The effects of postmenopausal hormone replacement therapy on hemostatic variables: a meta-analysis of 46 studies.

The aim of the study was to summarize and reanalyze all available data from the literature to study the overall effect of postmenopausal hormone replacement therapy (HRT) and its various forms on hemostatic variables. Studies were identified from literature searches by Medline and Index Medicus, review articles and personal communications. Reference lists of all articles were checked to find additional studies. Principal investigators were contacted and asked to provide additional data if required. Data were collected separately for each factor of the hemostatic system. Studies written in any language were included. Each collection of studies was analyzed using standard methods for meta-analysis. A total of 76 arms of 48 studies were eligible for analysis. This included 6,119 women using HRT and 24,974 non-users. The age of investigated women was 40-68 years. HRT was associated with significantly decreased levels of fibrinogen, factor VIII, antithrombin III, and proteins C and S, but significantly increased plasminogen levels. HRT with estrogen alone or in combination with progestins, oral vs. transdermal regimens, different estrogen preparations and various progestins induced significantly different changes in many cases. In conclusion, HRT was associated with changes that could explain the increased rate of venous thrombotic events, and also with some changes that could account for beneficial vascular effects. Surprisingly, the addition of progestins induced favorable changes in many cases. Also, transdermal use was associated with more beneficial effects than oral regimens in some cases.

Postmenopausal hormone replacement therapy and cardiovascular mortality in Central-Eastern Europe.

BACKGROUND: The leading cause of death among elderly women is cardiovascular (CV) disease in the United States and in Western Europe as well. The protective effect of postmenopausal hormone replacement therapy (HRT) on coronary heart disease has been verified in epidemiologic studies. There are no data available on the rate of HRT use in Eastern Europe. Our goals were to study the rates of HRT in Eastern Europe, to compare them to those of the United States and Western Europe, as well as to compare their CV mortality rates. METHODS: The use of HRT in Eastern Europe was calculated from sales records obtained from all pharmaceutical companies that ship HRT preparations to the given area. Data on HRT in Western countries were taken from the literature. Mortality rates were obtained from the World Health Organization. RESULTS: The rate (mean +/- SD) of HRT in Eastern Europe was 2.88 +/- 2.67%, whereas 12.67 +/- 9.97% in Western Europe and the United States, p < .05. The cardiovascular mortality rate per 100,000 women older than 45 years in Eastern Europe was higher (1766 +/- 158.3) than in the Western countries (1155 +/- 164.1, p < .001). CONCLUSIONS: The rate of HRT is markedly lower. whereas CV mortality rates are notably higher in Eastern Europe than in the United States or Western Europe. Because HRT seems to be underutilized in Eastern Europe, to increase its use might be an important tool to improve CV mortality rates. However, due to the risks associated with HRT, other measures to prevent coronary heart disease, such as smoking cessation programs, and other efforts should also be considered in Eastern Europe.

[Therapeutic importance of the diagnosis of Kallmann syndrome]. / A Kallmann-kór kórismézésének terápiás jelentósége.

Hyposmia with hypogonadotropic hypogonadism was diagnosed as Kallmann syndrome in a 24 years old dizygotic female twin. This syndrome indicates the importance of smell in the sexual development through the progenitor cells in the olfactory placode because luteinizing-hormone-releasing hormone (LHRH) secreting cells of hypothalamus arise from these cells. In addition, substitution therapy may be successful in the treatment of the lack of secondary sex traits and primary amenorrhoea as the presented case demonstrated.

Luteal insufficiency as the primary cause of habitual abortion--its successful treatment.

In order to assess luteal insufficiency as a causative factor in habitual abortion, serial progesterone determinations were accomplished. Luteal insufficiency was proved on the basis of progesterone values by criteria elaborated by the author in 151 of 160 unselected patients with a history of 2-6 (mean 3.3) unsuccessful pregnancies. Normalization of luteal function before conception resulted in birth in case of 148 (92.5%) and first or second trimester abortion in case of 12 women (7.5%). 148 women with physiological luteal function delivered 205 newborns from 192 pregnancies (in 44 patients two, in 11 patients twin pregnancies and in one case a trigeminal pregnancy). Out of 12 twin pregnancies 10 terminated with mature, one with immature (complicated with uterus bicornis) births and one terminated with spontaneous abortion. One from the two trigeminal pregnancies resulted in immature birth and one in a spontaneous abortion in the second trimester. Fifteen pregnancies conceived in the group of 13 women with uterus bicornis or septus resulted in 13 mature and one premature births and the sole twin pregnancy case ended with immature birth. Based on the results achieved so far, the author regard the treatment of luteal insufficiency--beside the proving the aetiology--as the most successful therapy for habitual abortion.

[Calcipenic osteopathy in transfusion hemosiderosis and idiopathic hemochromatosis]. / Calcipeniás osteopathia transzfúziós haemosiderosisban és idiopátiás haemochromatosisban.

Bone metabolism studies were performed on 5 patients with transfusion haemosiderosis (2 male, 3 female; mean age: 30.8 years) and 5 patients with idiopathic haemochromatosis (2 male, 3 female; mean age: 48.8 years). In the majority of the patients, the modern osteodensitometric method showed a significant decrease of the mineral content of the trabecular and cortical bones. Low calcitonin and dehydroepiandrosterone-sulphate concentrations were measured in the majority of the patients with calcipenic osteopathy. Besides marked bone loss, hypogonadotropic hypogonadism was found in 3 male patients, while normal LH, FSH concentration values were measured in 3 female patients. The prolactin concentration was normal in all 6 patients. The authors suppose that besides the already known pathogenetic factors, insufficient calcitonin effect and especially the partial lack of dehydroepiandrosterone-sulphate can play a role in the development of bone loss connected with iron overload. Further study with a greater number of patients in required to support the above findings.

Is dehydroepiandrosterone-sulphate a possible pathogenetic factor in osteopenia of patients with iron overload?

Bone metabolism studies were performed on 5 patients with transfusional haemosiderosis (2 male, 3 female; mean age: 30.8 years) and 5 patients with idiopathic haemochromatosis (2 male, 3 female; mean age: 48.8 years). In the majority of the patients, the modern osteodensitometric method showed a significant decrease of the mineral content of the trabecular and cortical bones. Low calcitonin and dehydroepiandrosterone-sulphate concentrations were measured in the majority of the patients with calcipenic osteopathy. Besides marked bone loss, hypogonadotropic hypogonadism was found in 3 male patients, while normal LH, FSH concentration values were measured in 3 female patients. The prolactin concentration was normal in all 6 patients. The authors suppose that besides the already known pathogenetic factors, insufficient calcitonin effect and especially the partial lack of dehydroepiandrosterone-sulphate can play a role in the development of bone loss connected with iron overload. Further study with a greater number of patients is required to support the above findings.

Effects of GABA on the spontaneous muscular activity of the human fallopian tube ampullar segments in vitro.

The effects of gamma-aminobutyric acid (GABA) and some GABA ergic compounds were examined on the spontaneous contractile activity of the ampullar segment of human Fallopian tubes in vitro. In both circular and longitudinal smooth muscle layers, GABA increased the frequency, and decreased the amplitude of the contractions. In longitudinal muscle layer, this effect occurred independently of endocrine status, while in the circular muscle layer, the amplitude was affected only in follicular phase and in postmenopause, but not in the luteal phase. Baclofen mimicked the effects of GABA, whereas muscimol and bicuculline failed to influence the contractility. Our findings suggest that, in the ampulla of the human oviduct, GABAB-receptors may be involved in the regulation of motility, and thus in the modulation of ovum transport and fertility.

Data throwing more light on the causes of postpill amenorrhoea.

PIP: Post-pill amenorrhea was examined in a series of 64 Hungarian women by determining their serum levels of LH, FSH, prolactin, testosterone, dehydroepiandrosterone sulfate, estradiol and cortisol by radioimmunoassay. Subjects had taken the pills Infecundin, Ovidon, Bisecurin, Rigevidon, or Lyndiol for a least 6 months and had been amenorrheic at least 6 months. They were classified into groups as follows: hyperprolactinemic, hyperandrogenic, early menopausal, hypothalamic regulation disorder, and low-normal estradiol. Overweight was most often associated with hyperprolactinemia, hypothalamic disorder and hyperandrogenic women. LH was highest in the hyperandrogenic and hypothalamic groups. FSH was highest in ovarian insufficiency (p0.01). Free testosterone was low in hyperprolactinemia. Dehydroepiandrosterone was highest in hyperprolactinemia, reflecting adrenal function. Cortisol levels did not differ significantly. The results pointed to the fact that post-pill amenorrhea is not a single clinical entity, but a collection of individual disorders.^ieng

Endocrine factors in the etiology of endometrial carcinoma.

In the blood of 39 women with endometrial carcinoma the FSH, LH, estrone, androstendion, estradiol and dehydroepiandrosterone were determined by the RIA method. Compared to the control group the estrone (303.3 +/- 44.3 pmol/l), estradiol (165.2 +/- 29.4 pmol/l) and the androstendion (5.24 +/- 0.44 nmol/l) were significantly higher. The source of the increased estrogen levels was mainly of adrenal origin. The peripheral conversion, i.e. aromatization of androstendion into estrone was particularly marked in the case of adipose patients. The unbalanced estrogen effect in the absence of progesterone is one of the decisive factors in the etiology of endometrial carcinoma.

[Hysterosalpingography with the Foley catheter]. / Hysterosalpingographie mit Foley-Katheter.

Five-hundred hysterosalpingographies with Foley-catheter were investigated and compared to that made with Schultze-instrument. The investigations were performed in both phases in cases of cyclic menstrual bleeding. The advantages of the method used are the followings: simple, atraumatic, painless. There was no flow-back of the contrast material, the shape of the internal genitals was visible in the proper position, moreover, the present method allowed an observation in the original state of the shape of the internal os and the cervical canal by a x-ray-amplifier. The method simplified the hydrotubations during and after plastic surgery on the fallopian tubes. The method can not be employed in the case of Asherman's syndrome, where the uterine cavity is significantly narrowed.

Episodic secretion of hormones and the diagnostic value of single blood estimates. III. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, cortisol.

The episodic fluctuation of serum testosterone, androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS) and cortisol levels was analysed to determine the reliability of a single blood estimate in characterizing the mean value of a 4 h period. Radioimmunoassay of the steroids was performed in sera of 8 apparently healthy women in various phases of the menstrual cycle in 10 min intervals between 08 and 12 h a.m. Reliability criteria of the methods used were comparable to those in common use. The within-person fluctuation of individual values was determined by the coefficient of variation of single estimates, and the methodological error of the single estimates was characterized with the maximum increment from the mean at 95% confidential limits. A maximum deviation of 30.8, 28.6, 37.0, 25.0 and 61.2%, respectively, found in the above order of steroids, suggests several hormone estimations to be necessary for judging hormone availability in a subject.

Episodic secretion of hormones and the diagnostic value of single blood estimates. II. Progesterone, oestradiol and oestrone.

The episodic fluctuation of serum progesterone, oestradiol and oestrone levels was studied. Progesterone was determined in the luteal phase, oestradiol and oestrone concentrations were measured in the proliferative and luteal phases in 8 subjects in 10 min intervals between 08 and 12 h a.m. Reliability criteria proved the radioimmunological methods used to be comparable to those employed routinely. The within-person fluctuation of hormone levels characterized by the coefficient of variation of single estimates averaged 20.16, 23.0 and 11.6% for progesterone, oestradiol and oestrone, respectively. The considerable fluctuation of hormone concentrations suggest the importance of hormone measurements to control luteal function and folliculogenesis during the menstrual cycle.

Episodic secretion of hormones and the diagnostic value of single blood estimates. I. LH, FSH, prolactin.

The episode fluctuation of serum LH, FSH and prolactin levels in peripheral blood was studied to determine the reliability of single estimates of the average blood level. Radioimmunoassay of the hormones was performed in serum withdrawn every 10 min between 8 and 12 h a.m. from 8 healthy women in various periods of the menstrual cycle. The rate of fluctuation of the hormone levels was characterized by the within-person coefficient of variation of single estimates, which averaged 30.3, 15.1 and 19.2% for LH, FSH and prolactin, respectively. Due to a pronounced fluctuation of gonadotropin levels, analysis of several serum samples is recommended to approach the actual mean hormone level.

[Detection of corpus luteum insufficiency by histological study of the endometrium]. / Adatok a corpus luteum inszufficiencia felismeréséhez az endometrium hisztológiai vizsgálata kapcsán.

Characteristic morphologic alterations of endometrium following corpus luteum insufficiency are described. It is emphasized that in the majority of cases insufficiency of corpus luteum--which in 22 per cent of cases lies on the basis of functional sterility--brings about decreased output of progesterone in the luteal phase of the cycle and induces "disturbed secretion" i. e. hypoluteal transformation of endometrium. Another variant may also take place: normal function of the corpus luteum may last over a too short period inducing the shortening of the secretory phase and the early breakdown of the endometrium. Both, above mentioned mechanisms may inhibit the implantation of the fertilized ovum and lead to functional sterility.