S. Dendrinos

Thyroid autoimmunity in patients with recurrent spontaneous miscarriages

Recurrent spontaneous miscarriage (RSM) is a multifactorial problem. Auto- and alloimmune parameters have been implicated. Antithyroid antibodies (ATA) were tested in a group of women with RSM. The presence of antipatemal antibodies (APCA) was evaluated as an index of alloimmune contribution. Thirty euthyroid women with RSM (three or more consecutive miscarriages) aged 25–37 years were compared with 15 matched controls. Thyroid peroxidase (TPO) and thyroglobulin antibodies were tested with a chemiluminescence immunoassay and APCA were tested with a cross-match reaction. Results were compared using the chi-squared test. There was a higher frequency of ATA in women with RSM compared to controls (37% versus 13%, p < 0.05). Twenty of the women (67%) with RSM were tested negative for APCA, indicating an alloimmune contribution to their infertility. In this subgroup of women, the frequency of ATA continued to be higher than controls (40% versus 13%, p < 0.05). In conclusion, women with RSM, independent of APCA status, have a higher frequency of ATA. This may represent an additional marker for impaired regulation of the maternal immune system.

Effects of estrogen–progestin and raloxifene therapy on nitric oxide, prostacyclin and endothelin-1 synthesis

This randomized double-blind study was conducted to investigate the effects of 17β-estradiol plus norethisterone acetate, and raloxifene, on nitric oxide (NO), prostacyclin (PGI2) and endothelin-1 (ET-1) serum levels in postmenopausal women. Treatment was initiated after a 28-50 day placebo period. Fourteen women were treated daily with 17β-estradiol 2 mg plus norethisterone acetate 1 mg (E2 + NETA), and 14 with raloxifene HCl 60 mg for a period of 6 months. Serum NO, PGI2 and ET-1 levels were estimated at baseline, after placebo, and at months 3 and 6. E2 + NETA decreased NO levels significantly, while raloxifene did not cause any appreciable change. Both regimens decreased PGI2 levels and ET-1 levels significantly. Finally, E2 + NETA and raloxifene increased the NO/ET-1 ratio by 61.4% and 81.1%, respectively. In conclusion, both regimens may exert a cardioprotective effect by decreasing ET-1 levels and increasing the NO/ET-1 ratio. In contrast, both regimens had a negative influence on PGI2 levels.

Hysteroscopy in the evaluation of habitual abortions

Objectives To evaluate the incidence of structural uterine anomalies (SUAs) in women with habitual abortion (HA) as diagnosed by means of hysteroscopy and to study hysteroscopys therapeutic potential with regard to that pathology. Methods Forty-eight women with more than three consecutive pregnancy losses which occurred prior to the 20th week were included and hysteroscopy was performed on all of them. Results Twenty-five women (52%) had a normal hysteroscopy. The remaining 23 women (48%) presented SUAs: nine patients (19%) had intrauterine adhesions, four (8%) had submucous myomas, two (4%) had polyps and eight (17%) had congenital structural uterine anomalies (five cases of septate uterus and three of bicornuate uterus). Patients with abnormal hysteroscopy underwent appropriate therapy, when applicable. In the SUA group, 18 patients (78%) achieved a successful pregnancy, and five patients (22%) had another miscarriage. In the normal hysteroscopy group, eight patients (32%) achieved a successful pregnancy without additional treatment, 15 patients (60%) had recurrent miscarriages, and two patients (8%) had persistent secondary infertility. Conclusions SUAs were detected in nearly half of the patients with HA. After appropriate treatment when applicable, 78% of patients with SUAs achieved a successful ongoing pregnancy. Hysteroscopy has much to offer in the diagnosis and treatment of SUAs.

Circulating androgens are associated with mood disturbances in young postmenopausal women.

Abstract Objectives We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. Methods Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. Results The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = −0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = −0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. Conclusion Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women

OBJECTIVE To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. STUDY DESIGN Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. RESULTS No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). CONCLUSION Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.

Prevalence of vasomotor, psychological, psychosomatic and sexual symptoms in perimenopausal and recently postmenopausal Greek women: association with demographic, life-style and hormonal factors

Aim: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri- and recently postmenopausal women. Methods: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. Results: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r = −0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b = −0.158 and b = −0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. Conclusion: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms.

TCRγδ+ T Lymphocytes in Unexplained Recurrent Spontaneous Abortions

PROBLEM: It is generally accepted that the immune system and cellular immunity in particular are involved in the mechanisms affecting the outcome of gestation. In order to evaluate a putative role of lymphocytes in the immunological mechanisms of unexplained recurrent spontaneous abortions (URSA), we studied peripheral blood lymphocyte subpopulations in 244 women with URSA and 44 controls.
 METHOD OF STUDY: Direct immunofluorescence in whole blood with the appropriate combinations of monoclonal antibodies and flow cytometry was used.
 RESULTS: The study showed: a) a statistically significant increase of the mean CD4/CD8 ratio (2.12±0.84 vs 1.85±0.63, P=0,039); b) a statistically significant decrease of the mean value of the percentage of CD5+CD19+ lymphocytes (0.4±0.6 vs 1.4±0.78, P<0.0001); and c) a statistically significant increase of the percentage of T lymphocytes expressing TCRγδ (4.68±3.19 vs 2.61±1.14, P<0.0001). It should be noted that a statistically significant high number of women with URSA (72/195, 36.9%) showed an increased percentage of TCRγδ T cells (≥5%, where 5 equals the mean value +2 standard deviations (SD) of the mean value of controls), whereas such a high percentage was not found in any control subject.
 CONCLUSIONS: It seems that women who experienced URSA comprise a heterogeneous population, as far as immunological parameters are concerned. At least in a subgroup of them, TCRγδ+ T cells could be considered to play a role in the immune pathogenesis of fetal loss.

HLA-G in murine peripheral blood after interruption of pregnancy

HLA‐G antigens are highly expressed in maternal peripheral blood during early pregnancy in transgenic mice. In this study, we determined the levels of HLA‐G in white blood cells during early pregnancy and after interruption of pregnancy in triple transgenic mice (H‐2Kb/HLA‐G, hβ2m, and hCD2/hCD8‐TRI). The pregnancies were interrupted on day 7 using the anti‐progesterone agent mifepristone (RU486). Blood samples of 20 pregnant TRI mice were taken and the HLA‐G levels were determined on days 2, 4 and 6 of pregnancy and on days 9, 11 and 13 after fertilization. The monoclonal antibody W6/32, specific for monomorphic determinant HLA class I molecules, was used in combination with an immunolocalization method using a photonic microscope. The HLA‐G levels increased gradually on days 2, 4 and 6 of pregnancy, and the interruption of pregnancy on day 7 was followed by a decrease of HLA‐G levels. The data indicate that pregnancy is characterized by the early presence of HLA‐G in maternal peripheral blood in TRI transgenic mice and suggest that HLA‐G may serve as a useful indicator for pregnancy maintenance and well‐being.