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LHRH analogues (LHRHa) are used in the treatment of breast cancer that occurs in young women. Amenorrhoea induced by chemotherapy correlates with a reduced risk of recurrence disease. In premenopausal women, analogous LHRHs are used to suppress ovarian estrogen production, raising estrogen hormone levels to post-menopausal values and improving patient outcomes. Two large clinical studies have investigated the role of complete estrogen blockage in adjuvant hormonal treatment of premenopausal patients. Both studies showed the clinical benefit of ovarian suppression treatment, mainly associated with non-steroidal aromatase inhibitor exemestane in high-risk patients. In the recent years, hormonal treatments made available in clinical practice have considerably prolonged the median survival of patients suffering from endocrine-responsive metastatic breast cancer. Even in the premenopausal setting, CDK4/6 inhibitors in association with endocrine therapy have shown a marked improvement in patient outcomes. The safety and efficacy of this new class of drugs demonstrated in the MONALEESA-7 study in premenopausal women and in the premenopausal subgroups of the PALOMA-3 and MONARCH 2 studies support the use of hormone therapy and analogous LHRH combined with CDK 4/6 inhibitor in patients in premenopausal. Finally, LHRH analogues have been extensively studied in strategies for maintaining ovarian function and fertility preservation during adjuvant chemotherapy in younger patients.

Incidence of breast cancer (BC), particularly in younger women, has increased in last decade. About forty percent of all BC are observed in women under the age of 50 years and, accordingly, in pre-menopausal women. Luminal-like is the most common subtype. Pre-menopausal status is associated with clinical, social and psychological issues that must be addressed as part of oncology care to guarantee the best global health outcomes after treatment. This review aims to answer the most common questions on endocrine treatment in pre-menopausal women. In particular, it focuses on the decision-making process that drives the choice about ovarian function suppression, use of aromatase inhibitors, and duration of therapy.

More than 25 years ago, the iron hypothesis proposed that a state of sustained iron depletion or mild iron deficiency exerts a primary protective action against ischemic heart disease. Iron depletion leads to a decreased availability of redox-active iron in vivo. The amount of free iron available at sites of oxidative or inflammatory injury appears to be a function of the stored iron level. Depletion of iron levels by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduce atherosclerotic lesion size and increase plaque stability. In homozygous hemochromatosis there is commonly a defect that inhibits iron retention in macrophages. This defect may explain why atherosclerotic lesions appear to be less prevalent in this disorder. Findings of the "FeAST" trial have been recently reported. The trial assessed the potential benefit of mild iron reduction therapy in secondary prevention of cardiovascular disease. It was therefore not a fully valid test of primary prevention as postulated by the iron hypothesis. However, although no overall statistically significant cardiovascular benefit was found, in the youngest quartile at entry there were highly significant reductions in all cause mortality and in combined death plus non-fatal myocardial infarction and stroke in association with iron reduction therapy. The FeAST trial adds urgency to the initiation of new studies to assess the impact of maintenance of complete iron depletion in the primary prevention of cardiovascular diseases.

Background and Aims: The authors evaluated the accuracy of ultrasonographic findings compared to hysteroscopic and histological results in the diagnosis of anomalous uterine bleeding in menopause., Methods: Forty-eight women suffering from the above pathology and attending the Preventive Gynecology outpatient clinic of Department C of the Gynecology and Obstetrics faculty at Turin University during the period between September 1996 and July 1997, underwent first ultasonography using a transvaginal probe and then outpatient hysteroscopy with endometrial biopsy., Results: A total overlap between the ultrasonographic image, hysteroscopic results and histological diagnosis was only obtained in the group of menopausal patients., Conclusions: In line with the data reported in the literature, the authors imposed a cut-off endometrial thickness of 4 mm above which further diagnostic tests were performed using hysteroscopy with targeted biopsy.

Following a review of the literature, the authors examine the drugs which are currently used to treat anomalous uterine bleeding during menopause, illustrating their aims and justifying the rationale underlying their use. They conclude by stating that a satisfactory treatment often does not exist, but it is the task of the specialist to gauge the level and sequence of treatments in order to achieve the hoped-for result.

Background: The aim of this study was to determine the diagnostic value of hysteroscopy and transvaginal ultrasonography in patients with abnormal uterine bleeding (AUB) in the peri and postmenopausal period., Methods: 302 patients with AUB, underwent hysteroscopy and in 86 cases, also a transvaginal ultrasonography before hysteroscopy was performed. Results were compared with the histological diagnosis., Results: The diagnostic accuracy of hysteroscopy was very high in the cases of endometrial carcinoma (sensibility 100%, specificity 99%), and lower in the cases of endometrial hyperplasia (sensibility 69%, specificity 72%) and endometrial atrophy (sensibility 29% and specificity 97%). Sonography proved to be less reliable in the diagnosis of endometrial pathology (carcinoma: sensibility 57%, specificity 100%, hyperplasia: sensibility 62.5% specificity 63%). The results of this study show that sonography may be used as a first choice diagnostic test in the investigation of women with AUB., Conclusions: Hysteroscopy represent a second diagnostic step for achieving a proper histologic diagnosis.

The influence of timing of surgery in relation to menstrual period on survival of breast cancer patients has been both advanced advocated and disputed. A meta-analysis on published series showed a statistically significant overall odds reduction when surgery is performed in the luteal phase. The records of 165 premenopausal M- breast cancer women, not on hormonal therapies, consecutively operated on from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus operative radiotherapy, Node-positive patients received standard adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pathological T and N. In each model, patients were divided into two groups according to the criteria proposed by Badwe, Hrushesky, and Senie. Multivariate analysis showed a significant association between pT and pN and survival, whereas no association with survival was observed for timing of surgery according to Badwe or Hrushesky or Senie criteria (RR = 1.26, RR = 0.91, and RR = 0.88 respectively). Up-to-date agreement on the menstrual phase and relative expected better prognosis is still lacking.

A retrospective study on 300 women who attended the menopausal out-patient clinic of Physiopathology of Human Reproduction at Bari University Hospital from 1994 to 1995, was carried out to evaluate the incidence of climacteric syndrome in premenopause together with its correlations with the social and cultural environment. The results don't show differences between spontaneous and surgical menopause, and minor differences with premenopause. No relationship has been discovered between the onset of the menarche and the onset of spontaneous menopause. The hot flushes are more frequent in women with low level of learning.

The authors examine 162 cervico-vaginal smears of women in peri-menopause presenting cellular alterations (ASCUS). These patients were treated with a local topic therapy as the persistence of these alterations in 23 cases (14.2%) second level analyses were performed: gynecological visit, colposcopy and biopsy. In addition to inflammatory aspects 2 in situ carcinomas and 2 moderate dysplasias were recorded. We believe therefore that cytology could be a valid aid also in pre-menopausal women in the cervico-vaginal pathology.

The authors analyse two years' activities at the outpatient clinic set up for the prevention of menopause-related disorders at Mazzacorati Family Planning Clinic (USL 29-Bologna). They emphasise the fact that menopause is characterised by a complex interaction of biological, psychic and socio-cultural aspects with the result that requests for consultancy are extremely varied and sometimes, at least apparently, even contradictory. From these findings it emerges that in a sample of 440 women attending the centre, 28% requested information sessions and a further 10% expressed the need for a discussion focused on sexual problems. Moreover, while "hormone" therapy is currently positively accepted by the majority of women, the percentage of women refusing or suspending treatment is not negligible. It is worth recalling that 38% of women in pre-menopause, albeit strongly motivated to use an oral contraceptive, did not start treatment or suspended it within the first 6 months, although no collateral effects were reported, and 24% of women in spontaneous postmenopause did not commence hormone replacement therapy or suspended it in spite of having reached an acceptable level of wellbeing.

The radiologic identification of vertebral fractures is usually subjective and reproducibility is poor. This paper describes a new digital radiologic method to perform vertebral morphometry, i.e. osteoradiometry (ORM). Lateral radiographs of the thoracic and lumbar spine were obtained in 50 premenopausal women and digitalized by means of a video camera. A special computer software enables to calculate the anterior (Ha), middle (Hm), and posterior (Hp) heights of vertebral bodies (T4-L5) and the morphometric indices of vertebral fractures. ORM reproducibility was assessed by comparing repeated measurements made by two radiologists: the intra- and interobserver variation coefficients (CV) were respectively 1.5% and 2.3% for Hp; 1.3% and 2% for Hm; 1.4% and 2.1% for Ha. The normal range for vertebral dimensions was therefore established. The anterior and posterior heights increased from T4 to L2, but for L3-L5 the posterior height was lower than the anterior height (Ha/Hp > 1). Vertebral heights positively correlated with the standing heights of the subjects (r = 0.2, p < 0.05). Weight and the body mass index (BMI) were not correlated with vertebral heights. These normal values, compared with those found in osteoporosis patients, will allow to assess ORM diagnostic efficacy in identifying vertebral fractures.

The three standard projections relative to mammographies of 40 patients with breast cancer pre-operatively classified as T1-T2 were analyzed by computerized morphometric elaborations. This method si able to better define view of images, permetting pre-operative connection of staging, with an increment of 30% if confronted with histologic TNM (pTNM). The utilization of method is discussed to evaluate the best way for the local definition of tumor extension, permitting to use a correctly conservative surgery (quadrantectomy, tumorectomy) in a greater number of patients.

The authors inspected 112 patients with diagnostic urogynecologic and urodynamic criteria. They suffered from urinary stress incontinence. Forty patients effected rehabilitative therapy of the pelvic floor with visits twice weekly with a method which included: pelvic muscle exercises, biofeedback and functional electrostimulation. The patients were divided into two groups in accordance with the kind of urinary stress incontinence: in the first group there were patients with genuine urinary stress incontinence, in the second group patients with mixed urinary stress incontinence. The results at the end of treatment reported a proportion of success of 66% in the first group and of 54% in the second group.

The objective of this study was to evaluate the effect on vertebral and femural bone density of the gonadotropin-releasing hormone (GnRH) analog administration. The changes in mineral bone density after 6 months discontinuation of the GnRH analog treatment were also measured. Forty-three premenopausal women with regular cycles and suffering from uterine myomatosis have been selected for the study. Twenty-eight women (group A) were treated with Goserelin 3.2 mg given as a depot every 28 days for 6 months. Fifteen women were treated with 10 mg of medroxyprogesterone acetate (MPA) from day 16 to day 25 of each month for 6 months. Vertebral and femural bone density was measured (by Hologic QDR-X 1000) just before the start of the study, at 6 months of treatment and at 12 months (after 6 months of discontinuation treatment). Significant loss of vertebral bone density was demonstrated in women treated with GnRH analog. After six months of treatment discontinuation bone mineral density did not recover the pretreatment values. Bone femural density showed a not significant decrease in the GnRH analog group. In our experience, the treatment with GnRH analog in premenopausal women induces a reduction in lumbar bone density that is not reversible after the treatment withdrawal; for this reason it would be safe to add at the GnRH analog a therapy which can prevent the bone loss.

Hyperestrogenism is a powerful factor inducing the development of endometrial hyperplasia that in its turn may represent the first step in the natural history of endometrial carcinoma. During menopause it is possible to have a condition to relative hyperestrogenism induced by a residual hormonal activity and by aromatisation of androgens in the adipose tissue. Therapeutical approach in this pathology aims to control hyperplastic development of the endometrial mucosa and to exclude menometrorrhagia. This study has been performed according to an open uncontrolled design in 14 women (4 menopausal women) with abnormal uterine bleeding and hysteroscopic endometrial cystic or adenomatous hyperplasia. At the beginning and at the end of treatment all patients underwent routine biohumoral blood-tests, hysteroscopy and diagnostic curretage. The GnRH analogue (tryptorelin) 3.75 mg 1 ampoule i.m. every 28 days was administered during a 6-month treatment cycle. At the end of therapy bleeding had disappeared in all menopausal women; in the premenopausal group 8 patients have shown a normal menstrual cycle while 2 are still amenorrhoic. The final hysteroscopic evaluation displayed atrophic endometrium in 9 patients and simple proliferative endometrium in 5 cases. Safety was excellent: 3 cases of slight increase of systolic blood pressure and 1 case of slight increase of weight took place. Our results demonstrate therapeutic efficacy of GnRH analogues in the treatment of endometrial hyperplasia with menometrorrhagia either in premenopausal or menopausal women.

Abnormal uterine bleeding is one of the main indications for hysteroscopy in peri-menopausal age. Transvaginal ultrasound allows for an accurate study of the endometrium through the evaluation of thickness, homogeneity. The aim of this retrospective study was the evaluation of transvaginal ultrasound versus hysteroscopy in diagnostic approach to abnormal uterine bleeding in peri- and post-menopause. 130 Women referred to the Department of Obstetrics and Gynecology of the University of Pavia for abnormal uterine bleeding entered the study; all them underwent transvaginal ultrasound and hysteroscopy with directed biopsy, with histological diagnosis of benign endometrial disease. On the basis of endometrial thickness measured at ultrasound, premenopausal patients were divided into two groups, post menopausal patients into three groups, and for each group a comparison between hysteroscopic findings, histological diagnosis and echographic aspect was performed. A 100% correspondence between ultrasound, hysteroscopy and histology was found in the group of subjects with endometrial atrophy, with an endometrial thickness of 2.9 +/- 0.68 at ultrasound; in the remaining groups sensibility and specificity of transvaginal ultrasound seem to be lower. In our experience a cut-off of 4 mm can be established for endometrial thickness measured by transvaginal ultrasound. Values that are below this cut-off point are diagnostic for endometrial atrophy, precluding the need for more invasive examinations: a medical treatment can then be administered. On the contrary, an endometrial thickening of 4 mm or more requires an hysteroscopic examination with directed biopsy and histological diagnosis.

The authors evaluate the effectiveness of a therapy based on natural progesterone to be employed as a vaginal cream in the treatment of meno-metrorrhagia in peri-menopause in 40 patients who were not prepared to consider surgery as a solution for their problems. In the polycentric out-patient study this new preparation has proved to be efficacious and to induce a regression of the endometrial hyperplasia in more than 90% of patients subject to five months' treatment.

The authors base their argument on the concept that difficulties sometimes arise in performing hysteroscopy above all due to impediments to the introduction of the diagnostic instrument. They therefore report their experience of the pharmacological preparation of the cervix using the local application of prostaglandin vaginal bougie, gemeprost, for short intervals, between 15 and at most 30 minutes, above all when diagnostic hysteroscopy is performed in an out-patients setting. A total of 224 cases of hysteroscopy are analysed which are divided into two distinct groups: the first, a control group without preparation and the second which included 101 patients who underwent pharmacological preparation for 15 (29 women, group B) or 30 minutes (62 women, group C). Having described the method of examination, an analysis of the results confirms that the use of gemeprost facilitates the cervical stage of hysteroscopy, allowing the examination to be performed even in more complex conditions, such as post-menopause or during the secretive phase of the cycle.

In this study a good sensibility of ultrasound in identifying ductal disease was demonstrated. We evaluated the relationship between nipple discharge and ductal ectasia and the importance of the ectasia in maintaining nipple discharge. From our data the hypothesis of a possible role of oestroprogestinic hormones in the genesis or maintaining of ductal ectasia emerged.