Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
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PMID:Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. 153 21

To assess bone metabolism during treatment with gonadotropin-releasing hormone analogue (GnRHa), serum osteocalcin (BGP), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcitonin (CT), calcium (Ca) and phosphorus (P) were determined before and after 6 months of GnRHa treatment in 15 premenopausal women with clinically diagnosed endometriosis. The bone mineral content (BMC) of the lumbar spine (L3) was measured by single energy quantitative computed tomography in 9 women, and in 6 of these 9 women microdensitometry was performed simultaneously during the treatment. BMC decreased significantly to 92.5 +/- 6.8% (mean +/- SD) of the pretreatment value after 6 months of treatment. On the other hand, microdensitometry revealed no significant change during treatment. Serum BGP and ALP were significantly higher after 6 months of treatment than before treatment, indicating an increase in bone formation. These data indicate that the GnRHa treatment induces an increase in bone turnover and a significant bone loss.
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PMID:[Bone mineral content in premenopausal women treated with gonadotropin-releasing hormone analogue]. 161 17

Before treatment, the trabecular bone mineral content of the lumbar spine and femoral neck was not significantly different between endometriosis patients and age-matched controls (N = 26). In 17 subjects treated with a monthly goserelin implant, serum estradiol (E2) levels were suppressed into the menopausal range. Mean decreases from pre-treatment values in the lumbar spine and femoral neck were -5.7 and -3.8% at 3 months and -8.2 and -7.7% at 6 months of treatment, respectively; lumbar spine values were significantly different (P less than .05) from those of the control group, whose values changed little during the same period. Significant increases over baseline values were also observed in urinary calcium-creatinine ratio and serum alkaline phosphatase. In nine danazol-treated subjects, serum E2 levels were generally within the early follicular-phase range. There were no significant changes in bone assessments. Normal menses returned within 2 months after cessation of either medication. Six months after goserelin treatment, the lumbar spine and femoral neck bone mineral content was still reduced but to values not significantly different from the pre-treatment and control values; urinary calcium-creatinine ratio was decreased, whereas serum alkaline phosphatase was still elevated. The rapid and deep suppression of ovarian steroidogenesis by a monthly goserelin implant induced significant bone loss compared with the control and danazol groups. This loss was not reversed completely 6 months after cessation of treatment, but bone densities at that time were not different from those of controls. Studies of larger numbers of patients followed for longer periods will be required to resolve the question of complete reversibility.
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PMID:Bone mass in endometriosis patients treated with GnRH agonist implant or danazol. 182 35

Estrogen deficiency results in bone mass reduction of largely varying extent in postmenopausal females, indicating that additional mechanisms influence the response of bone. They are by no ways identified in either the animal experiment or under clinical conditions. In search for factors, conditioning the response of bone to estrogen deficiency, we have conducted a study in females under treatment with the GnRH agonist decapeptyl (D-Trp6-LHRH). This drug blocks ovarian function and was administered for treatment of endometriosis or uterine leiomyoma. We determined spinal (dual photon absorptiometry) and forearm (single photon absorptiometry) bone mineral density before and 3 and 6 months after the onset of therapy and measured biochemical parameters of bone metabolism. Our results showed an increase in bone turnover after initiation of estrogen deficiency, as indicated by the elevation of alkaline phosphatase and osteocalcin. This resulted in a secondary decrease in serum intact PTH and 1,25-dihydroxy-vitamin D3. Furthermore, we found a positive correlation between pretreatment values of serum 1,25-dihydroxyvitamin D3 as well as its decrease and the reduction in bone mass during GnRH agonist treatment. This demonstrates that the patients' metabolic conditions predict their response to estrogen deficiency.
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PMID:Bone mass reduction after estrogen deprivation by long-acting gonadotropin-releasing hormone agonists and its relation to pretreatment serum concentrations of 1,25-dihydroxyvitamin D3. 213 29

Recent studies have shown that treatment with the LHRH agonist nafarelin gives symptomatic and objective relief to women with endometriosis. Such a treatment, however, results in increased bone turnover and loss of bone mass. In the present study 17 women with endometriosis were treated with 400 mg nafarelin combined with 1.2 mg norethisterone (NET) for 6 months, followed by 6 months with only 1.2 mg NET. The data were compared to data from a previously published study of 9 women treated for 6 months with 400 mg nafarelin alone, followed by 6 months without treatment. In the group treated with nafarelin plus NET the biochemical parameter of bone resorption (fasting urinary hydroxyproline) remained virtually unchanged, compared to a highly significant increase in the nafarelin-treated group. Estimates of bone formation (serum alkaline phosphatase and plasma bone Gla protein) increased in the nafarelin plus NET group, but to only a minor extent compared to those in the nafarelin group. In addition, bone mineral in the forearm, the spine, and the total skeleton remained virtually unchanged in the group treated with nafarelin plus NET, compared to the bone loss of 2-6%/6 months in the nafarelin group. We conclude that addition of NET to nafarelin treatment of endometriosis seems to have a bone-sparing effect.
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PMID:Is it possible to prevent bone loss in young women treated with luteinizing hormone-releasing hormone agonists? 213 31

Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasally) and six patients danazol (600 mg day orally) for 6 months. Both treatments had already led to hypoestrogenism (E2 less than 21.6 pg/ml) after 3 months. They both were accompanied by an approximately 50% rise in 24-h urinary hydroxyproline output, suggesting accelerated bone resorption at 6 months; yet urinary calcium output did not change significantly. Serum osteocalcin rose by 80-120% and bone alkaline phosphatase activity by 34-40%, suggesting stimulated bone formation at the same time. No detectable changes ensued in cortical bone mineral content in the distal radius or in serum levels of calcium, calcitonin, parathyroid hormone, or aminoterminal propeptide of type III collagen. Three months after treatment, hydroxyproline output, serum osteocalcin and bone alkaline phosphatase were still elevated in women taking nafarelin, whereas only serum osteocalcin was elevated in women taking danazol. Our data thus suggest that bone turnover was increased during nafarelin and danazol therapy and that this effect was reversible.
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PMID:Evidence of similar increases in bone turnover during nafarelin and danazol use in women with endometriosis. 215 May 80

Oestrogen deficiency at the menopause is associated with changes in calcium and bone metabolism. Hypo-oestrogenism induced by the use of GnRH-agonists is clinically useful in the treatment of oestrogen-dependent diseases. This study was done to investigate calcium homeostasis and bone metabolism of pre-menopausal women in a GnRH-agonist-induced pseudo-menopause. Eighteen patients with endometriosis or uterine leiomyoma received monthly i.m. injections of 3.2 mg of long-acting D-Trp-6-LHRH over a 6-month period. Plasma oestradiol-17 beta and progesterone levels under treatment were significantly decreased to the levels of the early follicular phase. Plasma total calcium, serum osteocalcin and plasma alkaline phosphatase concentrations increased, while plasma phosphate levels did not change. Levels of 1,25-dihydroxyvitamin D3 decreased significantly, but 25-hydroxyvitamin D3 values remained constant. Trabecular bone mineral density of lumbar spine decreased continuously during the 6-month period. Nine women completed 6-9 months follow-up. In these women bone loss was reversible. Cortical bone measurements at the proximal radius showed no change during oestrogen deficiency. In conclusion, our findings demonstrate that GnRH-agonist-induced bone loss is reversible. Furthermore, they suggest that the state of pseudo-menopause induced by GnRH-agonist may serve as a model for further pathophysiological studies on calcium homeostasis and bone metabolism in the post-menopause.
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PMID:Reversible bone loss in women treated with GnRH-agonists for endometriosis and uterine leiomyoma. 252 52

The effects of the progestational compound dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one) on liver metabolism have been studied in 101 otherwise healthy women with endoscopically proven endometriosis. The women aged 17 to 45 years were treated with 2 mg dienogest in tablet form daily for 24 weeks. Aspartate amino transferase (ASAT), alanine amino transferase (ALAT), gamma glutamate transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDH), and total bilirubin (BILI) were determined in serum before and after 1, 3 and 6 months use of the progestin. During the therapy period no deviations from the normal ranges were found. There was a slight significant decrease of ASAT and ALAT and a slight significant increase of LDH and BILI (p less than 0.05) remaining within the normal laboratory values. Since no undesirable metabolic side-effects have so far been observed with dienogest, it may be considered an effective new alternative treatment for endometriosis.
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PMID:[Behavior of parameters of liver metabolism in intermediate-term use of the gestagen dienogest in the treatment of endometriosis]. 276 50

We investigated the determinants of bone formation at individual remodeling sites (BMUs) in cancellous bone from 8 osteologically normal, sex hormone-replete women with endometriosis. All were tetracycline double-labeled (2, 12, 2, and 4 day regime) before iliac bone biopsy. At each BMU the mineral apposition rate (MAR) was determined conventionally from the distance between label midpoints (MAR 1) and also from the distance between the mineralization front and the trailing edge of the second label (MAR 2). MAR 1 and 2 were compared with within-BMU measurements of osteoid width (O.Wi) and the activities of osteoblastic alkaline phosphatase (AP) and succinic dehydrogenase (SDH, an enzyme in the Krebs cycle), both quantitated by microdensitometry. A total of 143 BMUs were evaluated, of which 88 were satisfactory for all measurements and 132 were satisfactory for all but SDH. There was a weak correlation (r = 0.34) between MAR 1 and 2 at individual sites, with a mean difference of 0.49 micron/day (mean MAR 0.82 micron/day). The mean MAR of individual subjects tended to be either increasing or decreasing (F = 16.1, p < 0.01). In linear regressions, MAR 2 was statistically dependent on O.Wi, AP, and SDH (73% of the variance accounted for). In contrast, MAR 1 was weakly correlated with O.Wi and only 30% of its variance was accounted for by AP, SDH, and O.Wi. The variance in the MAR 2 data was inversely increased (p < 0.01) compared with MAR 1 as the number of days of bone formation represented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluctuation of mineral apposition rate at individual bone-remodeling sites in human iliac cancellous bone: independent correlations with osteoid width and osteoblastic alkaline phosphatase activity. 786 18

In a group of patients with endometriosis and in a control group of healthy women, the polymorphism of the following systems were studied: ABO and RH blood-group systems; serum proteins haptoglobin (HP), transferrin (TF), vitamin D-transporting protein (GC), protease inhibitor (PI), and the third component of the complement (C3); serum enzymes-amylase of the loci 1 and 2 (AMY1 and AMY2), pseudocholinesterase (E2), and alkaline phosphatase (PP); erythrocytic enzymes-acid phosphatase (ACP1), phosphoglucomutase (PGM1), superoxide dismutase (SOD-A), esterase D (ESD), and glyoxalase (GLO1). Statistically significant differences between the groups compared were established for five genetic systems: ABO, E2, C3, TF, and PGM1. Among patient with endometriosis, the rare alleles of the locus ESD-ESD5 and ESD7-were found, along with ESD 5-5 homozygotes. Several genetic loci can be involved in the pathogenesis of endometriosis; their products can be specifically realized due to peculiarities of biochemical reactions in the organisms of people predisposed to this pathology.
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PMID:[Genetic aspects of endometriosis: features of the distribution of polymorphic gene frequencies]. 910 63


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