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)

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

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

Eighty patients with different stages of genital endometriosis were treated with Zoladex, a gonadotrophin-releasing hormone analogue in a depot formulation, injected subcutaneously every 4 weeks. The stages of endometriosis (I-IV) were classified according to the revised American Fertility Society recommendations (AFS criteria) via pelviscopy before and after 6 months of treatment. Fifty-eight second-look pelviscopies were performed with the following objective changes after (before) treatment: Stage IV 0 (3); Stage III, 2 (13); Stage II, 12 (30); Stage I, 19 (12). Twenty-five patients presented with Stage 0 after therapy and were healed. All 57 symptomatic patients showed a subjective response to Zoladex therapy with a significant decrease of the total pelvic symptom score. Thirty-eight patients with infertility wished to become pregnant and so far 16 (40%) have conceived. During therapy, the serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol and progesterone were significantly suppressed. All patients were amenorrhoeic after 1-2 injections. Restoration of ovarian function with resumption of menstruation occurred within 57-92 days after the last injection of Zoladex (1-2 months after end of treatment). Side-effects were minimal and were those expected of the hypo-oestrogenic state, such as hot flushes, vaginal dryness and decrease of libido.
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PMID:Experience with a depot GnRH-agonist (Zoladex) in the treatment of genital endometriosis. 183 93

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.
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PMID:Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. 210 79

To evaluate the efficacy, safety and tolerance of the GnRH-analogue Buserelin in the treatment of endometriosis, we started a non-comparative study of 52 patients with various stages of endometriosis. The dosage of 900 mcg/d was administered 3 times daily intranasally for 6 months. The degree of the disease was evaluated before and at the end of treatment by pelviscopy and biopsy. A regression of the implant score was found in 88% of patients. The mean AFS score was reduced from 17.4 +/- 1.9 before medication to 7.2 +/- 8.2 after therapy. Endometriosis related complaints were significantly improved during treatment. After 6 months 75% of the patients were without lower abdominal pain, 98% without dysmenorrhoea, and 85% without dyspareunia. As a result of the induced low level of oestrogen, 60% of the patients claimed hot flushes, 12% sweating, reduced libido, and dry vagina. Bleeding (spotting, break-through bleeding, menstruation) occurred in 40% during the first month, and was continuously reduced during the following period. Before, during and after therapy, venous blood samples were drawn to check laboratory tests for blood count, clotting parameters, clinical chemistry, serum electrolytes, as well as liver and lipid metabolism. All values stayed within the normal range without significant changes. In the follow-up period of at least 12 months, we achieved an uncorrected pregnancy rate of 41% in the group of 34 women with primary or secondary infertility.
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PMID:[Ovarian suppression by the GnRH analog buserelin in the treatment of endometriosis. Clinical, biochemical and pelviscopic studies]. 214 92

Endometriosis is an extremely common gynaecological disease, affecting between 1 and 5% of women of reproductive age. Women with endometriosis typically present for medical care with one of more of the following problems: pelvic pain, infertility, or a large adnexal mass (an endometrioma). The primary treatment for an endometrioma is surgical. However, long term postoperative hormone therapy may be necessary to prevent new endometriomas from developing. There is no evidence that hormonal therapy of endometriosis will improve fecundability in women with endometriosis and infertility. Pelvic pain due to endometriosis can be successfully treated with hormonal agents in the majority of patients. Four basic hormonal regimens are currently available for the treatment of endometriosis: (a) danazol; (b) gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonists; (c) progesterones (progestins); and (d) combined estrogens and progesterones. Randomised, controlled, clinical trials suggest that danazol and the GnRH agonists are equally effective in the treatment of endometriosis. However, the side effects caused by danazol and the GnRH agonists are markedly different. Danazol produces androgenic side effects including weight gain, hirsutism, acne, oily skin and deepening of the voice. GnRH agonists produce side effects due to hypoestrogenism, including hot flushes, osteoporosis and dry vagina. The ideal drug regimen for the treatment of endometriosis remains to be developed.
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PMID:Endometriosis 1990. Current treatment approaches. 219 Jul 93

Tamoxifen, a non-steroidal antioestrogen, represents a significant advance in treatment of female breast cancer. In trials of tamoxifen as postsurgical adjuvant treatment of early breast cancer, disease-free survival is consistently prolonged, representing an enhanced quality of life in association with tamoxifen's favourable adverse effect profile. Moreover, overview analysis indicates a survival benefit of approximately 20% at 5 years for all women, most clearly evident in women over 50 years, while a survival benefit independent of menopausal, nodal or oestrogen receptor status has been demonstrated in some individual trials. Thus, for postmenopausal women, tamoxifen is clearly optimal adjuvant treatment, although the relative benefit of adjuvant chemotherapy in node-negative patients requires clarification. A survival benefit for women under 50 has not been clearly demonstrated in overview analysis, but is not precluded by these rather limited data, and adjuvant treatment of premenopausal women with tamoxifen may also warrant serious consideration. Response rates to tamoxifen in advanced breast cancer are around 30 to 35%, increasing with patient selection for oestrogen receptor positivity. Tamoxifen must be regarded as first-line endocrine treatment in postmenopausal women, and may represent an alternative to first-line ovarian ablation in premenopausal women. An emergent role in primary therapy of elderly and frail patients with operable disease is apparent. Tamoxifen is also of benefit following surgery in male breast cancer, and may have a role as first-line endocrine treatment. Tamoxifen also has a potential role in other hormone-sensitive malignancies such as pancreatic carcinoma, and in treatment of benign breast disease. Finally, tamoxifen has a place in treatment of male and female infertility. because of adverse effects is rarely necessary. The most frequent adverse effects are related to the drug's anti-oestrogenic activity, and include hot flushes, nausea and/or vomiting, vaginal bleeding or discharge, and menstrual disturbances in premenopausal patients. Thus, tamoxifen continues to play a major role in management of female breast cancer in both early and advanced stages of disease, with a place also in treatment of male breast cancer and of infertility.
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PMID:Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. 266 Nov 95

Focus in this discussion of the pharmacology of gynecology is on the following: vaginal infections; genital herpes; genital warts; pelvic inflammatory disease; urinary infections; pruritus vulvae; menstrual problems; infertility; oral contraception; and hormone replacement therapy. Doctors in England working in Local Authority Family Planning Clinics are debarred from prescribing, and any patient with a vaginal infection has to be referred either to a special clinic or to her general practitioner which is often preferable as her medical history will be known. Vaginal discharge is a frequent complaint, and it is necessary to obtain full details. 1 of the most common infections is vaginal candidosis. Nystatin pessaries have always been a useful 1st-line treatment and are specific for this type of infection. Trichomonas infection also occurs frequently and responds well to metronidazole in a 200 mg dosage, 3 times daily for 7 days. It is necessary to treat the consort at the same time. Venereal diseases such as syphilis and gonorrhea always require vigorous treatment. Patients are now presenting with herpes genitalis far more often. The only treatment which is currently available, and is as good as any, is the application of warm saline to the vaginal area. Genital warts may be discovered on routine gynecological examination or may be reported to the doctor by the patient. 1 application of a 20% solution of podophyllum, applied carefully to each wart, usually effects a cure. Pelvic inflammatory disease seems to be on the increase. Provided any serious disease is ruled out a course of systemic antibiotics is often effective. Urinary infections are often seen in the gynecologic clinic, and many of these will respond well to 2 tablets of co-trimoxazole, 2 times daily for 14 days. In pruritus vulvae it is important to determine whether the cause is general or local. Menstrual problems regularly occur and have been increased by the IUD and the low-dose progesterone pill. Infertility necessitates investigation. It is helpful to use the temperature chart method to determine whether the patient is ovulating. Oral contraception merits only passing mention, i.e., the introduction of a new sequential pill containing ethynloestradiol and levonorgestrol. There is always the question of a possible relationship between long-term OC use and the development of endometrial cancer. There are certain definite indications for hormone replacement therapy, i.e., hot flushes, sweating and atrophic vaginitis.
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PMID:The pharmacology of gynaecology. 744 23

Ovulation-induction agents are commonly used in the treatment of infertility in patients with or without ovulatory disturbances. These agents include clomifene, bromocriptine, gonadotrophin preparations and gonadotrophin-releasing hormone (GnRH) and its analogues. Each agent is associated with its own specific adverse effects. Although many of these adverse effects are benign and self-limited, some, in particular those effects associated with gonadotrophins, may be life-threatening. Commonly noted adverse effects encountered with the use of pharmacological agents to treat infertility include the following. Clomifene has been associated with hot flushes, multiple gestation, visual disturbances, cervical mucus abnormalities and luteal phase deficiency. Similarly, most of the adverse symptoms associated with bromocriptine are short-lived, such as nausea and postural hypotension. On the other hand, gonadotrophin therapy, even when used appropriately, may lead to the ovarian hyperstimulation syndrome (which is occasionally life-threatening) and a high incidence of multiple gestation. Pulsatile GnRH therapy maybe accompanied by similar adverse effects to those of gonadotrophins, but with a far lower incidence. With regards to the long term safety of these medications, the relationship between fertility drugs and epithelial ovarian cancer is controversial, and causality has yet to be proven. Indeed, a working knowledge of the many adverse effects associated with these medications is essential to any physician prescribing ovulation induction agents, in order to ensure maximum patient safety, compliance and understanding.
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PMID:Adverse effects of fertility drugs. 772 51

The development of ovulation-inducing drugs has enabled clinicians to more effectively treat the hypothalamic, pituitary, and ovarian abnormalities resulting in infertility. Pregnancy rates have been improved with the use of agents such as clomiphene citrate (CC), human menopausal gonadotropin [hMG or follicle-stimulating hormone (FSH) preparations], with gonadotropin-releasing hormone (GnRH) and its analogs, stimulating the development of multiple ovarian follicles and increasing the number of fertilizable oocytes. The use of these drugs is not without certain detrimental or "toxic" consequences. The negative effects from superovulation can occur during follicle development, decreasing the number of healthy oocytes and embryos capable of leading to viable pregnancy. Ovulation induction can lead not only to higher incidences of spontaneous abortions, and multiple and ectopic pregnancies, but also to poor pregnancy rates, due, in part, to asynchrony between embryonic development and the uterine environment. Diseases such as ovarian hyperstimulation syndrome (OHSS), resulting in the secretion of supraphysiologic levels of estradiol, can lend to severe health complications, possibly requiring hospitalization. Most drugs used for ovulation induction can lead to OHSS. Although incidences of OHSS following CC use are less frequent, CC has been associated with hot flushes, multiple gestations, visual disturbances, cervical mucus abnormalities, and luteal phase deficiency. Finally, there are reports that link any or all of the ovulation-inducing drugs with a higher incidence of ovarian and breast cancer, however, a cause-effect relationship has yet to be proven.
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PMID:Reproductive toxicity of ovulation induction. 898 29


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