Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty postmenopausal women were randomized to receive either continuous combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women) and were monitored to determine the relationship between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregular bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy were measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and endometrial flushing. The levels of PP14 in uterine flushings were significantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentrations of PP14 found in flushings after ccHRT were considerably greater than those found in flushings after tibolone; levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concentration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plasma and uterine CA125 were unchanged by either treatment. Histological analysis of the endometrium from women after 12 months of HRT treatment showed that 86% (6/7) of women on ccHRT had secretory activity as compared to 44% (4/9) women on tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were more likely to have irregular bleeding (P < 0.05). Our studies have shown that endometrial PP14 but not CA125 concentrations are raised to a significant degree by two different forms of period-free HRT regimens. Increased PP14 concentrations in uterine flushing may suggest endometrial stimulation of some form and predict the predilection to irregular bleeding. Thus uterine PP14 concentrations may be used to monitor endometrial responses in women on HRT.
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PMID:A prospective randomized controlled study comparing the morphological and biochemical responses of the endometrium to two different forms of 'period-free' hormone replacement therapy. 975 7

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

Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.
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PMID:A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology. 1138 99