Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beside well-established clinical benefits, the current doses of oestrogens may induce clinical side-effects leading to non-compliance and loss of efficacy. During a normal menstrual cycle the incidence of any cyclic discomfort is consistently reported to be lowest during the mild-follicular phase when plasma E2 remains between 60 and 150 pg/ml. The incidence of pregnancy-like symptoms such as bloating, breast tenderness and mood swings tends to increase in mid-luteal phase when E2 increases upto 150 pg/ml. On the other hand incidence of asthenia, sleep disturbances, depressive mood, headaches and migraines increase during perimenstrual days when E2 drops to 40 pg/ml or below. Accordingly experimental and human studies in castrated animals and postmenopausal women suggest that plasma E2 around 100 pg/ml is optimal for treatment of hot flushes, prevention of bone loss and cardiovascular protection. Due to large interindividual variation in estrogen clearance rate, it is unlikely that any standardized unique dose of oral or non-oral formulations will reproduce the optimal levels in all postmenopausal users. Efforts for individual titration are mandatory to improve compliance and actual efficacy on a long term. Because older postmenopausal women tend to have a better clinical tolerance to low E2 levels, objective markers of efficacy should also be identified when the aim of HRT is the prevention of osteoporosis or vascular diseases. In addition clinical and metabolic side-effects related to added progestins can be substantially reduced by the use of lower dose inducing amenorrhea and by progesterone instead of synthetic steroids.
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PMID:Hormone replacement therapy: clinical benefits and side-effects. 886 37

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.
Cephalalgia 1996 Nov
PMID:Alniditan in the acute treatment of migraine attacks: a subcutaneous dose-finding study. Subcutaneous Alniditan Study Group. 893 95

Twenty-four healthy women received 2.4 mg kg-1 dolasetron mesylate (1.8 mg kg-1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0.08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0.08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2 = 0.23 h) to MDL 74156 (mean t1/2 = 8.05 and 9.12 h after intravenous and oral administration respectively). MDL 74156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men.
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PMID:Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women. 915 83

The chemotherapy side-effects are insufficiently documented while they strongly condition patients' quality of life. The aim of the study was to assess by means of a self-administered questionnaire the somatic symptoms experienced by breast cancer patients during their NCF (mitoxantrone + cyclophosphamide + 5-fluorouracil) chemotherapy and to demonstrate the interest of this self-report by comparing the frequency of side-effects assessed by the patients to that noted by the physicians in medical records. The study was carried out among 44 patients receiving their chemotherapy + radiotherapy at the Paoli-Calmettes Institute (marseille) between July 1994 and May 1995. The questionnaire comprized of 17 symptoms evaluated in terms of frequency, duration/severity and distress. The most frequent symptoms are: hair loss and nausea (75%), hot flush (57%), lack of appetite and headache (46%) associated with distress in 67 to 100% of cases. Their frequency was underestimated by the physicians in medical records. This study showed a large discordance patient-physician in the assessment of chemotherapy side-effects. The type of tool presented in this study could complement the usual scales of toxicity that do not provide an estimation of true patients' experience.
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PMID:[Adjuvant chemotherapy with mitoxantrone, cyclophosphamide and 5-fluorouracil in breast neoplasms: therapeutic life]. 920 68

The clinical examinations covered 1710 women. The investigations were performed on 199 women with symptoms of menopause, who were selected and divided into two groups. The first control group (I) included 80 women employed in the Industrial Clothing Factory "Dana" in Szczecin, without contact with carbon disulphide. The second study group (II) comprised 119 women employed in the Synthetic Fibres Factory "Chemitex-Wiskord" and exposed chronically to carbon disulphide in concentration of 9.36-23.4 mg/m3. The microclimate conditions of the production halls in both groups were similar (Tab. 1). Menopause was present in 16.59% of women in the population chronically exposed to carbon disulphide, as compared with 8.05% in the normal population. Mean age at menopause in women of the first group was 48.1 years and 43.9 years in the second group. In the studied group of menopausal women retrospective estimation of menopausal and gestational cycles shows statistically significant increase in abortion and disorders of menstrual cycles (p < 0.001) (Tab. 2). The women chronically exposed to CS2 had significantly more frequently headaches, weight gain and loss of libido (p < 0.001). In the normal group fatigue, palpitations and hot flushes were found significantly more often (p < 0.001) (Tab. 4). The serum concentrations of estrone (p < 0.01), estradiol, progesterone, 17-hydroxyprogesterone were significantly decreased in women chronically exposed to CS2 (p < 0.001). No significant differences in the level of FSH or LH were noted between both groups (Tab. 3). The daily excretion of adrenaline and noradrenaline in urine concentrations of dopamine in plasma of women chronically exposed to CS2, was significantly lower (p < 0.001), but the serum concentrations of serotonin (Tab. 5), testosterone, dehydroepiandrosterone sulphate (DHAS) and prolactin in plasma were significantly higher (p < 0.001). No difference concerning the level in serum of dehydroepiandrosterone and beta-endorfine was found (Tab. 6). Significant negative linear correlations between serotonin and FSH (r = -0.45; p < 0.001), serotonin and daily excretion of adrenaline (r = -0.43; p < 0.01) or noradrenaline (r = -0.58; p < 0.001) were disclosed in the exposed group. In this group a positive correlation was noted between the concentration of serotonin and prolactin (r = 0.45; p < 0.001).
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PMID:[The effect of carbon disulphide on menopause, concentration of monoamines, gonadotropins, estrogens and androgens in women]. 947 21

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.
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PMID:Steroidal 'add-back' therapy in patients treated with GnRH agonists. 962 21

In an open, prospective, multicentre phase III clinical trial 73 patients with newly diagnosed, metastatic breast cancer were enrolled. Most of them were hormone-receptor-positive. All patients were pre- or perimenopausal and treated with monthly sc. injections of 3.75 mg leuprorelinacetate-depot as monotherapy until disease progression. 50/73 patients (68.5%) had low-risk metastatic disease. A marked reduction of gonadotropin levels resulted in a profound and sustained suppression of the oestradiol levels to castration range (30 pg/ml) during the entire treatment period. The overall response rate based on the best response during treatment was as follows: CR + PR in 25/73 (34.2%) [25.1-44.4%] and CR + PR + SD in 42/73 patients (58%) [47.2-67.4%] respectively. The median time to progression (TTP) was 6 months and the median overall survival (OS) 24.3 months. Both parameters differed significantly when responder (CR/PR) and non-responder (NC/PD) were compared: 18.6 +/- 2.4 [13.9-23.4] vs. 5.8 +/- 0.6 [4.7-7.0] months (TTP, p < 0.0001) and 41.5 +/- 3.0 [35.5-47.5] vs. 15.6 +/- 2.4 [11.3-20.5] months (OS, p = 0.0019). The median duration of response was 12 (range: 3-48) months. Premenopausal low-risk patients without previous adjuvant treatment after primary surgery showed the best response during the GnRHa treatment. The main side effects (hot flushes, increased sweating, headache etc.) were related to oestradiol suppression. Treatment was well tolerated leading in only one case to a premature withdrawal due to side effects. Leuprorelinacetate-depot is a safe and effective palliative drug for pre- and perimenopausal metastatic breast cancer patients. Like other GnRH-agonists which have been evaluated for this indication, leuprorelinacetate-depot can be used as first-line endocrine treatment in these patients.
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PMID:[Primary endocrine therapy as pre- and perimenopausal metastatic breast carcinoma with leuprorelin acetate depot. German Leuprorelin Study Group]. 965 99

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.
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PMID:Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study. 982 25

Menopause and the accompanying reduction in estrogen production may cause a number of symptoms in women which include hot flushes, sweating, mood and sleep disturbances, fatigue and urogenital dysfunction. The effectiveness of estrogen-based hormone replacement therapy (HRT) in ameliorating these symptoms, and in preventing long term sequelae such as osteoporosis, is well established. Comparative trials indicate that oral conjugated estrogens 0.625mg, oral ethinyl estradiol 0.02mg and transdermal estradiol 0.05mg have equivalent efficacy in relief of mild to moderate menopausal symptoms and prevention of bone mineral loss. Concomitant progestogen therapy is usually prescribed for women with intact uteri to protect against endometrial hyperplasia and carcinoma. The addition of progestogen maintains and may even enhance the bone-conserving effects of estrogen, and continuous regimens appear to reduce the incidence of irregular menses. Adverse reactions are predominantly local skin irritation with transdermal preparations (14% of patients) and systemic effects common to most forms of HRT including breast tenderness, flushing, headache and irregular bleeding, occurring in less than or equal to 2% of patients. Data concerning the effect of HRT on quality of life are limited, but most analyses have assigned utility values of 0.99 for mild and 0.95 for severe menopausal symptoms. However, recent clinical data suggest that these utility values may underestimate the impact of menopausal symptoms on quality of life. The cost benefit and cost effectiveness of HRT in the treatment of menopausal symptoms have not been fully researched, although preliminary results suggest that conjugated estrogens and transdermal estradiol compare well with alternative therapies such as veralipride and Chinese medicines. A Swedish study using a prevalence-based approach estimated that estriol treatment in all women with urinary incontinence aged greater than or equal to 65 years resulted in monetary savings compared with treating 20% of women. Cost-utility data indicated that the change in quality-adjusted life years (QALYs) with HRT was always positive, but the degree of change was determined by the baseline assumptions. Estimated changes in QALYs with HRT ranged from 0.006 for 5 years of treatment with unopposed estrogen in women with intact uteri, to 0.5 for 10 years of the same treatment in women with severe menopausal symptoms following hysterectomy. Compliance with HRT is suboptimal as 5 to 50% of women withdraw from therapy, thereby increasing costs per year of life saved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. 1014 33

An 8-week, randomized, double-blind study comparing the efficacy and tolerability of policosanol and acipimox was conducted in patients with type II hypercholesterolemia. Prior to entry into active treatment, all patients followed a standard cholesterol-lowering diet for 12 weeks. Sixty-three patients were randomized to receive either policosanol (10 mg/day) or acipimox (750 mg/day) tablets for 8 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly reduced total cholesterol (p < 0.0001) (15.8%), low-density lipoprotein (LDL)-cholesterol (21%) and the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (15.8%) and cholesterol to HDL-cholesterol (11.5%). Acipimox significantly lowered both cholesterol and LDL cholesterol by 7.5%. The percent changes of total cholesterol, LDL-cholesterol and both ratios were larger in the policosanol group than in the acipimox group. Both drugs were well tolerated. Acipimox significantly increased (p > 0.001) aspartate amino transferase levels but only four patients showed increases above the normal limit. Policosanol significantly reduced creatinine values (p > 0.05) but no patients had values out of the normal range. Four patients withdrew from the study (two from each group) but none withdrew because of adverse effects. No adverse effects were reported in the policosanol group, while five patients on acipimox reported adverse effects (hot flushes, nausea, vomiting, headache, hypochondrial pain and leg edema). These results indicate that policosanol (10 mg/day) was more effective and well tolerated than was acipimox (750 mg/day) in this study population.
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PMID:A comparative study of policosanol Versus acipimox in patients with type II hypercholesterolemia. 1064 16


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