Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behaviour of the concentration of the selected pituitary hormones during hot flushes at women after a surgical castration was evaluated. The inquiry concerned 42 women 46.7 +/- 3.4 years old, with a regular menstruation till the hysterectomy and the adnexectomy due to sexual organs diseases. The inquiry contained a determination, by means of radioimmunological methods, of the concentration of the hormones: LH, FSH, PRL, HGH, TSH in the blood serum taken at women 48 hours before the operation, on the 8th day after the intervention and 5 min after the hot flushes apparition. At the same time, the finger skin temperature and the pulse rate was taken. The rise in the finger skin temperature by 1.2 degrees C and the mean rise in the pulse rate by 11.3 beats/min during hot flushes were noticed. An important increase of the LH and HGH concentration during hot flushes was also observed.
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PMID:[Changes of pituitary hormone concentration during vasomotor disorders, in blood serum of women during the early phase after surgical castration]. 130 17

We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide.
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PMID:[Phase I study of FK 435]. 219 79

Org OD 14 is a new steroid drug taken orally that appears to act weekly but simultaneously on the estrogens, androgens and progestins. The drug eliminates blood FSH and LH in menopausal women without affecting PRL levels. It also proved more effective than a placebo in controlling hot flushes and related disturbances. The patients treated reveal no reduction in bone mineral content. The incidence of side effects was very low and comparable to the findings in the placebo-treated control group: in particular, there were no changes in body weight, hair distribution of blood pressure. Biochemical studies revealed no alteration in live enzymes, bilirubin, CBG, or cortisol. There was a slight reduction in glucose tolerance but long-term studies revealed no change in the glucoproteins. There was a certain drop in HDL-cholesterol with a tendency to normalise even the long-term and a simultaneous decrease in VLDL and triglycerides which should minimise the risk of cardiovascular pathology. No damaging interference with blood clotting was noted. It may be concluded that oral Org OD 14 is effective and safe for the treatment of menopausal patients.
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PMID:New steroid for the climacteric syndrome. 265 54

We administered ovine corticotropin-releasing factor (CRF) as a bolus intravenous injection (1 microgram/kg) at 09.00 and at 20.00 to assess the influence of circadian changes in the hypothalamic-pituitary-adrenal axis on the response to CRF. The increase in plasma ACTH levels after CRF was only slightly lower in the morning than in the evening. The plasma cortisol response to ACTH, however, was significantly greater in the evening than in the morning (p less than 0.005). At both times of day CRF administration had no effect on plasma concentrations of GH, PRL, LH, AVP, insulin, PRA or glucose. No effects were observed on the hematopoietic system, kidneys or liver. In addition, CRF had no effect on heart rate, blood pressure or respiratory rate at the dose employed. Approximately 10% of the subjects complained of a transient upper body and facial hot flush. These observations indicate that the magnitude of the plasma cortisol rise after CRF depends on the time of administration.
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PMID:Ovine corticotropin-releasing factor administration in normal men. Pituitary and adrenal responses in the morning and evening. 298 99

21 women with menopausal disorders were given veralipride, which is a benzamide derivative having a central anti-dopaminergic action. The LH, FSH and PRL plasma levels were controlled before and after treatment. Treatment, using veralipride at a daily dose of 100 mg for 20 days, improved the climacteric syndrome, and, in particular, the sudden hot flushes. The FSH plasma levels remained unchanged, the LH levels were reduced, although they remained high, and the PRL levels increased during the course of the treatment.
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PMID:[Effect of veralipride on LH, FSH, and PRL levels and on the climacteric syndrome]. 392 34

A double-blind cross-over study with Org OD 14 and placebo was performed in 82 menopausal patients presenting with hot flushes and associated symptoms. Patients were randomly allocated to Org OD 14 or placebo as first treatment, and switched to placebo or Org OD 14 as second treatment. Each treatment period lasted for 16 weeks; no wash-out period was introduced. Tablets containing 2.5 mg of Org OD 14 or matched placebo tablets were supplied. Data on the following variables were obtained and analysed by the non-parametric randomization test for paired observations: hot flushes, sweating, dizziness, palpitations, fatiguability, headache, sleeplessness, irritability, breathlessness, backache and loss of libido and, in 16 patients, on circulating levels of FSH, LH, PRL, T3, T4, cortisol (F), SHBG, TBG and CBG. Twenty patients (13 placebo, 7 Org OD 14) withdrew, because their symptoms did not improve and one patient withdrew for reasons unrelated to treatment, so that 61 patients completed the study. The data demonstrated a good clinical effect and statistically significant differences in favour of Org OD 14 for hot flushes and a number of associated symptoms. Many patients reported on a general feeling of well being and a mood-elevating effect following Org OD 14. Org OD 14 significantly suppressed FSH and LH levels, while those of PRL remained unchanged. Although there was slight suppression of TBG and T4 which attained statistical significance, there was no influence on the most important parameter, T3. SHBG levels were slightly suppressed, whereas F and CBG levels were unaffected.
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PMID:Placebo-controlled cross-over study of effects of Org OD 14 in menopausal women. 675 12

Recent basic and clinical advances have consolidated the concept of tissue-selective estrogens, i.e. molecules that express different degrees of partial agonist, full agonist or antagonist activity in different tissues or cells. Delta8,9-Dehydroestrone sulfate (delta8,9-DHES) is a conjugated estrogen and a component of conjugated equine estrogens (CEE). It is metabolized in the human in at least a 1:1 ratio to its 17beta form, 17beta-delta8,9-DHES. To evaluate its activity in different clinical and biochemical parameters, a clinical research study was conducted with delta8,9-DHES and estrone sulfate as a comparator in postmenopausal women. Delta8,9-DHES was given orally at a daily dose of 0.125 mg for 12 weeks in a group of 10 women. Two additional groups of women received either estrone sulfate alone (1.25 mg/day) or the combination of delta8,9-DHES and estrone sulfate at the previously specified doses. A significant and consistent suppression of hot flushes (number, severity, and total score) was observed with delta8,9-DHES, reaching more than 95% suppression in all parameters of vasomotor symptoms. This level of activity was equal to that obtained with the much higher dose of estrone sulfate, and it was sustained for the duration of the treatment period (12 weeks). Measurements of a bone resorption marker, i.e. urinary excretion of N-telopeptide, demonstrated that delta8,9-DHES at 8 weeks produced a degree of suppression (40%) similar to that observed with the higher dose of estrone sulfate. Gonadotropin secretion (FSH and LH) was significantly suppressed in women receiving delta8,9-DHES, similar to that observed with estrone sulfate alone or with the combination of the two. Other parameters, such as total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol were not modified significantly, whereas serum globulins (sex hormone-binding globulin and corticosteroid-binding globulin) showed only marginal increases after delta8,9-DHES administration. Taken together with preclinical data, it is found that delta8,9-DHES is an active estrogen with a distinct pharmacological profile that results in significant clinical activity in vasomotor, neuroendocrine (gonadotropin and PRL) and bone preservation parameters, whereas displaying little or no efficacy, at the dose tested, on other peripheral parameters normally affected by estrogens. Collectively, this information supports the concept that delta8,9-DHES is an integral component of CEE, with distinct tissue selectivity contributing to the CEE's overall clinical activity, and places this estrogen as a distinct member of a novel class of centrally active molecules with unique peripheral tissue selectivity.
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PMID:Estrogen activity and novel tissue selectivity of delta8,9-dehydroestrone sulfate in postmenopausal women. 1037 4