Alexander E. Albrecht

Androgen Serum Levels in Women with Premature Ovarian Failure Compared to Fertile and Menopausal Controls

OBJECTIVE The purpose of our study was to examine androgen serum levels and bone density in women with premature ovarian failure (POF) compared to healthy normal controls. STUDY DESIGN Thirty-three women 19-35 years of age with idiopathic POF were compared to 33 well-matched women with normal ovarian function and 32 healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP), androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS Women with POF showed statistically significantly lower concentrations of 17-OHP, A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile controls. No differences were found between POF and PMP women concerning estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant differences were found between women with POF and fertile controls whereas PMP women proved to have significantly lower DHEAS concentrations than fertile controls. Women with POF had the highest IGF-1 serum concentrations and PMP women the lowest. CONCLUSION An important decrement of ovarian steroids and bone density was noticed in women with POF, while the time since menopause had no influence on androgen concentrations. The hormone concentrations in women with POF are similar to those observed in normal PMP women with the exception of DHEAS and IGF-1 levels.

Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women

OBJECTIVES The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. METHODS The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. RESULTS It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. CONCLUSIONS The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.

Unexpected pregnancy during hormone-replacement therapy in a woman with elevated follicle-stimulating hormone levels and amenorrhea.

Pregnancy in patients with hypergonadotropic amenorrhea, although previously reported, remains quite rare. Women may conceive spontaneously or following different regimens of ovulation induction, thus indicating that ovarian failure is not always permanent. The case of an 18-year-old woman with premature ovarian failure, who conceived during hormone-replacement therapy, is reported. During hormone-replacement therapy, elevated gonadotropin levels returned to the physiologically normal range. It is suggested that this restored the receptors to luteinizing hormone and to follicle-stimulating hormone, which might have been downregulated. This hypothesis is supported by previous results from clinical trials and experimental work on a rat model.

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women

OBJECTIVE To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. METHODS Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. RESULTS Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. CONCLUSION Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.

Hysterectomy increases the symptomatology of postmenopausal syndrome

The purpose of our investigation was to verify whether or not women who have undergone hysterectomy react differently to the menopause compared with women who have not. The study was performed in a prospective documentation on 203 women, and the assessments of discomforts were provided by the patients themselves using questionnaires. For statistical purposes, the Mann-Whitney test and chi 2 test were used. In both groups of patients--with and without hysterectomy--a determination was made concerning the significance of differences in the degree of intensity of problems: breast tension (p < 0.05), muscle pains (p < 0.05), palpitations (p < 0.05) and dizziness (p < 0.01). Concerning the frequency of climacteric symptoms, a significant difference was noted for urogenital ailments. While only 29.6% of women who had not been operated on complained about discomfort caused by atrophy of the urogenital tract, the number of women with such discomfort who had had a hysterectomy was 42.6% (p < 0.01). In other words, women who underwent hysterectomy suffered more discomfort and showed frequent symptoms of urogenital atrophy.

Hormonal breast augmentation: prognostic relevance of insulin-like growth factor-I.

Many women would like to after their breasts but are deterred by the risks involved. Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases. These circumstances urged us to perform this pilot study using a non-invasive method that involved the application of 17 beta-estradiol as it is known that estradiol enhances expression of insulin-like growth factor-I (IGF-I) which can promote growth in breast tissue. Forty-five women were included in the study. Their breast volume, IGF-I, prolactin (PRL) and estradiol levels were measured before treatment and between each application of 80 mg estradiol polyphosphate. The womens satisfaction with the results obtained was also subsequently evaluated. In 21 women (46.7%), breast size increased from 824.3 +/- 13.7 mm to 898.5 +/- 12.5 mm after 6 months. In these women a significant increase in IGF-I values was noted after 4 weeks of treatment. The increase in IGF-I values was not statistically significant in the remaining women. In addition, treatment was not successful in these women. IGF-I concentration seems to be of prognostic value as far as the response of breast tissue to estrogen stimulation is concerned. If IGF-I levels do not increase within 1 month, treatment should be discontinued. If IGF-I values do increase, this indicates that treatment is likely to be successful and can therefore be continued.

Altered growth hormone (GH) secretion in women gaining weight during hormone replacement therapy (HRT)

OBJECTIVES The relationship between GH response to GHRH-stimulation and changes in body weight in pre- and postmenopausal women before as well as after 4 and 20-22 weeks of oral HRT was tested. METHODS 18 postmenopausal women (FSH > 30 mU/ml) were compared to 18 premenopausal women suffering from post-pill amenorrhoea (FSH < 10 mU/ml). Both patient-groups reported an anamnestic increase in body weight during former use of sex hormones. In addition 18 postmenopausal women without anamnestic weight change were studied. RESULTS A significant reduction in GH response to GHRH stimulation was observed during the first month of HRT in both groups gaining weight. However, the body mass index of the patients reverted to pretherapeutic levels after 5 months of HRT. In all patients, a small but statistically significant increase in IGF-1 levels was registered during HRT. These changes in GH stimulation testing and IGF-1 levels were accompanied by distinct changes in body weight. No alterations in GHRH response were observed in those patients whose body weight did not increase. CONCLUSIONS Our results confirm that in predisposed women, HRT is associated with increments in body weight as well as with changes in the GH-IGF-1 axis.

Impact of Maternal Anthropometry and Smoking on Neonatal Birth Weight

The purpose of this study was to determine the effect of maternal pre-pregnancy body mass index (BMI) and maternal smoking habits on neonatal birth weight. We reviewed 10,240 normal singleton term pregnancies between 1985 and 1995 at the University Department of Obstetrics and Gynecology, Vienna. Birth weights of infants of overweight smokers were greater than those of smokers in general and similar to birth weights of nonsmokers, but smoking did have a fetal growth-retarding effect in overweight smoking mothers. Infants of underweight mothers who increased their daily cigarette consumption during pregnancy had significantly lowest birth weight. Our results suggest that the negative effects of smoking during pregnancy cannot be mitigated by a higher pre-pregnancy BMI and/or an improved weight gain during pregnancy. Especially the infants of underweight mothers benefit from their mothers’ decision to cease smoking.

Idiopathic hypereosinophilic syndrome and pregnancy

presented with a generalized erythema. Treatment with prednisone, 15 mg every other day, resolved the erythematous, itchy rash. The diagnosis of an idiopathic hypereosinophilic syndrome was made by consecutive exclusion of parasitic, collagenvascular and allergic diseases. Physical examination was essentially normal except for a grade 2/6 systolic and a grade 1/6 diastolic murmur of the mitral valve. Laboratory analysis included a normal hemoglobin level (13 g/dl), platelet count (260,000/mm3) and hematocrit value (39.3%). The white blood cell count (WBC) was 29,200 cdmm with more than 70% eosinophils. An echocardiogram and cardiac catheterization revealed a hemodynamic relevant mitral valve regurgitation and a mild mitral valve stenosis without evidence of mural thrombi, vegetations, or decreased chamber size from endocardia1 fibrosis. The lungs were clear to auscultation and an ECG showed normal sinus rhythm with signs of discrete left atrial enlargement. Ultrasound examination showed a bichorionic twin pregnancy of 11 weeks with equal biometry and no structural anomalies. Continuation of pregnancy was favored because of an optimistic maternal attitude and because severe restrictive endomyocardiopathy could be excluded. Echocardiographic follow up examinations showed that the persistent mitral valve regurgitation remained asymptomatic and stable during the following weeks. Throughout her pregnancy, the patient was normotensive and had no evidence of renal deterioration. An intermediate rise of eosinophils to 35,000 cuimm required an augmentation of the daily prednisone dosages up to 75mg for a period of five weeks. This was reduced in steps over four weeks to a daily maintenance dose of 25mg. Despite careful monitoring the patient presented with premature rupture of membranes and effective contractions at 30 weeks of gestation. An i.v.-antibiotic regimen with amoxicillin was initiated to avoid fetal infection, combined with tocolytic therapy for the initial 12 hours until repetitive spontaneous decelerations and subsequent prolonged bradycardia of one fetus necessitated immediate Cesarean delivery under general anesthesia. The two male infants weighed 1350 g and 1180 g and had Apgar scores of 8/9/10 and 7/8/9, respectively, at 1, 5 and 10 minutes. The cord blood pH was 7.2817.22 and 7.2417.18, respectively, for venous and arterial cord blood samples. The immediate neonatal period was complicated by transient hyperbilirubinemia of both new-borns, which resolved after a short course of phototherapy. The infants did well subsequently and were discharged at 56 days of age weighing 2100 and 2200 g, respectively. Neither infant showed any sign of hypereosinophilia within their first six months of life. At 10 months postpartum the mother’s WBC count stabilized to the 15,000to 20,000 cuimm range, with 50% to 70% eosinophils, which required continuation of the immunosuppressive regimen. References

Absorption of orally supplied natural estrogens correlated with age and somatometric parameters

The plasma levels of estradiol were studied in 20 postmenopausal women over a period of 8 h following the ingestion of a single dose of 2 mg estradiol valerate and 2 mg micronized estradiol. The determined plasma estradiol concentrations were correlated with somatometric characteristics and age. Twenty-six postcephalic body measurements, the body weight and six skin-fold thickness measurements were taken and the body mass index computed; estradiol serum concentration was measured before and after administration of micronized estradiol and estradiol valerate, respectively. It was shown that estradiol concentrations obtained after estradiol valerate and micronized estradiol ingestion were dependent on the patients age as well as on the constitutional type. Additionally, we found that there were differences in the reachable estradiol plasma concentrations following the application of the two preparations. Our results justify the individual and differentiated estrogen replacement therapy of the postmenopausal woman.