Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption.

Emerging risk factors and assessment of organ damage in postmenopausal hypertensive women.

The numerous risk factors for acute cerebrocardiovascular events present in postmenopausal women have attracted a multidisciplinary approach. In hypertensive patients and postmenopausal intensive alike, the need for stratification of risk based on blood pressure, association of other risk factors and organ damage is becoming more and more evident. This study investigated some emerging factors, such as endothelial dysfunction, adhesion molecules and elevated homocysteine levels that may be markers of organ damage. It also examined the current importance of carotid US intima-media thickness assessment, cardiac US imaging and 24 hour ambulatory blood pressure monitoring (ABPM) in detecting organ damage. The study results indicated that the conventional stratification of cerebrocardiovascular risk in these patients is changing. The new approach in postmenopausal hypertensives tends to assess the presence of other emerging factors. Furthermore, assessment of organ damage is crucial for determining disease development and outcome that may be positively influenced by suitable pharmacological treatment.

Effects of long-term hormone replacement therapy on arterial wall thickness, lipids and lipoproteins, fibrinogen and antithrombin III.

We aimed to study the effects of hormone replacement therapy (HRT) in menopausal women on lipoproteins, blood coagulation, arterial blood pressure and markers of atherosclerosis. A total of 186 postmenopausal women were studied; 98 used HRT (0.625 mg 17 beta-estradiol plus 10 mg progestin) and were followed for 48 months, and were matched with 98 women without therapy. Low-density lipoproteins, high-density lipoproteins, triglycerides, antithrombin III, systolic and diastolic arterial pressure and intima-media thickness were measured at 6, 12, 24, 38 and 48 months. In users of HRT, we found a significant reduction of the lipoproteins, triglycerides, systolic and diastolic pressures and intima-media thickness; however, we found an increase in high-density lipoproteins and anthitrombin III in comparison with non-users. This study has shown a protective effect of HRT on such risk factors and on certain markers of atherosclerosis.

Response of biochemical markers of bone turnover to estrogen treatment in post-menopausal women: evidence against an early anabolic effect on bone formation.

Bone loss following menopause can be prevented or reduced by estrogen replacement therapy (ERT). The primary action of estrogen on bone is generally considered to be antiresorptive, but some evidence would also suggest a stimulatory effect on bone formation. The aim of this study was to assess the effect of ERT on biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline), and of bone formation (bone-specific alkaline phosphatase--B-ALP, and the C-terminal propeptide of type I collagen--CICP) in a group of 25 postmenopausal women with no evidence of osteoporosis. Since the suggested anabolic effect of estrogen seems to take place in the early period of ERT, we measured the response of markers immediately before and after the start of treatment (30, 60, 120 and 180 days). The markers of bone resorption started to decrease at 30 days and remained low thereafter. We also observed a similar decrease in serum levels of B-ALP and CICP, reflecting a reduction of bone formation rate. Our data would indicate that ERT at the given dose does not have early anabolic effects on bone, in addition to its recognized suppressive effect on bone resorption.

Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness.

AIM: our study assessed whether minor or major hormonal deficiency influenced oxidative status and vascular wall structure in menopausal women. METHODS: the study series was made up of 62 non hypertensive non diabetic menopausal women (mean age 52.3+/-4.7 years) divided into two groups depending on duration of menopause (group 1 duration 0-5 years; group 2 duration over 5 years). Total cholesterol (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), malondialdehyde (MDA) and common carotid artery wall intima-media thickness (IMT) were determined in the entire series. RESULTS: mean TC, LDL-C, TG, MDA and IMT values were higher in group 2 than group 1. The intergroup difference between MDA (P<0.007) and IMT values (P<0.006) values was statistically significant. CONCLUSIONS: the study revealed a close temporal correlation between plasma oxidative stress and carotid wall IMT, jeopardizes vascular wall status as menopause proceeds.

[Impact of neoangiogenesis on the survival of patients of patients with stage Ib-IIb cervical carcinoma]. / Impatto della neoangiogenesi sulla sopravvivenza delle pazienti con carcinoma della cervice stadio Ib-IIb.

The survival of patients with cervical cancer has not improved much over the past few years. Cervical cancer is characterised by a degree of heterogeneity. Some patients undergoing surgery die a few months after diagnosis and treatment, whereas others live for longer and metastases only occur at a later stage. Over the past few years a new prognostic factor of cervical cancer has been identified. Neoangiogenesis can predict the possible metastasization of lymph nodes, disease-free survival, recidivation and therefore which patients require specific postoperative adjuvant therapies. This oncogenetic model, which also correlates the degree of neoangiogenesis with metastasization, and hence the level of tumour aggression, has been well demonstrated in lung cancer and skin melanoma. The microscopic discovery of increased tumour vascularization might be a useful independent prognostic factor in patients otherwise regarded as low risk. Cervical cancer with intense neoangiogenesis at an early phase may undergo rapid growth, early invasion and an increased capacity for metastasization. Neoangiogenesis is expressed as the density of microvessels inside the stroma of the neoplasm in invasive cervical cancer. It is predictive of recurrent disease and mortality independent of other prognostic factors. Patients with a high density of microvessels have a risk of fatal recidivation. The quantification of angiogenesis in primary tumours may be a useful prognostic factor in patients with cervical cancer. The quantification of neovascularization in neoplasms today is made easier by immunohistochemical staining procedures with greater specificity and sensitivity compared to conventional stains. It is to be hoped that this method will be used systematically by pathologists in biopsies to identify the most appropriate surgical and adjuvant therapies.

Behaviour of the carotid wall in menopausal women with and without arterial hypertension.

OBJECTIVE: A study was conducted on the carotid vascular wall to evaluate its behaviour in postmenopausal women suffering from arterial hypertension compared to normotensive postmenopausal women. METHOD: Intima-media thickness(IMT) of carotid artery was determined by ecoduplex scanner in 182 postmenopausal women (age range 40-60 years) divided in four age classes (40-45, 46-50, 51-55, 55-60 years). Ninety-one women presented normal arterial blood pressure (SBP 136.6+/-11.7 and DBP 82.3+/-8.9 mmHg) and 91 were hypertensive (SBP 172.6+/-11.7 and DBP 97.4+/-6.6 mmHg). RESULTS: The normotensive women presented the following IMT values: 1.19+/-0.21 mm (40-45 years), 1.21+/-0.25 mm (46-50 years), 1.25+/-0.20 mm (51-55 years), 1.25+/-0.20 mm (55-60 years). IMT values in hypertensive women were: 1.75+/-0.25 mm (40-45 years), 1.77+/-0.30 mm (45-50 years), 1.91+/-0.28 mm (51-55 years), 2.02+/-0.33 mm (55-60 years). ANOVA test was performed in both groups of women and did not show any significant difference in the four age classes of normotensive women. On the other hand it revealed a statistical significance between 40-45 and 46-50-year-old hypertensive classes (P<0.001) and between 51-55 and 55-60-year-old hypertensive clases (P<0.02). CONCLUSIONS: There was a correlation between age and IMT in the arterial hypertensives, especially in two older classes, and between the duration of menopause and IMT values. The results indicated that carotid wall thickening was constantly higher in hypertensive women compared with normotensive ones.

[Controversies on the staging of microinvasive cervix carcinoma]. / Controversie sulla stadiazione del carcinoma microinvasivo della cervice.

Controversies regarding the nosographical classification and staging of microinvasive cervical cancer are still the subject of debate largely based on two schools of thought: one privileges the morphovolumetric criterion, while the other, in an attempt to overcome one of the general aims of FIGO staging, pragmatically assigns a therapeutic orientation to it and proposes staging criteria that the opposing school finds arbitrary and not satisfactory for prognostic purposes. The key point that generates most of the dissension is the correctness of the biopsy procedures and the histological process used to examine material. The general rules for FIGO staging are rightly based on the limitation that clinical staging cannot be modified, even when subsequent histological or surgical findings show a different extension of the disease. But this is true of "clinical" carcinomas for which the diagnostic and staging criteria are still mainly clinical using procedures that have been classified by FIGO itself. However, in those cases where the diagnosis of staging is exclusively microscopic, as in IA, clear indications should be given regarding the procedures and failure to observe them should preclude staging.

[Tamoxifen and giant endometrial polyps]. / Tamoxifene e polipi endometriali giganti.

Tamoxifen is a synthetic non-steroid anti-estrogen that has been used effectively for several years in the adjuvant treatment of breast cancer. Although its therapeutic effect is due to its anti-estrogenic properties, the drug also shows modest type B estrogen-receptor agonist activity during the menopausal period in which estrogens are at a low level. Owing to the fall in estrogen levels in menopause, tamoxifen provokes an up-regulation of both estrogen and progesterone receptors at an endometrial tissue is a direct consequence of this. This proliferation, which is the result of an inappropriate response of the basal layer and the basis for the onset of hyperplasia and polyps in the tissue. At standard therapeutic dosages, tamoxifen in postmenopausal women is associated with the onset of alterations in the vaginal and endometrial epithelium. Cases of endometrial hyperplasia, endometrial polyps, adenomyosis, endometriosis and fibromyomas are described in the literature. Endometrial polyps represent the most common pathology associated with TAM in women with previous breast cancer in menopause. The estrogenic stimulus to polyps following TAM treatment may be considerable, resulting in their growth to sizeable proportions, causing metrorrhagia and suspected neoplastic pathology. Two cases of patients receiving adjuvant treatment with tamoxifen for previous breast cancer, who presented two giant endometrial polyps of uncommon dimension, are reported.

[Screening strategies for vulvar preneoplastic and neoplastic lesions]. / Strategie di screening delle lesioni preneoplastiche e neoplastiche della vulva.

BACKGROUND: Although they cover superficial areas, preneoplastic and neoplastic lesions of the vulva are often diagnosed late. The reasons for this delay is the low incidence of this invasive neoplasm, the advanced age of patients, the non-specific symptoms mainly taking the form of itch, burning, dyspareunia and blood loss, which are also compatible with a non-neoplastic infective pathology. The late diagnosis of carcinoma of the vulva may also be linked to the inadequate examination of the external genitals by doctors as a result of insufficient specific knowledge. Epidemiological data and the natural history of VIN lesions and carcinoma of the vulva argue that mass screening is not feasible, but an adequate programme of early diagnosis must be introduced. Early diagnosis is linked to three key elements: targeted anamnesis, clinical examination and the appropriate use of the various diagnostic procedures. Vulvoscopy represents the most reliable method, above all because it allows a biopsy to be taken of any suspected lesion. METHODS: From January 1992 to December 1998, a total of 1678 vulvoscopies were performed at the Institute of Clinical Obstetrics and Gynecology of the University of Catania in patients aged between 16 and 82 years old. Biopsies were taken of all suspected lesions. RESULTS: Sixty-nine cases of VIN (4.11%) were diagnosed: 28 VIN1, 24 VIN2 and 17 VIN3. Lesions were only symptomatic in 39.1% of cases. CONCLUSIONS: The association of vulvoscopy with biopsy of suspected lesions, even in the absence of vulvar symptoms, represents the most efficacious method for the diagnosis of intraepithelial lesions.

Angiogenesis as a prognostic factor in cervical carcinoma.

Angiogenesis and other prognostic factors have been studied among 32 recurrences and 28 deaths of 420 patients with cervical carcinoma operated in the 1st Department of Obstetrics & Gynecology of Catania University. Prognostic factors were studied in comparison with a group of patients still alive and NED was followed for more than 60 months independently of stage and node involvement. Angiogenesis, nuclear grading 3, and lymphovascular invasion were factors common to all patients with negative prognosis. It seems that in the presence of these negative prognostic factors, we should adopt a more aggressive attitude in both our surgical strategies and adjuvant therapies, particularly preferring chemotherapy where angiogenesis is more significant.

Endometrial cancer: our experience.

The Authors have referred to their experience based on 293 endometrial cancer patients operated at the II University Gynecological Clinic in Catania, between 1975 and 1989. Many prognostic indicators such as stage, histologic grade, myometrial invasion depth, lymph-node metastasis, non-neoplastic endometrium histology, tumor size and histology were studied; the Authors affirm the validity of two risk factors such as tumor size and the histology of the non-neoplastic endometrium, readily observable by hysteroscopy during the preoperative assessment and which are well correlated with the depth of myometrial invasion and lymph node methastasis.

The evaluation by means of ultrasounds of the bladder residue after gynaecological operations.

An echographic study of the bladder in 42 patients after gynaecological operation has been carried out to evaluate the urinary residue. We prove that we have a better approximation to the real urinary volumes, using the ellipsoid formula that permits the measuring of the longitudinal, front-rear and lateral-lateral diameters of the bladder; then we elaborated tables that gave us directly the quantity of urine in the bladder of the three diameters echographically measured.

Postoophorectomy bone loss is associated with reduced bone Gla protein serum levels: a possible effect of osteoblastic insufficiency.

To further investigate the relationship between oophorectomy (OF) and mineral bone loss, 15 women who underwent total hysterectomy and bilateral oophorectomy were studied for 12 months after surgery. Mineralometric and metabolic data were obtained before and after 3, 6, and 12 months. The women lost bone mineral content (measured by single photon absorptiometry) at the same rate they lost cortical and trabecular bone, suggesting that bone loss after OF is a generalized phenomenon. Our data also show that an increase in bone resorption takes place only in the first period after OF; the persistency of a negative bone balance up to 12 months, accompanied by a reduction of osteocalcin serum levels, may be dependent on a reduced bone formation, probably due to osteoblastic insufficiency.

Prostaglandins and the contractile function of the human oviductal ampulla.

Millimeter-wide muscle strips were prepared from the circular and longitudinal musculature of the oviductal ampulla of fertile women. These specimens were mounted in organ baths for isometric recording of contractile activity. The two types of strips exhibited similar rhythmic spontaneous activity which was found to be present in all phases of the menstrual cycle. Prostaglandin E2 (PGE2) caused an inhibition of contractile activity in both the circular and longitudinal layers, whereas PGF2 alpha induced a marked excitatory response in the specimens. Administration of prostacyclin (PGI2) also elicited an excitatory effect although much less pronounced that that of PGF2 alpha. Pretreatment with ETA, a blocker of endogenous prostaglandin synthesis, abolished the spontaneous contractile activity in a concentration-dependent manner. It is concluded that the ampullary portion of the human oviduct possesses pharmacological properties which differ in certain important respects from those of the isthmus. A shift in the tissue levels of endogenous prostaglandin levels may occur in sequence with ovulation and the pattern of the prostaglandins synthesized seems to be appropriate for the contractile function of the various tubal segments during ovum transport in women.