Daniel Ayalon

The effects of hormone replacement therapy in normal postmenopausal women: Measurements of Doppler-derived parameters of aortic flow

In this study the effects of hormone replacement therapy on cardiac function in healthy postmenopausal women were evaluated by Doppler echocardiography that was performed before (T1) and 2.5 months after the initiation of hormone replacement therapy (T2) in the peak estrogenic phase. The following parameters of aortic flow were measured: peak flow velocity, acceleration time, and ejection time. Additional parameters were calculated: flow velocity integral and mean acceleration. The study group included 24 postmenopausal women aged 43 to 60 years (mean 51.6 years). The control group consisted of 19 postmenopausal women aged 46 to 60 years (mean 53.5 years) who were not receiving hormone replacement therapy and who underwent the same evaluation. There were no changes in all Doppler parameters between T1 and T2 in the control group. However, in the study group there were significant increases in peak flow velocity (108.3 +/- 16.7 cm/sec at T1 vs 123 +/- 20.7 cm/sec at T2; p = 0.002), flow velocity integral (17.7 +/- 3.9 vs 21.5 +/- 4.7 cm; p = 0.0003), mean acceleration (11.5 +/- 1.9 vs 13.1 +/- 2.6 m/sec/sec; p = 0.001), and ejection time (324 +/- 37.6 vs 348.8 +/- 40.7 msec; p = 0.002). There was no change in acceleration time (94.8 +/- 6.6 vs 95 +/- 10.9 msec). These results demonstrate that estrogens increase both stroke volume and flow acceleration. The latter probably reflects a combination of enhanced inotropism and vasodilatation. We assume that the cardioprotective effect of hormone replacement therapy in postmenopausal women may be due not only to changes in lipid profile but also to direct effects of estrogens on central and peripheral hemodynamic parameters.

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.

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

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. (Menopause 1998;5:79–85. ± 1998, The North American Menopause Society.)

Menopause-Related Changes in Left Ventricular Function in Healthy Women

Using technetium scans, this study was aimed at examining possible changes in left ventricular function related to the natural process of cessation of ovarian estrogen production. Fourteen healthy postmenopausal women, divided into two groups according to the time-lapse from menopause (A > 3 years; B < 5 years), underwent a technetium heart scan. The two groups did not differ in heart rate, blood pressure, double product, systemic vascular resistance and cardiac index. The mean end-systolic volume in group A was 14.9 and 25.7 ml/m2 in group B (p = 0.003). The mean pressure/volume ratio was significantly higher in group A than in group B (8.6 vs. 4.7 mm Hg/ml/m2, p = 0.02). Peak ejection rate and peak filling rate were also significantly greater in group A compared to group B (3.3 vs. 2.8 end-diastolic volumes/s, p = 0.02; 2.8 vs. 2.1 end-diastolic volumes/s, p = 0.001, respectively). Our findings suggest that women at an early phase of menopause have a higher degree of myocardial contractility than women of a similar age whose menopause is of longer duration.

Effect of Estradiol on Rat Ileum

1. Sex hormones may influence gastrointestinal motility and thus may be responsible for symptoms that are common during pregnancy or hormone replacement therapy. The purpose of this study was to evaluate the effect of estradiol on the gut. 2. Segments of rat ileum (n=9) were suspended in an organ bath and exposed to increasing concentrations of carbachol, in the presence or absence of 17beta-estradiol. 17beta-estradiol markedly reduced the force developed by the ileum in response to carbachol. 3. These results suggest that estradiol reduces gastrointestinal motility.

Diagnosis of a small ovarian tumor (androgen secreting) by magnetic resonance: A new noninvasive procedure

Virilizing ovarian tumors are rare and establishing their exact location before operation is difficult. We report a case in which a small left ovarian tumor was seen with magnetic resonance imaging.

Effects of Short-Term Treatment with Gonadotropin-Releasing Hormone (GnRH) or Ethinyl Estradiol on the Pituitary Responsiveness to GnRH

In 4 patients with hypothalamic amenorrhea, the pituitary responsiveness to an intravenous challenge of 20 micrograms synthetic gonadotropin-releasing hormone (GnRH) was evaluated before and following a 3-days treatment course with GnRH (100 micrograms/per day i.m.) or ethinyl estradiol, (100 micrograms/day orally). The amenorrheic patients all had normal or reduced levels of serum gonadotropins, no evidence of galactorrhea and no other endocrine abnormality. Following GnRH treatment basal luteinizing hormone levels as well as the luteinizing hormone and follicle-stimulating hormone responses to GnRH were markedly reduced when compared with responses to GnRH before the treatment. Responses to GnRH were significantly augmented after treatment with estrogens. In patients with previous treatment with GnRH the augmented estrogen-induced LH response to GnRH was abolished. These preliminary results support the pathophysiological concept that in amenorrheic patients with hypothalamic dysfunction long-term administration of GnRH does not result in an improvement but rather in a deterioration of pituitary gonadotropic function.

Month 3 and month 6 measurements of bone mineral density predict the annual outcome in postmenopausal women with osteoporosis in whom alendronate was added to long-term HRT.

OBJECTIVEnTo examine the predictive value of bone mineral density measurements done as early as months 3 and 6 after initiation of alendronate therapy (10 mg daily) in osteoporotic women already using long-term hormone replacement therapy.nnnMETHODnLumbar spine and femoral neck bone density (DPX by Lunar) were performed at baseline, 3, 6, 12 months of combined therapy. The study group included 45 women at baseline, but 2 dropped-out at day 67 and at month 6 because of gastric complaints, leaving 43 women for analyses.nnnRESULTSnGroup characteristics at baseline were as follows: mean age 61+/-5 years, mean duration of HRT use 7+/-3 years, lumbar spine bone density 0.863+/-0.089 g/cm(2), with a t-score of -2.75+/-0.8 S.D., and femoral neck density 0.706+/-0.085 g/cm(2) with a t-score of -2.28+/-0.7 S.D. Bone density increased during 1 year of combined therapy, totaling a 3.2% gain for the spine and a 2.4% gain for the femur. Most of the annual change was already observed at month 3: 2.1% for the spine and 1.4% for the femur. Moreover, the baseline to month 6 percentage difference showed a very good correlation with the yearly outcome (r=0.74, P<0.001 for both spine and femur). When different arbitrary cut-off definitions for a successful treatment (1%, 1.5% or 2% gain in density) were used in analyses, in the majority of cases the bone density at 1 year, whether elevated or not, could be predicted by months 3 and 6 results. Although urine deoxypyridinoline decreased throughout the study period, demonstrating a significant time trend (P=0.001), the baseline to month 3 changes did not correlate with baseline to annual bone density results.nnnCONCLUSIONSnIn specific clinical settings when patients or physicians are looking for a good way to anticipate whether additional alendronate in hormone users would turn out to be beneficial, bone density measurements performed as early as 3-6 months after initiation of therapy might give the answer.

Sonographic monitoring of ovarian volume during LHRH analogue therapy in women with polycystic ovarian syndrome.

Polycystic ovarian disease is characterized by menstrual disorders, infertility, obesity, and large ovaries. Large ovaries with multiple cysts are the direct cause of the high incidence of ovarian hyperstimulation during ovulation induction. Lately, gonadotropin‐releasing hormone (GnRH) analogues have been employed to decrease ovarian steroidogenesis and thus reduce the incidence of ovarian hyperstimulation. In this study the ovarian size was ultrasonographically assessed during chronic GnRH analogue treatment, revealing a significant reduction in ovarian volume. This decrease in volume results in a reduced incidence of hyperstimulation, and we think the ultrasonic scanning can be effectively used to assess the success of GnRH treatment.

Dopaminergic regulation of prolactin secretion in the hyperprolactinemic syndrome.

The prolactin responses to an oral challenge of L-dopa (0.5 g) and bromocriptine (2.5 mg) were studied in 31 hyperprolactinemic females without radiological abnormalities of pituitary fossa, in 12 hyperprolactinemic patients with minor radiological evidence suggesting the presence of a pituitary adenoma and in 16 normal volunteers in the early puerperium with physiological hyperprolactinemia. Administration of bromocriptine was followed by a similar suppression of prolactin secretion in the functional as well as the adenomatous hyperprolactinemic patients. By contrast, a significantly blunted response to L-dopa was noted in the patients with pathological hyperprolactinemia (with and without radiological abnormalities of the pituitary fossa). These results suggest that the L-dopa suppression test might serve as a reliable indicator to detect prolactin-secreting microadenomas in patients with persistent hyperprolactinemia and radiologically normal pituitary fossae.