Short- and long-term effects of hormone replacement therapy (transdermal estradiol vs oral conjugated equine estrogens, combined with medroxyprogesterone acetate) on blood coagulation factors in postmenopausal women.

We compared the effects on hemostatic variables of transdermal estradiol and oral equine conjugated estrogens (CEE), both combined with medroxyprogesterone acetate, in 40 postmenopausal women, 22 randomly allocated to transdermal estradiol and 18 to CEE. Antithrombin III (AtIII), fibrinogen, factor VII, factor VIII and tissue plasminogen activator before and after venous stasis were measured at the start of therapy and after two and four months in all patients, and after 12 months in a subgroup of 21 patients (12 from the estradiol and nine from the CEE group). In the short-term study (two and four months), analysis of variance did not reveal any significant difference between treatments for any of the hemostatic variables. A significant treatment by time interaction was found only for fibrinogen levels: at two months they were significantly higher in the estradiol group. In the long-term study (12 months), a significant decrease in AtIII and a significant increase in factor VIII were observed in both groups, without differences between treatments. The clinical relevance of the observed changes is doubtful, but nevertheless they should be considered in a more extensive evaluation of the potential cardiovascular risk and benefits of hormone use.

[Transdermal estrogenic therapy in menopause]. / Terapia estrogenica per via transdermica in menopausa.

The availability of percutaneous estrogenic preparations capable of directly entering the bloodstream, avoiding the liver, has opened new prospects in the treatment of the climacteric syndrome. The purpose of our work has been to compare the effectiveness and tolerability of a percutaneous 17-beta-estradiol-oral progestin association with an all oral association of conjugated estrogens and progestins and to evaluate the ability to control menopausal symptoms and biohumoral characteristics. 42 (1 to 7 years postmenopausal) heavily symptomatic patients were selected at the "Centro per lo studio e la terapia del climaterio" in Milan and divided in two equally sized groups. One group was treated using the percutaneous therapy, the other with the all-oral one. The results show that percutaneous administration leads to a quicker control of vasomotor symptomatology and metabolic effects similar to oral administration.

Diagnostic outpatient aspiration curettage. Two years experience.

Endometrial aspiration curettage was performed on 1001 women, without anaesthesia. Our experience confirms that Vabra-curettage is, for patients, a simple and well tolerated sampling technic. We were not able to perform the technic in 18 patients for close cervical stenosis. In 41 patients the samples were quantitatively not adequate for a correct histological diagnosis. In all these cases a control by D & C was performed, in general anaesthesia, and no proliferative pathology was found. The most common presenting symptom in Intraepithelial Carcinoma of Endometrium (ICE) and in carcinoma was abnormal vaginal bleeding; nevertheless 5 cases of ICE and 2 cases of adenocarcinoma did not show any symptom. This study confirms that systematic screening of asymptomatic perimenopausal and postmenopausal women may lead to the discovery of occult endometrial cancers, some of which are advanced.

[Substitution estrogen therapy in the prevention of postmenopausal osteoporosis and cardiovascular diseases. Results of long-term therapy]. / La estrogeno-terapia sostitutiva nella prevenzione dell'osteoporosi e della patologia cardiovascolare in postmenopausa. Risultati del trattamento a lungo termine.

In the present report, the current approach to the prevention of metabolic damage deriving from oestrogen deficiency involves the use of protocols that vary in the type of hormone employed and the mode of its administration. A homogenous group of 28 postmenopausal women was treated with natural conjugates oestrogen (0.625 mg per diem per os) on a continuous basis plus MAP (10 mg per diem per os) for 12 days a month. The metabolic effect of the oestrogen replacement therapy was assessed annually by blood chemical screening of the lipid situation and the phosphocalcium balance. Computerised radial bone mineralometry using SPA technique was also performed. A smaller group of 19 court of the 28 patients was also subjected to transversal assessment of vertebral BMD using the DXA technique. The results in this latter group were compared with those in 19 women not given oestrogen treatment who had been postmenopausal from 5-7 years. Results after 60 months of treatment confirm the efficacy of oestrogen therapy in preventing the deterioration of the lipid profile and the loss of bone mass after menopause.

Plasma FSH, LH and prolactin levels in postmenopausal women undergoing cyclofenil treatment.

Ten postmenopausal women were studied in an attempt to identify the mechanism of action of cyclofenil, a non-steroidal anti-estrogen which has proved to be effective in the climacteric syndrome. A double-blind inter-patient clinical investigation was undertaken, with patients assigned randomly to treatment for 10 days with cyclofenil, 400 mg/day, or else conjugated estrogens, 1.25 mg/day, always given orally at 8 a.m. Serum FSH, LH and PRL levels were determined daily 2 days before, during and for 2 days after treatment. On the first and tenth day of treatment, five blood samples were drawn between 8 a.m. and 4 p.m. to ascertain if there was any drug-induced variation in the hormonal secretory patterns. Furthermore, endometrial biopsies of all patients were taken before and immediately after the 10-day treatment. In 5 patients, endometrial biopsies were repeated after 3-6 months of therapy with cyclofenil. The results indicate that cyclofenil has two opposing actions on the hypothalamic-hypophyseal axis, one estrogen-like, in that it depresses serum FSH levels, and the other antiestrogen-like, in that it depresses serum PRL levels. They also show that at both the peripheral and the central level cyclofenil is a drug of first choice for postmenopausal women at risk for endometrial and mammary neoplastic pathology.

Bromocriptine induced pregnancy in two cases of euprolactinemic hypothalamic amenorrhea.

Two euprolactinemic women with hypothalamic amenorrhea, previously unsuccessfully submitted to clomiphene citrate therapy, were treated with bromocriptine. PRL secretion was studied in basal conditions and under dynamic tests: TRH and chlorpromazine. Serum FSH, LH and 17-beta-estradiol were determined before and during the treatment. Both patients conceived, and one delivered a healthy baby at term. Bromocriptine appears to be an effective drug for treating women with hypothalamic amenorrhea, particularly those unresponsive to clomiphene.

Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy.

OBJECTIVE: Our purpose was to clarify the mechanisms by which postmenopausal estrogen replacement therapy exerts its protective effect on cardiovascular risk. STUDY DESIGN: By means of a bidirectional Doppler ultrasonographic system we measured pulsatility index variations the internal carotid artery and middle cerebral artery in 25 early postmenopausal women during a 6-month period of hormone replacement therapy. Transdermal estradiol (50 micrograms/day) was continuously administered. A 12-day course of medroxyprogesterone acetate (10 mg/day) was added every second month. RESULTS: The pulsatility index showed a significant (p = 0.0001) reduction in both arteries after 6 weeks. At 22 weeks a 25% reduction was measured. No variation of the estrogen-induced pulsatility index reduction was observed at the end of every cyclic progestogen supplementation. CONCLUSIONS: In early postmenopausal women hormone replacement therapy causes a rapid reduction of pulsatility index in brain arteries. Cyclical progestational supplementation does not modify this positive effect on reactivity of the blood vessels.

Gonadotropin releasing hormone agonist therapy and its effect on bone mass.

The effects on bone mass of a 6 month therapeutic cycle with a gonadotropin releasing hormone agonist (GnRHa) were studied in 22 patients, ten affected by pelvic endometriosis and 12 by uterine fibroids. All patients were subjected to preliminary full examinations to confirm their diagnosis (laparoscopy for the endometriosis group and precise ultrasound volume measurements for uterine fibroids group). Before the beginning of treatment, bone mineral density (BMD) was measured in each patient both on the distal third of the forearm, with single-photon absorptiometry, and on the lumbar spine (L1-L4), with dual photon absorptiometry. The gonadotropin releasing hormone agonist used was buserelin. In the first week of therapy 0.5 mg of the drug was administered subcutaneously thrice daily. In the following 25 weeks the same drug was given intranasally, at a dosage of 300 micrograms again three times a day. Bone mass measurements, both at the peripheral and at the axial site, were repeated at the end of the 26-week therapeutic cycle and then again 6 months later. At the 26th week, a significant decrease of BMD was observed at both sites. The loss was 1.5% (p less than 0.05) on the lumbar spine, and 2.1% (p less than 0.05) on the radius. No bone mass restoration took place in the following 6 months. On the contrary, a less significant but discernible trend towards a further bone loss was apparent in the BMD values measured 6 months after the end of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Current significance of the endocrine monitoring in the treatment of amenorrhea]. / Significato attuale del monitoraggio endocrino nel trattamento della amenorrea

PIP: The use and limitations of various endocrine monitoring tests in the diagnosis and treatment of amenorrhea are discussed. 100 cases of amenorrhea were studied by measuring serum gonadotropins, estradiol, and prolactin levels under basal conditions and after administration of luteinizing hormone-releasing hormone, ethinyl estradiol, and clomiphene citrate. The ethinyl estradiol test was found to be particularly significant in determining the response of the hypothalamus-pituitary gland system to the gonadal signal. The patients who showed positive or negative responses to the ethinyl estradiol test showed similar responses to clomiphene, which appears to indicate that the latter has a similar estrogenlike action; it is concluded that the estrogen test may have prognostic value for the purpose of clomiphene treatment. Although the tests described are useful, much further research is necessary to determine the neuropsychic control mechanism which governs the development of the menstrual cycle, and it is often very difficult or impossible to reach a correct diagnosis of the causes of amenorrhea, which is a very aspecific symptom.^ieng

The use of cyclofenil in menopausal women.

On the basis of some reports, a double-blind experimental trial comparing the activity of cyclofenil, estradiol valerate and placebo in post-menopausal disturbances was carried out. 60 women among those attending the menopausal clinic and affected by climateric disorders have been treated. The objective criterium for the admission had been established on the basis of the value of plasma FSH (greater or equal to 800 ng/ml). Besides the gynecological examination (including objective and subjective examination, hormone dosage, endometrial biopsy) patients underwent psychological examination (individual interview and psychometric tests) before and after 28 days of therapy The statistical evaluation of the results obtained with the 3 drugs showed a statistically significant difference between the placebo and the active compounds: no significant difference between cyclofenil and estradiol valerate was observed.

Cyclic hormonal replacement therapy after the menopause: transdermal versus oral treatment.

In an open, randomized, comparative, between-patient trial, 45 postmenopausal women were treated for 4 months with cyclical transdermal oestradiol 0.05 mg per day or oral conjugated equine oestrogens 0.625 mg per day, in both cases, plus, medroxyprogesterone acetate 10 mg per day on the last 8 days of each cycle. Similar relief from postmenopausal symptoms was obtained with both treatments. Post-treatment histological evaluation of the endometrium did not reveal neoplastic or hyperplastic change in any patient. Early follicular-phase plasma oestradiol levels were observed only after transdermal oestradiol. There was a significant reduction in serum total cholesterol and LDL cholesterol in both treatment groups, with no difference between treatments, whereas serum triglyceride levels were decreased only by transdermal oestradiol. Plasma calcium and phosphorus fell significantly and serum intact parathyroid hormone rose significantly, with no difference between the therapies. No significant changes were observed in clotting factors. Transdermal oestradiol appears to be an effective and safe hormonal replacement therapy, and this route of administration may be responsible for the more useful action of the drug on serum lipids and plasma oestradiol levels.