Influence of gonadal hormones on neurotransmitters, receptor, cognition and mood.
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Affect↗
Biomedical subjects
U Halbreich
Publications and source records attributed to U Halbreich.
Depression, natural killer cell activity, and cortisol secretion.
Natural killer (NK) cell activity was evaluated in 34 ambulatory patients with Major Depressive Disorder (MDD) and 21 healthy controls. No mean differences between the groups were found. However, female depressives (n = 19) exhibited higher NK activity than female controls (n = 14). The relationship between cortisol secretion and NK activity was examined using an integrated cortisol value derived from multiple blood samples taken between 1:00 and 4:00 PM. This comprehensive assessment of cortisol secretion circumvents spurious "single stick" cortisol values and provides a more accurate determination of hypercortisolemia than the dexamethasone suppression test. NK activity in depressives with cortisol hypersecretion (greater than 11 micrograms/dl) (n = 7) was no different than NK activity in depressives and controls with normal cortisol secretion. Furthermore, there was no correlation between cortisol secretion and NK activity in any of the groups. These results indicate that decreased NK activity is not a consistent finding in MDD and cannot be predicted by the presence of hypercortisolemia in these patients.
Adult↗
Hirsutism in chronic psychiatric patients.
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Female↗
Influence of age, sex and diurnal variability on imipramine receptor binding and serotonin uptake in platelets of normal subjects.
Imipramine (IMI) binding and serotonin (5-HT) uptake were determined in platelets of 98 healthy volunteers; and their association with age, sex and circadian rhythm were evaluated. A large interindividual variability was found for both IMI and 5-HT parameters. There was a negative correlation of IMI affinity constant (Kd) and binding (Bmax) with age, but no such correlation of 5-HT affinity constant (Km) or uptake (Vmax). Significant age-related diurnal variability was found for 5-HT Km in the whole group as well as for IMI Kd in males, but not in females. There was no significant correlation between 5-HT Vmax and IMI Bmax. Our results underscore a cautious approach to the interpretation of platelet serotonergic studies. In light of the multiple variables influencing the results, the usefulness of IMI or 5-HT as clinical markers should be re-evaluated.
Adult↗
Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes.
Gonadal hormones are believed to be involved in the pathophysiology of premenstrual changes (PMC) possibly through their interaction with neurotransmitter systems in the brain. The serotonergic system, an important central modulator of mood and behavior which is involved in the pathophysiology of affective disorders has been suggested to play a role in the genesis of dysphoric PMC. Blood platelet serotonin (5-HT) uptake and imipramine (IMI) binding have been shown to share similarities with serotonergic mechanisms in the brain thus enabling the study of serotonergic mechanisms. In this study, we report on platelet 5-HT uptake and IMI receptor binding which were simultaneously studied in women with PMC. Subjects with PMC showed a large interindividual variability with no consistent typical pattern or change during the late symptomatic as compared to the early nonsymptomatic luteal phase. Their IMI receptor binding, however, was lower compared to controls already during the early luteal phase before they developed symptoms and was similar during the symptomatic phase. This might suggest a preexistent vulnerability to the development of dysphoric PMC that might be related to impaired gonadal hormone modulation of the serotonergic system.
Adult↗
Elimination of ovulation and menstrual cyclicity (with danazol) improves dysphoric premenstrual syndromes.
OBJECTIVE: To assess whether the therapeutic effect of danazol on premenstrual syndromes (PMS) is associated with suppression of ovulation. DESIGN: After 1 month on placebo, we administered 200 mg/d of danazol for 90 days to 24 women with dysphoric PMS. Symptoms during ovulatory cycles were compared with anovulatory periods. SETTING: Outpatient PMS program in a general hospital. PATIENTS: Twenty-four women who had dysphoric PMS and otherwise were physically and mentally healthy. INTERVENTIONS: None (except the oral medication). MAIN OUTCOME MEASURE: Prospective daily monitoring of symptoms with the Daily Rating Form, before, during, and after treatment. RESULTS: Twenty of 23 anovulatory periods were symptom-free versus 6 of 32 ovulatory periods (chi 2 = 15.63, P = 0.0002). CONCLUSION: The beneficial effect of danazol as treatment depends mostly on achieving an an-ovulatory state and elimination of hormonal cyclicity and not on the drug per se.
Adult↗
Menstrual irregularities associated with bupropion treatment.
The authors report two cases of menstrual irregularities associated with bupropion treatment. This is the first report of such an association, and it is supported by data collected by the Burroughs Wellcome Co. Since the mode of action of this effective new antidepressant is basically unknown and does not operate through any of the putative mechanisms of the classical antidepressants, its side effect profile is of heuristic as well as practical importance.
Adult↗
Prevalence and severity of premenstrual changes after tubal sterilization.
Many women report an association between tubal sterilization and the premenstrual syndrome. While early reports suggested such a linkage, more recent studies failed to confirm this association. In an attempt to elucidate the alleged association of tubal sterilization with premenstrual changes, we compared the severity of symptoms and their possible correlates with hormonal levels in 78 sterilized and nonsterilized women with prospectively confirmed premenstrual syndrome. No significant difference could be demonstrated between the groups in both the retrospective and prospective evaluation of the severity of premenstrual syndrome symptoms as well as in luteal hormonal levels. Our data confirm that premenstrual symptoms probably are not associated with tubal sterilization.
Adult↗
Estrogen replacement in postmenopausal disorders.
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Climacteric↗
Plasma MHPG and age in detoxified alcoholics.
Plasma levels of 3 methoxy, 4-hydroxy phenylethyl glycol (MHPG) of detoxified alcoholics were found to be positively correlated with age as previously found with normal subjects. The slope of the regression line of plasma MHPG and age of the alcoholics in remission was significantly steeper than that of normal controls, indicating a faster age-related increase of MHPG in alcoholics.
Adult↗
Treatment of premenstrual syndromes with progesterone antagonists (e.g., RU-486): political and methodological issues.
The effect of political and social considerations on development and availability of medication is exemplified by the debate of the progesterone antagonist RU-486 and its indications. Premenstrual syndromes (PMS) are quite prevalent. In some women they are severe enough to warrant treatment, but at present there is no single treatment modality that has been shown to be effective with most women with PMS. Increased levels of progesterone and/or its fluctuations during the luteal phase have been suggested as possible factors in the pathophysiology of PMS. Therefore, progesterone antagonists represent a very promising avenue for treatment of a subgroup of PMS, and some other hormonally-related dysphoric disorders as well. Regretfully, because of the abortant properties of these compounds, they are the subject of a fierce debate and political considerations in the United States, and their availability for treatment trials of other indications in women is limited. It is hoped that progesterone antagonists will eventually be introduced for studies of their treatment and efficacy when indicated.
Abortion, Induced↗
Gonadal hormones and antihormones, serotonin and mood.
Gonadal hormones influence activity of several monoaminergic neurotransmitters, and this might be one of the mechanisms by which these hormones are involved in modulation of behavior. Gonadal hormones' levels and mood fluctuate along the normal menstrual cycle; therefore, this might provide a model for the study of the interaction among hormones, mood, and other biochemical variables. The administration of gonadal hormones' antagonists ("antihormones") and the study of their central nervous system (CNS) and behavioral consequences may further elucidate hormonal-neurotransmitter interaction. We have studied several aspects of the serotonergic system along the menstrual cycle. Results show that imipramine receptor-binding in platelets is decreased in women with premenstrual dysphoric changes in the early luteal phase, 5 to 7 days before development of symptoms and shortly after the substantial periovulatory changes in gonadal hormones. The cortisol and prolactin responses to tryptophan were blunted during the late luteal phase compared with the midfollicular phase, and the cortisol, but not prolactin, responses to the serotonergic agonist 1-(m-chlorophenyl) piperazine, (mCPP) was also blunted during that period. An altered postsynaptic serotonergic responsivity might be suggested in these cases. The role of ovulation and gonadal hormones is further demonstrated by the elimination of dysphoric symptoms by the ovulation suppressant danazol.
Affect↗
Gonadal hormones, sex and behavior.
Gender differences have been demonstrated in several regions of the central nervous system (CNS) in animals and humans. These differences change with development and aging and are probably influenced by hormones. Gender differences have been demonstrated clinically in the prevalence of some mental disorders and responses to psychotropic medications. Gonadal hormones might be involved in these differences as well as in differential cognitive functions. The two genders also differ in the aging process. While it is well known that changes in the pituitary gonadal system influence the aging process in women, preliminary data described here demonstrate the association between pituitary-gonadal hormones and the aging process of sexual desire and activity in men. The changes in levels of gonadal hormones might contribute to the pathophysiology of dysphoric cyclic disorders and increased vulnerability to affective disorders in women. This vulnerability might be related to hormonal fluctuations over time as well as to alteration in internal oscillators and time-related functions.
Aging↗
Plasma melatonin levels in depressed patients before and after treatment with antidepressant medication.
Daytime melatonin was measured by radioimmunoassay in 113 depressed outpatients before and after treatment with imipramine, mianserin, phenelzine, and placebo. At baseline, elevation of daytime melatonin values above expected levels suggests nonspecificity of the assay. After 6 weeks of treatment, melatonin levels were somewhat lower in patients on imipramine, mianserin, and placebo and slightly increased in patients treated with phenelzine. Changes in melatonin levels during treatment were significantly different for phenelzine compared with the other treatments. These findings are consistent with alterations in beta-adrenergic functioning or changes in serotonin levels.
Adolescent↗
Screening and selection process for studies of menstrually-related changes.
The screening process of women who volunteered to participate in "studies of the menstrual cycle" is described. It is demonstrated that in order to arrive at a desired number of subjects who meet criteria for premenstrual changes and are in a good physical and mental status, one should recruit an extremely large number of candidates to start with. The yield of each screening procedure is presented. It is clear that fulfillment of inclusion and exclusion criteria can be obtained by a phone interview while important criteria can be clarified only by prospective monitoring of symptoms and personal structured interviews. Methods and procedures that can improve yield and decrease effort in recruitment are suggested.
Advertising↗
Liver function, plasma dexamethasone, and DST results in detoxified alcoholics.
Alcohol abuse, alcohol withdrawal, and deterioration of hepatic function have been associated with abnormal dexamethasone suppression test (DST) results. Chronic alcohol abuse may also directly alter the pharmacokinetic disposition of dexamethasone. Plasma dexamethasone concentrations following a DST were determined in 53 detoxified alcoholics. Those with abnormal liver function had higher 4 p.m. plasma dexamethasone concentrations and lower DST cortisol concentrations. Those with normal liver function had lower plasma dexamethasone and higher DST cortisol concentrations consistent with induction of hepatic metabolic enzymes from chronic use of alcohol. The data indicate that liver function is one of the variables influencing dexamethasone disposition and DST cortisol suppression.
Adult↗
Hypothalamo-pituitary-adrenal activity in endogenously depressed post-traumatic stress disorder patients.
We studied the hypothalamo-pituitary-adrenal (HPA) system in Vietnam veterans with post-traumatic stress disorder (PTSD) who also met Research Diagnostic Criteria for endogenous depression (MDD-ED). Over half also abused alcohol, and many complained of pain-confounding factors usually associated with increased HPA activity. Nonetheless, not even one patient had elevated basal plasma cortisol concentrations or an abnormal dexamethasone suppression test (DST); the subjects' post-dexamethasone cortisol values and plasma cortisol per ng plasma dexamethasone were in the low-normal range. These results highlight the biological heterogeneity of endogenous depression and its possible influence by past psychological trauma, and they raise questions about the use of current typological criteria for research purposes.
Adult↗