Clinical evidence for predominance of delta-5 steroid production in women with polycystic ovary syndrome.

CONTEXT: In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway. OBJECTIVE: This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women. DESIGN: We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women. SETTING: The study was conducted in a General Clinical Research Center in an academic medical center. PARTICIPANTS: Women with PCOS (age, 18-37 yr; n = 10) and normal ovulatory controls (age, 18-37 yr; n = 11) were recruited. INTERVENTIONS: For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 µg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 µg of recombinant hCG. MAIN OUTCOME MEASURE(S): We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration. RESULTS: In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women. CONCLUSION: In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.

The association between lower extremity continuous peripheral nerve blocks and patient falls after knee and hip arthroplasty.

BACKGROUND: Continuous peripheral nerve blocks (CPNB) may induce muscle weakness, and multiple recently published series emphasize patient falls after postarthroplasty CPNB. However, none have included an adequate control group, and therefore the relationship between CPNB and falls remains speculative. METHODS: We pooled data from 3 previously published, randomized, triple-masked, placebo-controlled studies of CPNB involving the femoral nerve after knee and hip arthroplasty. RESULTS: No patients receiving perineural saline (n = 86) fell (0%; 95% confidence interval [CI] = 0%-5%), but there were 7 falls in 6 patients receiving perineural ropivacaine (n = 85; 7%; 95% CI = 3%-15%; Fisher's exact test P = 0.013). CONCLUSIONS: Our analysis suggests that there is a causal relationship between CPNB and the risk of falling after knee and hip arthroplasty.