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Trisomy 7 mosaicism and manifestations of Goldenhar syndrome with unilateral radial hypoplasia.

We describe a girl born to a mother who took birth control pills and antihistamines during the first trimester of pregnancy. Congenital abnormalities included plagiocephaly, abnormalities of left ear, facial asymmetry, abnormalities of head hair pattern, cleft lip and palate, bifid tongue, left torticollis, hemivertebrae, left radial hypoplasia and absent thumb, left inguinal hernia, patient ductus arteriosus, narrowing of the thoracic aorta, and hypoplastic right pulmonary artery. The karyotype obtained from peripheral lymphocytes and from fibroblasts from the left side of the body was 46XX whereas fibroblasts from the right side revealed 46XX/47XX+7 mosaicism.

Child↗

Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive.

To determine whether the long-term exposure to a monthly injectable contraceptive, containing dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg, induces significant changes on the serum estrogens profile and ovulation return in women, a study in chronic users was undertaken. Ovarian function was assessed for 3 months following a single injection of the contraceptive agent in a group of women (n = 7) who have been on this formulation for an average period of 6.7 years and in a non-user control group (n = 7). The serum concentrations of 17 beta-estradiol, estrone and progesterone were measured in samples drawn at regular intervals throughout the entire study. The endometrial bleeding pattern was recorded in all subjects. The results indicated that the post-injection serum estradiol maximum levels (exogenous peak) occurred significantly earlier (p less than 0.05) in chronic users as compared with the non-user control group. Baseline serum estrone concentrations were slightly higher in chronic users than those observed in the control group, while the values of serum 17 beta-estradiol did not exhibit significant differences among the two groups. Ovulation was documented within 60-90 days after injection in all subjects from both groups. A similar length of the first bleeding-free period was observed in all participants. The overall data provide evidence of a moderate increase of estrone, one of the still active metabolic conversion products of 17 beta-estradiol, in the sera of chronic users of this combined contraceptive without affecting its pharmacodynamics.

Adult↗

Clinical aspects of three new progestogens: desogestrel, gestodene, and norgestimate.

Three new 19-nortestosterone progestogens, which are chemically related to levonorgestrel, are now clinically available in combination oral contraceptives in Europe. Desogestrel and norgestimate must be transformed to metabolites for all or part of their biologic activity; gestodene is active in its original form. Compared with present low-dose monophasic and triphasic levonorgestrel formulations, the new combinations appear to be equivalent in efficacy and type and frequency of side effects. Cycle control may be slightly improved with the gestodene preparation and somewhat poorer with the desogestrel regimen. As with the present triphasics, most changes reported in coagulation indexes for the new combinations remained within normal limits, as did changes in carbohydrate and lipid metabolism. There is no present evidence that either the norgestimate or aesogestrel formulation provides a clinical improvement over the levonorgestrel triphasic. In the gestodene combination, the progestogen's increased biologic activity allows further reduction of total steroid dose.

Carbohydrate Metabolism↗

Biomaterials for drug delivery systems.

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Biocompatible Materials↗

Changes in unbound sex steroids and sex hormone binding globulin--binding capacity during oral and vaginal progestogen administration.

Four groups of five cycling women each received either a contraceptive vaginal ring containing a combination of either levonorgestrel or norethindrone with estradiol or oral contraceptives containing a combination of either dl-norgestrel or norethindrone with ethinyl estradiol. Pretreatment as well as 2- and 7-week treatment serum samples were assayed for sex hormone binding globulin-binding capacity (SHBG-BC), estradiol, non-SHBG-bound estradiol, testosterone, and non-SHBG-bound testosterone, d-norgestrel, non-SHBG-bound d-norgestrel, and norethindrone. SHBG-BC was significantly increased in the norethindrone oral contraceptive group, unchanged in the norgestrel oral contraceptive group, and significantly reduced in both contraceptive vaginal ring groups. These findings indicate that the positive effect of oral ethinyl estradiol on SHBG-BC offsets the suppressive effects of d-norgestrel on SHBG-BC, while the estradiol in the d-norgestrel or norethindrone contraceptive vaginal rings is insufficient to alter the suppressive effect of d-norgestrel or norethindrone on SHBG-BC. In contrast, the ethinyl estradiol in the norethindrone oral contraceptive overcame the suppressive effect of norethindrone on SHBG-BC, resulting in a significantly increased SHBG-BC level. Although total circulating estradiol was significantly decreased in the contraceptive vaginal ring groups, the percentage of unbound serum estradiol was significantly increased in both contraceptive vaginal ring groups and significantly reduced in the norethindrone oral contraceptive group. Although total circulating testosterone was significantly reduced only in the norgestrel oral contraceptive group, the percentage and mass of unbound testosterone were significantly decreased in the norethindrone oral contraceptive group, while the percentage of unbound testosterone was significantly reduced in the norgestrel oral contraceptive group and significantly increased in the norethindrone contraceptive vaginal ring group. As levels of unbound (biologically active) steroid differ markedly from levels of total steroid, it is essential to measure levels of non-SHBG-bound estradiol and testosterone in order to determine effects of steroidal contraceptives on physiologically active circulating endogenous steroids.

Adult↗

The acceptability of a progestagen-only contraceptive during breast-feeding.

The acceptability of an oral contraceptive containing norethisterone 0.35 mg was investigated in a group of mothers followed-up at 6 months post-partum. Eighty-four mothers out of a total of 203 (41%) had used this preparation while breast-feeding and 37 (44%) of these were still taking it at the time of follow-up. The most frequent reason for discontinuation was cessation of breast-feeding. The overall duration of breast-feeding did not appear to differ between this group and a group using occlusive methods of contraception. Uterine bleeding during therapy was related to duration of breast-feeding, with 68% of women who breast-fed for longer than five months remaining amenorrhoeic. Irregular bleeding occurred in 12% of the women who breast-fed for longer than 5 months compared with 43% of those who stopped breast-feeding within the first 3 months. In only 9% of cases was the pill discontinued because of side effects, including irregular bleeding.

Administration, Oral↗

The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids.

Patients taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine together with their oral contraceptive steroid may suffer contraceptive failure because of the enzyme-inducing properties of these anticonvulsants. We have examined, in six women, the effect of sodium valproate, an effective broad spectrum anticonvulsant, on the area under the plasma concentration versus time profile (AUC) of ethinyloestradiol (EE2) and levonorgestrel (Ng). Prior to sodium valproate therapy the mean AUC for EE2 was 880 +/- 109 pg/ml X h (+/- S.E.) and for levonorgestrel it was 29.1 +/- 2.9 ng/ml X h (n = 4). Between two and four months after sodium valproate therapy the mean AUC figures had not changed significantly, the figure for EE2 being 977 +/- 130 pg/ml X h and for levonorgestrel 29.2 +/- 1.9 ng/ml X h (p greater than or equal to 0.1 in each case). We conclude that sodium valproate in the dose used (200 mg b.d.) does not interact with oral contraceptive steroids.

Adolescent↗

The effects of oral contraceptives on respiration.

The effect synthetic progestins found in current oral contraceptives may exert on respiratory function has not been thoroughly investigated. This study monitored potential changes in respiratory parameters 3 and 6 months subsequent to beginning administration. Static and timed spirometric maneuvers showed significant increases in only tidal volume (P = 0.01). Ventilatory response to treadmill exercise monitored the oxygen uptake, CO2 elimination (VCO2), minute ventilation (VE), and respiratory exchange ratio at each of four workloads. An analysis of the covariance (ANCOVA) for the slopes revealed no significant variation between test periods. The ANCOVA for the means showed increases in VE and VCO2. These results suggest a stimulatory role for synthetic progestins, although ventilatory performance in response to moderate exercise does not appear compromised.

Adult↗

Endocrine aspects of acne.

In summary, the diagnostic tools are now available to ascertain whether elevated levels of androgens underlie some cases of acne vulgaris. Awareness of androgen excess as a contributing factor in acne may help to identify patients who would benefit from endocrine evaluation and, possibly, from hormonal therapy.

Acne Vulgaris↗

Medical management of endometriosis-associated pain.

In the coming years, basic science research into the mechanisms of endometriosis development and persistence almost certainly will open new avenues for treatment. A wide armamentarium of medical therapies already exists, however. The efficacy of most of these methods in reducing endometriosis-associated pain is well established. The choice of which to use depends largely on patient preference after an appropriate discussion of risks, side effects, and cost. Typically, oral contraceptives and NSAIDs are first-line therapy because of their low cost and mild side effects (Box 6). Because of its greater potential for suppressing endometrial development, consideration should be given to prescribing a low-dose monophasic oral contraceptive continuously. If adequate relief is not obtained or if side effects prove intolerable, consideration should be given to the use of progestins (oral, intramuscular, or IUD) or a GnRH agonist with immediate add-back therapy. Progestins are less expensive, but GnRH agonists with add-back may be better tolerated. If none of these medications proves beneficial or if side effects are too pronounced, then repeat surgery is warranted. The surgery may have analgesic value and serves to reconfirm the diagnosis. Finally, if endometriosis is identified at the time of surgery, then consideration should be given to prescribing medical therapy postoperatively.

Anti-Inflammatory Agents, Non-Steroidal↗

Delayed interval delivery of two remaining fetuses in quintuplet pregnancy after embryo reduction: report and review of the literature.

A case report is presented with a prolonged interval between delivery of 25 days. A quintuplet pregnancy resulted from hormonal stimulation of ovulation. Two fetuses remained after an embryo reduction was performed at 11 weeks gestation. At 22.5 weeks gestation the first twin (310 g) was delivered after spontaneous rupture of membranes. Using tocolytic agents, the second twin (710 g) was born at 26 weeks of gestation. This case is discussed and a review of the literature is given.

Abortion, Induced↗

[Clinical observation and preliminary study of termination of early pregnancy by administration of yellow daphne].

74 cases of early pregnancy with periods of amenorrhea of 36-69 days from the last menses were terminated by using a single dose intrauterine instillation of Wikstro-Emia Chamaedaphne Meisn Alcohol Solution (WCMAS). According to the dosages used, they were divided into 3 groups: 0.2gm, 0.4gm, and 0.6gm of WCMAS. The efficacy of the different dosages was evaluated. The most successful in the termination of early pregnancy (less than 56 days) was the 0.4gm group, the effective rate being 96.6%, and the complete abortion rate being 93.3%. The average duration of complete abortion in all was 21.3 hours, and the averge duration of vaginal bleeding was 10.9 days. Although amount of bleeding was regarded as a little greater than that of normal menstruation by some patients, yet there were no serious side effects occurring, except that some patients experienced some subjective lower abdominal pain and vomiting. Serum hCG and progesterone were determined by radioimmunoassay technique in 31 cases, and it was found that the hCG and progesterone levels both declined rapidly at 12 hours and fell to 35.5% and 46.4% respectively 24 hours after injection. Under microscopic examinations necrotic degeneration was observed in most of the chorionic villi, and marked necrosis and hemorrhage in the decidua. The granulocytes in the decidua also decreased in amount. 48 cases were followed up recently; no side effects were found and there was no interference with re-pregnancy.

Abortifacient Agents↗