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Biomedical subjects

T Luukkainen

Publications and source records attributed to T Luukkainen.

At least 55 records · Page 3Linked to original sources

Intracervical release of ST-1435 for contraception.

Seven women used an ST-1435-releasing intracervical contraceptive device (ST-ICD), inserted immediately after the cessation of menstrual bleeding. Patterns of bleeding and clinical performance were evaluated and plasma concentrations of ST-1435, estradiol, progesterone and gonadotropins were measured by radioimmunoassays. The results of ten months of treatment are presented. There were no uniform patterns of bleeding. No hormonal side-effects were registered. The plasma concentration of ST-1435 reached 100 pg/ml within two hours after insertion of an ST-ICD. No ovulations occurred during the initial three months of treatment. A rapid decline in the plasma concentrations of ST-1435 was observed; during the tenth month the concentration of ST-1435 was under the sensitivity of the radioimmunoassay of ST-1435. Hence, the release of ST-1435 from Silastic was too rapid for long-acting contraceptive purposes.

Adult↗

Immediate postabortal contraception with Norplant: levonorgestrel, gonadotropin, estradiol, and progesterone levels over two postabortal months and return of fertility after removal of Norplant capsules.

Six Silastic levonorgestrel-releasing capsules, Norplant, were introduced subcutaneously into the ventral aspect of the left forearm or upper arm of thirteen patients immediately after first trimester pregnancy termination. Blood samples were taken twice a week over two months after abortion and from one subject over one month after removal of Norplant capsules. Plasma concentrations of levonorgestrel were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. If removal of Norplant capsules took place because of planning pregnancy, the subjects were asked to inform us if they had become pregnant. During the first month after abortion the mean levonorgestrel concentration (489 pg/ml) was statistically significantly higher than during the second month (237 pg/ml). The mean estradiol values fell to prefollicular levels within four days, remaining a little suppressed. The mean progesterone concentrations were below 2 ng/ml three days after abortion. Three subjects had a transient increase in plasma progesterone concentrations nine days after abortion. Thereafter no ovulatory progesterone concentrations were seen. The LH concentrations ranged within normal values of the follicular phase and FSH values were just beneath the lower limit of follicular phase FSH values, apart from a few peaks, indicating mild suppression. After removal of Norplant capsules, progesterone concentrations increased to ovulatory levels fifteen days after removal. The Norplant capsules were removed from two subjects because of planning pregnancy and they delivered healthy babies 9.5 and 12.5 months after removal.

Abortion, Induced↗

Pituitary and ovarian function and clinical performance during the use of a levonorgestrel-releasing intracervical contraceptive device.

A levonorgestrel-releasing intracervical device (ICD) was inserted postmenstrually to twenty-one voluntary women. Eight subjects gave blood samples twice a week during the initial three months of use of the ICD and during the seventh and twelfth months of use. Clinical performance was studied; plasma concentrations of levonorgestrel were measured by radioimmunoassay and the effects of the treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. The results of the first year are presented. Dysmenorrhea, menstrual flow and the number of days of bleeding decreased during the first treatment year. Three spontaneous expulsions occurred; two at the very beginning of the treatment and one after six months of use. Side-effects were few. The plasma level of levonorgestrel remained fairly constant during the observation time of 12 months. Thirty-one of the 36 cycles were ovulatory as judged by plasma progesterone elevations. No pregnancies occurred during the study period of one year.

Adult↗

Pharmacokinetic observations on ST-1435 administered subcutaneously and intravaginally.

Plasma levels of ST-1435 were determined by radioimmunoassay in 36 women and three men during treatment with subdermal capsules releasing ST-1435. The total lengths of the capsules used were 180 mm, 90 mm, 30 mm, 15 mm and 7.5 mm. A linear correlation between the mean plasma concentrations of ST-1435 and capsule length was found during the treatment period studied. However, great interindividual variation in plasma levels of ST-1435 between study subjects having similar capsules was observed. In comparison with the mean plasma concentrations in the initial months, only less than half of these plasma concentrations of ST-1435 were measured after six months of treatment, which indicates a short lifetime for this contraceptive system. In two women the disappearance of ST-1435 from the circulation was studied by measuring ST-1435 concentrations in the plasma after removal of a contraceptive vaginal ring (CVR) releasing ST-1435. Triphasic disappearance curves of ST-1435 were found, with half-lives 0.7-1.0 h, 3.1-4.0 h, and 10.7.3-11.8 h.

Adult↗

Factors affecting the clinical performance of Nova T and Copper T 200.

In a randomized comparative use-effectiveness study of the copper-releasing intrauterine devices (IUDs), Nova T and Copper T 200, an analysis was made of the differences in women between the participating countries and of the influence of various factors on pregnancy rate and rates of terminations. In a cohort of 1865 women the five-year gross cumulative pregnancy rates were 3.4 per 100 women for Nova T and 8.7 per 100 women for Copper T 200. The rate of unwanted pregnancy was significantly related to the type of IUD, the country, and the age of the women. Prognostic factors for expulsion or removal of the device were age, country, parity, previous use of IUD, previous vaginal delivery, and previous abortion. The differences among the results for the participating countries may reflect the effects of different policies in clinics.

Abortion, Induced↗

Ovarian function in amenorrheic and menstruating users of a levonorgestrel-releasing intrauterine device.

The ovarian function of 20 healthy users of a levonorgestrel-releasing intrauterine device was studied by measurements of plasma estradiol, progesterone, and levonorgestrel concentrations. Eight subjects were amenorrheic, and 12 had regular menstrual bleeding. Seventy-five percent of the subjects in both groups had ovulatory cycles. There was no difference between the mean levonorgestrel concentrations in the amenorrheic and regularly menstruating subjects. Estradiol function was undisturbed in the amenorrheic subjects with ovulatory cycles. The effect of levonorgestrel as a cause of amenorrhea is thought to be mainly of local nature. The intrauterine administration of levonorgestrel had only an occasional and weak effect on ovarian function.

Adult↗

Five years' experience of intrauterine contraception with the Nova-T and the Copper-T-200.

A randomized study was performed for the comparison of two copper-releasing intrauterine contraceptive devices (IUDs), the Nova-T and the Copper-T-200, simultaneously in Denmark, Finland, and Sweden. Five years' experience demonstrated that Nova-T users had a significantly lower pregnancy rate than Copper-T-200 users. The Pearl index over 5 years was 0.8 for Nova-T users and 2.0 for Copper-T users. The performance and tolerance of the Nova-T were less affected by parity and age than was the performance of the Copper-T. Infections were treated by removal of the device and with antibiotics. The cumulative rate of removals because of infections and suspected infections was below 5 with both devices over 5 years. The copper wire in the Nova-T has a silver core which prevents corrosion-induced fragmentation of the wire. Hence, the effective lifetime of this device is more than 5 years. The results indicate that the Nova-T, which is easy to insert and remove and is associated with a low pregnancy rate and a low medical termination rate, is a real improvement over other IUDs.

Adult↗

Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes.

A number of physiological and synthetic progestins were tested for their ability to compete with [3H]dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells. As compared to the reference compound dexamethasone (relative receptor binding affinity defined as 100%), two potent synthetic progestins with a pregnane-type structure, megestrol acetate and medroxyprogesterone acetate, were found to display a considerable binding affinity towards the receptor (46 and 42%, respectively). The relative binding affinity of the naturally occurring ligand, cortisol, to the receptor was clearly lower (25%). The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid. No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [3H]Org 2058 was used. Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions. These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures. The progestin effect appears to be mediated through a radiosensitive (suppressor) subpopulation of T lymphocytes. In contrast, the synthetic progestins related structurally to 19-nortestosterone, norethisterone and d-norgestrel, were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions. These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character (e.g. suppression of the pituitary-adrenal axis) might be expected when these compounds are used in pharmacological doses.

DNA Replication↗

Vaginal contraception with gossypol: a clinical study.

A clinical study concerning the vaginal contraceptive efficacy of gossypol acetic acid was performed. Fifteen women who had undergone tubal sterilization volunteered for the study. The effect of vaginal gossypol-containing gel on spermatozoa was determined by postcoital tests performed in subjects without and after using gossypol gel. After gossypol application, the number of spermatozoa found in cervical mucus was greatly decreased and, in eleven of the fifteen women, all spermatozoa seen were immobilized. In four cases a few poorly motile spermatozoa were seen but they showed no forward progression. We have previously reported that gossypol has an inhibitory effect on herpes simplex virus type 2 in vitro. This anti-viral property of gossypol makes it particularly attractive as a topical barrier contraceptive. The present study shows that gossypol is also promising as a vaginal contraceptive agent in human in vivo experiments.

Adult↗

Two years' experience with two levonorgestrel-releasing intrauterine devices and one copper-releasing intrauterine device: a randomized comparative performance study.

A randomized comparative performance study of two levonorgestrel intrauterine devices (IUDs) and a copper (Nova-T) IUD (Leiras, Turku, Finland) was performed at two clinics in Finland and one in Brazil. The 24-month cumulative event rates per 100 women are reported. Six thousand woman-months of use were recorded with the levonorgestrel IUD and 3000 with the Nova-T device. Pregnancy rates at 2 years of use were 0.6 and 0 with the two levonorgestrel IUDs and 3.3 with the Nova-T IUD. Removal rates because of bleeding and/or pain were low with all three IUDs: 7.5, 7.6, and 7.1, respectively, at 24 months. Recordings of the number of days of bleeding showed significantly fewer days of bleeding during use of the levonorgestrel IUDs than the Nova-T IUD from the second month of use onward, until the end of the second year. No infections were recorded in association with use of the levonorgestrel IUDs, and only one termination because of infection was recorded for the Nova-T IUD. The continuation rates of use at 24 months were 66.6, 60.7, and 71.9 for the two levonorgestrel IUDs and the Nova-T IUD, respectively; the differences were not statistically significant.

Adolescent↗

Levonorgestrel in milk and plasma of breast-feeding women with a levonorgestrel-releasing IUD.

A levonorgestrel-releasing intrauterine contraceptive device was used by 10 breast-feeding women beginning 6 weeks after delivery. Two models of IUD were used. One released 10 microgram (5 patients), the other 30 microgram (5 patients) of levonorgestrel per day. Plasma and milk samples were collected 8 times over a 3-month period and the concentrations of levonorgestrel determined by radioimmunoassay. An improved and sensitive method for the determination of levonorgestrel in milk was developed. A column chromatographic purification of a milk extract before radioimmunoassay made possible the use of large milk samples in order to improve the sensitivity. The plasma concentrations during the follow-up period were 207 +/- 64 pg/ml (mean + SD) in the 10 microgram and 235 +/- 87 pg/ml in the 30 microgram/day releasing IUD groups. The milk levonorgestrel concentrations were 56 +/- 35 and 57 +/- 34 pg/ml, respectively. The plasma to milk ratio of levonorgestrel was initially 100:15 and at the end of the 3-month follow-up period 100:25. There were no significant differences in the milk and plasma concentrations between the study groups. The total amount of levonorgestrel excreted per day in 600 ml breast milk is approximately 0.1 per cent of a daily dose of 30 microgram.

Breast Feeding↗

Duration of breast-feeding and development of children after insertion of a levonorgestrel-releasing intrauterine contraceptive device.

IUDs releasing levonorgestrel, 10 micrograms per day (30 patients) and 30 micrograms per day (40 patients), and copper-releasing IUDs (Nova-T) (40 patients) were inserted six weeks after delivery in 110 breast-feeding amenorrheic women. The infants were carefully followed-up by recording monthly weight gain and growth, age of eruption of the first tooth, age of being able to walk without support and morbidity to infective diseases. No differences were noticed between the study groups. Plasma samples were collected from 13 children at the age of eight months, while the mothers were breast-feeding. Six mothers had a levonorgestrel-releasing IUD and seven others the Nova-T or no hormonal or intrauterine contraceptive. No differences were noticed between the groups in Na, K, Cl, Ca, P, protein, albumin, creatinine, urate, Fe, cholesterol, triglyceride, bilirubin, alkaline phosphatase, aspargine aminotransferase, alanine aminotransferase, lactate-dehydrogenase or high density lipoprotein cholesterol serum concentrations in the children. The duration of breast-feeding and initiation of supplementary feeding was recorded. The continuation of breast-feeding 75 days after the insertion of a 30-micrograms per day levonorgestrel-releasing IUD was 56 percent while in the Nova-T group only 21 percent had discontinued which is a statistically significant difference (p less than 0.05); later the difference disappeared. Compared with the lactation time of their previous breast-feeding reported by women in both groups, the present lactation time increased by ten weeks. The infants received substitute foods including substitute milk, juices, etc., in the Nova-T group at 3.9 months and in the levonorgestrel-releasing IUD group at 3.4 months after delivery.

Adolescent↗

Pituitary and ovarian function during contraception with one subcutaneous implant releasing a progestin, ST-1435.

Three women received one subcutaneous SilasticR capsule containing 40 mg of ST-1435 for contraception. Plasma levels of ST-1435, a 19-norprogesterone derivative, were measured during the treatment period of 13-15 months. The effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. The mean concentrations of ST-1435 during the treatment varied from 52 to 220 pg/ml in different subjects. These low concentrations of progestin were sufficient to suppress ovulation and make the implant effective for more than one year. No mid-cycle gonadotropin peaks were observed during the treatment. The subjects showed constantly low estradiol levels, thus also indicating a suppression of follicle development. Regular cyclic activity of the pituitary and ovaries, without the occurrence of ovulation, was observed in one subject. Increasing levels of estradiol parallelled a decrease of FSH and LH. It therefore seems that the negative feedback action of estradiol on gonadotropin release is unaffected but the positive feedback action of estradiol on LH appears to be blocked by the progestin ST-1435.

Contraceptive Agents, Female↗

Return of fertility after the removal of Nova T or copper T 200.

The return of fertility after removal of Nova T or Copper T 200 IUDs was studied in 150 women who had a removal for planning pregnancy in a study performed for the comparison of the clinical performance of these IUDs in Denmark, Finland, and Sweden. There was no significant difference in the return of fertility of women having used either device. The cumulative probability of pregnancy per 100 women after the removal of the IUD, as a net rate, was 77.3 at one year, 88.9 at two years and 92.4 at three years. The return of fertility was analyzed separately for those women who had used their IUD for less than two years and for two or more years. The duration of the use had no significant effect on the return of fertility. The outcome of pregnancy, the birth weight, the condition at delivery and the sex ratio of the newborns were normal in the participating countries.

Adolescent↗