Screening for activated protein C resistance before oral contraceptive treatment: a pilot study.

The feasibility and cost-effectiveness of screening women for congenital thrombophilic alterations before oral contraceptive (OC) treatment was investigated. A total of 525 women (mean age 21.9 years, 73% aged < 25 years) were examined before their first OC course. At first screening, completely normal results were recorded in 485 (92.4%) women, the remaining showing single (n = 34) or multiple (n = 6) alterations. At second examination (possible in 37 of 40), activated protein C resistance (APCR) was confirmed in 21 cases (4.0%, 18 with factor V Leiden), protein C, or protein S reduction in 8 (1.5%) and 2 (0.4%) cases, respectively. No cases with antithrombin III deficiency were detected. The global estimated cost ($US) to detect one altered case was: $7795 for protein S, $2696 for antithrombin III (no case found), $1374 for protein C and $433 for APCR. The present study confirms that extensive thrombophilic screening before OC treatment is not currently advisable. APCR assessment, however, seems to have a favorable cost-effectiveness ratio: the alteration is frequent and has a synergistic effect with OC; sensibility and specificity of some methods are good; family history is unreliable to single out possible carriers; finally, carriers can be fully informed of their increased thrombotic risk if treated with OC and can receive thromboprophylaxis during life situations associated with high thrombotic risk (e.g., pregnancy and puerperium).

PIP: This article investigates the feasibility and cost effectiveness of screening women for congenital thrombophilic changes before oral contraceptive (OC) treatment. The study population included 525 women who were examined before their first OC course between September 1995 and May 1997 in Bologna, Italy. A completely normal result was seen in 92.4% women during the first screening, which was conducted before the first OC course. The second examination showed that activated protein C resistance (APCR) was confirmed in 21 cases (4.0%, 18 with factor V Leiden), and protein C and protein S reduction in 8 (1.5%) and 2 (0.4%) cases, respectively. Antithrombin III deficiency cases were not detected. The detection of one altered case is estimated to cost $7795 for protein S, $2696 for antithrombin III, $1374 for protein C, and $433 for APCR. The study confirmed that extensive thrombophilic screening before OC treatment was not advisable. However, APCR assessment was found to be cost-effective. The alteration was frequent and APCR had a synergistic effect with OC, and the sensibility and specificity of some methods for detection of APCR are good. Family history is not reliable for identifying possible carriers for the thrombophilic trait. Carriers can be fully informed of their high risk if treated with OC and can receive thromboprophylaxis in conditions where thrombotic risk is high.

[Hypothalamic phospholipid liposomes in the treatment of the climacteric syndrome]. / I liposomi di fosfolipidi ipotalamici nel trattamento della sindrome climaterica.

Phospholipid liposomes have a dopaminergic effect on the human brain. Changes in prolactin and growth hormone secretion have been observed in humans given phospholipid liposomes. The authors have investigated the therapeutic efficacy of hypothalamic phospholipids in the menopausal syndrome. The study was an open trial on 37 outpatients treated with 1 and 2 ampoules i.m. of a preparation of phospholipids (in the form of unilamellar liposomes) for a period of six months. The therapeutic effects were assessed by means of the Hamilton rating scale, MMPI (Minnesota multiphasic inventory test), and a list of psychosomatic symptoms (LSP). In the patients no change in FSH, LH, PRL, or E2 secretion was observed, whereas the neurotic symptomatology appeared remarkably reduced.

Danazol reverses endometrial hyperplasia to normal endometrium.

Danazol, an isoxazol derivate of ethinyltestosterone, was used in the treatment of thirtyone postmenopausal patients with endometrial hyperplasia at the dose of 400 mg/day for three months. A profound growth-inhibitory effect of danazol on human endometrium was previously suggested. The present study shows that this compound is effective to reverse the endometrial hyperplasia to normal endometrium in 97% of cases. Atrophic changes of endometrial hyperplasia to normal endometrium after danazol-treatment were observed in 68% of patients. These results strongly suggest that danazol has a significant antiproliferative effect on the endometrium.

Dopaminergic control of sympathetic activity and blood pressure in haemodialysis patients.

Bromocriptine was used to test the hypothesis that the abnormality of the dopaminergic system described in haemodialysis patients may cause enhanced sympathetic activity and high blood pressure. Bromocriptine significantly reduced supine mean blood pressure and plasma noradrenaline. Moreover, although the increments in plasma noradrenaline during tilt tests were reduced by bromocriptine there was a significant improvement in the response of blood pressure. These results suggest that dopaminergic control of sympathetic activity may be impaired in haemodialysis patients and may be a cause of high blood pressure. Moreover, a restoration of a normal relationship between noradrenaline and adrenergic receptors would be consistent with the present results.

Estrone sulphate and estrone splanchnic extraction in postmenopausal women.

The splanchnic extraction of estrone sulphate (E1 S) and estrone (E1) was calculated in post-menopausal women undergoing cardiac catheterization for diagnostic purposes. The results showed a net uptake for E1 by the splanchnic area, liver included, whereas the splanchnic extraction of E1 S was not similar for each subject. Anyway the results clearly showed that the splanchnic area does not release significant amount of E1 S into the blood in the post-menopausal women.

Estrogen provocation test: lack of correlation between LH and 17-beta-estradiol basal levels and LH peak response in hypothalamic chronic anovulation.

Estrogen provocation test was performed in 27 women with hypothalamic chronic anovulation: all patients received I mg of estradiol benzoate (EB) as a single im injection. Plasma 17-beta-estradiol (E2) levels were monitored during the test performed and then compared; no significant correlation was found between mean basal values of LH and E2 and the LH peak response (r = 0.246, P = 0.108 for LH; r = 0.124, P = 0.278 for E2). These data seem to indicate that basal LH values reflect the tonic secretion but not the hypothalamic responsiveness to the estrogen positive feedback; moreover, this latter seems not be influenced by the endogenous E2 levels.

Induction of ovulation with cyclophenyl.

The results of 495 cycles of treatment with Cyclophenyl given to 286 women suffering from amenorrhea, oligomenorrhea or persistent anovulation are reported. In 61 cases the drug solved the problems of infertility, with a success rate of 43%. The over-all success rate was 58% (288 ovulatory cycles produced in 495 treatment cycles). In detail:--in cases of prolonged amenorrhea, with plasma estradiol levels lower than 50 pg/ml, the positive results were only 15%;--in cases of short-term amenorrhea, with plasma estradiol levels lower than 50 pg/ml, the success rate was only 18%;--in cases with prolonged amenorrhea but with plasma estradiol levels higher than 50 pg/ml, the success rate was 43%;--in cases of short-term amenorrhea with plasma estradiol levels higher than 50 pg/ml, the success rate was 68%;--in cases of oligomenorrhea and of persistent anovulation, the success rate was 72%.