Contraceptive delivery systems最新文献

Women with small uterine cavities and narrow cervical canals in particular suffer from symptoms such as discomfort, pain, cramps, bradycardia, syncope, and epileptoid convulsions during IUD insertions. These problems can be avoided by paracervical block (PCB) with syringe and needle, which may, in rare cases, entail hazardous side effects. These can be eliminated by the use of Jet Injection PCB. The Jet Injector deposits a 2% or 3% anesthetic solution paracervically submucously under high carbon dioxide pressure. The patient's fear of injection with a needle is avoided. The method can be applied by paramedics since intravascular application of anesthetic solution is impossible. The use of a more concentrated anesthetic solution allows dose reduction and the method of dispersion of the micro-drops ensures a more rapid onset. Premedication is not required and disposable material is economized on. This study is based on the application of Jet Injection PCB before insertion of medicated IUDs in 447 women; 60% nulligravidae, 14% nulliparous with abortion(s), 13% primiparae, and 13% multiparous. Age ranged from 15-47 years.

A Finnish multicenter study was carried out on 157 healthy fertile volunteers (2157 cycles) to evaluate an oral normophasic contraceptive preparation comprising 7 tablets of 0.050 ethinyl estradiol followed by 15 tablets of 0.050 mg ethinyl estradiol + 0.125 mg desogestrel. Bleeding patterns, side effects, liver function, and dropouts were recorded, as well as the development of the endometrium. No pregnancies occurred. Irregular bleeding (spotting and breakthrough bleeding) occurred in 12% of the 1st treatment cycle and in only 4% after 1 year's treatment. The most common side effects were nausea and headache. 17 women dropped out because of subjective side effects after 12 treatment cycles. No changes of any clinical importance were seen in mean body weight or liver function tests. Most of the endometrial biopsies showed a secretory pattern with mild hypoplasia. No hyperplastic or malignant changes were seen.

The response of human postmenopausal endometrium to standard, oral doses of an estrogen alone (estrone sulfate) and to an estrogen plus a progestin (medroxyprogesterone acetate; MPA) was evaluated by scanning electron microscopy and transmission electron microscopy. Endometrial biopsies were obtained over a 4-year period from 12 patients with well-established ovarian failure. Biopsies were taken before the initiation of therapy and during each mode of hormonal treatment. The ability of estrone sulfate alone to stimulate growth of the endometrium was shown during the 1st treatment cycle when the atrophic epithelial cells transformed into tall columnar cells which synthesized and released some secretory products. Unopposed estrogen therapy led to excessive ciliation and breakthrough bleeding. Addition of MPA to the estrone sulfate regimen produced a progestational endometrium. The epithelial cells had ultrastructural features of those in normal postovulatory endometrium, including nucleolar channel systems. MPA elicited deciliation and transformation of ciliated cells into secretory cells. Stromal cells hypertrophied, the vascular endothelium thickened, and bleeding subsided. Estrogen-progestin therapy as tremendously more physiological than unopposed estrogen therapy.

Electron microscopy was performed on testicular biopsies from men during a contraceptive regimen with d-norgestrel and testosterone enanthate. There was a considerable reduction of spermatogenesis, the seminiferous tubules being lined with a low epithelium of early spermatogenetic cells and only few late stages and spermatozoa. At the ultrastructural level, no qualitative changes could be observed in any of the tubular cells, a fact that seems to be of significance in contraception where any possible change should be entirely reversible.

Progestogens may have profound effects on lipid metabolism. Effects are generally dose-related and are more pronounced with 19-nor testosterone derivatives. Progestogens suppress circulating levels of high-density lipoprotein cholesterol (HDL-C) and increase circulating low-density lipoprotein cholesterol. Therefore, over a long period of time, the risk of atherosclerosis may increase. Although contraceptive use of depot medroxyprogesterone acetate (DMPA) reduced HDL-C levels by 15-20%, the levels generally remain within the normal range. Progestogens such as DMPA usually do not have any influence on fasting triglyceride levels. Some progestogens produce changes in the composition of phospholipids, but not DMPA. Progestogen effects on lipid metabolism are different from estrogen effects alone or estrogen-progestogen combinations. Increased risk of cardiovascular disease in longterm DMPA users is probably very small, but may become more significant when coupled with high risk factors. 10 years ago, most of the undesirable metabolic changes associated with the use of oral contraceptives were attributed to the estrogen component. 2 recent findings illustrate that certain progestogens can create metabolic havoc. 1) There is a strong association between depressed circulating levels of HDL-C and risk of serious cardiovascular disesase. 2) Certain progestogens are capable of substantially depressing the circulating levels of HDL-C, whereas estrogen actually elevates HDL-C. This does not prove that progestogens cause cardiovascular disease, but this possibility should be considered.

The synthesis of poly (ortho esters) by the condensation of diols and diketene acetals and the in vitro drug release from devices containing norethindrone or levonorgestrel and either Na2C03 or Na2S04 is described. Drug release kinetics are rationalized in terms of an osmotically driven water imbibition and release of the steroid from the swollen polymer. No polymer erosion occurs when Na2C03 is used. When Na2S04 is used, polymer erosion does take place but lags drug release. As expected from the known acid lability of ortho ester linkages, drug release is strongly dependent on the pH of the external environment and a dramatic increase occurs between pH 5.5 and 5.0. The glass transition temperature of the poly (ortho esters) can be continuously and predictably varied between 115 and 20 degrees Celsius by using an appropriate ratio of 1,6-hexanediol, and trans-cyclohexanedimethanol in the condensation reaction with the diketene acetal. Polymer hydrophilicity can be varied by the incorporation of varying amounts of the hydrophilic diol diethylene glycol into the polymer. Molecular weight control can be readily achieved by skewing the stoichiometry, and polymers with weight average molecular weights between 20,000 and in excess of 100,000 have been produced. Hydrolytic degradation of the poly (ortho esters) produces the expected products.

The influence of oral contraception with 0.5 mg ethynodiol diacetate (Femulen) on blood lipid and glucose tolerance test (GTT) was studied in a group of 14 nulliparous women ages 17-24 years before and 3 months after treatment. In another group of 13 women of matched age, contraception was managed by providing a combined pill (estrogen and progesterone). The continuous treatment of ethynodiol diacetate did not result in the increase in serum cholesterol and triglyceride levels and did not affect the GTT, as observed when the combined pill was administered. Femulen had no side effects, except for 2 cases of vaginal spotting. Ethynodiol diacetate does not induce the decrease in high-density lipoprotein cholesterol levels which is an anti-risk factor for the prevention of accelerated atherosclerotic disease. Oral contraception with this pill is indicated for all women, especially when there is an absolute contraindication for the use of combined pills

48 volunteers using either a Lippes Loop D or a T Cu 220C IUD who subjectively observed an increase in menstrual bleeding associated with IUD use received 250 mg naproxen 3 times/day during, or for 5 days of, their menstrual period. Results were compared with those on administration of placebo. Of the 48 women studied, 14 had hypermenorrhea (average 133.4 ml/menstrual cycle; heavy bleeding group) and 34 had blood loss within the normal range (average 47 ml; normal group). The study consisted of measuring menstrual blood loss (MBL) during the 1st (control cycle). During the 2nd cycle, the women received placebo medication 3 times/day for the 5 days of menses; results were not significantly different from control values. Naproxen was administered during the 3rd and 4th cycles (treatment); a significant reduction in the amount of MBL was observed in the group of women with heavy bleeding. During the 1st treatment cycle, a reduction of 42.8% was observed and during the 2nd treatment cycle, the reduction was 24.2%. In the group of women with MBL within the range of normal, no significant change in the amount of menstrual bleeding was observed in the treatment cycles as compared with the control cycle or placebo administration.