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Biomedical subjects

E D Johansson

Publications and source records attributed to E D Johansson.

At least 19 recordsLinked to original sources

Ovarian function during use of a levonorgestrel-releasing IUD.

Ovarian function was studied for two complete menstrual cycles in 9 regularly menstruating women and for 8 weeks in three amenorrhoeic women who had used levonorgestrel-releasing IUDs (LNG-IUD) for more than four years. Nine patients using copper IUDs (Nova-T) were studied for two complete menstrual cycles as controls. According to progesterone levels, 15/17 cycles in women using LNG-IUDs were ovulatory, whereas only 8/17 cycles showed normal follicular growth and rupture as judged by ultrasound. In ovulatory cycles, the peak progesterone levels were lower than in the controls. The preovulatory estradiol and LH peak levels were also lower than in control subjects. SHBG levels were lower in LNG-IUD users than in copper IUD users. It is concluded that, although the dose of levonorgestrel released from the IUD is very low, it probably exerts an effect on the gonadotrophin secretion, which disturbs follicular development in many of the women studied, which in addition to the local effect on the endometrium, contributes to its high contraceptive efficacy.

Adult

Subdermal norethindrone pellets -- a method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.

Adult

Plasma levels of norethindrone and effect upon ovarian function during treatment with silastic implants containing norethindrone.

The study was made to evaluate the effect upon the ovarian steroid pattern during treatment with subcutaneously implanted silastic rods containing norethindrone. Four rods, each containing 37 mg norethindrone (NET), were implanted subcutaneously in five women and left in place for 135--200 days. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. After an initial peak found in all subjects, the plasma level of NET declined. Great day-to-day variations of NET were found. Ovulations were suppressed during treatment in three subjects. One subject had regular ovulations throughout treatment and in one subject a single ovulation was recorded. Peaks of estradiol without subsequent ovulation were found in two subjects. The bleeding pattern was irregular; three subjects had varying degrees of spotting and bleeding, two subjects were amenorrheic. The average daily release rate was 300/micrograms, calculated from the amount of steroids lost from the removed rods. This study indicates that the release of steroid from four NET rods is high enough only initially to completely inhibit ovulation.

Adult

Plasma levels of norethindrone after single oral dose administration of norethindrone and lynestrenol.

Single oral doses of 0.3 mg, 0.5 mg and 5 mg Norethindrone (NET) and 0.5 mg and 5 mg Lynestrenol (lyn) were given to five women. Lynestrenol is probably metabolized through NET and exerts its main biological activity as NET. Plasma concentrations of NET were determined by a radioimmunoassay at different intervals after administration of the tablets. Peak concentrations of NET were found within two hours after intake of each table. The plasma half life of Net after NET and lyn administration for the period 8-24 h was 8-11 h. No significant difference was found between the half life of NET and the NET tablets and after the lyn tablets. When 5 mg NET was given the plasma half life of NET for the period 24-72 h was around 10 h and this was significantly shorter than the half-life of NET after 5 mg lyn, which was 16 1/2 h. The systemic availability of the drugs was estimated by calculating and comparing the areas under the plasma concentration versus time curve (AUC). 0-24 H. The AUC 0.24 after 0.3 MG NET was almost identical to the AUC 0.24 after 0.5 mg lyn. The AUC 0-24 after 0.5 mg NET was significantly larger than after 0.5 lyn. No difference was found between the AUC 0-24 after 5 mg lyn and 5 mg NET. This study supports the concept of a conversion from lyn to NET. It also shows that there were only minor pharmacokinetic differences between the drugs when all samples were measured as NET.

Administration, Oral

Pituitary responsiveness to luteinizing hormone-releasing hormone during treatment with subdermal D-norgestrel implants in women.

It has previously been reported that subdermal implants containing d-norgestrel inhibit ovulation through blockage of the positive feedback action of estrogen on luteinizing hormone (LH) release. In this study 100 micrograms of LH-releasing hormone (LRH) were injected intravenously to test the pituitary reserve capacity for gonadotrophin secretion in three women with three 40 mg d-norgestrel rods implanted subdermally for more than one year. The gonadotrophin release to LRH varied and seemed related to the ovarian steroid concentrations at the time of the LRH infusion in a manner similar to that seen during the normal menstrual cycle. It is concluded that low plasma levels of d-norgestreol do not inhibit the pituitary responsiveness to LRH. The results indicate that the blocking action of the gestagen on the positive feedback of estradiol on LH release occurs at the hypothalamus or higher CNS centers.

Adult

Serum concentrations of estrone, androstenedione, testosterone and sex-hormone-binding globulin in postmenopausal women with breast cancer and in age-matched controls.

The concentrations of estrone (E1), androstenedione (A), testosterone (T) and sex-hormone-binding globulin (SHBG) in the serum were determined in 122 postmenopausal women, unselected with respect to age and stage of disease and with a newly diagnosed breast cancer. The results were compared with those in 122 age-matched women without breast cancer, selected from the population register. The patients were found to have a significantly higher mean level than the controls of E1 (132 and 108 pmol/l), A (2.5 and 1.6 nmol/l) and T (1.54 and 1.38 nmol/l) and a lower level of SHBG (40.2 and 47.3 nmol/l) in the serum. A multiple regression analysis revealed in the control group that the serum level of E1 was significantly correlated to A (r = 0.48, p less than 0.001) and T (r = 0.45, p less than 0.001). In the patient group E1 was only slightly correlated to T (r = 0.25, p less than 0.01) and not to A (r = 0.10, p greater than 0.05). A significant negative correlation was found between SHBG and weight in both groups. Otherwise no significant correlations were found between any of the hormone levels and age, stage of disease of weight. It was concluded that an increased availability of A and T, leading to an increased androgenic stimulation--and therefore decreased SHBG--and an increased E1 level, is the most reasonable explanation for the findings. The lack of correlation between E1 and A in the patient group is however difficult to explain and the results do not seem to fit into a definite hypothesis.

Age Factors

Transfer of estradiol to human milk.

A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg. of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg. of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditions is calculated to be less than 100:10.

Estradiol

Vaginal progesterone for contraception.

Silastic vaginal rings impregnated with progesterone (P) or progesterone and estradiol (E) were used in nine women for thirty 21-day cycles to study the effect on ovarian function. The average daily rates of release of P and E from the rings were 2.2 mg/day and 220 microgram/day, respectively. In anovulatory treatment cycles the mean plasma level of P was 0.9 ng/ml. E levels fluctuated in the range seen in normally cycling women due to endogenous E production. In a menopausal woman the E levels increased to 50 to 100 pg/ml during treatment and FSH levels declined. Ovulation occurred in 18 (60%) of the treated cycles, and resulted in one pregnancy. Although the results rule out the use of these rings for contraceptive purposes, they indicate that at higher dosages the Silastic vaginal ring offers a mode of administration of natural steroids to be used in hormonal contraception.

Contraceptive Agents, Female

Serum FSH, LH and oestrone levels in postmenopausal patients on oestrogen therapy.

Serum FSH, LH and oestrone levels were determined in postmenopausal women before and at 1, 3 and 6 months after the onset of cyclical treatment with 0.05 mg of ethinyl oestradiol (n = 19) or 2 mg of oestradiol valerianate (n = 20). Most samples from the women taking oestradiol valerianate were also analyzed for oestradiol. Vaginal smears were obtained from all patients. Although all women were relieved of vasomotor symptoms, the FSH levels usually exceeded the fertile range. Ethinyl oestradiol reduced FSH by 70 to 75 per cent and LH by 30 to 40 per cent while oestrone was increased by 20 to 40 per cent. In the women taking oestradiol valerianate, FSH and LH levels were both reduced by 20 to 25 per cent wheras serum oestradiol increased by 200 to 300 per cent and oestrone increased by 600 to 700 per cent. The mean vaginal maturation value rose equally in the two groups but 40 per cent of the patients in both groups showed no change in the value. There was no correlation between the appearance of vaginal endocrine smears and hormone levels.

Estradiol

Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin).

Peripheral plasma from five postmenopausal women was analyzed for oestrone and oestradiol during 48 hours after administration of 1.25 mg Premarin (conjugated equine oestrogen) orally and vaginally. Oestrone and oestradiol were separated on columns of Sephadex LH 20 before radioimmunoassay. Administration of 1.25 mg of Premarin produced a marked increase in plasma oestrone levels and 24 hours after treatment the oestrone levels were still above follicular phase levels. The plasma pattern of oestradiol was similar but the elevation was less pronounced. The biological activity of Premarin as indicated by depressed gonadotrophin levels was similar with the intravaginal and oral routes of administration.

Administration, Oral

A radioimmunoassay of oestrone in plasma. Plasma levels of oestrone and oestradiol in oophorectomized Rhesus monkeys during treatment with subcutaneous implants containing oestrone.

A highly specific antiserum to oestrone was used to develop a sensitive radioimmunoassay. Plasma was generally analysed without prior separation of the oestrogens. A small amount of plasma (0.1-0.2 ml) was extracted once with diethyl ether. The above and previously described radioimmunoassays were used to estimate plasma levels of oestrogens in oophorectomized monkeys treated with subcutaneous oestrone implants. Three monkeys received a rod containing 40 mg of oestrone. The rods were kept in place for about one year. The release rates from the rods were calculated. The oestrone plasma levels were initially high (370-500 pg/ml). In about 3 months they had fallen to a level of 50-100 pg/ml which was maintained till the removal of the rods. A rise in the oestradiol plasma levels was also observed. It is concluded that rods are suitable for administration of oestrone.

Animals

Plasma levels of non-conjugated oestrone in high risk pregnancies.

Plasma levels of non-conjugated oestrone were measured with a radio-immunological method in women with complicated pregnancies during the last trimester. A comparison was performed between values of normal pregnancies from a previous report (3) and those of pathological pregnancies. Women with severe pre-eclampsia were found to have low values and to some extent the oestrone level could predict fetal outcome. In pregnant patients with long-standing diabetes mellitus the plasma levels of oestrone seemed to be higher than those of uncomplicated pregnancy. In women with pregnancies complicated by Rh-isoimmunization, oestrone plasma levels were similar to those found in normal pregnancies.

Antibody Formation