[Contraceptive methods].
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Contraceptive Agents, Female↗
Biomedical subjects
J Toivonen
Publications and source records attributed to J Toivonen.
[Postcoital contraception].
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Contraceptive Devices, Female↗
Five years' experience with levonorgestrel-releasing IUDs.
Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.
Adult↗
Contraception with subdermal ST-1435 capsules: side-effects, endocrine profiles and liver function related to different lengths of capsules.
One Silastic capsule of 15 mm, 20 mm or 30 mm length was inserted subcutaneously into the ventral aspect of the left forearm or upper arm of 28 healthy women during menstrual bleeding or not later than on the seventh day of the menstrual cycle. A new capsule of the same length was inserted after six months and both capsules were removed twelve months after the first insertion. Side-effects, including changes in body weight, blood pressure, menstrual bleeding and liver function test results, were registered. Blood samples were taken from selected subjects twice a week during the 1st, 2nd, 3rd, 6th, 7th and 12th month of use. Plasma concentrations of ST-1435 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. There were no differences in hormonal side-effects between subjects who had a 30 mm capsule or subjects who had 20 mm or 15 mm capsules, but subjects who had 20 or 15 mm capsules had significantly longer bleeding or spotting periods in comparison with subjects who had a 30 mm capsule. There were no changes in blood pressure, body weight or liver function test results in comparison with pre-insertion values. The plasma level of ST-1435 was not significantly higher during the use of 30 mm capsules than during the use of 20 or 15 mm capsules. During the use of the shorter ST-1435 capsules, plasma estradiol elevation and slightly suppressed FSH were seen, while the use of longer capsules resulted in a slight suppression of LH. Progesterone concentrations during monitored cycles indicated anovulation. No pregnancies occurred during the study period of one year. The continuation rate at one year was 71% in the 30 mm capsule group and 57% in the 20 and 15 mm capsule groups taken together.
Adult↗
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↗
Postabortal contraception with norethisterone enanthate injections.
Intramuscular injection of 200 mg norethisterone enanthate (NET-EN) was given to five women on the day of first trimester abortion. The injection was repeated twice at eight-week intervals, and thereafter at twelve-week intervals for one year. Plasma samples were collected for FSH, LH/hCG, estradiol, progesterone and norethisterone (NET) determinations. NET-EN did not affect the elimination of hCG, estradiol or progesterone. Plasma NET concentrations reached a peak (5.5-11 ng/ml) in about ten days after the injection and declined constantly thereafter, to levels of 0.18-0.64 ng/ml at 8 weeks after the injection. NET-EN postponed the increase in FSH secretion until 17-20 days after the injection, i.e. until plasma NET concentrations fell below 3 ng/ml. In three out of five women some follicular activity was present 5 weeks after NET-EN injection as evidenced by increased plasma estradiol concentrations. No ovulation occurred within 8 weeks after NET-EN injection, as judged by low progesterone values. There was a definite accumulation of NET during the first six months, when NET-EN injections were given at eight-week intervals. Mean plasma NET concentrations increased from 0.34 ng/ml at eight weeks to 0.78 ng/ml at 24 weeks. When the injection interval was increased to twelve weeks, the plasma NET concentrations prior to the next injection started to decrease. This was accompanied by increased follicular activity, culminating with one ovulation observed. It is concluded that in this population of women, an injection interval of less than twelve weeks is needed for ovulation inhibition.
Abortion, Legal↗
Effect of progesterone, administered via intravaginal rings, on serum concentrations of oestradiol, FSH, LH and prolactin in women.
Intravaginal rings containing progesterone were inserted on Day 5 of the cycle to 8 healthy, normally menstruating women. Blood samples were taken during Days 4--22 of the cycle at 2--3-day intervals. The plasma progesterone levels obtained after the insertion were between 7.5 and 21 nmol/l. Four subjects showed no increase in plasma oestradiol concentrations. The subjects showing increased plasma oestradiol levels also showed a positive feedback on LH, resulting in ovulation or an LH peak. The results suggest that progesterone may have a local inhibitory effect on the follicular oestradiol production.
Adult↗
Intracervical release of levonorgestrel for contraception.
Twenty-one women used a levonorgestrel-releasing intracervical contraceptive device, which was designed to release 20 microgram/ay. The devices were inserted after cessation of menstrual bleeding. Patterns of bleeding and clinical performance wer evaluated and plasma concentrations of levonorgestrel, estradiol and progesterone in selected subjects were measured by radioimmunoassay. The results of the initial 90-day treatment are presented. Levonorgestrel was detected in peripheral plasma by 30 minutes after insertion of the device. Considerable variation of plasma levonorgestrel concentrations was observed between subjects, but within each subject, the plasma level of levonorgestrel was very stable with time. Of 24 cycles monitored by blood sampling, 19 were ovulatory. One subject did not ovulate at all. During the first 30-day period of treatment, frequent intermenstrual bleeding or spotting periods occurred. Two spontaneous expulsions occurred 9 and 22 days after insertion. Both of these subjects were nulligravidas. Side-effects were few and no pregnancies occurred during the study period.
Adult↗
Return of ovulation after abortion and after discontinuation of oral contraceptives.
The return of ovulation after abortion and discontinuation of oral contraceptives was determined by plasma progesterone measurements. Plasma samples were obtained from 67 women at 3 to 6 weeks after abortion and in two groups of postabortion women at 3 to 6 weeks after cessation of oral contraceptives. In the first of these latter two groups, 50 women started taking the pills (containing 30 microgram of ethinylestradiol and 150 microgram of levonorgestrel) immediately after abortion, and the second group of 29 women started taking the pills from the first postabortion menses. Ovulation had recurred in 34% of the women 3 weeks after abortion and in 78% of the women at 6 weeks. The return of ovulation had occured in approximately 55% at 3 weeks after cessation of oral contraceptives in both groups. At 6 weeks after cessation, approximately 85% of women had ovulated in both groups. Luteal function in these two groups was found to be equal and was significantly better in both groups than during the first postabortion cycle (P < 0.005). It is concluded that the early return of ovulation after abortion makes it necessary to commence effective contraception immediately after abortion. The immediate administration of oral contraceptives after abortion does not affect the return of ovulation after discontinuation of oral contraceptives.
Abortion, Legal↗
Pituitary and gonadal function during the use of progesterone- or progesterone-estradiol-releasing vaginal rings.
Six women used polysiloxane vaginal rings impregnated with progesterone, or progesterone and estradiol. Nineteen 3-week treatment cycles were studied. Subjects kept records of bleeding. Plasma progesterone, estradiol, and gonadotropins were measured by radioimmunoassay. The patient acceptance was poor. None of the subjects experienced regular withdrawal bleedings during the treatment-free week. Fifty-three percent of the cycles were ovulatory as judged by plasma progesterone, but the plasma concentration of progesterone was low during the luteal phase. However, no pregnancies were discovered during the study period. Several high estradiol peaks were present during the treatment. Plasma LH fluctuated in the range of the normal menstrual cycle. Some suppression of plasma FSH was observed. The combination of estradiol and progesterone in the rings caused stronger suppression of FSH, but no diminution in the rate of ovulations or in disturbances of bleeding were observed in comparison to rings impregnated only with progesterone. Rings released the same amounts of progesterone in vitro and produced plasma concentrations which varied between 0.4 and 1.9 ng/ml.
Adult↗
The use of a contraceptive vaginal ring governed by the pattern of individual uterine bleeding.
Contraceptive vaginal rings (CVR) releasing levonorgestrel and estradiol were used for contraceptive purposes in eight women. They were instructed to remove the CVR for five days only, in the case of bleeding. Three selected subjects were followed by plasma sampling during the first 60 days of treatment. Plasma concentrations of levonorgestrel, progesterone, estradiol and gonadotropins were determined. All subjects kept bleeding records and were controlled clinically in the course of treatment. The subjects were protected an average of 163 days by the CVR. Three subjects used the CVR 170--180 days without removing it and two subjects had to remove the CVR only once. Two subjects experienced quite regular bleedings, and metrorrhagic bleeding was present in one case. No pregnancies were observed during the follow-up period of 1304 days. Clinical examination revealed no pathological findings. The vaginal mucosa tolerated the treatment well. Out of those subjects who were followed by plasma sampling, pituitary suppression was more marked in the subject with continuous use of CVR.
Adult↗
Bleeding and ovulation control with use of a small contraceptive vaginal ring releasing levonorgestrel and estradiol.
Levonorgestrel and estradiol releasing contraceptive vaginal rings (CVR) with an outer diameter of 50 mm were used by twenty women. The treatment was given in three-week cycles followed by one treatment-free week. The treatment was planned to cover six cycles. All subjects kept records of bleeding and were controlled clinically in the course of treatment. Three subjects were followed by blood sampling. Plasma levonorgestrel, estradiol, progesterone and gonadotropins were determined. The subjects experienced no difficulties in using the CVR and 90 per cent continued the treatment through the whole experimental period of six months. One subject discontinued after three cycles because of irregular bleedings and one subject after five cycles because of urinary discomfort. Regular bleedings were observed only in three subjects and in nine cases the bleeding started with the CVR in situ during the last days of the three-week treatment period. Breakthrough bleeding occurred in the remaining eight subjects. The subjective side-effects were as follows: weight gain in four subjects, oedema in one subject and urinary discomfort in one subject. Pituitary function was not generally suppressed as judged by plasma gonadotropins. Out of the three subjects studied, two experienced ovulatory plasma progesterone concentrations.
Body Weight↗
Intravaginal contraception with the synthetic progestin, R2010.
Four women used polysiloxane vaginal rings of core design containing 50 mg of norgestrienone (17 alpha-ethynyl-17 beta-hydroxy-estra-4,9,11,trien-3-one). The treatment was given in three-week cycles, leaving one treatment-free week between the cycles. The patterns of bleeding were registered and plasma norgestrienone (R2010), estradiol, progesterone, and gonadotropins were determined. Altogether twelve cycles were studied. The patterns of bleeding were unsatisfactory; only one subject had regular bleedings, and two of these were preceded by a luteal phase. The mean plasma concentration of norgestrienone (R2010) produced by the rings was 0.9 ng/ml. Ovulation was observed in 25% of cycles studied. Some follicular activity was present in every subject as judged by estradiol peaks. Excluding LH peaks in subjects who ovulated, mild pituitary suppression was achieved by this treatment. The only side-effect complained of was acne in one subject. The ring was regarded as easy to use.
Adult↗
Plasma progesterone concentrations after administration via intravaginal rings.
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Evaluation Studies as Topic↗
Pituitary and gonadal function during the use of norgestrelestradiol vaginal rings.
Four women used polysiloxane contraceptive rings (CVR) impregnated with d-Norgestrel and estradiol for contraceptive purposes. The treatment was given in three-week cycles, leaving one treatment-free week between the cycles. Subjects were followed by blood sampling twice a week for three or four treatment cycles. Plasma concentrations of d-Norgestrel, estradiol, progesterone, and gonadotropins were determined by radioimmunoassay. The bleeding patterns were very acceptable. One subject experienced acne and weight gain, but no other side-effects were observed. Furthermore, no local irritation was found during the follow-up period of six or seven months. The individual variation in the mean plasma concentrations of d-norgestrel was between 3.2 and 1.1 ng/ml. Apart from one case, the highest individual levels were observed at the beginning of the first treatment cycle. Plasma estradiol was low during the treatment, but in some cases low post-insertion peaks were observed. No ovulatory progesterone values were found. Plasma LH was generally suppressed, but FSH was not. During the treatment-free week increasing concentrations of both LH and FSH were found, indicating an activation of pituitary function.
Adult↗