Vasectomy--a note of concern.
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Ethics, Medical↗
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Role of colony-stimulating factor-1 in reproduction and development.
The CSF-1 null mouse, osteopetrotic, has provided a powerful model in which to study the biological functions of CSF-1. In this review, I will describe our studies that have used this mouse model to determine the impact of a lack of CSF-1 on developmental processes and in reproduction. A role for CSF-1 in reproduction was originally suggested by the sex steroid hormone-regulated uterine epithelial synthesis of CSF-1 and the expression of its receptor in trophoblast and decidual cells. Studies on the fertility of CSF-1 deficient osteopetrotic mice (csfmop/csfmop) mice confirmed this suggestion and in addition revealed an unexpected function for CSF-1 in male fertility. In both sexes, CSF-1 appears to regulate gonadal steroidogenesis, probably through its action on macrophages that are abundant throughout the ovary and testis. In the female, CSF-1 affects ovulation in vivo and in vitro, and impacts the preimplantation embryo, increasing both its rate of development and the number of trophectodermal cells in the blastocyst. CSF-1 also has a role in mammary gland development during pregnancy, since at mid-gestation in csfmop/csfmop mice, ductal branching is impaired, and after partiturition, there is a failure to switch to lactation. The relative failure of csfmop/csfmop mice to respond to external stimuli also suggested a role for CSF-1 in the brain. CSF-1 mRNA is expressed in a regional specific manner in the brain through development whilst the CSF-1 receptor is expressed throughout the brain in microglia. CSF-1 is neurotrophic in embryonic neuronal cultures and its absence in csfmop/csfmop mice results in severe electro-physiological abnormalities in the cortex. This suggests that CSF-1 is a neurotrophic factor acting through the microglia. The pleiotropic roles for CSF-1 in reproduction and in the brain suggest that CSF-1 exerts many of its action through the trophic activities of cells of the mononuclear phagocytic lineage.
Animals↗
[Sex differences in demands made on medical services. Results of the SOMIPOPS health survey].
Data of the nationwide health survey SOMIPOPS show a higher number of physician visits for females than for males. Females report a total annual rate of 6,6 visits per person while males made 4,8 visits per person. Females have seen a gynecologist once a year. They report higher perceived morbidity than males which is considered to be the principal determinant of use of health services. Visits made for disorders of the female reproductive system accounts for 13,9% of the female visits. Preventive reasons for the last visit are more frequent among females.
Adult↗
Effect of intrauterine devices on menstrual blood loss.
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Adult↗
Luteinizing hormone determinations obtained with either a monoclonal and a polyclonal antibody radioimmunoassay and their correlations with clinical findings.
Detection of circulating levels of gonadotropin is fundamental in reproductive physiology and related disorders. The advent of monoclonal antibodies might supply the clinician with faster and more accurate estimates of these hormones. We have evaluated the hormonal determinations provided by a monoclonal assay and those generated from our previous assay, produced by the same manufacturer, based on polyclonal antibodies. Comparison was performed on blood samples collected from volunteers with regular menstruation (n = 51) or patients attending our Clinic. The correlation between data provided by the two assays fluctuated from the almost complete overlap of the physiological menstrual cycle to the striking dissociation of the patients (n = 13) receiving a Gonadotropin Hormone-Releasing Hormone analog for gonadotropin suppression. Intermediate coefficients of correlations were recorded in normal subjects undergoing a Gonadotropin Hormone-Releasing Hormone stimulation test (n = 12) and in patients with functional hypothalamic amenorrhea (n = 19) or polycystic ovarian disease (n = 37). Values obtained with the monoclonal assay tended to be lower than those recorded with the previous system. A closer correlation with the clinical findings was observed in the hormonal values originated with the monoclonal assay.
Amenorrhea↗
Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome characterized by familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts. This dominant disorder is caused by germline defects in one of at least five DNA mismatch repair (MMR) genes: hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 (GTBP). Germline mutations of hMSH2 and hMLH1 are also frequently identified in families not fulfilling all the Amsterdam criteria, thereby demonstrating that the involvement of these genes is not confined to typical HNPCC. To evaluate the respective involvement of the various MMR genes in typical and incomplete HNPCC syndromes, we have performed an analysis of the hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in a large series of French kindreds (n=75) with colorectal tumors and/or aggregation of extracolonic cancers belonging to the HNPCC spectrum. Mutational analysis has been performed in all families, without preselection for the tumor phenotype. We have detected 26 pathogenic germline mutations of the hMLH1 and hMSH2 genes and several novel variants of the hPMS1, hPMS2, and hMSH6 genes. Our data confirm that, regardless of the type of families and the tumor phenotype, hPMS1, hPMS2, and hMSH6 germline mutations are rare in familial aggregation of colorectal cancers. Furthermore, they suggest that the presence of multiple primary malignancies in a single individual and the observation of extracolonic tumors in relatives of a colorectal cancer patient should be included among the guidelines for referring patients for genetic testing.
Adaptor Proteins, Signal Transducing↗
The effects of intrauterine contraceptive devices on the ultrastructure of the endometrium in relation to bleeding complications.
The effects of inert (Lippes Loop D and Dalkon Shields) and medicated (copper 7, copper T, and Progestasert) intrauterine contraceptive devices (IUDs) on the ultrastructure of the endometrium were studied in intact human uteri. The most striking morphologic changes induced by the inert and copper-bearing devices were erosion of the surface epithelium and extensive microthrombosis in stromal capillaries of the endometrium in contact with the device. These abnormalities were associated with extravascular thrombi, erythrocytes, and fibrin deposition in the adjacent stroma. Capillary microthrombosis and leukocyte infiltration into the uterine cavity were most extensive around the active part of the copper-bearing devices. With the Progestasert erosion of surface epithelium was rarely seen, but the intact epithelial lining had fewer ciliated cells with flattened and shortened cilia. Large dilated venules were a common finding below the surface epithelium adjacent to the active part of the Progestasert; capillary microthrombosis was found only below the inert arms of the Progestasert. The vascular response of the endometrium to IUDs appears, therefore, to be directly related to the type and proximity of the device. The morphologic changes induced in both surface epithelium and the microvasculature of the endometrium are the likely explanation of the uterine bleeding problems associated with IUDs but are probably intrinsic to the mode of action of the IUD in interfering with implantation.
Adult↗
Menstrual bleeding with copper-covered intrauterine contraceptive devices.
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Adult↗
Effects of hormonal and nonhormonal contraceptives on lactation and incidence of pregnancy.
From June 1974 to June 1976, 665 women who had given birth to full-term infants and who were willing to nurse the infant were admitted to this study. At three to six weeks postpartum, subjects chose which of four study groups to join. One-hundred-forty-three mothers chose Group I, exclusive lactation with no contraception; 109 chose Group II, lactation and intrauterine contraception (IUD); 228 chose Group III, lactation and an intramuscular injection of 150 mg medroxyprogesterone acetate (Depo-Provera Sterile Aqueous Suspension, DMPA) given every three months; and 185 chose Group IV, lactation and one tablet of 0.6 mg Clogestone Acetate given daily. Mother and child were examined monthly until the child's spontaneous weaning, the mother's dropout, or the study's close in 1979. Mothers from Group I (exclusive lactation) were dropped from study when they requested and were prescribed a contraceptive. During the first six months of study, the percent of mothers who dropped out of Groups I, II, III, and IV for personal or medical reasons was 28.0, 16.5, 11.4, and 27.1, respectively. Pregnancies began to occur in the sixth month postpartum. Overall, pregnancies occurred in 6% of mothers in exclusive lactation, 3% of mothers protected by an IUD, and 8% of mothers protected by Clogestone. No pregnancies occurred in the 228 women receiving DMPA. Some mothers in the Clogestone or DMPA groups were still breast-feeding their children two or three times a day at the study's close, at which time the child was three or more years of age. No ill effects were observed in growth and development of these children during the study. The DMPA group had the most mothers who were breast-feeding for more than 20 months.
Adolescent↗
Immunohistochemical staining of von Willebrand factor in endometrium of women during the first year of Norplant implants use.
The mechanisms responsible for Norplant implants-induced menstrual irregularities remain poorly understood. It is unclear whether local changes in endometrial haemostasis are involved. The aim of the present study was to examine the immunohistochemical staining for von Willebrand factor (vWF) in endometrial biopsies taken from 37 women exposed to Norplant implants for 3-12 months and to compare it with 73 controls at various phases of the normal menstrual cycle. The vWF staining intensity was quantified by subjective scoring and by objective computerised colour image analysis. Results from the Norplant implants group were additionally correlated with their bleeding patterns, endometrial histology, and plasma oestradiol (E2) and progesterone (P4) levels. No differences were found between control and Norplant implants subjects in the localization of vWF staining, which was specifically confined to the endothelium of endometrial blood vessels. vWF staining intensity in Norplant implants endometrium was significantly lower than in controls during mid cycle, and reached a mean (+/- SE) level (subjective staining score 2.05 +/- 0.13, n = 37) in the range of the early proliferative and mid secretory phase normal endometrium; nevertheless, it remained significantly higher than that of menstrual and late secretory phase normal endometrium. No significant variations in vWF staining could be related to either the histology of the endometrium or the bleeding pattern of the users. Correlation of vWF staining with either serum E2 or serum P4 prior to biopsy, or to the number of days of Norplant implants exposure revealed no significant relationships. However, vWF staining was positively correlated (r = 0.419, P < 0.01) to the number of bleeding/spotting days within a 90-day reference period prior to biopsies being taken. These results demonstrate that there are major differences in the mechanism responsible for normal menstruation and Norplant implants-induced intermenstrual bleeding and spotting, and show that menstrual disturbances associated with the use of Norplant implants are unlikely to be due to changes in vWF levels in endometrial endothelial cells.
Adult↗
Variables associated with peripartum traits in dairy cows. II. Interrelationships among disorders and their effects on intake of feed and on reproductive efficiency.
Daily individual voluntary intakes of dry matter (DM % of body weight) and estimated net energy (ENE, Mcal/100 kg) by 89 Holstein cows were compared between day 220 of gestation and day 30 postpartum over a 21-month period. The purpose was to compare effects of diet and health status (control vs. abnormal) on intakes of DM and ENE. The cows were fed either chopped hay, hay crop silage (HCS) or corn silage (CS). Compared to controls, voluntary intakes of DM and ENE were decreased (most to least) in cows with fat cow syndrome (FCS), parturient paresis (PP), mastitis (MST), retained fetal membranes-metritis (RFM-M), and displaced abomasum (DA) prepartum and FCS, DA, PP, RFM-M and MST peripartum. Cows fed hay had a lower incidence of RFM-M (28%) than cows fed HCS (57%) and CS (47%) as well as superior reproductive efficiency subsequently (89% conceived vs. 72% and 78%, respectively).
Journal Article↗
The gonadal axis in men with schizophrenia.
The typical onset of schizophrenia during late adolescence and early adulthood has stimulated interest in the potential contribution of hypothalamo-pituitary-gonadal (HPG) axis abnormalities to this disorder. Previous investigations of reproductive hormone function in men with schizophrenia suggest diminished activity of the HPG axis. These studies have been hampered, however, by methodologic limitations. We have attempted to address these limitations by rigorous determination of gonadotropin and gonadal hormone levels, and attention to demographic and diagnostic variables. In contrast to prior studies, our results indicate that schizophrenic patients do not show statistically significant differences from healthy volunteers with respect to luteinizing hormone pulsatility, response to gonadotropin-releasing hormone challenge, and testosterone secretion. Due to the small number of subjects, however, these findings must be regarded as preliminary and warrant further study.
Adult↗
A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism.
Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.
8,11,14-Eicosatrienoic Acid↗
Kinetics of nonpeptide antagonist binding to the human gonadotropin-releasing hormone receptor: Implications for structure-activity relationships and insurmountable antagonism.
Numerous nonpeptide ligands have been developed for the human gonadotropin-releasing hormone (GnRH) receptor as potential agents for treatment of disorders of the reproductive-endocrine axis. While the equilibrium binding of these ligands has been studied in detail, little is known of the kinetics of their receptor interaction. In this study we evaluated the kinetic structure-activity relationships (SAR) of uracil-series antagonists by measuring their association and dissociation rate constants. These constants were measured directly using a novel radioligand, [3H] NBI 42902, and indirectly for unlabeled ligands. Receptor association and dissociation of [3H] NBI 42902 was monophasic, with an association rate constant of 93+/-10 microM(-1) min(-1) and a dissociation rate constant of 0.16+/-0.02 h(-1) (t(1/2) of 4.3 h). Four unlabeled compounds were tested with varying substituents at the 2-position of the benzyl group at position 1 of the uracil (-F, -SO(CH3), -SO2(CH3) and -CF3). The nature of the substituent did not appreciably affect the association rate constant but varied the dissociation rate constant >50-fold (t(1/2) ranging from 52 min for -SO(CH3) to >43 h for -CF3). This SAR was poorly resolved in standard competition assays due to lack of equilibration. The functional consequences of the varying dissociation rate were investigated by measuring antagonism of GnRH-stimulated [3H] inositol phosphates accumulation. Slowly dissociating ligands displayed insurmountable antagonism (decrease of the GnRH E(max)) while antagonism by more rapidly dissociating ligands was surmountable (without effect on the GnRH E(max)). Therefore, evaluating the receptor binding kinetics of nonpeptide antagonists revealed SAR, not evident in standard competition assays, that defined at least in part the mode of functional antagonism by the ligands. These findings are of importance for the future definition of nonpeptide ligand SAR and for the identification of potentially useful slowly dissociating antagonists for the GnRH receptor.
Binding, Competitive↗
Use of phenytoin in pregnancy for epileptic seizure prevention: a case report.
Epilepsy is the most common neurological disorder in women of reproductive age. Phenytoin is one of the most frequently prescribed antiepileptic drugs. Although the vast majority of women with epilepsy have normal pregnancy outcomes, certain fetal anomalies and pregnancy complications are associated with epilepsy and phenytoin use. Appropriate midwifery care of women with epilepsy includes consultation and co-management with an obstetrician and a neurologist. The clinical course of a woman with epilepsy taking phenytoin is presented.
Abnormalities, Drug-Induced↗
The role of 17 beta-hydroxysteroid dehydrogenases.
The biological activity of steroid hormones is regulated at the pre-receptor level by several enzymes including 17 beta-hydroxysteroid dehydrogenases (17 beta -HSD). The latter are present in many microorganisms, invertebrates and vertebrates. Dysfunctions in human 17 beta-hydroxysteroid dehydrogenases result in disorders of biology of reproduction and neuronal diseases, the enzymes are also involved in the pathogenesis of various cancers. 17 beta-hydroxysteroid dehydrogenases reveal a remarkable multifunctionality being able to modulate concentrations not only of steroids but as well of fatty and bile acids. Current knowledge on genetics, biochemistry and medical implications is presented in this review.
17-Hydroxysteroid Dehydrogenases↗
Medical comorbidities in the treatment of epilepsy.
The treatment of epilepsy extends far beyond seizure control. Many comorbidities have a significant impact on the medical management and quality of life of patients with epilepsy. In this review, we examine interactions between epilepsy and some common medical conditions. Psychiatric disorders with a high prevalence in epilepsy include mood disorders, anxiety disorders, and psychosis. Depression is common, psychosis occurs both in direct relation to seizures and interictally, and suicide rates are increased. Changes in sexual function and reduced fertility and marriage rates are described, including a discussion of polycystic ovary syndrome, which is increased in women with epilepsy. The effects of other chronic medical comorbid conditions are reviewed, including the effects of antiepileptic medications on bone health and the impact of renal insufficiency on pharmacological therapy of epilepsy.
Comorbidity↗
Amniotic fluid and umbilical cord blood concentrations of antidepressants in three women.
BACKGROUND: Pregnancy and the postpartum period are a time of increased risk for women to develop mood disorders. As such, the reproductive safety data on antidepressant use during pregnancy have rapidly expanded over the last decade; however, there is relatively sparse information on maternal/fetal exchange of these medications and no data reporting their concentrations in amniotic fluid. METHODS: We report on three women treated during pregnancy with fluvoxamine, sertraline, and venlafaxine, respectively. Amniotic fluid at amniocentesis and umbilical cord blood and maternal blood at delivery were collected and analyzed for antidepressant concentrations using high performance liquid chromatography with UV detection. RESULTS: Antidepressant and metabolite concentrations were detectable in all amniotic fluid samples, though parent compound concentrations were less than maternal serum and umbilical cord blood concentrations. No adverse effects of the medication were reported. CONCLUSIONS: The presence of these antidepressants in amniotic fluid suggests that fetal exposure to these medications is continual and may occur through a variety of paths, thus accounting for increased fetal exposure. These paths include circulatory via placental passage, gastrointestinal via fetal swallowing, and respiratory secondary to fetal lung absorption.
Adult↗