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.

[Prospectives of the study of seminal fluid in the diagnosis of infertility]. / Prospettive di studio del plasma seminale nella diagnostica dell'infertilità.

Biochemical components usually evaluated in seminal plasma are lower than those in blood serum. In this study the concentration of different constituents in seminal plasma has been analyzed: creatinine, urea, glucose, uric acid, sodium, potassium, triglycerides, cholesterol, bilirubin, alkaline phosphatase, glutamic oxalacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), cholinesterase, creatin phospho chinase (CPK), gamma glutamyl transpeptidase, lactic dehydrogenase (LDH), proteins, in comparison with the concentrations of the same constituents in blood. With the exception of uric acid, all the biochemical components in the seminal plasma were either significantly higher or lower than in blood serum, an index of the complexity of the mechanism regulating the presence and distribution of the single components in seminal plasma compared with blood serum. Isoelectro-focussing for proteins showed, in seminal plasma, a higher quantity of fragments and a different distribution of this in comparison with blood serum.

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)

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes.

During a six-month randomized study involving 460 post-menopausal women, transdermal estradiol has proved to be as effective as oral conjugated equine estrogens in the control of menopausal symptoms and to produce similar estrogenic effects on the endometrium. The group of patients treated with transdermal estradiol showed better compliance and had fewer drop-outs. Moreover, the quality and duration of menstrual bleeding were considered more physiological in the transdermal estradiol group than in the orally treated patients. The trial was carried out with the co-operation of 17 Italian University Centres, under the supervision of Ciba-Geigy Italy S.p.A. Medical Department.

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.

[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.

Breast carcinoma and plasma 17-beta-estradiol binding.

The data relating to plasma steroid binding and transport (usually measured with dehydrotestosterone) are controversial. The plasma E2 binding of 79 breast carcinoma patients, 19 premenopausal and 60 postmenopausal, were compared to 46 controls, 21 premenopausal and 25 postmenopausal. In this study the authors removed the endogenous steroids with charcoal, incubated the plasma with 17-beta-E2 in non-saturation conditions, and used ammonium sulfate to precipitate the complex. The authors chose 17-beta-E2 as ligand because the plasma steroid binding system has not been shown to be homogeneous and because this binding function may vary independently for the different steroids. In these patients, the E2 binding was significantly (P less than 0.01) increased (85 +/- 11 pg/ml and 73 +/- 13 pg/ml in premenopausal and postmenopausal) compared to the normal controls (59 +/- 7 pg/ml and 58 +/- 5 pg/ml in premenopausal and postmenopausal women. It is still unclear whether this is a primary increase of the binding capacity or a reaction of the host for sequestering excess circulating E2. However, the small percentage of false-positives and false-negatives suggests that E2 binding could be used as a tumor marker in breast carcinoma.

Endometriosis and infertility: our experience over five years.

During a 5-year period, we diagnosed endometriosis by laparoscopy in 163 infertile patients (7.9% of the infertile population). Seventy-one women presented with minimal endometriosis, 32 women a mild form, 38 women a moderate form and 22 women a severe form. Only 40 patients (24.5%) were found to have endometriosis as the only abnormality in a complete fertility work-up. One hundred and twenty patients were treated with Danazol (600 mg daily for 4-6 months) and 33 of them conceived (27.5%). Twenty-eight patients received conservative surgical treatment associated with Danazol therapy and 11 of them conceived (39.2%). In the 15 patients with minimal endometriosis, who had no therapy but expectant management, there were two conceptions within one year (13.3%). The anticipation of minimal disease in patients with endometriosis as the only abnormality produced about the same results as achieved by active treatment (pregnancy rate of 33.3% after expectant management and 36.3% after treatment). These results suggest that minimal endometriosis can be anticipated only when there are no co-existing factors of infertility.

Current status of hormone receptor measurements in cancer patients.

Despite increasingly sophisticated techniques, improvements in the correlation between laboratory findings and tumor response to endocrine therapy have not been obtained by hormone receptor studies. A possible explanation is that present knowledge of the mechanisms of the endocrine stimulus is incomplete. Some aspects of the present model, (elevated conjugated steroid levels, multiplicity of the plasma proteins capable of binding hormones, pulsatility of the plasma protein bond and of the receptor system for steroids), are still unclear and thus are not used in diagnosis. By evaluating these factors it will probably be possible to correlate better laboratory data with clinical findings.

Development of laboratory hormone tests and their application in the monitoring of cancer patients.

In the endocrinologic study of dysplastic and neoplastic pathologies of hormone-dependent organs we propose the determination not only of the plasma levels of the "total" hormone but also those of the free hormone as well as the plasma/hormone binding capacity and the kinetics of the plasma/steroid interaction.

Patterns of transport and binding of sex steroids.

The seminal plasma-sex steroid binding kinetic was evaluated by measuring the amount of labeled hormone extractable after 5 sec to 100 min of incubation. For testosterone in normal subjects, a peak of binding was reached after 30 sec of incubation. In subjects with severe oligoasthenospermia the kinetic pattern for testosterone was different but similar to the binding kinetic between seminal plasma of normal men and estradiol. The phenomena did not occur with frozen plasma samples.

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.

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.