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)

The objective was to assess the efficacy and acceptability of a new transdermal norethisterone device as part of a hormone replacement therapy (HRT) regimen. The design was an open prospective clinical assessment for 6 months. The setting was the Academic Unit of Obstetrics and Gynaecology, Royal London Hospital, Whitechapel, London. Eighteen patients of confirmed menopausal status were recruited. Therapy consisted of continuous application of Estraderm TTS 50 (Ciba Laboratories) for a 28-day period, with the additional application of two norethisterone acetate patches in the last 12 days of this period. This schedule was repeated for six cycles. The main outcome measures were symptom and menstrual data--haematological indices, hepatic and renal function; lipid parameters; endometrial biopsy. The results showed a significant improvement in the patients' symptoms of hot flushes and sweating (P = 0.03). Of the 15 women who completed at least 6 months of medication, withdrawal vaginal bleeding was established at regular intervals in 9. One patient had a local irritant reaction to the patch. There were no significant changes observed in haematological indices, hepatic and renal function. There was a slight but not statistically significant decrease in the HDL cholesterol fraction when the patient was in the norethisterone phase of the cycle, but no change was observed between the beginning and end of the study. Histological examination of the endometrial biopsies showed features of secretory activity in 56% of samples after 6 months. There was no evidence of hyperplasia, pre-malignant or malignant changes in the remaining biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormone replacement therapy by the transdermal administration of oestradiol and norethisterone. 801 5

In a prospective, comparative study 68 men were treated for hot flushes after androgen deprivation therapy for prostate cancer. Complete responses (elimination of hot flushes) were rare in patients receiving either combined phenobarbital plus ergotamine or clonidine. Of the men receiving either diethylstilbestrol or megestrol acetate 70% had a complete response, while another 20% had a greater than 50% decrease in the severity of hot flushes. Based upon a lower incidence of side effects, oral megestrol acetate was the preferred treatment for hot flushes in this study.
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PMID:A prospective comparison of treatments for symptomatic hot flushes following endocrine therapy for carcinoma of the prostate. 820 42

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.
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PMID:Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. 836 20

Three sequential oestradiol valerate (E2V) and cyproterone acetate (CPA) combinations based on 11 days of oestrogen and 10 days of oestrogen-progestogen administration were investigated during hormone replacement therapy in two prospective, double-blind randomized trials. Treatment A comprised 2 mg E2V and 1 mg CPA, treatment B, 1 mg and 0.5 mg and treatment C, 2 mg and 2 mg, respectively. During treatment A hot flushes (P < 0.0001), night sweating (P < 0.0001), depression (P = 0.0001), dizziness (P = 0.0001) and insomnia (P = 0.003) decreased significantly. The only side effect was breast tenderness, which was experienced by 18% of the women. Weight and blood pressure, thyroid, adrenal, liver and kidney functions, parathyroid hormone and vitamin D, platelets and blood cell counts did not change during the 12 months of therapy. In the women who received treatment A the menstrual flow became less abundant during the early months of treatment (P < 0.0001), the menses being scanty in around 30% of the women, while some 10% had amenorrhoea. Spotting occurred in 10-20% of the subjects. Endometrial biopsies were atrophic in 10% of the women, whereas a normal secretory phase was observed in 45% and irregular secretion in 45%. After careful analysis using visual analog scales, these findings were interpreted as indicating a high-normal progestational effect. In comparison with the pattern observed in normal menstrual cycles the women who received treatment A had a more heterogenic glandular epithelium, with more papillae, larger stromal cells, a more pronounced decidual reaction and more fibrinoid material. No cases of hyperplasia were seen. Treatment B was less effective than treatment A in relieving climacteric complaints. Irregular bleeding was troublesome in over 20% of cases and amenorrhoea occurred in 50%. Endometrial biopsies were atrophic in 57% of the women. The effectiveness of treatment C in alleviating flushes, sweating, dizziness and depression was the same as that of treatment A. The decrease in menstrual flow during the early months and the incidence of amenorrhoea (approx. 10%) and atrophic endometria (approx. 10%) were comparable. Detailed analysis revealed that C had an even stronger progestational effect than A. It was concluded that A was the treatment of choice in comparison with B and C. It proved highly effective in treating climacteric complaints, had no side effects apart from breast tenderness, provided good cycle control and induced a physiological secretory transformation of the endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endometrial effects during hormone replacement therapy with a sequential oestradiol valerate/cyproterone acetate preparation. 838 51

Combination oral contraceptive (COC) users have reduced risks of ovarian and endometrial cancer, but COCs have not reduced breast cancer risk. We have previously argued that a hormonal contraceptive with substantially lower doses of sex-steroids should reduce breast cancer risk by decreasing the breast epithelial cell proliferation below usual premenopausal levels. We report here the preliminary results of a pilot trial with such a prototype contraceptive consisting of an agonist of gonadotropin releasing hormone (GnRHA) administered with low doses of an oral estrogen (0.625 mg of conjugated estrogen, CE, for 6 days every week) and intermittent oral progestogen (10 mg of medroxyprogesterone acetate, MPA, for 13 days every 4 months). Eighteen subjects at five-fold or greater increased breast cancer risk were entered and randomized -12 to the contraceptive arm and 6 to a control arm. The principal endpoints included tolerance of the regimen, vaginal bleeding patterns, and the regimen's effect on the endometrium, bone metabolism, and lipids. A symptom questionnaire was used to assess tolerance; the contraceptive subjects had fewer symptoms following initiation of the regimen. This results from the elimination of symptoms associated with the luteal phase of the menstrual cycle, commonly referred to collectively as premenstrual syndrome, PMS. The few occurrences of hot flushes or vaginal dryness that did occur were eliminated by small increases in estrogen dose (0.9 mg CE). Scheduled vaginal bleeding occurred associated with most periods of progestogen administration. Unscheduled bleeding or spotting was infrequent and decreased with time on the regimen. A beneficial rise in high-density lipoprotein cholesterol was evident in the contraceptive subjects. Despite the use of an estrogen dose which is known to prevent loss of bone mineral density in normal postmenopausal women, an annualized loss of 1.9% was seen in contraceptive subjects. It is hypothesized that this is secondary to inhibition of ovarian androgen production by the GnRHA, which may additionally account for changes in libido occasionally reported with GnRHA. The study continues with the addition of a small dose of androgen to replace that lost by the action of the GnRHA.
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PMID:Pilot trial of a gonadotropin hormone agonist with replacement hormones as a prototype contraceptive to prevent breast cancer. 839 Mar 40

The introduction of steroid "add-back" regimen draws on the recognition that several clinical entities targeted for treatment with GnRHa are not "six-month diseases". Included under this heading are individuals suffering from symptomatic endometriosis (not desirous of pregnancy), uterine fibroids (ineligible or disinterested in definitive surgical therapy), ovarian hyperandrogenism, premenstrual syndrome, menopausal transition, or dysfunctional uterine bleeding. A six month course of therapy with a GnRHa does not adversely affect lipoprotein economy and therefore presumably the corresponding cardiovascular risk. A six month course of GnRHa therapy appears to be associated with a substantial decrease (of up to 8.2%) in lumbar bone density, a phenomenon which may not be entirely reversible six months after discontinuation of therapy. In principle, steroid "add-back" therapy should diminish some or all of the side effects associated with GnRHa therapy, may provide a medical treatment option for patients representing a high surgical risk, and may delay surgical intervention if desired. On the other hand, a steroid "add-back" therapy may delay tissue diagnosis, be associated with a substantial cost as well as with the need in parenteral route of administration. Norethindrone-only (but not medroxyprogesterone acetate-only) "add-back" regimens have proved promising in the context of endometriosis. Non-concurrent estrogen/progestin "add-back" regimens proved promising in the context of uterine fibroids. Substantial additional studies would have to be carried out to validate the utility of steroid "add-back" regimens. Special emphasis will have to be placed on the evaluation of long-term utility with an eye towards assessing clinical efficacy, impact on lipoprotein economy, impact on bone density, impact on urogenital tissues, and impact on the hot flash. The concurrent or non-concurrent use of non-steroid "add-back" regimen will also most likely constitute a major component of future studies.
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PMID:Long-term gonadotropin-releasing hormone agonist therapy: the evolving issue of steroidal "add-back" paradigms. 858 24

Depot medroxyprogesterone acetate (DMPA) is an aqueous suspension of 17-acetoxy 6-methyl progestin administered by intramuscular injection for long-term contraception. This highly effective injectable formulation of medroxyprogesterone acetate (MPA) has a prolonged duration of action since the progestin is released slowly from the muscle. MPA is detected in the serum within 30 minutes after an injection of 150 mg. Serum concentrations vary between individual women but generally plateau at about 1.0 ng/mL for about three months, after which there is a gradual decline. In some women, MPA can be detected in the serum for as long as nine months after a single injection of 150 mg. The circulating MPA initially inhibits the midcycle leutinizing hormone (LH) peak, but LH and follicle stimulating hormone (FSH) levels remain in the range of those for the luteal phase of a pretreatment control cycle. Since ovulation is inhibited, serum progesterone levels remain low (< 0.4 ng/mL) for several months following an injection of DMPA. When MPA levels fall below 0.1 ng/mL, ovulation resumes. Thus, return to fertility is delayed for several months if a woman wishes to conceive after receiving one or more injections of DMPA. Following an injection of DMPA, serum estradiol levels initially are in the early to midfollicular phase range (mean approximately 50 pg/nL). Serum estradiol levels begin to rise about four months after a single injection when MPA levels fall below 0.5 ng/mL. For women who have used DMPA for several years, serum estradiol levels range between 10 and 92 pg/mL, with mean levels of about 40 pg/mL. Despite these low levels of estradiol, hot flushes are a rare event, and the vaginal epithelium remains moist and well rugated. Women using DMPA for several years do not observe a change in breast size. DMPA causes the endometrium to become atrophic, with small, straight endometrial glands and decidualized stroma. The cervical mucus remains thick and viscid. DMPA is a very effective form of contraception because of its multiple mechanisms of action and slow release into the circulation.
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PMID:Pharmacokinetics of depot medroxyprogesterone acetate contraception. 872

In an open, prospective clinical trial enrolling 205 patients, efficacy and safety of the gonadotropin-releasing hormone agonist leuprorelin acetate depot (LAD) in the treatment of patients with advanced prostatic carcinoma were assessed. 3.75 mg of the LAD formulation was injected subcutaneously in monthly intervals. The primary objective of this study was to evaluate the efficacy of the analogue in producing and maintaining castration levels of testosterone over a > 3-year follow-up period and to determine its safety profile. Median pretreatment serum testosterone levels fell from 350 to 21 ng/dl after 4 weeks and 20 ng/dl after 45 months. The long-term clinical efficacy of the LAD formulation can be expressed by best treatment response over time. These respective figures read as follows: 10.7% complete response; 49.8% partial response; 34.1% no change; 1.5% progression, and 3.9% no data available. The median time to progression was 12 (15 +/- 11) months. Median survival time calculated by Kaplan-Meier exceeded 42.5 months for patients on monotherapy and 30.9 months for those on combination therapy. Hot flushes which were related to androgen deprivation were the most common side effects. Patients and treating physicians judged tolerability of LAD in more than 90% as good. Androgen deprivation remains the mainstay of hormone-dependent advanced carcinoma of the prostate. Up to now, surgical castration has been considered the standard method. LAD is an advantage in the endocrine treatment of advanced prostatic carcinoma and is a good alternative to castration.
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PMID:Efficacy and safety of leuprorelin acetate depot for prostate cancer. The German Leuprorelin Study Group. 877 14

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.
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PMID:A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma. 882 90

Leuprorelin acetate is a synthetic nona-peptide analogue of the naturally occurring gonadotrophin releasing hormone LH-RH (hypothalamus), used in the treatment of sterility, endometriosis or prostatic cancer. In a 35 year old woman, treated with leuprorelin acetate, after 5 months treatment, the side-effects (hot flushes, sweating, sleeping disorders), appeared to be rather unbearable. Medication was ended. The endocrine reversion to the normal physiological balance was association with high fever (38.9 degrees C) during an 8 day period. Increasing scotomas resulted in a gradual loss of eyesight in one eye, associated with a normal visual acuity. Unilateral papilloedema was observed, indicating the possibility of tumor cerebri. Fluorescein angiography demonstrated an intense leakage of the right optic disc. No signs of retinal vascular malformations were seen. The eye pressure was normal. No signs of hemorrhages were observed. Visual field examination showed an enlarged blind spot with a few scotomas above the centre of fixation. CT scan of the brain was normal, the cerebrospinal fluid (CSF) was normal, indicated by IgG production. Six months after ending the leuprorelin acetate treatment, the eyesight was spontaneously 100% recovered. It is most likely that leuprorelin acetate is responsible for the emergence of pseudotumor cerebri. As described by Prof. Sidi et al(1), leuprorelin strongly induces increased liquor pressure, being the intermediate mechanism between hormonal treatment and an ante grade mechanical force, on the optic nervus. Because of the risk of permanent loss of eyesight, it is strongly advised to verify eye parameters conscientiously during leuprorelin treatment.
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PMID:Pseudotumour cerebri as a side effect of leuprorelin acetate. 886 6


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