Intraepithelial G3 adenocarcinoma of the endometrium after tamoxifen treatment.

CASE REPORT: In this paper we describe a case of endometrial carcinoma observed in a post-menopausal patient who was treated with tamoxifen for 5 years after a mastectomy for cancer. She came to our department because of vaginal bleeding 2 years after the end of tamoxifen treatment. TREATMENT: She underwent hysteroscopy and a D and C. A polypoid endometrium completely filled the uterine cavity and was carefully removed by curettage; histology showed a highly undifferentiated neoplasia with a component of serous adenocarcinoma, which was likely to originate from endometrial polyps. OUTCOME: The patient underwent radical hysterectomy, but no residual tumor was found in the uterus or in the tubes, ovary, or pelvic nodes, in spite of its low differentiation grade and high potential aggressiveness, and even though the patient was already symptomatic. Two years after surgery the patient is disease free, which is consistent with the evaluation of the surgical specimen, but unusual in poorly differentiated neoplasms.

Menopause rather than estrogen modifies plasma homocysteine levels.

OBJECTIVES: To investigate the effects of transdermal estrogen replacement therapy (ERT) on plasma homocysteine levels in postmenopausal women who underwent total hysterectomy with bilateral oophorectomy. METHODS: In two-phase open longitudinal prospective study we compared 28 premenopausal women and 35 healthy postmenopausal patients to evaluate the effect of transdermal estrogen treatment (TTS 50 twice-weekly) on plasma homocysteine levels after 6 and 12 months of therapy. RESULTS: The study showed statistically relevant differences (P<0.05) in baseline plasma homocysteine concentration between the patients in premenopausal and in postmenopausal status. No difference in the plasma homocysteine levels was observed after 6 and 12 months of ERT on postmenopausal patients. CONCLUSIONS: Surgically postmenopausal women have higher plasma homocysteine concentrations than premenopausal women, but transdermal estrogen treatment for 12 months in postmenopausal women does not modify homocysteine levels.

Endometrial histologic changes in post-menopausal breast cancer patients using tamoxifen.

OBJECTIVE: The aim of this study was to evaluate the effect of tamoxifen on the endometrium of post-menopausal women with breast cancer and to examine the relationship between ultrasonography, hysteroscopy and histopathologic changes. METHOD: Included in this longitudinal study were 303 post-menopausal women taking 20 mg daily of tamoxifen. Hysteroscopy was performed in 83 patients with an endometrial thickness of only >or=5 mm and 34 with vaginal bleeding also. Forty-five asymptomatic patients (control group) underwent hysteroscopies. RESULT: The most frequent outcome in patients with endometrial thickness of only >or=5 mm was an atrophic endometrium in an empty cavity (79.5%) whereas simple hyperplasia (35.3%) was found in women with vaginal bleeding. Carcinoma was diagnosed in seven cases (5.9%). In the control group, no endometrial cancer was found. CONCLUSION: This study suggests that patients with a thickness >5 mm should be offered a whole hysteroscopic evaluation, whenever bleeding is reported.

[The rationalization of the follow-up of hormonal replacement treatment in menopause]. / Razionalizzazione del follow-up del trattamento ormonale sostitutivo in menopausa.

BACKGROUND: Decision making about the opportunity of starting or continuing hormone replacement therapy (HRT) in menopause should rely on an overall evaluation of its risks and benefits for the women's health; the evaluation of HRT cost-benefit ratio, however, should include its possible outcomes from an economical point of view. In this view, and with the certainty that menopausal patients should be protected by proper treatments, our case series has been evaluated in order to improve the quality of our clinical schedules for both their access to HRT and the treatment follow-up. METHODS: Two groups of patients have been considered the first one consisted of 560 women observed during '97 for climacteric symptoms and candicated to begin HRT. The second one consisted of 100 women on HRT for 1 to 6 years. In the first group we considered which test and with which frequency were responsible for stopping or delay the beginning of therapy; while in the second group we evaluated the reasons for stopping treatment. RESULTS AND CONCLUSIONS: On the basis of our experience, the exams required before starting HRT seem to be the following: patient history, mammography, densitometry and endometrial sample as well as the parameters of glucose lipidic, coagulative and hepatic metabolism. Densitometry is useful in the annual follow-up only in patients with bone alterations from the beginning. The same exams seem required for the follow-up, with the exception of bone densitometry which should be performed yearly only in patients with bone demineralization.

Transdermal estroprogestins versus transdermal estrogen plus oral dihydrogesterone replacement in menopause.

We studied 18 early (6 to 36 months) postmenopausal patients with a mean age of 51 years (47-53), who had never undergone hormone replacement therapy before and had no contraindications to hormone replacement. All cases of menopause were spontaneous. The treatment consisted in the continuous transdermal administration of 17-beta-estradiol (50 microg/daily) by skin patch to be replaced every 84 hours. The patients were further treated with a two-week progestogen administration every fortnight. This consisted of transdermal norethisterone acetate (0.25 mg/daily) combined with estradiol in the same patch in the first year, and oral dihydrogesterone (10 mg/daily) in the second year, without wash-out period. Before treatment (T0), and at the 12th (T1) and 24th (T2) month we measured the body mass index, the arterial blood pressure (AP), lipoproteins, coagulation parameters and bone metabolism parameters. The systolic pressure presented mean values (+/-SD) equal to 128.5+/-10.2 mmHg (T0), 131.1+/-7.4 mmHg (T1) and 130.4+/-7.5 mmHg (T2). Diastolic pressure values showed mean value ranging from 85.4+/-8.7 mmHg (T0) to 83.9+/-5.3 (T1) and 83.4+/-5.8 mmHg (T2). The detailed analysis of values of triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B and coagulation parameters at different times of therapy showed no statistically significant changes. With regard to bone metabolism, no statistically significant changes from baseline values were observed in parathormone, alkaline phosphatase, calcitonin, urinary calcium/creatinine ratio, and bone mineral content expressed by the bone density.

Transdermal estrogen therapy in menopause. Eighteen months follow-up.

In this study we evaluated different metabolic parameters and bone mass, before and after 18 months of treatment by transdermal estradiol associated with oral sequential MPA in menopause. We treated 46 physiologically postmenopausal patients (44-55 years old) for at least six months, by TTS/E2 50 mcg for 3 weeks and MPA 10 mg for the last 12 days of estradiol treatment. The fourth week was free of therapy. Before treatment and after 18 months, we evaluated bone density (BMC/BW), body mass index (W/sqH), systolic and diastolic blood tension, lipid parameters, coagulation parameters, mineral metabolism with statistical elaboration of our results. After therapy we found a significant decrease in diastolic blood tension, a significant reduction in triglyceride levels and a slight but significant increase in HDL-cholesterol levels. The only variation in coagulation parameters was a decrease of circulating fibrinogen. No variation occurred in the body mass index, mineral metabolism or bone density. In conclusion even long term transdermal treatment seems metabolically well tolerated and very useful in relieving neurovegetative climacteric symptoms and dystrophic genital ones.

Hormonal contraception in perimenopause.

PIP: To examine the effects of the new oral contraceptive containing ethinyl estradiol 30 mcg and desogestrel 150 mcg in perimenopausal women, 18 women over 40 took this pill and were tested before and after 12 months for blood lipid factors, blood pressure, weight and sex hormone binding globulin. There were no complaints of side effects serious enough to warrant discontinuation. No significant differences were found in total cholesterol, HDL-cholesterol, apoprotein Au or B, triglycerides or phospholipids. A significant increase in sex hormone binding globulin, from 32.5 to 61.6, was found. This small study therefore suggests that the newer oral contraceptives can safely be used in perimenopausal women when they need absolute contraception.^ieng

Hormonal receptors in vulvar tissues.

Since 1982 we have been associating the study of hormonal receptors with the histological examination of the vulvar lesions in an attempt to interpret the action mechanism of steroids on the vulva, to find possible correlations between histological pictures and receptorial order and to find a possible predictive "marker" toward therapeutic and prognostic ends. In our Laboratory assays for androgen, estrogen and progesterone receptors were performed with the Dextran-Charcoal technique in 41 patients with vulvar dystrophy; 20 of whom had atrophic dystrophy and 21 with hypertrophic dystrophy. Another 24 patients with vulvar carcinoma were studied; 23 with epidermoid carcinoma of various differentiation grades and only one case of Paget's Disease. None of the three receptors assayed could be considered a predictive or prognostic marker in the approach to neoplastic forms. The levels of the progesterone receptor appears increased in the case of dystrophies. This justifies the hypothesis of a hormonal involvement in the pathogenesis of the lesion, as has already been documented by the beneficial effects of therapy with topical steroids.

Progestinic treatment of mastodynia. New suggestion for the follow-up.

The problem of progestin treatment for benign breast disease and mastodynia is still dividing Clinicians and Searchers: the traditional methods of clinical investigation and follow-up do not allow any further step in the debate. In this work we evaluated the role of E2/Progesterone R.I.A. and thermography in monitoring the effect of progestin on BBD and found that only the latter can give useful informations, insufficient, however, to direct the treatment. If we want to be able to select the patients suitable to be treated by progesterone, we must know the tissutal hormone receptivity and be able to reexamine it during the treatment to verify the effectiveness of the administered drug. These informations can be obtained through the assay of Estradiol and Progesterone Receptors in the most accessible hormone-dependent tissue: the endometrium. Our data point out a quite different behaviour of Estradiol and Progesterone cytoplasmic Receptors in the endometrium of women with mastodynia and controls. The knowledge of these informations in the single patient will let us come out from subjectivity when deciding about BBD therapy or when trying to correct unsatisfactory treatments.

Vaginal delivery after previous cesarean section.

The Authors evaluate the percentage of vaginal delivery after previous cesarean section, in a group of 57 patients. Results show that 34% of the patients delivered spontaneously, and when recurring causes are excluded the percentage rises to 39%. The Authors conclude that a careful monitoring of labour can prevent unnecessary cesarean section in patients who underwent previous surgical delivery.

Endometrial hormone-receptor assay: a new tool in the investigation on mastodynia. Preliminary report.

As breast dysfunctional pathology does not appear constantly correlated to significant variations of steroid plasma levels, we purposed to verify whether the control of tissutal mechanism of hormone vehiculation can provide more reliable informations, in order to identify early endocrine disorders and to check more properly the effectiveness of the treatment from both a qualitative and a quantitative standpoint. In this view we assayed the receptors for estradiol and progesterone in the endometrium of women with mastodynia and healthy controls, to verify whether endometrial tissue receptivity may be useful in the control of breast tissue receptivity; in fact, both the tissues are hormone-dependent and equally exposed to the hormones of the menstrual cycle.

GnRH-test after high-dose MPA in women with post-menopausal LH-preferential release.

The association between post-climacteric LH-preferential release after GnRH-Test and the occurrence of benign or malignant estrogen dependent diseases makes the Authors evaluate the variations induced in such type of hypophyseal response by MPA, administered in the same doses as in the hormonal therapy of cancer. MPA lowered both the basal gonadotropin secretion and the amplitude of the response to the neurohormone, suggesting the hypothesis of a possible direct inhibitory action of the hormone on the hypophysis. The persistence of LH-preferential release after the ten day treatment with MPA 200 mg daily might be explained by the lack of modifications induced by the hormone on the levels of cytoplasmic E2-receptors, on which seems based LH-preferential release.

Possibilities of clinical utilization of GnRH-test in menopause to identify the woman at risk for hormone-related pathology.

The authors evaluate the reliability of GnRH-Test in menopause in detecting the substratum at risk for the development of endometrial cancer. The study was carried out on 30 women affected with endometrial cancer and 30 controls; the examination of the individual curves of gonadotropin values in each patient led to observe LH preferential release in 23 out of 30 cancer patients and in 10 out of 30 controls. The difference of response between the two groups in highly statistically significant (0.0005 less than p less than 0.001). However, the predictive-value of the Test in relation to the detection of the substratum at risk, is about 70%; this apparently unsatisfactory result may be corrected by the finding that about 30% of endometrial cancers seem to develop independently from estrogens. GnRH-Test in menopause might then prove to be highly reliable in predicting the occurrence of estrogen-dependent endometrial malignancies, and may be particularly useful in detecting the substratum at risk among those women presenting no risk-factors, who otherwise might escape careful medical controls.

Hormonal profile following total abdominal hysterectomy and bilateral salpingo-oophorectomy in post-menopausal endometrial carcinoma.

The Authors report the results of study carried out on ten post-menopausal patients affected with endometrial carcinoma (FIGO stage I & II) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). Estradiol, Testosterone and Prolactin plasma levels were assayed before surgery and in the 2nd, 10th and 30th post-operative day. The evaluation of the data supports the opinion that in postmenopause Estradiol origin is mainly extraglandular and the ovaries produce Testosterone; the evaluation of Prolactin levels before and after surgery, at last, cannot rule out the hypothesis of an hypothalamo-pituitary disfunction in post-menopausal patients affected with endometrial cancer.

Post treatment behaviour of cervical intraepithelial neoplasia - grade III.

The behaviour in time of cervical intraepithelial neoplasia grade III has been evaluated in 141 patients treated for CIN III. It was observed that surgery ensures the higher healing-rate, whether hysterectomy or conization are performed, while diathermocoagulation seems unsatisfactory. Colposcopy, colpocytology and sight biopsies of the cervical canal, portio and vagina, which provide a precise lesion-map, are then essential investigations to make the subsequent treatment a truly radical one. A very close monitoring of patients, treated for CIN III, seems required in the first year after surgery, when we observed the highest rate of persistence and recurrences, while, subsequently, their incidence decreases as time passes by.

Nephrotic syndrome in pregnancy: cortisone and prednisolone treatment: clinical case.

A case of a woman affected by a nephrotic postnephritic syndrome and treated during pregnancy with cortisone and prednisolone, is reported. The patient delivered at the 40th week of gestation a neonate with no malformations or clinical signs of adrenal deficiency. No interference between corticosteroid therapy and estrogen metabolism was noticed, and the intrauterine fetal growth, evaluated measuring the biparietal diameter, appeared normal.

GnRH--test in menopause. Its possible use in identifying the subjects at risk for dysplastic endometrial pathology.

The Authors, after reviewing the results of their previous studies on the endocrine situation in post-menopausal endometrial carcinoma and considering what emerges from the present work, suggest GnRh-Test as a mean to better identify the subjects at risk for this neoplasia; in patients already affected with endometrial cancer, it could be an indirect index in recommending or not endocrine therapy.

Steroidogenesis in menopause and endometrial pathology.

After considering the postmenopausal variations in the hypothalamic-hypophyseal-ovarian feed-back system, the Authors review the medical literature about ovarian and adrenal contribution to postmenopausal steroidogenesis. Comparisons are made between postmenopausal sex-hormone levels in controls and in endometrial cancer affected patients; estradiol is given the main attention: its higher level in cancer patients seems closely related to their higher mean weight; indeed, no estradiol level difference is found between patients and controls correctly matched as to the body weight. The possible role of estradiol in the pathogenesis of endometrial cancer is then discussed basing on data obtained from women affected with diseases generally considered to be estrogen dependent.