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)

A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N-demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622.
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PMID:[Phase I study of NK 622 (toremifene citrate)]. 146 43

A systems model, providing an estimation of fatigue and fitness levels was applied to a 1-year training period of six elite weight-lifters. The model parameters were individually determined by fitting the predicted performance (calculated as the difference between fitness and fatigue) to the actual one. The purpose of this study was to validate the systems model by comparing the estimated levels of fatigue and fitness with biological parameters external to the model calculation. The predicted and the actual performances were significantly correlated in each subject. The calculated fitness and fatigue levels were related to serum testosterone concentration, testosterone: cortisol and testosterone: sex hormone binding globulin ratios. The best results were obtained by the comparison between fitness and testosterone levels, which varied in parallel in each subject. In two subjects this correlation was significant (r = 0.91, P less than 0.05, and r = 0.92, P less than 0.01). The fitness changes calculated in each subject between the 15th and the 51st weeks of training were significantly correlated with the changes in serum testosterone concentration measured in the same period (r = 0.99, P less than 0.001). For the whole group testosterone and fitness variations were also significantly intercorrelated (r = 0.73, P less than 0.001). Correlations, less homogeneous and less significant, were calculated also for other hormones and ratios. These results suggest that (1) the relationships between training and performance can be described by the systems model, (2) the estimated index of fitness has a physiological meaning. The fatigue index remains to be clarified.
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PMID:A systems model of training responses and its relationship to hormonal responses in elite weight-lifters. 228 97

Seventeen patients with irregular menstrual periods and androgenic symptoms such as excessive hair growth, acne, and oily skin were treated with spironolactone. The basal levels of serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and luteinizing hormone (LH) were significantly higher in the patients than in the controls. After a 4-week treatment with spironolactone, serum T and DHT showed significant decreases. Before treatment, the serum sex hormone binding globulin (SHBG) levels were significantly lower in the patients than in the controls. After initiation of the spironolactone treatment, the SHBG levels tended to increase but not significantly. Spironolactone treatment resulted in the improvement or disappearance of acne in 4 of 5 patients who suffered from this ailment. Improvement of hirsutism was obtained in 2 of 10 patients. Although 4 oligomenorrheic patients and 6 amenorrheic patients showed anovulatory bleeding but did not ovulate, 2 patients in the amenorrheic group ovulated. Two patients complained of tiredness and weakness, and 2 others of polyuria and polydipsia. Both groups showed only temporary symptoms, so treatment was not interrupted. Spironolactone has beneficial effects on ovarian function and few side effects, so it may prove to be an effective anti-androgen, especially for hyperandrogenic anovulatory patients.
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PMID:Spironolactone therapy for hyperandrogenic anovulatory women--clinical and endocrinological study. 395 Apr 64

Previous studies have demonstrated that full recovery from weight loss may take months or years. The present investigation examined short-term recovery (5 wks "post") of physical performance (muscular strength, muscular power, vertical jump), body composition, metabolic hormones (testosterone, luteinizing hormone, sex hormone binding globulin, insulin-like growth factor-1, triiodothyronine, thyroxine, thyroid binding globulin, and thyroid-stimulating hormone) and metabolic markers (transferrin, ferritin, prealbumin, glycerol, nonesterified fatty acids, high-density lipoproteins, and lactate) in 10 healthy young men after an 8-week Army course with an energy deficit (1000 kcal/d) and loss of body mass (-12%). Subjects ate ad libitum after the course ended ("post"). Body composition was determined by dual-energy X-ray absorptiometry; strength from a simulated power clean, power from body mass and jump height, and metabolic hormones were measured in morning-fasted blood by radioimmunoassay. With the exception of transferrin and glycerol, all study parameters were significantly (p<.05) altered by the training course. At 5 weeks post fat-free mass along with all physical performance measures returned to initial levels; however, fat mass had significantly (p<.05) increased over initial levels. Also, with the exception of lactate, all measured hormones and markers were close to initial levels and within normal ranges. Reported complications during recovery included sleep irregularities, diarrhea, loss of motivation and feelings of fatigue. While the long range effect of this energy deprivation experience is uncertain, these data do suggest that severe weight loss does not result in lasting alterations of the contractile and metabolic properties of skeletal muscle in young, lean, healthy men.
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PMID:Physical performance and metabolic recovery among lean, healthy men following a prolonged energy deficit. 929 70

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.
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PMID:Long-term interferon-alpha therapy does not affect sex hormones in males with chronic hepatitis C. 933 29

Testosterone (T) is an important component of female sexuality, enhancing interest in initiating sexual activity and response to sexual stimulation. Testosterone is also associated with greater well-being and with reduced anxiety and depression. Clinical and biochemical definitions of T deficiency have not been established; hence, the prevalence of this condition is not known. However, surgically menopausal women are among the populations most likely to experience T deficiency, a syndrome characterized by blunted or diminished motivation; persistent fatigue; decreased sense of personal well-being; sufficient plasma estrogen levels; and low circulating bioavailable T (either a low total T/sex hormone binding globulin (SHBG) ratio or free T in the lower one-third of the female reproductive range); and low libido. Exogenous estrogen, particularly when administered orally, increases SHBG, which, in turn, reduces free T and estradiol (E2). After oophorectomy, levels of T and its precursor, androstenedione, decline by approximately 50%. T replacement continues to be evaluated as an adjunct to estrogen replacement therapy, particularly for women with androgen deficiency symptoms, surgically menopausal women and women with premature ovarian failure. In the United States, oral methyltestosterone is the common product currently approved for androgen replacement in women. The best product specifically designed for women has yet to be determined, as standardized, long-term, randomized, control clinical studies are lacking and product refinement continues.
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PMID:Testosterone deficiency in women. 1130 77

Aging in men is associated with a progressive but variable decline in androgen production. In aging men there is also an increased occurrence of symptoms such as lack of concentration, nervousness, impaired memory, depressive mood, insomnia, lack of energy and general sense of well-being, decreased libido and erectile dysfunction, periodic sweating, bone and joint complaints, reduction of strength and increased adiposity. This ill-defined male climacterium syndrome is often referred to as "andropause", with the underlying implication that it is at least in part related to (relative) androgen deficiency. Recently an "aging males" symptoms' (AMS) rating scale was developed aimed at a more systematic description of severity of symptoms related to a clinically defined "male climacteric". We studied the relationship of male climacteric symptoms as assessed by the AMS with androgen levels and other questionnaires assessing the perception of health and well-being. Serum levels of sex steroids, sex hormone binding globulin and gonadotropins were measured in blood samples of 161 healthy, ambulatory, elderly men, aged 74-89 years who also completed the AMS scale. Mean value of total, free and bioavailable testosterone in this group was 401.6, 6.8 and 151.4 ng/dl, respectively, with 24.7, 32.4 and 52.2% of the values under the normal range for young men. The results of the AMS scores mostly suggested mild psychological and mild to moderate somatovegetative symptoms. However, clear sexual symptoms were reported in 88% of cases. None of the three AMS domain scale scores significantly correlated with testosterone, free testosterone or bioavailable testosterone. Significant correlations were observed between results for the AMS scores and those for other health questionnaires, but none of the subscores for the latter questionnaires correlated with androgen serum levels. In conclusion, the results of this study have shown that, as assessed by the AMS, healthy ambulatory elderly males over 70 had a high perception of sexual symptoms with mild psychological and mild to moderate somatovegetative symptoms. These data failed to support the view that in healthy elderly men, "climacteric symptoms" can predict androgen levels.
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PMID:Perception of males' aging symptoms, health and well-being in elderly community-dwelling men is not related to circulating androgen levels. 1460 1

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.
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PMID:Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. 1567 38

The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.
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PMID:A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire. 1680 Mar 91

Hypopituitarism is the partial or complete insufficiency of anterior pituitary hormone secretion and may result from pituitary or hypothalamic disease. The reported incidence (12-42 new cases per million per year) and prevalence (300-455 per million) is probably underestimated if its occurrence after brain injuries (30-70% of cases) is considered. Clinical manifestations depend on the extent of hormone deficiency and may be non specific, such as fatigue, hypotension, cold intolerance, or more indicative such as growth retardation or impotence and infertility in GH and gonadotropin deficiency, respectively.A number of inflammatory, granulomatous or neoplastic diseases as well as traumatic or radiation injuries involving the hypothalamic-pituitary region can lead to hypopituitarism. Several genetic defects are possible causes of syndromic and non syndromic isolated/multiple pituitary hormone deficiencies. Unexplained gonadal dysfunctions, developmental craniofacial abnormalities, newly discovered empty sella and previous pregnancy-associated hemorrhage or blood pressure changes may be associated with defective anterior pituitary function.The diagnosis of hypopituitarism relies on the measurement of basal and stimulated secretion of anterior pituitary hormones and of the hormones secreted by pituitary target glands. MR imaging of the hypothalamo-pituitary region may provide essential information. Genetic testing, when indicated, may be diagnostic.Secondary hypothyroidism is a rare disease. The biochemical diagnosis is suggested by low serum FT4 levels and inappropriately normal or low basal TSH levels that do not rise normally after TRH. L-thyroxine is the treatment of choice. Before starting replacement therapy, concomitant corticotropin deficiency should be excluded in order to avoid acute adrenal insufficiency. Prolactin deficiency is also very rare and generally occurs after global failure of pituitary function. Prolactin deficiency prevents lactation. Hypogonadotropic hypogonadism in males is characterized by low testosterone with low or normal LH and FSH serum concentrations and impaired spermatogenesis. Hyperprolactinemia as well as low sex hormone binding globulin concentrations enter the differential diagnosis. Irregular menses and amenorrhea with low serum estradiol concentration (<100 pmol/l) and normal or low gonadotropin concentrations are the typical features of hypogonadotropic hypogonadism in females. In post menopausal women, failure to detect high serum gonadotropin values is highly suggestive of the diagnosis. In males, replacement therapy with oral or injectable testosterone results in wide fluctuations of serum hormone levels. More recently developed transdermal testosterone preparations allow stable physiological serum testosterone levels. Pulsatile GnRH administration can be used to stimulate spermatogenesis in men and ovulation in women with GnRH deficiency and normal gonadotropin secretion. Gonadotropin administration is indicated in cases of gonadotropin deficiency or GnRH resistance but is also an option, in alternative to pulsatile GnRH, for patients with defective GnRH secretion.
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PMID:Hypopituitarism. 1707 46


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