Acquired activated protein C resistance in postmenopausal women is dependent on factor VIII:c levels.

Activated protein C (APC) resistance is an established risk factor for venous thromboembolism. In 5% to 10% of patients with venous thromboembolism, the APC resistance phenotype is observed in the absence of factor V Leiden mutation. Moreover, some physiologic and pathologic conditions are associated with an "acquired" APC resistance, not caused by the Leiden mutation, such as inflammatory diseases, pregnancy, or oral contraceptive therapy. Several studies have demonstrated the effect of menopause on the hemostatic system, but no data are available about APC resistance. We found a high prevalence of APC resistance in postmenopausal women, not associated with factor V Leiden mutation. The mechanism that underlies this acquired APC resistance may be related to the higher levels of factor VIII, which showed a strong inverse correlation with APC resistance, whereas no correlation was found between the normalized APC ratio, factor V levels, and protein S values. Higher levels of factor VIII correlated with a marker of coagulation activation, such as prothrombin fragments 1 plus 2. Therefore, to identify women receiving hormone replacement therapy who have a greater risk for deep venous thrombosis, the APC resistance coagulation test should be used instead of the genetic study.

Morphological and functional aspects of the endometrium of asymptomatic post-menopausal women: does the endometrium really age?

The morphological and functional aspects of the endometrium were investigated in 28 asymptomatic post-menopausal women to evaluate the ageing phenomenon of this tissue. Haematoxylin-eosin staining showed an atrophic endometrium in 12 cases and a hyperplastic endometrium in the other 16 cases. Masson's trichrome identified moderate fibrosis in all post-menopausal endometrial stroma. Immunohistochemical analyses were performed on the endometrial specimens to evaluate the distribution of the capillary system, the cellular proliferation index and the presence of oestrogen and progesterone receptors. Our data showed a discrepancy between the morphological pictures and the functional aspects of the post-menopausal endometrium. In fact, the morphological pictures suggested an involution of this tissue according to the increase in collagen fibres, the decrease in vascular distribution and the frequent atrophic patterns. On the other hand, data from steroid receptors and the cell proliferation index suggest that post-menopausal endometrium is an active structure. So, endometria from normal post-menopausal women appear to be in a more quiescent state than in a really atrophic condition. This leads to the question: does the endometrium really age?

Usefulness of early morning urine estrone-3-glucuronide assay in the monitoring ovarian secretory function in precocious puberty.

To evaluate the usefulness of the urinary estrone-3-glucuronide (EI-3-G) in the monitoring of the ovarian function in girls, we studied 11 girls with idiopathic central precocious puberty (ICPP) treated with LHRH analogs (LHRHa) for 2-5 years. Plasma LH, FSH, 17-beta-Estradiol (E2) levels, early morning urine (EMU) E1-3-G concentrations, were assessed before and 3, 6, 12 months after the onset of treatment. As expected, mean basal plasma LH, FSH and E2 concentrations, as well as mean basal EMU E1-3-G levels were significantly (p < 0.01) higher in patients studied than in normal, age matched, prepubertal controls. Three out of the 11 sexually advanced girls showed undetectable (< 15 pg/ml) basal plasma E2 values. On the contrary, in each patient studied, individual basal E1-3-G levels were higher than in normal age-matched prepubertal girls. LHRHa treatment significantly suppressed both basal and peak stimulated plasma gonadotropins, plasma E2 and EMU E1-3-G. However, while serum E2 levels were below the assay detection limit, not allowing to assess the degree of gonadal suppression, E1-3-G urinary concentrations were detectable in each subject treated, in the range of the normal prepubertal values. EMU E1-3-G determination seems to be a very sensitive and reliable approach to the monitoring of the effectiveness of LHRHa treatment in sexually advanced girls, allowing to detect very low estrogen concentrations and to achieve the desired ovarian suppression.

Precocious puberty: auxological criteria discriminating different forms.

It may be possible to recognize different forms of precocious puberty at the first evaluation. In a group of 26 sexually precocious girls we used Bayley-Pinneau predicted adult height (P.A.H.) to discriminate patients with 'poor' or 'good' height prognosis. Patients with evidence of impaired height prognosis (P.A.H. < -1 SDS) (Group 1) were immediately treated with LH-RH analogs, while patients with unimpaired height prognosis (P.A.H. > -1 SDS) (Group 2) were followed without therapy. Two yr of treatment significantly improved P.A.H. in Group 1 patients, from a mean of -1.68 +/- 0.4 to a mean of -0.57 +/- 0.6 (SDS) (p < 0.01). After the 2 yr observation period, Group 2 patients showed no significant variation of P.A.H. (from a mean of 0.45 +/- 0.8 to a mean of 0.33 +/- 0.6). The retrospective analysis of the growth pattern changes in the two Groups seems to indicate that LH-RH agonist treatment improves height potential in girls with initial poor height prognosis and that girls with initial good height prognosis maintain an unimpaired growth potential.

Desogestrel in monophasic E/P combination: monitoring of endocrine parameters and evaluation of hemostatic function.

The Authors evaluated modifications in androgenic pattern as well as in parameters of androgenic function and coagulation in a group of women treated with a combination contraceptive containing Ethinyl estradiol and desogestrel.

Platelet and coagulation functions during triphasic oestrogen-progestogen treatment.

The purpose of this investigation was the longitudinal evaluation of the hemostatic system before and after 1, 3, and 6 months of treatment with a triphasic oestrogen-progestogen combination. No changes of circulating platelet aggregates, as an index of in vivo platelet aggregability, and of megathrombocytes, an indirect evaluation of accelerated thrombocytopoiesis, were observed. A very slight, but significant, increase of Fibrinopeptide A (FPA), a reliable index of thrombin formation, was found only after 1 month of treatment; after 3 and 6 months, the increase of FPA was not homogeneous and not significant. Antithrombin III activity (AT III) showed no modifications after the first month; after 3 months AT III increased to a small extent, and after 6 months it was similar to basal values. Our findings indicate that the triphasic combination does not modify platelet functions and induces a low-degree activation of coagulation counteracted by an increased activity of the physiological inhibitors of blood clotting.