilical arterial serum (UAS) at delivery. A paired-sample study design was used. RESULTS: Whereas mean levels of ICa2+ did not change significantly (p > 0.05) during labor, the mean (+/- SE) MVS levels of IMg2+ and total magnesium (TMg) fell from 0.50 +/- 0.01 and 0.80 +/- 0.02 mmol/L, respectively, on admission to 0.46 +/- 0.01 and 0.68 +/- 0.01 mmol/L (p < 0.01 and p < 0.001, respectively) at delivery. The ionized fraction, expressed as a percent (IMg2+/TMg x 100), increased from 62.8 +/- 2.1% to 67.8 +/- 1.2% (p < 0.05). In the UVS, the mean IMg2+ level (0.52 +/- 0.02 mmol/L) and the mean ionized fraction (73.6 +/- 1.7%) were higher than in MVS on admission or at delivery (p < 0.05 for all comparisons). The mean IMg2+ level in UAS (0.50 +/- 0.02 mmol/L) was lower than in UVS (p < 0.05), but higher than in MVS at delivery (p < 0.01). Finally, there were significant positive correlations between levels of magnesium (Mg) in MVS and in the UAS or UVS. CONCLUSIONS: The observation that UAS levels of IMg2+ and TMg were similar to the MVS levels on admission despite the fall in maternal levels during labor points to the presence of homeostatic mechanisms in the fetus and placenta. It is possible that the presence of a higher fraction of unbound, free magnesium in UVS enhances magnesium transport to the fetus and thus homeostasis. Finally, we hypothesize that the fall in the levels of the biologically active form of Mg during labor may be yet another manifestation of the known stress responses to labor.