Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gonadal steroids--estrogens and androgens--appear to have a mood-elevating, psychotonic effect. The improved sense of well-being and increased vigor probably is engendered by restoration of somatic efficiency and psychic equilibrium. 1. The male climacteric, as observed in a limited number of men, is associated with a low level of serum testosterone. The levels of follicle-stimulating hormone and luteinizing hormone are not elevated because estrogen concentration continues unaltered well into old age. Androgen replacement therapy often lessens fatigue, depression and headaches, and headaches, and improves libidinous drives. 2. In the aging female, many climatric symptoms other than those due to vasomotor instability were heretofore considered merely coincidental. Recent studies suggest that the metabolism of cerebral hormones is markedly influenced by endogenous and exogenous gonadal steroids. Thus, postmenopausal depression, headaches, and nervousness may be hormone-dependent symptoms. 3. The incidence of endometrial cancer is no greater and is probably less in estrogen-treated women than in women not treated with estrogen, if regular cyclic courses of an oral progestogen are added to the regimen.
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PMID:Update on the male and female climateric. 48 57

The purpose of this study was to investigate whether continuous infusion of an anabolic steroid, stanozolol, would alter skeletal muscle size and performance in sedentary male mice. The study was performed as a preliminary to an investigation on the effect of anabolic steroids on skeletal muscle regeneration in the mdx mouse, an animal model used for the study of Duchenne muscular dystrophy. Skeletal muscle structure and contractile behavior, and heart, liver, kidney, and testis wet weights were assessed after 3 or 6 wk of continuous exposure to one of two concentrations of stanozolol. Continuous release pellets containing either a high (1.5 mg) or low (0.5 mg) concentration of stanozolol were implanted into 8-wk-old C57BL/6J male mice. Control mice were implanted with pellets containing the drug vehicle. Stanozolol infusion had no significant effect on the contractile strength or mass of either fast-twitch extensor digitorum longus or slow-twitch soleus muscle. The resistance to fatigue of both muscles, assessed in vitro, was unaffected by stanozolol; however, postfatigue recovery of soleus twitch and tetanic tension after 3 wk of treatment was significantly (P < 0.05) increased in high-dose mice compared with control and low-dose mice. Androgen-sensitive muscles, bulbocavernosus and levator ani, were significantly (P < 0.05) increased in wet weight after 3 wk of stanozolol treatment, but were not significantly different from control muscles after 6 wk, suggesting that continuous infusion produced a tolerance to the drug. Similarly, heart wet weight was significantly (P < 0.05) increased in stanozolol-treated mice compared with control after 3 wk, but not after 6 wk. Testis wet weight was significantly (P < 0.05) decreased in low-dose mice compared with control mice at 3 wk, but not at 6 wk. Plasma testosterone concentration was not significantly different between any of the groups after 3 or 6 wk of treatment. This study suggests that in the absence of other factors (e.g., high-intensity exercise or other degenerative changes in muscle fibers), continuous infusion of an anabolic steroid produces no significant effect on the growth, contractile strength, or endurance of hindlimb skeletal muscles.
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PMID:Effect of continuous infusion of an anabolic steroid on murine skeletal muscle. 847 3

In 1% of women, premature ovarian failure develops by 40 years of age, a condition causing amenorrhea, infertility, sex steroid deficiency, and elevated gonadotropins. Early loss of ovarian function has significant psychosocial sequelae and major health implications. These young women have a nearly two-fold age-specific increase in mortality rate. Among women with spontaneous premature ovarian failure who have a normal karyotype, half have ovarian follicles remaining in the ovary that function intermittently. Indeed, pregnancies have occurred after the diagnosis of premature ovarian failure. Thus, premature ovarian failure should not be considered as a premature menopause. Young women with this disorder have a 5% to 10% chance for spontaneous pregnancy. Attempts at ovulation induction using various regimens fail to induce ovulation rates greater than those seen in untreated patients; however, oocyte donation for women desiring fertility is an option. Young women with premature ovarian failure need a thorough assessment, sex steroid replacement, and long-term surveillance to monitor therapy. Estrogen-progestin replacement therapy should be instituted as soon as the diagnosis is made. Androgen replacement should also be considered for women with low libido, persistent fatigue, and poor well-being despite taking adequate estrogen replacement. Women with premature ovarian failure should be followed up for the presence of associated autoimmune endocrine disorders such as hypothyroidism, adrenal insufficiency, and diabetes mellitus.
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PMID:Premature ovarian failure. 992 18

Androgen suppressive maneuvers still represent the gold standard for prostate cancer patients. However, they are associated with side effects (fatigue, sexual impotence, hot flushes, anemia, anxiety, depression and osteoporosis) all of which have a negative impact on quality of life. Nonsteroidal antiandrogens compete with dihydrotestosterone for the linkage of its own receptors. These compounds are commonly used in combination with suppressive maneuvers. However, there is a growing experience with them as monotherapy, based on the possibility to spare gonadal function and therefore prevent the effects related to its suppression. Many studies have demonstrated the feasibility and safety of this approach, which can represent a valuable alternative to suppressive maneuvers for patients wishing to retain sexual function, especially for those without distant metastases. Unfortunately, none of the comparative studies performed so far had the power to detect the equivalence between monotherapy and castration.
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PMID:Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? 1093 69

A 23-year-old female patient presented with hirsutism and fatigue nine months after delivery. Endocrine assessment showed high testesterone, DHEA-S and androstenedione levels. Abdominal computed tomography and ultrasonography revealed the presence of a large tumor in the right renal region. Right adrenalectomy was performed resulting in a diagnosis of a functional adrenal tumor. Pathological examination showed a steroidogenically active tumor. Adjuvant chemotheraphy was administered postoperatively. At three months following surgery all endocrinological tests normalized, but liver metastases were detected by abdominal CT. Eight months after the operation the patient died of hepatic and renal failure. Androgen-secreting adrenal tumors are seen very rarely, yet the prognosis is poor due to their agressive nature.
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PMID:A young female patient with an androgen-secreting tumor: a rare malignant disease. 1121 93

Klinefelter's syndrome (KS) concerns men and is usually characterized by tallness, underdeveloped testes and sterility. It is generally due to the 47,XXY genotype, ie one extra X chromosome in each cell. Its estimated frequency among newborn boys is 1/500 to 1/700. It seems that 64% KS would be undiagnosed. Abnormally low levels of testosterone blood values are very common in this syndrome. In this case, replacement androgen therapy should be initiated (ideally at the age of 11-15) which prevents osteoporosis and enhances secondary sexual features. Case report - Since early childhood, Mr X has been shy, passive with few friends. When he was 13 years old, the school physician noted a delay of puberty and referred him to an endocrinologist who diagnosed KS. Androgen therapy was introduced but rapidly stopped, because the boy and his parents thought it was useless. Mr X consulted a psychiatrist at the age of 21. He presented a schizo-affective disorder with influence syndrome, auditory and visual hallucinations, labile mood with disinhibited and depressive periods. He was admitted in a psychiatry ward of a general hospital. An endocrinologist confirmed the diagnosis of KS and found very low blood testosterone levels. Besides lithium and risperidone which had already been introduced before the hospitalization, androgens (testosterone undecanoate) were very progressively given to Mr X with a daily psychiatric evaluation. One month after discharge, a major depressive episode led to the adjunction of citalopram. After one year of follow-up, Mr X shows increased social adjustment and enhanced interest; the influence syndrome has partially regressed and his mood is more stable. Discussion - In the years '60 and '70, systematic screenings in psychiatric hospitals have detected 1.3% KS among hospitalized boys, ie 10 times more than in the general population, and 0.6 to 1% KS among hospitalized men. A large variety of psychiatric disorders have been described. Boys presenting KS are usually described as shy, with little energy and initiative, and few friends. They cry more often than compares. Neuropsychological studies demonstrate significantly lower verbal IQ than controls, while performance IQ is generally normal and global IQ is in the normal range with large individual variations. Language acquisition is always delayed. However, agressiveness is not increased. In his follow-up study of 20 years, Nielsen at al found more psychiatric disorders among KS patients, compared to a group of hypogonadal patients at first examination (mean age=27 years). After 20 years follow-up, however, no significant difference remained between the two cohorts concerning the frequency of psychiatric hospitalizations or mental diseases. Several hypotheses have been proposed to explain psychological aspects of KS such as low levels of androgens during foetal and child development, personality disorder related to hypogonadism, delay of mitosis of cells with an extra X chromosome, but none of them is able to explain the specificity of psychological problems associated with KS. Concerning therapeutic aspects, specialists prone substitutive androgen therapy in case of too low testosterone blood levels, from the time of increase in FSH (around the age of 11-15). It prevents osteoporosis, backache and excessive tiredness often found in males with KS; testosterone also improves social drive, mood, concentration and ability at work. If KS diagnosis is made at adult age, androgen therapy has also shown some efficacy, though less than if started earlier. Due to the oral and written language problems of KS boys between 5 and 12 years of age, Graham et al. recommend anticipatory guidance for these boys. In addition, they insist on the importance of the information of the parents, language therapy, the reduction of the length of the instructions given by schoolmasters and specially stimulating and stable childhood conditions. Though it is generally thought that androgens increase agressiveness, we found no consistent data in litterature proving that the restoration of physiological androgen blood levels increases crimes nor aggressiveness. In the contrary, Miller and Sulkes described four cases of KS men presenting chronic fire-setting behaviors. Testosterone was introduced. For three of them, follow-up was available: their behavior seemed improved and none of them recurred. However, the initiation of androgen therapy for patients with severe psychiatric illness should be done very carefully. Conclusion - The Klinefelter's syndrome is frequent and, if not diagnosed (which seems to be the most common case), these men have higher risks to develop psychiatric disorders. Therefore, child psychiatrists and psychiatrists should evoke that diagnosis when they examine boys or men who present typical physical traits of KS (tallness, underdevelopped testes) associated to school problems and/or psychiatric disorders. Indeed, if the diagnosis is confirmed by an endocrinologist and a genetic testing, psychological follow-up and testosterone undecanoate treatment (in case of abnormal testosterone blood levels) should be initiated. This therapy generally improves physical well-being and improves mood, concentration, capacity at work. There is no consistent data in the litterature proving that restoring physiological testosterone blood levels would be dangerous for KS men presenting severe psychiatric troubles. However, this should be discussed in each situation with caution, and androgens should be introduced very progressively.
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PMID:[What is the interest of Klinefelter's syndrome for (child) psychiatrists?]. 1209 88

The role of androgen treatment in women remains controversial. The proposed "Female Androgen Insufficiency Syndrome" (Fertility and Sterility, April 2002) describes a number of non-specific symptoms including unexplained fatigue, decreased well being/dysphoric mood and/or blunted motivation and diminished sexual function. An estimated 40% of women experience sexual dysfunction, highlighting the need for ongoing research into this field in order to fully define the possible contribution of androgen insufficiency. The increasing availability of products, such as dehydroepiandrosterone (DHEA) supplements also points to the need for controlled studies to assess the safety of these and other preparations. Measurement of androgens in women requires sensitive assays with the ability to detect low levels and a narrow range with precision. Normal ranges of androgens for women of reproductive and post-reproductive age remain poorly defined. Debate exists as per importance of measurement of free versus total testosterone, with the "free androgen index" offering an alternative method of assessment of testosterone availability. Testosterone treatment is being developed for women in the form of transdermal patches, gels or cream, with percutaneous implants in common usage in some countries. Recent research has highlighted alternative means of administration, such as oral inhalation or buccal lozenge. DHEA is widely available in some countries. Research to date has demonstrated improvements in libido and sexual function, mood and well being. Evidence points to other potential benefits of androgen treatment, including preservation of bone mass, a possible protective role in breast cancer and beneficial effects on cognition. Adverse effects of androgen treatment in women are dose-dependent and include virilisation, mood disturbance and acne. These are uncommon if appropriate doses are administered and highlight the need for treatment to be closely monitored clinically and biochemically. Beneficial effects of testosterone treatment in post-menopausal women with lowered androgen levels have been well documented, and preliminary evidence suggests a role for treatment in pre-menopausal women with symptoms and lowered testosterone levels.
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PMID:Androgens in women. 1294 23

Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 alpha-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and sexual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel, a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful in American patients, who have benefited from its availability for almost 3 years. Furthermore, in phase II and III clinical studies, the intramuscular injection of 1000 mg testosterone undecanoate every 12-15 weeks has led to extremely stable serum testosterone levels for a prolonged period of time and has resulted in excellent efficacy. It is very likely in the future that these products will be the mainstay of testosterone supplementation. Whereas the indication for testosterone substitution for men with classical forms of hypogonadism is unequivocal, the use of testosterone in men with age-associated hypogonadism is less uniformly accepted. Yet, the few studies addressing this question indicate that men with testosterone serum levels below the lower normal limit for young adult men and with lack of energy, libido, depressed mood and osteoporosis may benefit from testosterone supplementation. However, it should be kept in mind that the experience documented in studies is limited. Nevertheless, serious side-effects, especially in regard to the prostate, did not occur, with the longest study extending over 3 years.
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PMID:Testosterone supplementation: what and how to give. 1462

Androgens are important determinants of body composition in men. Androgen-deprivation therapy, the mainstay of treatment for advanced prostate cancer, increases fat mass and decreases lean body mass. These adverse changes in body composition may contribute to treatment-related fatigue, fracture risk, insulin resistance, and increased cardiovascular disease risk. Potential strategies to treat or prevent these adverse body composition changes include exercise training, alternative forms of hormonal therapy, and insulin-sensitizing agents.
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PMID:Changes in body composition during hormonal therapy for prostate cancer. 1504 79

There are many treatment options for female sexual dysfunction (FSD), with the optimal therapy depending on the etiology of the problem. The cause of sexual dysfunction is multifactorial and may include psychological problems such as depression or anxiety disorders, conflict within the relationship, partner performance and technique, issues relating to prior abuse, medical illness, medications, fatigue, stress, or gynecological problems that make sexual activity uncomfortable. The role of low androgen concentrations in FSD is gaining increasing attention. Available therapeutic options include adjusting medications, counseling, treating depression or anxiety, reducing stress and fatigue, sex therapy, devices, estrogen therapy for genitourinary atrophy, and possibly vasoactive substances. Although no androgen therapies are currently approved by the Food and Drug Administration for FSD, they are being used in clinical practice, and early clinical trial results suggest that they may be both effective and safe in the treatment of FSD, specifically low libido. Androgen therapy should be considered primarily in women who have a physiological reason for reduced androgen concentrations, including aging, hypopituitarism, oophorectomy, or adrenal insufficiency. Products in use include oral methyltestosterone and dehydroepiandrosterone, topical testosterone ointment, and testosterone implants and injections. Products available for men, including skin patches and gels, are currently being studied at doses appropriate for women. Possible risks include hirsutism, acne, liver dysfunction, lowering of the voice, adverse lipid changes, virilization of a female fetus, and, as androgens are aromatized to estrogens, potentially the risks of estrogen therapy.
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PMID:The role of androgens in female sexual dysfunction. 1506 34


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