Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats.

To understand how female sex hormones influence homeostatic mechanisms of sleep, we studied the effects of estradiol (E(2)) replacement on c-Fos immunoreactivity in sleep/wake-regulatory brain areas after sleep deprivation (SD) in ovariectomized rats. Adult rats were ovariectomized and implanted subcutaneously with capsules containing 17beta-E(2) (10.5 microg; to mimic diestrous E(2) levels) or oil. After 2 wk, animals with E(2) capsules received a single subcutaneous injection of 17beta-E(2) (10 microg/kg; to achieve proestrous E(2) levels) or oil; control animals with oil capsules received an oil injection. Twenty-four hours later, animals were either left undisturbed or sleep deprived by "gentle handling" for 6 h during the early light phase, and killed. E(2) treatment increased serum E(2) levels and uterus weights dose dependently, while attenuating body weight gain. Regardless of hormonal conditions, SD increased c-Fos immunoreactivity in all four arousal-promoting areas and four limbic and neuroendocrine nuclei studied, whereas it decreased c-Fos labeling in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Low and high E(2) treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and locus coeruleus. The high E(2) treatment decreased c-Fos labeling in the VLPO under nondeprived conditions. These results indicate that E(2) replacement modulates SD-induced or spontaneous c-Fos expression in sleep/wake-regulatory and limbic forebrain nuclei. These modulatory effects of E(2) replacement on neuronal activity may be, in part, responsible for E(2)'s influence on sleep/wake behavior.

Norplant implants in the UK: first year continuation and removals.

Norplant implants are a long-term, reversible hormonal method of contraception consisting of six flexible capsules placed subdermally in the inner aspect of the non-dominant arm. Norplant implants were introduced into the UK in October 1993 although they had been used previously in some countries for up to ten years. The insertion and removal techniques require skills training and therefore it is important to assess early experience with the method. This survey looks at the first year continuation rate of Norplant implants in the UK from a total of 2,129 insertions. From these insertions, 133 removals were documented and described, using a checklist of features. The continuation rate for Norplant implants use was 96.5% at six months and 85.2% at one year. None of the reasons for discontinuation were of a serious nature. The most common reason given was menstrual change (50.4% of all removals, 3% of all women included in the survey), which is in line with other reported studies. Of the removals, 71.5% were reported as straightforward (of these 65.6% were completed within 20 minutes). In the first year of use, Norplant implants were associated with high continuation rates and the removal procedure was, in the majority of cases, completely straightforward.

PIP: In early 1995 in the UK, 1577 family planning providers working in the community, who had undergone clinical training of Norplant implants as part of the Hoechst Roussel Ltd. clinical training program, completed a questionnaire designed to determine how many insertions and removals had been performed by each provider and how many had been performed by a Norplant implants trainer on the provider's patients as part of the formal training program. 195 providers completed an additional questionnaire that provided dates of all the insertions and removals done on their patients before and including February 14, 1995, and all details on each specific case. The 6-month cumulative continuation rate stood at 96.5%. The 1-year cumulative continuation rate stood at 85.2%. Menstrual change accounted for the removal in 50.4% of removal cases. 68.5% of removals did not occur under the supervision of the clinical training program. In 52.7% of these unsupervised removals, the removal was the first performed by the provider. The standard technique using straight and curved forceps was the technique used for 70.3% of removals. 71.5% of removals were classified as straightforward, 65.6% of which were done in less than 20 minutes. Supervised removals were significantly less likely to be straightforward than unsupervised removals (relative risk = 0.72). The leading features of removals were the measurement of more than one visit to complete the removal (13.5%) and that the procedure lasted more than 45 minutes (9.8%). There were no reports of contraceptive method failure. These findings suggest that Norplant has a good continuation rate and a high rate of straightforward removals.