Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A survey of recent trials of new injectable hormonal contraceptives, progestogen-only, levonorgestrel esters, and once monthly injectables, follows a brief review of all the experimental long-acting contraceptive modalities, injectables, implants, vaginal rings, and hormone-releasing IUDs. Currently medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are being used by 7 million women. WHO is conducting dose reduction trials and studies of bioavailability in various national populations. Even though a dose of 100 mg DMPA every 3 months has been satisfactory for contraception, 150 mg is still recommended until further pharmacodynamic data are available. Some populations, notably Thais and Mexican women, have higher peaks and more rapid elimination rates of DMPA, while Chinese women show slower elimination and higher blood levels of NET-EN. Extensive studies of new synthetic esters of levonorgestrel have proceeded to Phase II clinical trials with levonorgestrel butanoate. This ester is an effective contraceptive for 3 months at 12.5 mg, or 5-6 months at a dose of 25 or 50 mg. Trials of combined estrogen and progestogen injectables once-monthly have been ongoing for 10 years. The ratio of the 2 components is as important as the amounts. 2328 women from 12 countries participated in trials of DMPA 25 mg-estradiol cypionate 5 mg, and NET-EN 50 mg-estradiol valerate 5 mg. The continuation rate was better than that for 3-monthly progestogen-only injectables, because of less irregular bleeding. A combined injectable called Cyclofem, DMPA 25 mg-estradiol cypionate is being introduced in several countries. The steadily increasing demand for long-acting injectables prompts development of better formulations.
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PMID:Long-acting hormonal contraceptives for women. 195 67

A phase III randomized clinical trial was undertaken to compare the efficacy, side effects and acceptability of a combined monthly injectable preparation containing NET-oenanthate (NET-OEN) (50 mg) plus oestradiol valerate (E2 Val.) (5 mg) with NET-OEN only (200 mg) given every two months. A total of 849 subjects were observed for 7817 woman-months of contraceptive use. Net discontinuation rates due to involuntary pregnancy at 12 months were 0.2 and 1.1 per 100 users for one monthly and two monthly injectable preparations, respectively. Although the monthly preparation was found to be efficacious and the subjects using the monthly preparation had a better bleeding pattern, the net discontinuation rate at 12 months due to menstrual disturbances did not show any significant difference between the two preparations. With proper counselling and motivational strategies, it is likely that acceptability of monthly injectables can be further enhanced.
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PMID:A multicentre phase III comparative study of two hormonal contraceptive preparations NET-OEN (50 mg) + E2 valerate (5 mg) given every month and NET-OEN (200 mg) given every 2 months as intramuscular injection--a report of 12-month study. Indian Council of Medical Research Task Force on Hormonal Contraception. 196 85

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRH-a) is associated with side effects secondary to the induced hypoestrogenic state. In an effort to ameliorate these symptoms, 10 patients with symptomatic endometriosis self-administered the GnRH-a [D-His6(Imbzl)-Pro9-NET]-GnRH in combination with norethindrone daily for 24 weeks. Painful symptoms were significantly suppressed after therapy (P less than 0.005). Objective review of photographs taken at laparoscopy before and after therapy demonstrated significant reduction of visible implants (P less than 0.005). Vasomotor symptoms were minimized when compared with a group of 16 patients previously treated with GnRH-a alone. Bone mineral density of the distal radius assessed by single photon absorptiometry was not reduced during therapy, although lumbar spine bone density assessed by quantitative computerized tomography was minimally but reversibly reduced. No metabolic derangements were detected. The combination of norethindrone with GnRH-a is a well tolerated and effective means of treating symptomatic endometriosis.
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PMID:The effects of combining norethindrone with a gonadotropin-releasing hormone agonist in the treatment of symptomatic endometriosis. 210 56

The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), total and absolute free testosterone were investigated in groups of 10 healthy volunteers. All preparations contained about the same amount of ethinylestradiol but they differed in type and/or dose of progestagen. The progestagens studied were: levonorgestrel (LNG; in mono- and triphasic preparations), norethisterone (NET; in monophasic preparation), desogestrel (DSG; in mono- and biphasic preparations) and gestodene (GSD; in triphasic preparation), all 19-nortestosterone derivatives, and the anti-androgen cyproterone acetate (CPA) in a monophasic preparation. Differences observed in SHBG level, which reflect the estrogen-androgen balance, can be attributed to the intrinsic androgenic (or anti-androgenic) properties of the progestagens, and were in agreement with the results of published receptor binding studies, performed in vitro. Based on our results the following ranking (high to low) can be made with respect to the androgenicity of the preparations: monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA. An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG, a marker for estrogenic activity. All preparations containing a 19-nortestosterone derived progestagen, independent of their type and dose, induce a similar rise in CBG, whereas the preparation with cyproterone acetate induced an even higher CBG level. Irrespective of the effect on total testosterone, which varies between the preparations, the absolute free testosterone level decreased to a comparable degree for all preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone. 213 43

Acute intermittent porphyria is a genetic disease in which endogenous hormones affect clinical expression. Premenstrual exacerbations can occur, sometimes often, in women with this disease. Gonadotropin releasing hormone analogues can prevent ovulation by reducing secretion of luteinizing hormone and follicle-stimulating hormone. In six patients with well-documented acute intermittent porphyria and frequent cyclical exacerbations, daily administration of an agonistic gonadotropin releasing hormone analogue, ([ImBzl]-D-His6,Pro9-NET)gonadotropin releasing hormone, intranasally or subcutaneously for as long as 26 months reduced or eliminated premenstrual attacks and caused only minor side effects. Adjustments in dosage or route of administration were sometimes needed. We conclude that endocrine manipulation by treatment with a gonadotropin releasing hormone agonist will prevent neurovisceral attacks of acute intermittent porphyria due to cyclical changes in endogenous hormones and is a safe alternative to exogenous steroids, which may induce attacks of this disease.
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PMID:A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria. 219 28

The effect of norethisterone enanthate (NET-EN) on cervical mucus protein, sialic acid and some enzymes (e.g. peroxidase, alkaline phosphatase and alpha-amylase) were studied in adult female rats. One mg NET-EN every 12 days was found to be an effective contraceptive dose of this drug in this species, acting primarily through the cervical mucus. NET-EN produced a highly significant increase in protein content and peroxidase and alkaline phosphatase activities. However, sialic acid content and amylase activity did not exhibit any definite pattern after NET-EN therapy. The increased protein content together with persistent elevated levels of peroxidase and alkaline phosphatase corroborates the hypothesis that NET-EN creates a progestogenic phase which prevents sperm penetration and thus conception.
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PMID:Alterations in protein, sialic acid and some enzymes in cervical mucus of female rats during NET-EN treatment. 244 83

4 groups, each of 6 healthy volunteer female subjects aged 18-40 years, participated in this study designed to determine the effect of some contraceptive steroids on 2 plasma proteins -- sex hormone binding globulin (SHBG) and ceruloplasmin (CP). The pills were taken daily for 20 days, starting within the 1st 5 days of the menstrual cycle. There was no significant difference between the groups in the pre-treatment values. In Group LNG150 (150 mcg levonorgestrel), SHBG concentrations decreased, the decrease being statistically significant both in actual concentration and percentage change within 2-3 days of starting treatment. As pill-taking continued, SHBG concentrations declined further, and by the end of the treatment period they were less than half of the pretreatment value. Recovery was slow. In group EE30, LNG150 (ethinylestradiol 30 mcg and levonorgestrel 150 mg), no significant change occurred in SHBG concentrations during treatment. In Group EE35, NET1000 (ethinylestradiol 35 mcg and norethisterone 1000 mcg), SHBG increased, the value on days 2-3 of treatment being significantly higher than pretreatment. A steady state appeared to have been reached by days 7-8 and for the remainder of the treatment period the increase varied from 180-200% of the pretreatment value. The return to pretreatment values was slow. Women in Group EE35, NET600 (ethinylestradiol 35 mcg and norethisterone 600 mcg) also showed a rise in SHBG concentrations, which was greater than that observed in Group EE35, NET1000. In Group LNG150, CP concentrations slowly decreased during pill-taking, but the decrease did not reach statistical significance until days 14-15 of treatment; at this time the concentrations were about 15% lower than pretreatment. Despite stopping treatment, concentrations continued to decrease and were more than 25% lower by day 8 posttreatment. In Group EE30, LNG150, CP concentrations were significantly higher than pretreatment by days 2-3 and values continued to increase to the day of treatment. Women in Groups EE35, NET 1000 and EE35, NET600 showed a similar pattern, but the maximum percentage increase was higher, about 100%, compared to 75% in Group EE30, LNG150. Differences in the responses of ostensibly closely related proteins of hepatic origin, i.e., SHBG and CP, to the OCs demonstrate that neither can be extrapolated to other pharmacodynamic responses.
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PMID:Effect of some oral contraceptives on serum concentrations of sex hormone binding globulin and ceruloplasmin. 249 34

The authors employed a gonadotropin-releasing hormone agonist (GnRH-a) (D-His6-pro9-NET-GnRH) to treat 19 patients with symptomatic uterine leiomyomata, by daily subcutaneous injections (4 micrograms/kg) for 6 months. After therapy, patients were followed for 6 months without any therapy. Uterine volumes were measured by serial pelvic examinations and pelvic sonography. Measurements of serum estradiol, luteinizing hormone, and follicle-stimulating hormone were used to assess treatment response. Pituitary desensitization and hypoestrogenemia were achieved in all within 8 weeks, and in 18 of 19, hypoestrogenemia was maintained for the duration. Uterine volume at the conclusion of therapy (207.5 +/- 152.7 ml) was significantly reduced in all patients when compared with pretreatment sizes (420.8 +/- 276.4, P less than 0.05). Side effects included hot flashes (78%), vaginal dryness (32%), and transient frontal headaches (55%). All patients reported partial or complete relief from their symptomatic leiomyomata. Uterine volume at the conclusion of follow-up (345.4 +/- 195.7 ml) was greater than at the conclusion of therapy. Menses resumed in all patients within 4 to 8 weeks. In conclusion, GnRH-a therapy does not provide definitive therapy for symptomatic uterine leiomyomata but is effective in reducing the size of leiomyomata as a temporary measure. Gonadotropin-releasing hormone agonist therapy may be useful as an adjunct before myomectomy or hysterectomy and deserves further investigation.
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PMID:Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata: long-term follow-up. 249 32

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.
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PMID:Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin. 252 62

The most effective, convenient, reversible method of birth control is considered to be long-acting progestogen injections. Used by over 90 countries, Depot medroxy-progesterone acetate (DMPA, Depo-Provera, Upjohn) has yet to be approved by the U.S. Food and Drug Administration. The reluctance of the FDA to approve DMPA and much of the controversy surrounding this method revolve around the results of testing done on animals who were given large doses of the progestogen over a long period of time and developed tumors. However, the large body of research and records on this method that have been compiled over the past 30 years is positive. The injectable method works like oral contraceptives, inhibiting ovulation. Changes in menstruation have been the chief complaint of women who use this method; however, the duration and frequency of spotting and bleeding diminish over time. Other side effects of DMPA and Norethindrone enanthate (NET EN, Noristerat, Schering) are discussed. Also discussed is the history of development and testing for the 2 methods and subdermal implants, specifically Norplant.
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PMID:Injectable contraception. 252 77


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