Absence of dysplasia in the excised specimen following loop electrosurgical excision procedure (LEEP) for treatment of cervical intraepithelial neoplasia (CIN) 2/3 is an occasional finding of uncertain clinical significance. We evaluated several factors including age, liquid-based Pap (LBP) test, human papillomavirus (HPV) load before treatment, and HPV typing as predictors for absence of dysplasia. Absence of dysplasia in LEEP specimens was analyzed in terms of factors for recurrent disease after LEEP conization In total, 192 women (mean age, 39.3+/-8.4 years; range, 24 to 70 years) with biopsy-proven CIN 2/3 were treated by LEEP conization. Age, LBP test, histological grade, HPV load, and HPV DNA typing were evaluated as possible predictors of the absence of residual dysplasia or recurrent disease. Of the LEEP specimens, 34 (17.7%) showed no dysplasia in preoperative biopsies from patients with proven CIN 2/3. Low HPV load (/=400 RLU) were significant factors for recurrence. Absence of dysplasia in LEEP specimens occurred in 17.7% of our specimens. Prediction of the absence of dysplasia in LEEP specimens was associated with low HPV load. Residual/recurrent disease after LEEP was associated with a positive resection margin and high viral load, and was not associated with absence of dysplasia in LEEP specimens. Even if there is no dysplasia in conization specimens, close follow-up for residual/recurrent disease is needed.

Randomized clinical trials (RCTs) using delayed hormone treatment (HT) have failed to validate the reduction in cardiovascular disease-associated events found in observational studies of early menopausal HT (MHT). The Timing Hypothesis--effects of differences between the chronologic age/length of postmenopause of study participants--continues to be questioned as an explanation for the discrepant outcomes. We reviewed evidence regarding the basis of the hypothesis and its suitability to explain differences in outcomes between MHT and HT trials. Literature review. Reports of laboratory, animal, and human clinical studies support the differential effect of HT on normal versus diseased vessels. Age and time since menopause have been related to the extent of vascular disease in women. There is ample evidence of the validity of the Timing Hypothesis as an entity and as an explanation of the different outcomes of observational studies and RCTs. The available delayed HT RCT data do not rule out the validity of the Timing Hypothesis or protection by MHT against cardiovascular events. Cardiovascular disease remains the single largest cause of death in women, and research on its prevention by MHT should be the highest national priority.