Gonadotropin-releasing hormone-induced rise in cytosolic free Ca2+ levels: mobilization of cellular and extracellular Ca2+ pools and relationship to gonadotropin secretion.

Addition of GnRH to pituitary gonadotrophs preloaded with Quin 2 resulted in a rapid (approximately 8 s) mobilization of an ionomycin-sensitive intracellular Ca2+ pool. A second component of Ca2+ entry via voltage dependent channels contributed about 45% of the peak cytosolic free Ca2+ concentration ([Ca2+]i). Thereafter, influx of Ca2+ via voltage-sensitive and -insensitive channels is responsible for maintenance of elevated [Ca2+]i during the second phase of GnRH action. Addition of inositol 1,4,5-trisphosphate (IP3) to permeabilized pituitary cells resulted in a Ca2+ transient, released from a nonmitochondrial pool, which maintained ambient free Ca2+ concentration around 170 nM in an ATP-dependent mechanism. Successive stimulations of the cells with IP3 produced an attenuated response. Elevation of the gonadotroph [Ca2+]i by ionomycin, to levels equivalent to that induced by GnRH, resulted in LH release amounting to only 45% of the response to the neurohormone. Activation of the voltage-dependent Ca2+ channels by the dihydropyridine Ca2+-agonist [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate (BAYK8644)] stimulated LH release, 36% of the GnRH (100 nM) response being reached by 10(-8) M of the drug, both [Ca2+]i elevation and GnRH-induced LH release were inhibited similarly (40-50%) by the dihydropyridine Ca2+-antagonist nifedipine. The results indicate that peak [Ca2+]i induced by GnRH in pituitary gonadotrophs is derived mainly from ionomycin-sensitive cellular stores most likely via IP3 formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptors for gonadotropin releasing hormone are present in rat oocytes.

Specific receptors for gonadotropin releasing hormone (GnRH) in the rat oocyte have been identified by using two independent methods. Light microscopic autoradiography, utilizing an iodinated biologically active photoaffinity derivative of GnRH, revealed specific binding of the neurohormone to rat oocytes. Furthermore, the presence of GnRH-receptor is also evident from indirect fluorescent immunocytochemistry that shows binding of GnRH-receptor antibodies to rat oocytes which is neither detected with non immune serum nor with antiserum depleted of GnRH-receptor antibodies. These antibodies to the GnRH-receptor, also bind to both cumulus and granulosa cells but not to rat basophilic leukemia cells. The presence of specific GnRH receptors on rat oocytes provides an experimental basis for understanding the molecular events involved in GnRH-induced oocyte maturation.

Cytosolic free calcium levels in cultured pituitary cells separated by centrifugal elutriation: effect of gonadotropin-releasing hormone.

The cytosolic concentration of free Ca2+ ([Ca2+]i) in normal rat pituitary cells separated by centrifugal elutriation was monitored with the fluorescent Ca2+ indicator Quin 2. GnRH (10(-7) M) induced a rapid rise (6-8 sec) in the gonadotroph's [Ca2+]i, followed by a plateau phase of prolonged elevated [Ca2+]i which lasted about 15 min. The stimulatory effect of GnRH was dose dependent, with an ED50 of 10(-9) M, and was blocked by the potent antagonist [Dp-Glu1,pclPhe2,DTrp3.6]GnRH. GnRH elevated [Ca2+]i only in gonadotroph-enriched cell fractions, whereas TRH and GH-releasing factor (GRF) elevated [Ca2+]i in mammotroph- and somatotroph-enriched cells fractions, respectively. A rapid increase (first phase) in [Ca2+]i induced by GnRH was observed in Ca2+-free medium containing EGTA, but this rapid phase was terminated within 2 min. Readdition of Ca2+ to the medium induced a second slower rise in [Ca2+]i (plateau phase). Addition of K+ caused a rapid rise in [Ca2+]i, which was dependent on extracellular Ca2+, but was not affected by prior stimulation with GnRH. On the other hand, stimulation of gonadotroph's [Ca2+]i response by GnRH desensitized the cells to a subsequent GnRH challenge within the time frame studied. These findings indicate an elevation of [Ca2+]i induced by GnRH, TRH, and GRF in their respective separated target cells in the rat pituitary. The rise in [Ca2+]i in GnRH-stimulated gonadotrophs originates partly from intracellular Ca2+ pools and partly from influx of Ca2+ across the cell membrane.

The effect of the hypoestrogenic state, induced by gonadotropin-releasing hormone agonist, on Doppler-derived parameters of aortic flow.

The effect of the hypoestrogenic state, induced by a GnRH agonist (GnRH-a), on cardiac function in healthy young women, was evaluated by Doppler echocardiography performed before treatment and when serum 17 beta-estradiol levels were suppressed by GnRH-a to 36.7 pmol/L. The following parameters of aortic flow were measured: peak flow velocity, ejection time, and acceleration time. Additional parameters calculated were flow velocity integral, cardiac index, and mean acceleration. The study group included 15 menstruating women, aged 25-42 yr (mean, 33 yr), with symptomatic fibroids, endometriosis, or scheduled for in vitro fertilization, who were treated with a GnRH-a. There were significant decreases in peak flow velocity (99 +/- 11 vs. 86 +/- 11 cm/s; P = 0.0004) and cardiac index (3.0 +/- 0.7 vs. 2.5 +/- 0.5 L/min.m2; P = 0.002). A decrease that did not reach statistical significance was noted in flow velocity integral (18.9 +/- 2.7 vs. 16.5 +/- 3.4 cm; P = 0.07). Mean acceleration was decreased significantly (12.6 +/- 2.6 vs. 10.8 +/- 1.8 m/s.s; P = 0.01), but no significant changes in acceleration time (81 +/- 16 vs. 83 +/- 10 ms; P = 0.7) or ejection time (296 +/- 25 vs. 295 +/- 27 ms; P = 0.8) were observed. These results indicate that estrogen deprivation is associated with smaller stroke volume and flow acceleration and might suggest that hypoestrogenism has a direct effect on cardiovascular performance.

Correlation between PGE2 production and suppressor activity of alveolar macrophages from patients with interstitial lung diseases.

The suppressive activity of alveolar macrophages (AM) obtained from bronchoalveolar lavage (BAL), on PHA stimulation of autologous peripheral blood lymphocytes (APL) was evaluated. The effect on lymphocyte stimulation was evaluated by coculturing the AM and APL cells at a ratio of 1:1. PGE2 released by AM during the culture period was measured by a radioimmune assay. The patients included in the study were 11 cases with interstitial lung disease (ILD), 8 cases of lung cancer (CA), and 5 controls (CO). Addition of AM of patients from the CA group resulted in slight suppression of lymphocyte stimulation in 4 cases, slight enhancement in 3 cases and no effect in one case. AM from the CO group induced slight suppression in 4 out of 5 cases. AM from all 11 ILD cases exerted a significant high suppressive activity (65.6% +/- 18.2 - P less than 0.001 by comparison with the CO and CA groups). In ILD cases, a dichotomous pattern was found in regard to relation between high suppressive activity of AM and release of PGE2: in idiopathic pulmonary fibrosis (IPF) patients, high suppressive activity of AM (70.4% +/- 15.4) correlated well with elevated secretion of PGE2: 3.58 +/- 0.26 ng/ml/10(5) cells (P less than 0.02 compared to CO). AM from sarcoidosis patients suppressed PHA stimulation by 61.6% +/- 19.3 but secreted only 0.357 +/- 0.26 ng/ml/10(5) cells of PGE2 (P less than 0.02 compared with the idiopathic pulmonary fibrosis group). Therefore, it seems that other factors, in addition to PGE2, might be involved in the suppressive activity of AM from interstitial lung diseases.

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension.

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.

Calcium-dependent actions of gonadotropin-releasing hormone agonist and luteinizing hormone upon cyclic AMP and progesterone production in rat ovarian granulosa cells.

The Ca2+ dependency of the direct stimulatory effect of the gonadotropin-releasing hormone (GnRH) agonist analog [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide (GnRHa) on progesterone production was investigated and compared to that of luteinizing hormone (LH) in rat granulosa cells from preovulatory follicles. Removal of extracellular Ca2+ by EGTA, or the use of the Ca2+ channel blockers verapamil and La3+, resulted in complete inhibition of GnRHa-induced progesterone production and a partial inhibition of LH-stimulated progesterone production (80, 80 and 50% inhibition respectively for EGTA, verapamil and La3+). Removal of extracellular Ca2+ increased the ED50 for LH-induced cAMP production by four-fold (from 80 to 330 ng/ml) and decreased maximal nucleotide formation by 44%. LH-induced cAMP production was also inhibited partially by verapamil (35%) at 10(-4) M drug concentration. GnRHa had no effect on cAMP production in the presence or absence of Ca2+. GnRHa and LH were found to have maximal effects on progesterone production at about 0.5 mM of Ca2+ in the incubation medium. On the other hand the stimulatory effect of dibutyryl cAMP [Bu)2cAMP) on progesterone production showed little dependency on extracellular Ca2+. The calmodulin antagonist trifluoperazine (TFP) caused concentration-dependent inhibition of the stimulatory action of GnRHa and LH on progesterone production with IC50 values of 3 and 8 microM, respectively. The stimulatory effect of (Bu)2cAMP on progesterone synthesis was attenuated by verapamil and TFP. These results indicate that the direct stimulatory effect of GnRH on ovarian progesterone production is absolutely dependent on Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effects of hormone replacement therapy on Doppler-derived parameters of aortic flow in postmenopausal women.

Eighteen postmenopausal women were examined by Doppler echocardiography before initiation of HRT (T1), then after ten weeks (T2) and one year (T3). This study group was compared with another in which HRT was not used. Flow velocity integral, which correlates with SV, and MA, an indicator of cardiac contractility, were calculated. In the study group, PFV was 107 +/- 18 cm/s at T1 and increased significantly at T2 and T3. Ejection time, which was prolonged at T2 compared to T1, returned to its basal value at T3. Flow velocity integral increased at T2, but this change was only partially sustained at T3. Mean acceleration maintained its increase throughout T2 to T3. None of the Doppler parameters showed a significant change in the controls from T1 to T3. Our results suggest that the peripheral hemodynamic effects of HRT, such as vasodilatation, are transient, whereas the central effects (increased inotropism) are long-lasting.

The effects of sublingual estradiol on left ventricular function at rest and exercise in postmenopausal women: an echocardiographic assessment.

OBJECTIVE: To evaluate the acute hemodynamic effects of 4 mg estradiol given sublingually. DESIGN: Rest and exercise echocardiographies were performed prior to estradiol administration. Then, another set of tests was done post-dose: rest examination at 1 h post-dose, isometric exercise at 65 min post-dose, and dynamic exercise at 100 min post-dose. RESULTS: The administration of 4 mg sublingual estradiol to 24 postmenopausal women (aged 48-58 years) was followed 60 min post-dose by a surge in mean estradiol serum levels (1759 +/- 704 pg/ml). At rest a slight drop in systolic and diastolic blood pressure was measured after estrogen ingestion: 132 +/- 24 mm Hg versus 127 +/- 21 mm Hg, p < 0.05; 83 +/- 11 mm Hg versus 78 +/- 10 mm Hg, p < 0.02. There were no changes in resting heart rate, double product, or vascular resistance. The left heart cavities became smaller: the left atrium diameter decreased from 33.7 +/- 4 mm to 32.3 +/- 4 mm, p < 0.01; the end-systolic diameter decreased from 24.9 +/- 3 mm to 23.6 +/- 4 mm, p < 0.01; the end-diastolic diameter decreased from 44.5 +/- 4 mm to 42.7 +/- 4 mm, p < 0.01. The peak aortic blood flow velocity fell from 120 +/- 19 cm/s to 116 +/- 22 cm/s (p < 0.05), and the flow velocity integral fell from 26.3 +/- 4 cm to 24.9 +/- 5 cm (p < 0.01); the cardiac output underwent a small change, with borderline significance: 7 +/- 2 L/min versus 6.7 +/- 2 L/min, p = 0.06. Only minor changes in the hemodynamic and echocardiographic parameters were recorded after estrogen for both isometric and dynamic exercises. Analyses were also made for two subgroups: 13 normotensive women were compared with 11 hypertensive women. The post-estrogen decreases in resting blood pressure and in peak blood velocity were observed only in the hypertensive subjects, whereas the changes in heart dimensions and in flow velocity integral were the same in both subgroups. CONCLUSIONS: Sublingual estradiol was associated with acute hemodynamic alterations mainly at rest but also after exercise.

Suppressive action of norethisterone enanthate and acetate on gonadotropin. (FSH and LH) levels. Radioimmunoassay in eugonadal and postmenopausal women.

PIP: The suppressive action of norethisterone enanthate and acetate on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was studied by radioimmunoassay in postmenopausal and normally menstruating women. Postmenopausal women, injected with 200 mg of norethisterone acetate, intramuscularly, showed a marked, rapid, and prolonged decrease in serum LH levels. FSH also declined but the decrease was less rapid, less pronounced, and briefer. 1 month after injection, FSH values had returned to pretreatment levels. Oral norethisterone acetate, administered in .3 mg/day doses for 16 days to postmenopausal subjects, did not produce a statistically significant change in serum FSH levels, although serum LH concentrations gradually declined until the end of the treatment period. An oral dose of .3 mg./day of norethisterone acetate suppressed FSH and LH peaks in normally menstruating women who had displayed the peaks prior to treatment. Baseline levels of FSH and LH, however, were not lowered.^ieng

Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein.

Chromosomal translocations that disrupt the molecular organization of transcription factors are typical of a variety of solid and hematopoietic cancers. Alveolar rhabdomyosarcoma (ARMS), a paediatric soft tissue malignant tumour, is characterized by the recurrent translocation t(2;13)(q35;q14) that fuses the 5' DNA binding domain-encoding sequences of the Pax3 gene with the 3' sequences of the FKHR gene. The insulin-like growth factor (IGF) system has an important role in muscle development as well as in the aetiology of paediatric sarcomas, including ARMS. In the present study the potential regulation of the IGF-I receptor (IGF-I-R) gene by PAX3-FKHR at the transcriptional level was investigated. PAX3-FKHR was able to transactivate the IGF-I-R promoter in sarcoma-derived cell lines, whereas PAX3 exhibited a reduced potency in comparison to the fusion protein. Furthermore, transfection of the chimera induced a significant increase in the endogenous levels of IGF-I-R protein, suggesting that the IGF-I-R gene is a physiologically-relevant molecular target for the PAX3-FKHR oncogene.

Induction of ovulation in amenorrheic patients with gonadotropin-releasing hormone and human menopausal gonadotropin.

In five hypothalamic amenorrhea patients who underwent chronic intermittent gonadotropin-releasing hormone (GnRH) therapy for induction of ovulation, small doses (2 to 4 ampules/day) of human menopausal gonadotropin (hMG) were administered 9 to 32 days after the start of GnRH treatment. In seven treatment cycles, the addition of hMG initiated a sudden rise of 17 beta-estradiol concentrations, followed by a luteinizing hormone and follicle-stimulating hormone surge and ultrasonographic evidences of ovulation. Four of five patients conceived (singleton pregnancies) after the first or second treatment course. There were no clinical signs of ovarian hyperstimulation. Combined therapy of GnRH and hMG may be useful, therefore, for the treatment of hypothalamic amenorrhea patients who demonstrate prolonged follicular phases or luteinized unruptured follicle syndrome under chronic treatment with pulsatile GnRH alone.

Combined transvaginal tubal catheterization and adhesiolysis of filmy uterine synechiae performed with a newly developed device under the guidance of digital road mapping fluoroscopy.

Transcervical fallopian tube catheterization is rapidly gaining favor as a minimally invasive diagnostic and therapeutic technique. On occasion, the presence of filmy adhesions not identified on HSG obstruct the passage of the cannula to the cornual angle. We describe the design and operative characteristics of a new transcervical adhesiolysis device that if used under the guidance of DRM mapping, can restore the shape of the uterine cavity and allow completion of the procedure during the same session.

Digital road mapping image--a novel fluoroscopic real-time guide for selective transcervical catheterization in the treatment of proximal tubal obstruction.

Ten infertile women 20 to 40 years of age, with a standard HSG diagnosis of unilateral proximal tubal obstruction, underwent a transvaginal catheterization and recanalization of the fallopian tubes. To set a fluoroscopic real-time guidance technique for improving the results of transvaginal catheterization and recanalization of the fallopian tubes and to increase its marginal safety, catheterization was performed under digital road mapping guidance. Transcervical catheterization resulted in an immediate patency of the obstructed tube in all 10 women. Three women conceived 2 to 3 months after the procedure. The improved catheterization technique enables good results in the diagnosis and treatment of proximal tubal obstructions.

Immunoreactive insulin in serum and seminal plasma of diabetic and nondiabetic men and its role in the regulation of spermatozoal activity.

Concentrations of immunoreactive insulin (IRI) and, in some cases, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in serum and seminal plasma (SP). IRI levels were usually higher in SP. They were unaffected by masturbation; circulating testosterone, LH, and FSH levels were also unaffected. The IRI concentration was higher in the second (vesicular) fraction of split ejaculates. Semen quality was unrelated to IRI in SP in normal and diabetic (chlorpropamide-maintained) men. The addition of insulin in vitro to washed spermatozoa from diabetic and nondiabetic men had no effect on oxygen and glucose uptake or on lactate production and spermatozoal motility. Furthermore, administration of L-arginine to infertile men for 3 months (4 gm/day) was followed in four of seven men by significant increases in IRI concentrations in blood and SP. However, neither semen quality nor fertility was improved.

Experimental extension of the time interval between oocyte maturation and ovulation: effect on fertilization and first cleavage.

OBJECTIVE: To test the hypothesis that impaired fertility in human patients with high LH concentrations throughout the follicular phase of the menstrual cycle reflects premature maturation of their oocytes. DESIGN: Previous information that resumption of meiosis is induced by lower hCG concentrations than that required for stimulation of follicular rupture was confirmed and used for establishment of a rat animal model in which oocyte maturation and ovulation can be separated experimentally. In further experiments hypophysectomized, pregnant mare serum gonadotropin (PMSG)-primed, immature female rats injected with 1.1 IU of hCG, a dose found to induce maturation in 72.9% +/- 6% of the rats with no effect on ovulation, were administered with a second injection of an ovulatory dose (4 IU) of hCG, 24 hours later. The ovulated eggs were subjected to IVF. RESULTS: Fertilization and first cleavage in oocytes recovered from our experimental animal model were similar to that observed in control PMSG-primed, either hypophysectomized or intact rats, treated by a single injection of 4 IU of hCG. CONCLUSIONS: The extension of the time interval between oocyte maturation and ovulation in the rat does not result in a lower rate of fertilization or a reduced incidence of cleavage. However, an inferior developmental capacity of these embryos cannot be ruled out.

Weight loss in patients treated long-term with levodopa. Metabolic aspects.

Seven aged Parkinsonian patients treated with levodopa (average dose 3-4 g daily for 1-3 years), showed a considerable weight loss. They were compared to two control groups of elderly and young volunteers after levodopa stimulation and after oral glucose tolerance tests. It was found that after levodopa administration the plasma free fatty acids, glucose, growth hormone and cortisol were significantly higher in the Parkinsonian group than in the young control group and only slightly higher than in the aged control group. It was also found that the serum insulin was significantly higher in Parkinsonian patients than in the aged control group. We think that the metabolic disturbances found in Parkinsonian patients are not solely due to levodopa administration but may be due to ageing processes. We suggest that weight loss in the older Parkinsonian patients treated over long periods with high doses of levodopa, is due to the enhancement of the lipolytic activity of the ageing fat cells caused by high levels of circulating insulin.

The measurement of progesterone in serum by a non-competitive idiometric assay.

A novel non-competitive idiometric time-resolved fluoroimmunoassay for the determination of serum progesterone was developed, based on the use of two types of anti-idiotypic antibody that recognize different epitopes within the hypervariable region of the primary antiprogesterone antibody. The first anti-idiotype, the betatype, competes with progesterone for an epitope of the primary antiprogesterone antibody at the binding site. The second anti-idiotype, the alphatype, binds to the antiprogesterone antibody in the presence of progesterone, but does not bind to the betatype antiprogesterone complex due to epitope proximity. In the present configuration, the biotinylated alphatype was captured onto anti-biotin IgG which was immobilized on microtiter wells. Reaction mixtures containing europium-labeled antiprogesterone antibody complexed sequentially with progesterone in standards or serum samples and with the betatype anti-idiotypic antibody were then reacted with the immobilized alphatype anti-idiotypic antibody. After 30 min of incubation, the fluorescence of europium is measured by time-resolved fluorescence and is proportional to the concentration of progesterone over the range 0-320 nmol/mL. The method demonstrates good sensitivity, precision, and comparability with a direct competitive radioimmunoassay. The idiometric assay for progesterone is suitable for dipstick technology and biosensors.

Is idiopathic atrial fibrillation caused by occult thyrotoxicosis? A study of one hundred consecutive patients with atrial fibrillation.

In this study we evaluated the possible relationship between idiopathic atrial fibrillation and occult thyrotoxicosis, diagnosed by lack of response of thyroid stimulating hormone to administration of thyrotropin releasing hormone. Three groups were compared: 25 patients with idiopathic atrial fibrillation; 52 with cardiovascular atrial fibrillation; and 27 with sinus rhythm. Patients were excluded with any clinical evidence of thyrotoxicosis or with elevated serum FT4 level, as well as those with diseases or on medications known to be associated with a diminished response to administration of the releasing hormone. A flat test (lack of response) was found in only 4% of the patients. There was no significant difference among the 3 groups. Based on these data we believe that there is no relationship between idiopathic atrial fibrillation or any other type of atrial fibrillation and occult thyrotoxicosis.

The effect of oophorectomy and estrogen replacement therapy on Doppler derived parameters of aortic flow.

OBJECTIVES: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. METHODS: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery - the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. RESULTS: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. CONCLUSIONS: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.