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

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding. 130 44

In an open prospective study with therapeutic monitoring, 34 women with climacteric symptoms, FSH > 40 IU/L and LH > 25 IU/L were treated for 12 months with an estradiol-depot-patch (Estraderm TTS) 50 micrograms twice a week and medroxyprogesterone acetate 10 mg tablets from 12th to 25th day of cycle. During the first months a significant improvement was seen in hot flushes and other climacteric inconveniences in terms of Kupperman's menopause index. During the study period FSH and LH were suppressed and the estrogen values were normalized. The fraction of free estradiol compared to protein bound estradiol remained unchanged during the whole treatment. The serum-lipids and serum-SHBG at inclusion were within normal limits and did not change during 12 months of treatment. Thus from these parameters no sign of any liver induction was seen. Ten patients had short term skin symptoms while four withdrew from the study because of persistent skin symptoms. Nine patients withdrew from the study, in five cases this was related to the therapy while in the other four it was due to other causes. Twenty-five (74%) women wished to continue the treatment after 12 months.
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PMID:Long-term treatment with transcutaneous estradiol and oral medroxyprogesterone acetate. 133 17

An approach employing a range of standardized questionnaires, which included the Nottingham Health Profile (NHP), the Psychological General Well-Being (PGWB) index and the Mood Adjective Check List (MACL), was used to assess health-related quality of life (QoL) in conjunction with a study comparing two doses of transdermal oestrogen (50 or 100 micrograms/24 h) combined with an oral progestogen (5 mg medroxyprogesterone acetate for 14 days each cycle). In addition to the QoL measures, climacteric symptoms were self-rated and also summarized by means of the Kupperman index. In all, 59 women, median age 52 (39-71) years, who completed 4 months of therapy were evaluated. The use of a battery of standardized questionnaires enabled a comprehensive evaluation to be made of perceived health, well-being and day-to-day functioning. Not only was symptomatic relief, e.g. reduced frequency of sweating episodes, sleep disturbance and hot flushes, observed during treatment, but there were also improvements in terms of sleep, energy and emotions. The frequency of health-related problems associated with paid employment, housework, social life, home life and sex life decreased, indicating enhanced ability to take part in daily activities. The PGWB index showed improvement in the subscales representing well-being, anxiety, depression, vitality, health and self-control, while the mood scales indicated that the women experienced less tension and more satisfaction. Although the results of this study need to be further documented on the basis of a placebo-controlled trial, the findings nevertheless imply that the use of a battery of standardized questionnaires optimizes the possibility of evaluating climacteric complaints reliably before and after treatment.
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PMID:A new methodological approach to the evaluation of quality of life in postmenopausal women. 150 61

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

A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16-week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume to original size has been usual in most of the 82 patients now in follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Efficacy of leuprorelin acetate depot in symptomatic fibromatous uteri: the Italian Multicentre Trial. 160 94

Premenopausal Study. Twenty-five pre- or perimenopausal patients with advanced breast cancer were treated with leuprorelin acetate 3.75 mg (n = 9) or 7.5 mg (n = 16) every 4 weeks. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses and there was no indication that the lower dose was less effective as an oestrogen suppressant. There were four objective responders to the 3.75 mg dose and six to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes, which occurred in 17 patients. Leuprorelin acetate is therefore an effective agent in the treatment of premenopausal breast cancer patients. There appears to be no major detriment to the use of 3.75 mg rather than the 7.5 mg dose. Postmenopausal Study. Fifteen postmenopausal patients with advanced breast cancer were treated with monthly injections of leuprorelin acetate 7.5 mg to assess the clinical activity and endocrine responses to treatment. None of the 15 patients showed an objective response to treatment, although four patients had stable disease for at least 6 months. Endocrine effects after 4 weeks' treatment included major suppression of serum gonadotrophins to below 10% of pretreatment values and decreases in the level of serum testosterone in 12 of 14 patients. In this group there were no changes in oestradiol levels, although we had previously observed suppression in postmenopausal patients treated with goserelin. In common with other gonadotrophin-releasing hormone analogues, leuprorelin acetate cannot be recommended as a treatment for postmenopausal breast cancer.
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PMID:Clinical and endocrine effects of leuprorelin acetate in pre- and postmenopausal patients with advanced breast cancer. 160 96

Ten pre-menopausal women with uterine leiomyoma were treated for 1 year with a monthly depot of luteinizing hormone-releasing hormone agonist (LHRA-a), goserelin, combined after the initial 3 months of treatment with conjugated oestrogens 0.3 mg (days 1-25) and medroxy-progesterone acetate 5 mg (days 16-25). Mean leiomyoma volume decreased by 49.3% during the first 3 months when goserelin alone was administered but did not change significantly during the 9 months of combination therapy. There were no significant changes in bone mass or high-density lipoprotein cholesterol during the study whereas hot flushes and menstrual blood loss were well controlled. These results indicate that ovarian suppression with a monthly depot of the LHRH-a, goserelin, combined after 3 months with low-dose hormonal replacement therapy reduced the size and the symptomatology of leiomyoma while preserving the bone mass.
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PMID:Maintained reduction of uterine leiomyoma following addition of hormonal replacement therapy to a monthly luteinizing hormone-releasing hormone agonist implant: a pilot study. 165 23

Cyproterone acetate is a progestational antiandrogen with potent antigonadotropic activity that results in rapid suppression of serum testosterone. Used as a single agent, cyproterone acetate yields a total androgen blockade. It may be combined with low-dose diethylstilbestrol, orchiectomy, or LHRH agonists to improve, in theory, the results of such therapy. In clinical testing, cyproterone acetate has proved equivalent to diethylstilbestrol with markedly less toxicity. It is useful in conjunction with LHRH agonists, either transiently to block the flare phenomenon, or continuously to block peripheral androgen receptors; the necessity for this latter action has not yet been proved. Cyproterone acetate may afford transient objective improvement in patients not responding to other forms of hormone deprivation. Experience in this role is limited. The drug may be used to suppress the hot flushes associated with orchiectomy or LHRH agonist therapy. Cyproterone acetate induces local tumor regression; owing to its reversible effects, it is useful as neoadjuvant or adjuvant androgen withdrawal therapy in patients with lower-stage disease undergoing radical surgery or radiotherapy. Adverse effects are mostly those related to hormone withdrawal, namely, impotence, infertility, and lassitude. Gynecomastia and breast tenderness occur in less than 18% and cardiovascular complications in approximately 10% of treated men.
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PMID:Use of cyproterone acetate in prostate cancer. 182 43

Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding.
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PMID:Bleeding patterns during continuous combined estrogen-progestogen therapy. 182 47

The medical management of endometriosis depends on the stage of the disease, the severity of symptoms, the age of the patient, and her future fertility intentions. The most widely utilized treatment modalities are expectant management, surgery, induction of a pseudopregnancy state with hormonal therapy, and induction of a pseudomenopausal state. Over 50% of women with mild endometriosis and 25% of those with moderate disease can conceive without surgical or pharmacologic intervention. Total hysterectomy or bilateral salpingo-oophorectomy represent the only curative form of treatment, but definitive surgery is recommended only in women who do not want to retain their reproductive function or in whom all previous medical and surgical efforts have failed. Pseudopregnancy therapy (administration of low-dose combined oral contraceptives or medroxyprogesterone acetate) eliminates cyclical changes in the endometrium and bleeding, but is associated with the side effects common to these agents and carries a 5-10% annual recurrence rate. During the 1970s, induction of a pseudomenopausal state through administration of oral danazol was the treatment of choice. In dosages of 100-800 mg day, danazol produces symptomatic improvement in 70-95% of patients and disease regression in 8595%; however, recurrence rates as high as 30-40% have been reported, and weight gains of 20-30 pounds are common. Recent studies have shown the gonadotropin releasing hormone agonist nafarelin to be as effective as danazol or combined oral contraceptives for the treatment of endometriosis. Hot flashes are the most common adverse effect, but are tolerated by the majority of patients. Nafarelin has the additional advantage of not requiring intramuscular injection or monthly office visits, but patients must be given detailed instructions about its intranasal administration.
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PMID:Pharmacologic management of endometriosis. 183 May 21


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