The effect of estrogen replacement therapy on zinc in serum and urine.

OBJECTIVE: To ascertain the influence of estrogen replacement therapy (ERT) on blood and urinary zinc in postmenopausal women. METHODS: Thirty-seven postmenopausal women aged 53.2 +/- 3.7 years were examined. All were treated with conjugated estrogens 0.625 mg and medroxyprogesterone acetate 5 mg. Zinc, magnesium, calcium, phosphate, and alkaline phosphatase levels in blood were measured before and after 6 and 12 months of treatment. Urinary excretion of zinc, magnesium, calcium, phosphate, and hydroxyproline were evaluated before and after 3, 6, and 12 months of therapy. Bone mineral density was examined before treatment and after 1.7 +/- 0.3 years of ERT. Subjects were classified by 1) initial bone mineral density values (osteoporotics less than 0.850 g/cm2) and 2) zinc excretion as elevated (greater than 600 micrograms/g creatinine). RESULTS: At baseline, the values of most markers of bone turnover were higher in the osteoporotic women (Hotelling test, P = .06). After 1 year of treatment, a higher decrease of most indices was observed in the osteoporotic patients, and no statistical difference was found between the osteoporotic and the normal groups (Hotelling test, P = .31). A consistent negative association was observed between changes in bone mineral density and urinary zinc excretion in the osteoporosis group. Estrogen replacement therapy reduced excretion of zinc, magnesium, and hydroxyproline in the elevated zinc excretion group. Zinc excretion decreased 35% after 3 months and 26% after 1 year of treatment. The serum tests, with the exception of alkaline phosphatase, showed only negligible changes during ERT. CONCLUSION: A significant decrease in zinc excretion was observed after 3 months of ERT. This change was more pronounced in women with osteoporosis and elevated zinc excretion. Because zinc excretion is almost uninfluenced by variation in diet, it may be used as an additional marker of changes in bone metabolism.

Hypocalciuria of preeclampsia is independent of parathyroid hormone level.

Hypocalciuria is a feature of preeclampsia. The roles of parathyroid hormone (PTH) and vitamin D 1,25(OH)2D3 (calcitriol) in its pathogenesis have not yet been determined. Fourteen preeclamptic women were compared with 12 women with chronic hypertension and 11 normotensives, all in the third trimester. Preeclamptics had the lowest urinary calcium excretion rate (62.1 +/- 32.8 mg/24 hours) compared with chronic hypertensive women (162.6 +/- 97.8 mg/24 hours) and normotensive controls (225.6 = 146.9 mg/24 hours) (P less than .05). Serum PTH was lowest in preeclamptics (9.8 +/- 5.5 pg/mL), in contrast to the chronic hypertensives (18.5 +/- 2.7 pg/mL) and normotensives (16.4 +/- 3.2 pg/mL) (P less than .005). Similarly, urinary cyclic adenosine monophosphate (cAMP) excretion was 2.9 +/- 1.4 mumol/24 hours in the preeclamptics, 5.1 +/- 1.7 mumol/24 hours in the chronic hypertensives, and 4.6 +/- 1.3 mumol/24 hours in the normotensive group (P less than .05). These data suggest that the mechanism of hypocalciuria in preeclampsia is independent of the PTH-calcitriol axis. Therefore, it is suggested that the hypocalciuria of preeclampsia is due to intrinsic renal tubular dysfunction.

Pregnancy after myocardial infarction: are we playing safe?

The safety of pregnancy after myocardial infarction remains a significant dilemma for both the obstetrician and the cardiologist. Only 20 cases of pregnancy after myocardial infarction have been reported. To clarify this problem, we add our experience of four such cases in which conception occurred 9 months to 9 years after myocardial infarction with no previous consultation. Each woman had an uneventful pregnancy with no cardiac or obstetric complications related to the myocardial infarction. All patients were under the strict supervision of an obstetrician and a cardiologist during pregnancy in our conjoined antepartum-cardiologic clinic. The mode of delivery in all patients was related to the obstetric indications. Our experience and the accumulated experience in the literature demonstrate good prognosis for patients who conceive after myocardial infarction.

Does hormone replacement therapy inhibit coronary artery calcification?

OBJECTIVE: To determine the association between the use of hormone replacement therapy (HRT) and coronary calcium, in postmenopausal women who had no history of coronary artery disease by double helical computed tomography (CT). METHODS: We used CT to compare the prevalence and extent of coronary calcium in 41 postmenopausal women who were on HRT from the first year of menopause and 37 age-matched controls who had never used HRT. RESULTS: Both groups had a similar rate of smoking, hypertension, a positive family history, and hypercholesterolemia. Coronary calcification was observed in 28.2% of the 78 women studied. The prevalence of coronary calcium was significantly lower among HRT users: six of the 47 (14.6%), compared with 16 of the 37 nonusers (43.2%) (P < .01). The recorded risk factors had no effect on the prevalence of coronary calcium. Stepwise logistic regression analysis, including age, coronary risk factors, and HRT use as independent variables, yielded HRT as the only variable determining the presence of coronary calcium (odds ratio = 0.2; 95% confidence interval 0.06, 0.63; P = .006). CONCLUSION: The lower incidence of coronary calcium in the HRT users suggests that HRT is associated with decreased prevalence of the coronary calcification.

High-order multifetal gestation--management and outcome.

During the period 1975-1989, 11 high-order (quadruplet or more) multifetal gestations reaching the second trimester were treated in our department. All pregnancies resulted from ovulation induction therapy. Premature contractions occurred in all cases. Two women delivered stillborn quadruplets vaginally at 25 and 26 weeks' gestation. Nine women had cesarean deliveries at 28-35 weeks; one fetus was stillborn and two of the 39 live-born infants died. Twenty-nine (74%) weighed less than 1500 g and 16 (41%) were below the tenth percentile for gestational age. Thirty infants have been followed for at least 2 years, corrected for gestational age; 21 (70%) are developing normally, two are severely handicapped with both cerebral palsy and mental retardation, four have mild motor delay, and three have mild motor and mental delay.

Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?

Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.

Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures.

Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.

The impact of hormonal therapy for infertility on the age at menopause.

OBJECTIVES: To look for possible association between past history of ovulation induction and age at menopause. DESIGN: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. PATIENTS: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. RESULTS: The age at the final menstrual bleeding was 46.4+/-5 in the study group, and 50+/-4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8+/-5 years. Smoking had a weak effect on the age at menopause (48.5+/-4 for current, vs. 49.9+/-4 for non- or past-smokers; P<0.03). CONCLUSIONS: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.

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.

Acceptability and skin reactions to transdermal estrogen replacement therapy in relation to climate.

The acceptability and skin reaction of Estraderm Transdermal Therapeutic Systems as a function of climatic variability were examined in various zones which alter considerably in their temperature and humidity. An open, noncomparative prospective study was carried out in four institutional out-patient menopausal clinics in varying climatic areas. Eighty symptomatic postmenopausal patients without previous estrogen replacement were examined. Estraderm T.T.S. 50 was applied twice weekly in four weekly cycles. Norethisterone-acetate tablets (1 mg), were taken orally for 12 consecutive days. Using a questionnaire, the subjects were asked about the efficacy of the treatment on postmenopausal symptoms, the adhesiveness and tolerability. The results were matched with the meteorological conditions. The duration of the study was 6 months. Acceptability of Estraderm T.T.S. is high (78.7%). Discontinuation of treatment was found in 21.3% of the study group. The main reason for discontinuation is due to skin reactions which occurred in 14 of the 80 patients (17.5%). Meteorological conditions in this study did not influence the rate of skin reactions. No difference in acceptability of the treatment was found in relation to the mean temperature and mean humidity as registered in the dry desert and the humid coastal areas.

Gender paradox in cardiac calcium deposits in middle-aged and elderly patients: mitral annular and coronary calcifications interrelationship.

OBJECTIVES: mitral annular calcification (MAC) occurs mainly in middle-aged and elderly patients and can lead to serious clinical consequences. Male predominance in the prevalence of coronary disease is well-established. Paradoxically, the prevalence of MAC, which is theoretically based on the same etiological mechanisms as coronary atherosclerosis, seems to be predominant in postmenopausal women. The goal of this work was to investigate gender influences on interrelationship between MAC and coronary calcifications (CC) in the same population of middle-aged and elderly patients with increased cardiovascular risk. METHODS: the study comprised 522 patients (284 men and 238 postmenopausal women, aged 52-80 years, mean 65+/-6), who were recruited to the International Nifedipine GITS Study of Intervention as a Goal in Hypertension Treatment (INSIGHT) study in our region. They underwent both fast spiral computed tomography of the heart and echo-Doppler. MAC was defined as advanced when its thickness was > or =5mm; otherwise it was defined as trivial. RESULTS: there were 37 (16%) women and 25 (9%) men with advanced MAC (AMAC), 97 (41%) women and 118 (42%) men with trivial MAC and 104 (44%) women and 141 (50%) men without MAC. The prevalence of any type of CC was significantly higher among men (P=0. 001). In sharp contrast to the distinct male predominance in coronary disease, AMAC was more prevalent among women. In patients without CC prevalence was 9 and 4%, increasing to 16 and 8% in those with nonsevere CC and to 38 and 14% in patients with severe CC, respectively (P=0.001). Multivariate analysis showed that AMAC can predict the presence of severe CC in women and men, with OR of 4.1 and 2.6 (CI 1.2-14.8 and 1.0-10.6) and coronary disease with OR of 2. 5 and 2.5 (CI 0.6-10.6 and 1.0-6.4), respectively. CONCLUSIONS: AMAC signifies a high probability of coronary atherosclerosis in patients of both genders. The inverted gender predominance in the prevalence of annular calcification and CC could be explained by additional etiological (likely osteoporotic) mechanisms of MAC development among postmenopausal women.

Dialysis during pregnancy in advanced chronic renal failure patients: outcome and progression.

Successful pregnancies in uremic women are rare. Early initiation of regular hemodialysis in pregnant moderately uremic women is debatable. We chose regular hemodialytic treatments in 2 pregnant patients with stable renal failure with the aim of improving fetal outcome. The first patient with reflux nephropathy arrived at our clinic in the 18th week of her second pregnancy, having a serum creatinine level of 4.5 mg/100 ml and a creatinine clearance (Ccr) of 15 ml/min. Regular hemodialysis was carried out from the 29th gestational week until delivery. A healthy female infant was born weighing 1,095 g at the end of the 36th week of pregnancy. The second patient had an immune complex nephritis with a serum creatinine of 4.2 mg/100 ml and a Ccr of 18 ml/min. Hemodialysis was performed regularly from the 13th gestational week until the 37th week and stopped when normal labor developed and a healthy female infant weighing 2,145 g was born. We believe that the early initiation of regular hemodialysis in these 2 patients contributed significantly to the successful outcome of their pregnancies.

Puerperal inversion of the uterus.

Puerperal inversion of the uterus is a complication of the third stage of labor. The two main reasons are excessive cord traction and Crede fundal pressure. Its frequency in Israel is unknown. A case of acute, complete inversion of the uterus is presented, treated promptly by immediate reposition and manual separation of the placenta. The various modes of treatment are discussed. Puerperal inversion is a rare and dangerous complication. Prompt diagnosis and the proper choice of treatment will decrease the morbidity and mortality associated with this complication.

Atrial natriuretic peptide plasma level remains unchanged in various hypertensive disorders of pregnancy.

The decreased volume of maternal extracellular fluid in preeclamptics may result in a different rate of atrial natriuretic peptide secretion and thus affect its plasma levels. Our objectives were to determine whether there was a difference in plasma levels of atrial natriuretic peptide in the various hypertensive disorders of pregnancy. Forty-nine pregnant women in the third trimester of pregnancy were evaluated: 21 with preeclampsia, 17 with chronic hypertension during pregnancy and 11 normotensives. The atrial natriuretic peptide concentration was 13.9 +/- 5.9 pg/ml, 17.8 +/- 13.5 pg/ml and 16.7 +/- 7.4 pg/ml in the preeclamptics, chronic hypertensives and normotensives, respectively. The differences between the three groups were not statistically significant. Atrial natriuretic peptide plasma levels remained stable in the various hypertensive disorders of pregnancy.

Fetal common cloaca--a case report and review.

A case is presented in which a huge cystic mass adjacent to the outline of a 29-wk fetus was identified by ultrasonography. After delivery this was proven to be a common cloaca in a fetus with multiple congenital anomalies. The possible mechanisms of this anomaly are discussed.

Major surgical complications of laparoscopy.

During the 15-yr period from 1965 to 1979, 6 major surgical complications were encountered among 2757 consecutive laparoscopies, yielding a rate of 2.1 per 1000. Five of the complications required exploratory laparotomy (in 2 patients with small bowel perforations, 2 patients with intraabdominal bleeding and 1 patient with severe peritonitis). In the 6th patient perforation of the uterine fundus occurred during laparoscopy performed because the presence of an adnexal mass was suspected at 15 wk gestation. Laparotomy in this patient was not performed since bleeding from the perforation site stopped spontaneously. Exploratory laparotomy rather than laparoscopy should be considered for evaluation of pelvic masses suspected after the first trimester of pregnancy. A small rate of major surgical complications of laparoscopy is to be expected even when accurate technique is used.

Excretion of total estrogens and estrone-3-glucuronide during treatment with human menopausal gonadotropins.

HMG treatment is usually monitored by the evaluation of the cervical mucus, the determination of plasma 17 beta-estradiol, total urinary estrogens, ultrasonographic evaluation or a combination of these. We evaluated the daily validity of estrone-3-glucuronide excretion in urine as an indicator of follicular growth and maturation in 28 infertile women who were treated with HMG (Pergonal 500). Total urinary estrogens and estrone-3-glucuronide were measured in 24 h urine collections, and 11 of the women collected the early-morning urine separately. This allowed comparison of the concentrations and excretion of total estrogens and estrone-3-glucuronide of the 24 h urine with that found in the urine collected overnight. This comparison was made on 83 urine samples. The correlation between either the total excretion per 24 h or the concentration per liter in the 24 h urine collection of the two systems of determination was good in all determinations. Also in the urine collected on the day prior to HCG administration, total estrogens measurement was in good correlation with the estrone-3-glucuronide. However, there was statistically a significant difference in the concentrations of total estrogens and estrone-3-glucuronide between the women who ovulated and those who did not. Estrone-3-glucuronide, when calculated as a percentage of the total estrogens, was 60.86% in the women who ovulated and 33.15% in those who did not. These results demonstrate that although estrone-3-glucuronide reflects ovarian function in women treated with HMG, it may serve as a better predictor to ovulation.

Laparoscopy in the management of uterine perforation.

The introduction of laparoscopy as a routine diagnostic tool for pelvic disorders has prompted its use in the management of uterine perforation as well. A retrospective review of 52 patients with uterine perforation secondary to curettage is presented. In 23 (44.2%) the curettage was discontinued, and the postperforation course was uneventful. Eight patients (15.4%) underwent immediate exploratory laparotomy without laparoscopy; in three of them no internal organ injury or bleeding was found. Eighteen patients (34.6%) underwent postperforation laparoscopy; seven of these women underwent subsequent laparotomy. The indications and objectives of postperforation laparoscopy are outlined. Its judicious use allows proper selection of patients for exploratory laparotomy.

Lupus anticoagulant. Significance in habitual first-trimester abortion.

Therapy with steroids and aspirin has been reported to benefit pregnancies in patients with lupus anticoagulant (LA). In this study, habitual first-trimester aborters with LA using steroids and aspirin were compared to a control group of untreated habitual aborters without LA. In habitual aborters with LA, 12 of 24 (50%) pregnancies reached the second trimester as compared to 8 of 22 pregnancies (36%) in the control group. Since the treated group did no better than the control group, LA probably is not a cause of first-trimester abortion. However, once the second trimester is reached, a 50% incidence of growth retardation was found, and 42% of fetuses died in the second or third trimester in treated LA patients. Treatment with steroids and anti-platelet aggregating agents may be necessary despite the attendant risks to prevent those sequelae in the second and third trimesters. There was a 29% live birth rate in treated LA patients; the rate was 36% in control patients. However, this rate was produced only by early intervention, which was unnecessary in the control patients.

Successful pregnancy in a woman with cyanotic congenital heart disease after a palliative pulmonary-systemic shunt. A case report.

A 20-year-old woman with cyanotic congenital heart disease composed of corrected transposition of the great vessels, severe pulmonic stenosis, atresia of the left pulmonary artery and a large ventricular septal defect, had a successful pregnancy following a pulmonary-systemic shunt (Blalock-Taussig). The hemoglobin decreased from 21 to 16 g/dL following the operation. The antepartum course was complicated by intrauterine growth retardation and pregnancy-induced hypertension. A normal fetal nonstress test and biophysical profile permitted continuation of the pregnancy until 38 weeks' gestation, with delivery of a healthy infant.