Endometrial thickness and histological abnormalities in women on hormonal replacement therapy: a transvaginal ultrasound/hysteroscopic study.

OBJECTIVES: The aim of this study was to assess if endometrial thickness could be used to select postmenopausal women on hormonal replacement therapy (HRT) at increased risk for endometrial abnormalities. The secondary aim was to assess if endometrial abnormalities were more likely to occur in patients with increased endometrial thickness or in patients with unexpected bleeding. METHODS: Bi-endometrial thickness was measured by transvaginal ultrasound (TVS) in postmenopausal patients on sequential or combined HRT regimens. Women following a sequential regimen underwent TVS examination immediately after their withdrawal bleed, always between 5 and 10 days after the last progesterone tablet. A hysteroscopy with endometrial biopsy was performed within 5 days after the TVS examination, when endometrial thickness was > or = 4 mm, or when unscheduled bleeding was observed. RESULTS: A total of 190 women were recruited. In 138 women on sequential regimens, the mean value of endometrial thickness was 3.6 mm +/- 1.5, and in 52 women on combined regimens it was 3.2 mm +/- 1.8 (P = n.s.) Twenty-eight patients (15%) had an endometrial thickness > 4 mm, 35 patients (18.4%) reported unexpected bleeding. The percentage of abnormal endometrial findings (9%; three of 35) in patients selected for unscheduled bleeding was significantly lower than the percentage of abnormal findings in patients selected for hysteroscopy for endometrial thickness > 4 mm (36%; 10 of 28) (P < 0.01). All patients with unexpected bleeding and endometrial thickness < or = 4 mm (24 cases) were found to have an atrophic endometrium. CONCLUSIONS: Endometrial thickness in patients on sequential HRT, measured soon after withdrawal bleeding, is not significantly different from thickness measured in patients on combined HRT. Patients on HRT with an endometrial thickness of > 4 mm could be considered for histological sampling. The prevalence of abnormal endometrial findings in patients with a thick endometrium is significantly higher than the prevalence observed in patients with unexpected bleeding.

Pelvic ultrasonography in normal girls and in girls with pubertal precocity.

UNLABELLED: This prospective study sought to evaluate the role of pelvic ultrasonography in differentiating between various types of pubertal precocity. A control group of 117 normal girls (aged 1.1-15.6) was studied and compared with 87 girls with premature sexual maturation (aged 1.1-9.2 y). Of these patients 19 had central precocious puberty (CPP), 48 had isolated premature thelarche (IPT) and 20 had premature adrenarche (IPA). Pelvic ultrasound variables evaluated were: (i) uterus: longitudinal diameter (uterine length), cross-sectional area (CSA) and fundo-cervical ratio; and (ii) ovaries: volume and morphology. Ovarian morphology was subdivided in 6 different appearances: solid, microcystic, paucicystic, multicystic, macrocystic, and major isolated cyst. In normal control girls, uterine length and CSA increased with age, although no cut-off values could be defined between different age ranges, and they were correlated with breast stage; fundo-cervical ratio was stable through childhood and increased after age 9. Ovarian volume was significantly greater in pubertal girls with breast stage 2 than in those with only pubic and/or axillary hair. There was a clear predominance of solid ovarian appearances in the age range 2-7, with the multicystic appearance being seen only after age 7, a minority being macrocystic. After age 10 all the different patterns were observed, and after age 13 the frequency of a macrocystic pattern increased. Significantly more mature ovarian appearances were observed in subjects with breast development compared with those without, independently of the presence of pubic hair. Patients with IPT had no significant differences in pelvic ultrasound measurements when compared with age-matched controls. All the different morphological ovarian appearances were observed in IPT, in contrast to age-matched controls, where only the less mature patterns (solid, micro- and paucicystic) were seen. Patients with CPP had significantly more mature patterns of ovarian morphology compared with age-matched controls, but did not differ from pubertal pre-menarcheal controls. Those patients with IPA differed from age-matched controls only in having significantly greater uterine length and CSA. Comparison of the pelvic ultrasound parameters between patient groups (IPT, CPP, IPA) and age-matched controls revealed significantly higher values in CPP for uterine length, uterine CSA and ovarian volume. Ovarian volume was also greater in IPT than in IPA. Ovarian morphology was significantly different in patients (IPT, CPP, IPA) compared with age-matched controls, but none of the ovarian morphological appearances was exclusive to a single condition. IN CONCLUSION: (i) pelvic ultrasound parameters increase progressively from birth to maturity, but no clear cut-off values can be established between age ranges; (ii) pelvic ultrasound variables reach adult values during puberty, with differences in the timing that may reflect geographical variations; (iii) the multicystic ovarian appearance occurs just before the onset of puberty; (iv) pelvic ultrasonography cannot always differentiate clearly between different disturbances of puberty and therefore cannot supersede other observations and investigations in the evaluation of pubertal disorders; and (v) in this study we propose a more detailed pelvic ultrasound terminology that can avoid apparent confusion in defining ovarian ultrasound appearance.

Transvaginal ultrasonographic characterization of ovarian masses: comparison of five scoring systems in a multicenter study.

The aim of this work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospective multicenter study. Four of the systems had previously been reported by Granberg, Sassone, De Priest and Lerner and the fifth is newly developed. A total of 330 ovarian neoplasms were collected in three different centers, which adopted the same diagnostic procedures. Of these, 261 masses were benign (mean diameter 50 +/- 26 mm) and 69 were malignant (mean diameter 69 +/- 33 mm) (prevalence 21%). The area under the receiver operating characteristic (ROC) curve for the multicenter score was 0.84. This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75. The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74% (Sassone score) to 88% (De Priest score > or = 5), and a specificity from 40% (De Priest) to 67% (multicenter); the highest positive predictive value was 41% (multicenter). With a cut-off level of 9, the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest (McNemar's test p < 0.0001). Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter, and when 19 borderline and 11 stage 1 cancers only were considered. For the clinical purposes of a screening test we also checked a possible cut-off level of > or = 8, which increased the sensitivity to 93% with a drop of specificity to 56%. With the use of the same criteria for the scores of the different authors, the following values were obtained for sensitivity: 96%, 81%, 93% and 90%; and for specificity: 23%, 56%, 28% and 49%. The multicenter score performed well at distinguishing malignant from benign lesions, and was better than the other four traditional scores, for both large and small masses. This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea. A completely reliable differentiation of benign from malignant masses cannot be obtained by sonographic imaging alone.

Sonographic endometrial thickness: a useful test to predict atrophy in patients with postmenopausal bleeding. An Italian multicenter study.

Eighteen centers took part in this prospective study into which 930 eligible patients were recruited. The selection criteria for admission were atypical bleeding after at least 6 months of postmenopausal amenorrhea, and absence of hormonal therapies for at least 6 months. The sonographic measurement of the maximum bi-endometrial thickness was made in a longitudinal plane. Sonographic measurements were always performed within 3 days prior to histological evaluation. In these patients the mean number of years from menopause (25-75th centile) was 6 (range 2-16). The prevalence of endometrial carcinoma was 11.5% and the prevalence of atrophy was 49.2%. The area under the receiver operator characteristic curves generated by sonographic thickness measurements reached the level of 85%, both for cancer and atrophy. The likelihood ratio for cancer, yielded by an endometrial thickness of < or = 4.0 mm, was 0.05, and for atrophy it was 7.1. This cut-off of > 4.0 mm yielded a sensitivity for the detection of cancer of 98% and a negative predictive value of 99%. The overall sensitivity and positive predictive value for atrophy achieved by this cut-off were 57.2% and 87.3%, respectively. A multivariate logistic model showed that age and body mass index were independent variables associated with a significantly higher risk of endometrial cancer. The post-test probabilities for cancer and atrophy were recalculated on the basis of the integration of age, body mass index and endometrial thickness. The estimated reduction of invasive procedures on the basis of this integration was 31%. Transvaginal sonographic measurement of endometrial thickness, integrated with individual risk factors, can help in the management of postmenopausal patients with atypical bleeding, with regard to either the need for histological evaluation in high risk cases, or the choice of possible expectant management. We have shown that an endometrial thickness of < or = 4.0 mm safely predicts endometrial atrophy and justifies expectant management when the patient understands the need for proper follow up. This could be achieved with a reduction in the use of invasive procedures without unwanted delay in cancer diagnosis.

The role of sonographically guided aspiration in the clinical management of ovarian cysts.

This study was undertaken to verify the role of fine-needle aspiration (FNA) followed by cytologic examination as a possible alternative to surgery in case of cystic pelvic masses. From January 1988 to March 1989, 204 patients with a proven cystic pelvic mass underwent FNA under sonographic guidance. In 20 cases the aspiration was performed transvaginally. Thirty-six patients were postmenopausal. In all cases the aspirated fluid was collected for cytologic evaluation. Other than one case of persistent hematuria, no complications occurred. The overall recurrence rate, verified 3 months from FNA, was 65%. Fifty-two per cent of patients developed a new cyst after a complete aspiration. Fifty-three patients underwent a laparotomy, allowing a comparison between cytologic and histologic patterns. The sensitivity of cytologic examination of aspirated fluids was 40% (3 of 5 malignancies were missed) and the specificity was 100% (no false positives were observed). We conclude that FNA might be proposed in young women with a unilocular ovarian cyst to avoid a surgical procedure. In postmenopausal women with a unilocular cystic mass 5 cm or less, FNA may be considered as an important step in the diagnosis. In all instances the ultrasonographic appearance of the cyst (echo texture and regularity of wall) and the characteristics of aspirated fluid are the most important findings. When the aspirated fluid contains mucus or blood, or when a complex mass is present, exploratory laparotomy or a laparoscopy is recommended.

A new association of ethinylestradiol (0.035 mg) cyproterone acetate (2 mg) in the therapy of polycystic ovary syndrome.

The authors treated 28 patients with polycystic ovary syndrome (PCOS) with the new preparation SH B 209 AE consisting of 0.035 mg of ethinylestradiol and 2 mg of cyproterone acetate (EE + CPA) throughout 12 months. From the analysis of the endocrine and clinical modifications induced by the drug along with the negligible incidence of side effects the conclusion can be drawn that this new estro-progestational association is indicated in the therapy of PCOS.

PIP: 28 patients with polycystic ovary syndrome were treated for 12 months with the new preparation SH B 209 AE, consisting of 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate. This was the first clinical trial of estroprogestational therapy on a homogeneous sample of women with polycystic ovary syndrome. Endocrine findings indicated a significant decrease in all hormonal parameters, the invariableness of prolactinemia, a considerable increase in sex hormone binding globulin (SHBG) at the 6th treatment cycle examination, a continuous significant decrease in 17 beta E2 and androstenedione from the 6th to the 12th treatment cycles. In terms of clinical findings, there was a significant decline in the severity of acne, seborrhea, and hirsutism during drug administration. The menstrual cycle in the 28 study subjects remained under control during treatment, and there were no pregnancies. Side effects such as weight gain, nausea, headache, and changes in libido were not reported. Overall, the findings of this study suggest that administration of the new monophasic contraceptive association SH B 209 AE can normalize endocrine patterns in polycystic ovary syndrome and improve its androgenic symptomatology. The low content of estrogen, the changes in clinical and hormonal parameters, the low incidence of side effects, and the good control of the menstrual cycle provided by this treatment make SH B 209 AE deserving of more widespread application.

A new method for free testosterone assay: clinical evaluation.

The Authors propose a new direct method for the determination of free Testosterone (F.Te). Our study was made following this method: 1) on a control group composed of 12 healthy men and 21 healthy women, and 2) on a group of 29 patients suffering from Polycystic Ovary Syndrome (PCOS) with clinical signs of hyperandrogenism. This pathological group presented acne and hirsutism in 95% of the cases. The Authors demonstrate how the determination of F.Te permits a 93.1% correct endocrinological diagnosis of hyperandrogenism.

Treatment of hypothalamic infertility with pulsatile GN-RH administration.

In this study the Authors have obtained an ovulatory response using intravenous Gn-RH treatment in four patients with hypothalamic hypogonadotropic amenorrhea. The Gn-RH was administered in a pulsatile manner with a small portable autoinfusion pump (Autosyringe, Inc., Hooksett). The ovarian follicular maturation, as it appears from the pelvic echography, was perfectly similar to that observed in a spontaneous ovulatory cycle. Endocrine picture by serial determination of gonadotropin; prolactin, estradiol and progesterone concentrations showed hormone values to be in the normal range. During the therapy no complications were observed; at the present time no pregnancy has occurred.

Profiles and endocrine correlations in endometrial carcinoma.

The Authors compared the mean LH, FSH, PRL, E1, E2, Testosterone, Androstenedione plasmatic levels in a group of post-menopausal women affected by endometrial carcinoma (EK), with those of a control group presenting clinical characteristics as close as possible to those of the pathologic group. The case series was significant. They found no significant difference between the two groups' hormonal levels. On the other hand, E1 levels were found to increase along-side with obesity. In patients affected by EK, E1 plasma levels significantly increased alongside with the post-menopausal age. Conversely, in the control group, this hormonal value significantly and progressively decreased from the menopause onwards. Furthermore, the Authors studied the effects of surgical intervention on the hormonal picture in EK bearers.