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)

In an open, multicentre study, transdermal administration of oestradiol (E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and 83.5% sweating before therapy, only 5.7% and 11.8%, respectively, reported these symptoms at the end of the trial. Furthermore, 97.6%, 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patients completing the treatment, of whom 78% were willing to continue the treatment after the trial. These results show that transdermal administration of E2 is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermal treatment to be superior to their previous oral replacement therapy.
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PMID:Transdermal oestrogen replacement therapy in a Finnish population. 177 81

The menopause results from the decreasing production of ovarian estrogens/progestins. This loss of ovarian hormones in 75-85% of women leads to a number of brain-mediated steroid-withdrawal symptoms, the most frequent being hot flushes. Thus, replacement therapy with a brain-enhanced estrogen delivery system (E2-CDS) with sustained release of estradiol (E2) in the brain may be more effective in the treatment of menopausal symptoms than currently used estrogens. The present study was designed to evaluate the effects of E2-CDS vs. E2, on the tail-skin temperature (TST) surge associated with administration of naloxone to morphine-dependent rats, an animal model for menopausal hot flush. Ovariectomized rats received a single or multiple doses of E2-CDS at 1.0 mg/kg body weight or E2 (0.5 mg pellet) weekly for 1 or 3 weeks before temperature recording. The mean maximal elevation in TST of the control animals was 6.4 +/- 0.2 degrees C. A single injection of E2-CDS attenuated the naloxone-induced rise in TST by 25%, while multiple injections resulted in significant attenuation of the rise in TST (3.4 +/- 0.6). By contrast, multiple implants of E2 pellet (3 pellets over 3 weeks) did not affect the surge of TST. Plasma E2 levels in animals treated with E2-CDS were slightly increased to 13 pg/ml for single-injected and to 44 pg/ml for multiple-injected rats. However, the E2-pellet treatment produced plasma E2 levels that were 2-fold greater than the E2 levels produced by multiple injections of E2-CDS. Plasma gonadotropins (LH and FSH) were significantly suppressed with the E2-pellet as well as the single and multiple E2-CDS treatment. Plasma prolactin levels were significantly elevated by E2 pellet and multiple injections of E2-CDS. The kinetic profiles of E2-CDS metabolites in plasma indicated an apparent t1/2 = 8 h for E2-Q+ and 3 h for E2. Collectively, these data support the view that E2-CDS may be potentially useful in the treatment of vasomotor hot flushes.
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PMID:Effects of a brain-enhanced estrogen delivery system on tail-skin temperature of the rat: implications for menopausal hot flush. 190 49

The estradiol transdermal therapeutic system is a cutaneous delivery device which delivers estradiol into the systemic circulation via the stratum corneum at a constant rate for up to 4 days. Physiological levels of estradiol (the major estrogen secreted by the ovaries in premenopausal women) can therefore be maintained in postmenopausal women with low daily doses because first-pass hepatic metabolism is avoided. In short term clinical studies, the beneficial effects of transdermal estradiol on plasma gonadotrophins, maturation of the vaginal epithelium, metabolic parameters of bone resorption and menopausal symptoms (hot flushes, sleep disturbance, genitourinary discomfort and mood alteration) appear to be comparable to those of oral and subcutaneous estrogens, while the undesirable effects of oral estrogens on hepatic metabolism are avoided. As with oral or injectable estrogen replacement therapy, concomitant sequential progestagen is recommended for patients with an intact uterus during transdermal estradiol administration, in order to reduce endometrial stimulation. Transdermal estradiol has been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse effect. The incidence of systemic estrogenic effects appears to be comparable to that observed with oral therapy. Thus, transdermal estradiol offers near-physiological estrogen replacement in postmenopausal women in a convenient low-dose form which may avoid some of the complications of higher dose oral therapy. Long term epidemiological studies are warranted to determine whether transdermal estradiol therapy provides protection against osteoporosis and fractures and cardiovascular disease equivalent to that offered by oral and injectable estrogens. However, despite the importance of such data, it seems reasonable to conclude at this stage of its development that transdermal estradiol represents an important advance in hormone replacement therapy.
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PMID:Transdermal estradiol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of menopausal complaints. 208 14

Estrogen therapy is extremely effective in relieving menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and certain psychological symptoms. The short term side effects from this therapy are usually mild and self-limiting. They are more common in women who commence hormone replacement therapy some years after the menopause than in those who start treatment at about the time of the ovarian failure. Pre-existing gynaecological conditions such as fibroids and endometriosis can be worsened by estrogen therapy. The majority of published studies suggest a beneficial effect of postmenopausal estrogen therapy on cardiovascular and cerebrovascular disease. These effects may be mediated by favourable changes in lipids, but other mechanisms may also be involved. It is uncertain whether the adverse changes in lipids caused by progestogen therapy will reduce any of the benefits of estrogen therapy on the cardiovascular system. Osteoporosis is the major bone disease of the Western world; long term estrogen therapy will prevent its development in most postmenopausal women. The risk of endometrial carcinoma is increased with unopposed estrogen therapy; this increased risk appears to be abolished if a progestogen is added at an adequate dose and duration for each cycle. The risk of ovarian or cervical cancer is not increased with estrogen therapy. There may be an increased risk of breast carcinoma with long term postmenopausal estrogen use, but the studies show inconsistent results.
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PMID:A risk-benefit assessment of estrogen therapy in postmenopausal women. 222 68

Twenty-four women with large, myomatous uteri, measuring between 218.7 and 2,920 cm3 were treated with gestrinone, a tri-enic steroid with antiestrogen and antiprogesterone properties. In order to saturate the receptors of the large myomata, the doses used to treat these women were twice the recommended dosage of 2.5 mg, 3 times weekly, used to treat smaller tumors. The treatment lasted 6 months to 1 year. In all cases there was a reduction in uterine volume. In the 24 patients, the mean uterine volume of 724.9 cm3 on admission decreased to 450.73 cm3 at 6 months. For 14 patients treated for a full year, the mean uterine volume of 689.73 cm3 decreased to 329.22 cm3. Menstruation was suppressed in all patients by the end of the 2nd month of treatment. Episodic bleeding occurred in 6 patients but in only 1 did this last longer than 1 week. Other symptoms such as pelvic discomfort and dysuria disappeared or were significantly alleviated by the 2nd month of treatment. Side effects included seborrhea, acne, nervousness, myalgia and arthraglia, hoarseness and mild hirsutism but all these symptoms were promptly reversed following discontinuation. The mean increase in weight was 3.4 kg in 6 months. No menopausal symptoms such as hot flushes and depression developed during this trial. Six patients complained of excessive sweating. Blood glucose creatinine, blood urea nitrogen, alkaline phosphatase, pyruvic and glutamic transaminases remained within the normal range.
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PMID:Treatment of large fibroids with high doses of gestrinone. 222 12

Premenopausal breast cancer patients frequently develop amenorrhea during adjuvant chemotherapy. Despite psychic distress and severe weight loss are possible causes for secondary amenorrhea in cancer patients, it is in this case due to the gonadotoxicity of the cytostatic drugs. Alkylating agents, such as cyclophosphamide, damage ovaries directly, resulting in ovarian fibrosis, atretic follicles and decline in estrogen production. Elevated plasma levels of LH and FSH show adequate reaction of the hypothalamohypophyseal unit. There is no change in the androgen production of stromal cells as well as in the plasma levels of prolactin and adrenal androgen precursors. Ovarian damage goes along with hot flushes, loss of libido and dyspareunia. The onset of amenorrhea is age- and dose-related. Commonly the changes are irreversible. Estrogen replacement therapy promptly removes menopausal symptoms but is contra-indicated regarding the possible hormone-dependence of the tumor. In this case low dose medroxy-progesterone acetate is indicated.
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PMID:[Effects of adjuvant chemotherapy of breast cancer on gonadal function]. 223 81

The effect transcutaneous oestradiol for four months supplemented by medroxyprogesterone (Perlutex) from the 12th to 26th day of every month was assessed in an open uncontrolled prospective investigation in 34 women with menopausal symptoms and follicle stimulating hormone greater than 40 international units and luteinizing hormone greater than 25 international units. A marked effect was found on sweating and hot flushes and other menopausal complaints as expressed by Kupperman's menopausal index. Serum oestradiol increased during the first two months to follicular phase values and this was followed by an unexplained decrease after the fourth month which did not, however, result in aggravation of the symptoms. No alterations were found in steroid-hormone-binding globulin, lipids and body weight. Whether the patients placed the plasters in the hip or abdominal regions was found to be of no significance. Seventeen patients had no side effects of the treatment. Nine patients had transient skin symptoms which disappeared spontaneously. Five patients had mastalgia which disappeared after reduction of the Perlutex dose. One patient developed metrorrhagia. A total of three patients abandoned the treatment: one on account of skin symptoms, one on account of high blood pressure and a third on account of psychiatric symptoms which were unrelated to the treatment. A total of 28 patients wanted to continue treatment after the fourth month.
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PMID:[Transcutaneous estradiol treatment in the climacteric]. 240 44

Two hundred perimenopausal women who suffered from several symptoms and signs of menopause participated in this 3-year prospective study. Because they were still menstruating more or less regularly, these women were afraid of becoming pregnant and asked for contraception as well as hormone replacement therapy (HRT). Therefore the HRT chosen was a low dose triphasic oral contraceptive. The patient population was divided into two groups; one group (100 women) took the triphasic contraceptive as HRT and the other group served as controls (100 women). During the three years of this study this form of HRT was demonstrated to prevent conception and bone-mass loss, combat vaginal dryness and sexual disturbances, eliminate hot flushes and profuse sweating, correct breast atrophy, and prevent or improve psycho-functional disturbances, such as depressive mood, loss of concentration, insomnia, nervousness, palpitations and fatigue. It was concluded, based on the results of this study, that the triphasic oral contraceptive is the treatment of choice in the prevention and treatment of menopausal symptoms during the perimenopause--when contraception is still required.
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PMID:Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three-year prospective study. 286 16

We have previously reported reversible hypogonadism induced by the intranasal administration of the luteinizing hormone-releasing hormone agonist buserelin as a new therapeutic approach for endometriosis. Thirteen patients were randomized to receive intranasal buserelin (400 micrograms 3 times a day) or subcutaneous buserelin injection (200 micrograms once daily) for a 6- to 9-month period. Both routes of administration were effective in inhibiting serum estradiol levels to near the menopausal range after 1 month of treatment. The two dosage regimens had also a comparable efficacy in alleviating endometriosis symptoms and in reducing the revised American Fertility Society scoring at laparoscopic examination. The implant score mainly decreased by more than 70%. The occurrence of side effects was similar in both groups, and side effects were mainly hot flushes, dyspareunia secondary to decreased vaginal secretion, and decreased libido. Results of hemogram, urinalysis, and serum biochemical and hormonal tests remained in the normal range. The ovulatory cycle rapidly returned after the cessation of treatment, and three pregnancies occurred in six previously infertile patients. Intranasal and subcutaneous buserelin were well accepted and equally effective in inhibiting the pituitary-ovarian function, which caused mild menopausal symptoms but an important regression of endometriosis.
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PMID:Efficacy of intranasal or subcutaneous luteinizing hormone-releasing hormone agonist inhibition of ovarian function in the treatment of endometriosis. 312 18

Estrogen replacement therapy is effective for the prevention and treatment of postmenopausal osteoporosis and should be offered to all women at high risk for osteoporosis. Such therapy is particularly beneficial for prevention of spinal compression fractures; in addition, it alleviates menopausal symptoms (hot flushes, genitourinary symptoms, and changes in mood). In each patient, these benefits must be weighted against the potential risks of endometrial hyperplasia and carcinoma, breast tenderness, hypertension, vascular headaches, and the inconvenience of menstrual bleeding if the uterus is intact. The risk of endometrial cancer associated with estrogen replacement therapy can be considerably reduced by the addition of a progestin, and other side effects can be diminished or eliminated by use of the new transdermal estrogen preparations. Thus, estrogen replacement therapy should be considered in all women who have experienced natural or surgically induced menopause, and it is advisable in women who have osteoporosis or an increased risk for this disorder and no contra-indications to its use. Estrogen replacement therapy should be instituted as soon after menopause as possible and seems to be well tolerated until at least 75 years of age.
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PMID:Estrogen replacement therapy: current recommendations. 328 71


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