The effect of ketoconazole on endocrine and reproductive parameters in male mice and rats.

Ketoconazole has been shown to reduce steroidogenesis by inhibiting the cytochrome P-450 enzymes in these pathways. This finding, along with the observation that the compound reduces sperm motility, led us to study the effectiveness of ketoconazole as a male contraceptive agent administered in acute and chronic studies of both rats and mice. Four hours after a single administration, male rats showed significant reductions in both serum testosterone and corticosterone levels that completely recovered (testosterone) or nearly recovered (corticosterone) 24 hours after administration. Chronic administration of ketoconazole to male rats and mice resulted in steroid levels comparable with those of control animals. Epididymal sperm motility was only slightly reduced in male mice 4 hours after administration of the drug. No effect on sperm motility was noted after chronic administration in either species studied. In vitro exposure of epididymal sperm to ketoconazole resulted in a significant reduction of sperm motility. Breeding trials after ketoconazole administration resulted in normal fertility and fecundity even at the highest dosage studied. The lack of correlation between steroid levels and sperm immobilization, along with rapid in vivo and in vitro effects on sperm motility, suggests that the reduction in sperm motility is not related to a decrease in steroid levels. From these data, the authors conclude that ketoconazole is probably not a viable approach to the development of a male contraceptive.

Pap smear adequacy: the role of clinician experience.

BACKGROUND AND OBJECTIVES: The Papanicolaou (Pap) smear is a widely accepted tool for the detection and prevention of cervical cancer. Under the Bethesda Scoring System, the key internal control for adequacy of the smear is the presence of endocervical cells. Over the past several decades, much effort has been undertaken to maximize the adequacy of this acquisition. The present study determined if Pap smear sample adequacy is related to clinician experience. METHODS: This study includes a retrospective analysis of 1,356 Pap smears acquired between January 1992 and January 1995. The procedures were performed by family practice residents and faculty physicians. Cervical smears were obtained with a combination of a cytobrush and an Ayre spatula and were placed on two slides. Adequacy was subsequently determined by a cytotechnologist. Chi-square analysis was used to determine if the adequacy rates for faculty and for PGY-1, PGY-2, and PGY-3 residents were significantly different. RESULTS: The adequacy rates for PGY-1, PGY-2, PGY-3 residents and faculty physicians were 80%, 89%, 89%, and 93%, respectively. The adequacy rates for the first-year residents were significantly different from that of all other studied groups. CONCLUSIONS: This study demonstrates the relationship between clinician experience and the ability to perform an adequate Pap smear. Considering the cost and potential medical risk of an inadequate Pap smear, family practice residency programs should increase the degree of PGY-1 education and experience in performing Pap smears.