Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological mechanisms through which oral contraceptives influence the central nervous system and produce depression were examined. Oral contraceptives reduce the level of serotonin and norepinephrine available at the central adrenergic receptor sites, alter folate and B12 levels, and perhaps influence hypothalamic releasing hormone levels. The level of serotonin is influenced in the following manner. The estrogens in oral contraceptives increase tryptophan available for the brain to convert to serotonin and tryptamine. Depression is associated with lower levels of serotonin, tryptamine, and perhaps tryptophan in the brain. Estrogens in oral contraceptives may also alter pryridoxal phosphate which in turn affects the production of serotonin. Oral contraceptives possibly lower norepinephrine levels by 1) decreasing tyrosine; 2) influencing coenzymes necessary to norepinephrine production; and 3) increasing monoamine oxidase levels. Oral contraceptives apparently inhibit the metabolism of folate and B12, and lower levels of these substances are associated with depressive symptoms. Decreased norepinephrine and serotonin levels may inhibit the release of gonadotrophin-releasing hormones, and these hormones may in turn influence behavior. Recommendations to clinicians were: 1) patients should be screened for a history of depression prior to prescribing oral contraceptives; 2) pill users should be monitored for depression; and 3) 25 mg daily of pyxidoxine should be administered if a patient taking oral contraceptives is deficient in B6.
 ...
PMID:Oral contraceptives and depressive symptomatology: biologic mechanisms. 3 42

59 pubescent rats in whom were determined proliferations and tumors in the spermatogenic epithelium were treated with large doses of estrogens, including sinestrol and diethylstilbestrol. 83 other animals were noted with proliferations and tumors in the testicular interstitial cells and were treated with large doses of androgens or progesterones. Treatment for both groups lasted 9-11 weeks, after which the morphological condition of the testes was examined and the content of luteinizing and follicle stimulating hormone was determined. Estrogens caused a depression of the follicle stimulating hormone and a simulataneous stimulation of luteinizing hormone which lead to the cessation of teratoma seminoma growth. The androgens and progesterones lead to a depression of luteinizing hormone which caused the cessation of tumor growth and to the resolution of proliferations in the interstitial cells.
 ...
PMID:[Hormontal treatment of pre-tumorous diseases of the testis in rats]. 85 73

In a review of mental health aspects of menopause, emphasis is laid on the psychiatric morbidity that precedes any somatic menopausal symptoms. Only sweating and hot flushes are directly related to the menopause. Complaints such as irritability, headaches, fatigue, depression, and ''mental imbalance'' increase prior to the menopause and decrease after it. Various situational factors have been considered as possible precipitants of emotional disturbances: a child marrying, or having 3 or more children. However, studies indicate that women in the year of the menopause were less likely to develop an episode of mental illness requiring admission to a hospital than at other times. Estrogens do improve symptoms of flushes, dryness and sweats. Changes in emotional imbalance are less clear. Women who come for treatment of menopausal symptoms may frequently be suffering from depression which makes toleration of these symptoms more difficult.
 ...
PMID:Mental health aspects. 95 92

The side effects of using estrogen treatments to relieve menopausal symptoms in women are presented. Estrogens are effective in relieving headaches, vertigo, palpitations, and nervous symptoms such as depression, as well as degeneration and atrophy of the genital organs. In Norway, 2.5% of women over 45 as compared with 50% in the U.S. use estrogens to relieve menopausal symptoms. The incidence of endometrial cancer has risen from 9.2/100,000 in 1955 to 15.4 in 1974. Increased susceptibility to endometrial cancer has been linked to long-term use of estrogens, obesity, hypertension, diabetes, and nulliparity. In American studies, Premarin has been associated with increased risk of cancer related to the chemical equilinine, which has a long half-life. After menopause, the need for estrogen is met by the conversion of androstenedione, which is produced by the adrenal gland. When estrogens are taken, it may result in an overstimulation of the endometrium, which could cause cancer. Estrogens have bene found useful and safe for short-term relief of menopausal symptoms, and any patient using estrogens should be under routine observation to prevent development of cancer.
 ...
PMID:[From the Adverse Drug Reaction Committee. Can long-term estrogen treatment induce uterine neoplasms in post-climacteric women?]. 125 36

This review of the effects of sex steroids and oral contraceptives (OCs) on neurologic function in health and disease covers the following: sex steroids and their interaction with neural tissues; the human menstrual cycle and OCs; and sex hormones and OCs in human neurologic disease, i.e., stroke (thromboembolic cerebral infarction, subarachnoid hemorrhage, vascular malformations, and cerebral venous thrombosis), migraine, movement disorders, nervous system neoplasm, and the peripheral nerve. The various sex hormones may exert their effects on the nervous system directly or undergo conversion to more active metabolites. Interactions of sex hormones with neural substrates subserve numerous activities essential to both the well-being and perpetuation of the individual and the species. These interactions are key to the sexual differentiation of the brain, control of the brain-pituitary-gonad axis, and to the establishment of normal patterns of sexual and aggressive behavior in both sexes. Additionally, they play a role in temperature regulation (progesterone), caloric homeostasis (estrogen), and possibly sensory discrimination. The potent influences exerted by sex steroids on catecholamine and indoleamine turnover and the colocalization of labeled E2 within catecholamine and luteinizing hormone-releasing hormone (LHRH) positive perikarya suggest that many of the physiologic effects of sex steroids are mediated by modulation of specific monoaminergic and peptidergic pathways. Estrogens and aromatizable androgens also induce irreversible structural alterations in the rodent hypothalamus during the neonatal and peripubertal periods that are predominantly synaptogenic. In adult mammals, estrogens induce pathologic changes in the hypophysiotropic hypothalamus that may contribute to reproductive senescence in some species. Data from a series of retrospective and prospective studies have implicated OC use as an independent risk factor for the development of hemorrhagic and nonhemorrhagic stroke. Hormonal changes accompanying the pregnant state and the estrogen (and possibly progestogen) content of OCs may be predisposing factors in thromboembolic cerebral infarction, subarachnoid hemorrhage, cerebral venous thrombosis, and bleeding from intracranial and spinal vascular malformations. There are well-documented temporal associations of migrainous headache with specific phases of the menstrual cycle and the modifying influences of pregnancy, the menopause, and OC use. Also well established are relationships between endogenous and exogenous sex hormones and chorea. Fluctuating sex steroids also influence neuropsychiatric states, such depression and neuroendocrine disorders.
 ...
PMID:Neurology of sex steroids and oral contraceptives. 302 81

The large body of evidence presented indicates that in the brain the action of sex hormones cannot be thought as restricted to the regulation of endocrine functions and mating behavior. Estrogens and progesterone seem to act in numerous regions of the CNS to regulate motor as well as limbic functions. Furthermore, the data reviewed indicate that these hormones may modulate neuronal activity through a wide variety of mechanisms. More studies should focus on such mechanisms in order to better understand the role of sex hormones in the CNS and to devise ways of limiting their effects on depression, epilepsy etc. It is known that in peripheral target organs these hormones modulate cell activities by binding to specific receptors which can recognize the DNA sequence and activate the transcription of selected genes (135, 136). There is evidence supporting the hypothesis that this mechanism of action has been conserved also in the brain. First, the brain receptors for progesterone and estrogens are functionally and biochemically indistinguishable from those in the periphery (4, 5): they may be concentrated in neuronal nuclei and bind chromatin "in vitro" (7). Second, a temporal relationship has been observed between administration of steroids and the increase of polymerase II activity (137) and protein synthesis (4, 5). Third, various hormone-induced behaviors may be blocked by inhibitors of the protein synthesis (138, 139, 140, 141). However, sex hormones must be capable to regulate neuronal functions by mechanisms other then genomic. In fact, the topical application of estrogen or progesterone on nervous tissue results in a rapid change of membrane potential (60, 71). Such a rapid effect is not likely to be the consequence of nuclear action, but rather must be related to events occurring on the cell surface. It has been hypothesized that sex steroids affect the fluidity of the cell membrane, therefore modifying the ion transport or neurotransmitter receptor activity (142). If this were the case we would expect to observe a similar effect after application of any steroid. Experimental evidence demonstrates that not all the steroids affect the nervous membrane potential. Moreover, two steroids, estradiol and progesterone, have been described to modulate membrane potential in an opposite way (66, 67, 69, 75). At the moment, there is no evidence for the presence of steroid receptors on neuronal membranes which could mediate the described phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Role of female gonadal hormones in the CNS: clinical and experimental aspects. 389 52

Whether the differences in progestin-estrogen formulations of oral contraceptives (OCs) lead to any clinically significant differences is an important question, even though the concept of "tailoring the pill to the patient" has assumed less importance as the hormonal dosages have decreased. Each component can be evaluated individually, but it is often difficult to predict the result of their combined action. All of the new low-dose formulations contain the same estrogen, ethinyl estradiol (EE). Although the type of progestin in low-dose OCs is probably of little significance for efficacy and cycle control, it may be more important in regard to lipid and carbohydrate metabolism. Combined OC therapy acts simultaneously at various levels of the reproductive system, and contraceptive efficacy of pills with less than 50 mcg of estrogen probably results from these combined actions. The action of estrogen and progesterone is synergistic: the sustained estrogen component exerts negative feedback on gonadotropin secretion, provides stability to the endometrium, and increases the potency of the progestational agent, while progestin can influence only estrogen-primed tissue. The progestin suppresses luteinizing hormone secretion; in addition, progestational influence dominates estrogenic influence in affecting the remainder of the reproductive system. Previous OC usage may delay pregnancy by several months but does not impair longterm fertility potential or increase congenital anomalies or abortions if conception occurs subsequent to the 1st post-pill cycle. Breakthrough bleeding, which occurs in 15% of users, is the single most frequent cause of pill discontinuation but appears to be of no medical consequence. Breakthrough bleeding and amenorrhea may be controlled by changing the pill formulation. Depression has been reported in 5% of OC users, but pill use appears to alleviate premenstrual tension. The individual patient's risk-benefit ratio must be considered when noncontraceptive uses of the pill are contemplated. OC use has been cited as a cure for dysmenorrhea, although the mechanism is uncertain. The possible preservation of fertility or prevention of progression of endometriosis with cyclic pill use should be investigated. The controlled sloughing of a uniformily thinning endometrium prevents and controls dysfunctional uterine bleeding, endometrial hyperplasia, and the anemia that results. Use of OCs has been recommended in treatment of hirsutism to suppress ovarian function when the hypersecretion of androgens is documented. Since both adrenal and ovarian androgens are often involved in hirsutism, the combined suppressive actions of OCs frequently are beneficial. Estrogens also decrease sebum production and often result in indirect acne improvement. Cyclic estrogen-progesterone therapy is recommended for inducing sexual maturation in primary amenorrhea secondary to gonadal failure.
 ...
PMID:Formulation and noncontraceptive uses of the new, low-dose oral contraceptive. 623 95

The evidence supports from clinical and epidemiological studies demonstrates that the prevalence of various neurological diseases changes with gender. The reason for the gender difference in these diseases is still unclear, but accumulating evidence suggests a link between gonadal hormone, such as estrogens, levels and the incidence of these diseases. Numerous reports support the idea that immunological processes contribute to the etiopathogenesis of the neurodegenerative disease, such as, Parkinson's or Alzheimer's disease; psychiatric disorders, such as schizophrenia or depression; multiple sclerosis or stroke. The neuroinflammation is regulated by numerous signal molecules, including cytokines. Estrogens have been shown to play a major role in inflammatory processes. One mechanisms by which estrogens could modulated the immune reaction is regulation of the cytokines expression. This article briefly describes different biological mechanisms underlying estrogen anti-inflammatory activity.
 ...
PMID:[Immunosuppressive aspects of estrogen]. 1456 Jul 2

Lifetime prevalence rates of depression are higher in women than men. Because this gender disparity appears after the onset of puberty and declines after menopause, gonadal hormones may play a role in women's increased vulnerability to dysphoric states. Estrogens have powerful effects beyond their role in reproduction. Fluctuations in estrogen occur naturally throughout the reproductive years and can be associated with disruptions in mood. Treatment for depression with exogenous estrogen has produced equivocal results. To shed light on the complex interactions among estrogens, serotonin, and mood, we briefly examine (a) central serotonin systems and their relationship to mood and mood disorders, (b) nonreproductive effects of estrogens on those systems, (c) potential points of intersection between serotonin systems and estrogens, and (d) research into the use of exogenous estrogen in depression in women. In conclusion, we reiterate the call for carefully controlled research into the etiology and treatment of depression in women.
 ...
PMID:The effects of estradiol on central serotonergic systems and its relationship to mood in women. 1790 67

The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tragic result of the 2002 WHI study. Although their hostility to estrogen therapy antedated these studies, the flawed data is now used as justification for the denial of estrogens for treatment of low bone density and various types of hormone responsive depression in women. Estrogens should be first choice therapy for osteoporosis in women under the age of 60 years, but in practice bisphosphonates, with its increasing number of long-term side-effects, has become first-line therapy for physicians. These side-effects include osteonecrosis of the jaw, mid-shaft femoral fractures and the need for proton pump inhibitors, which further reduce bone density and add to the fracture risk. Psychiatrists fail to use transdermal estradiol for postnatal depression, premenstrual depression and perimenopausal depression in spite of randomized trials demonstrating their efficacy. Selective serotonin reuptake inhibitor therapy for depression independently decreases bone density and is also responsible for loss of libido, loss of mental acuity and dependence. Thus postmenopausal women with vasomotor symptoms, depression, loss of libido, vaginal dryness or low bone density are frequently denied effective estrogen therapy and given a combination of low-cost generic prozac and fosamax, which is in danger of becoming a post-WHI nightmare drug PROFOX (PROzacFOsamaX). This can only be avoided if advisory bodies review the reassuring evidence concerning estrogen therapy in women under the age of 60 years and advise accordingly.
 ...
PMID:Why are physicians reluctant to use estrogens for anything--or do they prefer 'PROFOX'? 1946 68


1 2 3 Next >>