E. D. B. Johansson

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.

ANOVULATION, INADEQUATE LUTEAL PHASE AND POOR SPERM PENETRATION IN CERVICAL MUCUS DURING PROLONGED USE OF NORPLANTR IMPLANTS

Blood samples for progesterone assay were collected for a total of 49 cycles, from 27 volunteers using the NORPLANT system. Levonorgestrel determinations were carried out in the same samples. A group of 12 women with normal cycles were studied in the same manner to serve as controls. Of the 49 cycles studied, 20 (41%) were ovulatory. The mean levonorgestrel level in ovulatory patients was 0.34 +/- 0.11 ng/ml (S.D.) compared to 0.42 +/- 0.14 ng/ml (S.D.) in anovulatory cycles. Compared to the control group, progesterone levels were significantly lower for users of NORPLANT implants during days -12 to -10 (p less than 0.025), -9 to -7 (p less than 0.05), -6 to -4 (p less than 0.0005) and days -3 to -1 (p less than 0.01). Cervical mucus evaluations and post-coital tests were done around mid-cycle in 29 of the cycles studied. All samples of cervical mucus were of poor quality, viscous and scarce, with a mean SPK of 4.1 +/- 2.3 cm. Most had absent or atypical ferning. Twenty-one subjects (73%) had a post-coital score of 1, and 4 (14%) of zero. Thus, anovulation, inadequate luteal phase and the direct effect of the continuous administration of levonorgestrel over cervical function, all seem to contribute to the effectiveness of NORPLANT implants.

Radioimmunological Methods for the Estimation of Oestrone, Oestradiol 17β and Oestriol in Pregnancy Plasma

SummaryAntibodies to oestradiol-17β and oestriol have been produced by immunization of sheep with oestradiol-6-oxime and oestriol-6-oxime attached to bovine serum albumin (BSA). The antibodies were used in radioimmunoassays.In the oestradiol-17β assay the free and bound steroids were separated by means of dextran-coated charcoal. This technique caused a heavy stripping when tried in the oestriol assay. A new assay for oestriol in plasma was thus devised. In this assay, oestriol and antibody were incubated at 40d`C for 30 minutes. Free and bound steroids were separated with saturated ammonium sulphate. The specificity of the antibody raised after immunization with oestradiol-17β-6-oxime BSA was compared with a previously used antibody obtained after conjugation in the 17th position of oestradiol-17β to BSA. The former antibody had a higher specificity and crossreacted only 11 per cent with oestrone compared to 50 per cent for the latter. The oestriol antibody was highly specific, crossreacting only 13 per ...

The effect of various dosages of lynestrenol on the plasma levels of oestrogens and progesterone during the menstrual cycle in the rhesus monkey

Abstract The effect of daily oral doses of lynestrenol on the ovarian function was investigated in nineteen rhesus monkeys. The compound was given in four dose levels 0.05, 0.25, 1 and 2.5 mg daily throughout the menstrual cycle. Plasma samples collected before during and after treatment were analysed for their content of estrogen and progesterone. The low doses 0.05 and 0.25 had no effect on the occurrence of ovulation, the plasma levels of the ovarian steroids being similar to those seen during normal ovulatory cycles. Lynestrenol treatment at doses of 1 and 2.5 mg per day prevented ovulation. The estrogen levels in monkeys treated with 1 mg lynestrenol appeared normal, but the progesterone levels were never more than 0.4 ng/ml. In the monkeys treated with 2.5 mg lynestrenol the estrogen levels were below the lowest levels of the control cycles and the progesterone levels were less than 0.2 ng/ml. The female rhesus monkey appears to require about ten times more lynestrenol per kg body weight than women for suppression of ovulation. However, the plasma levels of norethindrone, which is the active metabolite of lynestrenol, required for ovulation inhibition does not appear to be grossly different from those found in women.

Evaluation of the prognosis of threatened abortion from the peripheral plasma levels of progesterone, estradiol, and human chorionic gonadotropin

In 69 women with threatened abortion (TA), the outcome of the pregnancy was compared to the plasma concentration of progesterone, estradiol and human chorionic gonadotropin (HCG) in a peripheral blood sample which was taken as soon as the diagnosis of TA had been made. The assay of HCG gave a very good prediction of the outcome and low levels indicated an inevitable abortion. The assays of progesterone and estradiol both rendered a more uncertain prediction and did not add further information for the evaluation of the prognosis. These findings might be explained by the different sites of production of these hormones, since in early pregnancy progesterone and estradiol are produced in both the corpus luteum graviditatis and the placenta while HCG is produced only in the placenta.

Menstruation span: a time-limited risk factor for endometrial carcinoma

A case‐control study was undertaken to investigate the influence of reproductive factors on the risk of developing endometrial carcinoma. The study comprised 254 women with newly diagnosed endometrial carcinoma, resident in a defined geographical area, and 254 age‐matched population controls. Nulliparity and late menopause were positively associated with endometrial carcinoma. Each additional full‐term pregnancy resulted in a decrease in the risk by 16%. The importance of parity and menopausal age decreased with increasing life span, and in women older than 69 years these two variables did not discriminate significantly between cases and controls. The calculated number of years of menstruation (the “menstruation span”) was used as a combined measure of the impact of parity, age at menarche and age at menopause on the risk of developing endometrial carcinoma. The patients had a significantly longer mean menstruation span than the controls (33.6 versus 31.2 years; p<0.001) and a longer span than 39 years gave a 4.2 times higher risk than one shorter than 25 years. It is suggested that the total length of time for which a woman is exposed to unopposed estrogen is important and that the effect of this hormonal influence is time‐limited.

Inhibition of the positive feedback of oestradiol during treatment with subcutaneous implants of d-norgestrel.

The effects of d-norgestrel (40 mg), contained in a single dimethylp olysiloxane rod implanted subcutaneously in the gluteal region, were studied in 4 women. The rods were left in place for 93-128 days. Based on the pattern of plasma progesterone levels; all of the subjects appeared to ovulate. However, the inhibition of the positive feedback effects of natural estrogens indicated that ovulation was suppressed. There was no increase in plasma progesterone concentrations over the 3-4 month treatment period. Plasma estradiol concentrations fluctuated irregularly and showed surges characteristic of the midcycle peak. Plasma gonadotropin levels fluctuated periodically, though midcycle peaks of luteinizing hormone (LH) and follicle stimulating hormone (FSH) did not occur. FSH and LH concentrations were low when estradiol concentrations were high, and vice versa. Plasma concentrations of the hormone were similar to those found during the 1st 6-8 hours after ingestion of low-dose d-norgestrel. All the subjects had unpredictable bleeding patterns during treatment.

Monophasic basal body temperature in ovulatory menstrual cycles

Abstract The plasma concentration of progesterone, the urinary excretion of estrogens, and the basal body temperature were followed in 17 normally menstruating women during 33 menstrual cycles. A monophasic basal body temperature was found in 4 cycles (12 per cent) in spite of the fact that the other parameters investigated suggested that ovulation had occurred. It is thus concluded that the registration of a monophasic basal body temperature during a menstrual cycle does not give sufficient information for the conclusion that the cycle is anovulatory.

Comparison of the metabolic effects of two hormonal contraceptive methods: An oral formulation and a vaginal ring II. Serum lipoproteins and apolipoproteins

In a long-term, prospective study the effects on lipoprotein lipids and apolipoproteins (apo) of a combined oral contraceptive (OC) (30 micro gram ethinylestradiol and 150 micro gram levonorgestrel) and a contraceptive vaginal ring (CVR) releasing estradiol (about 180 micro gram per day) and levonorgestrel (about 290 micro gram per day) were compared. The two treatments induced significantly different effects. In the OC group the lipoprotein-lipid concentrations showed only minor changes, but apolipoproteins (apo) B and A-I increased by about 15%. In contrast, during treatment with the CVR there was a 25% decrement of cholesterol in high density lipoprotein (HDL) and at most 10% in low density lipoprotein (LDL) cholesterol, with only minor effects on apo B and A-I. The ratio of LDL and HDL cholesterol increased in the CVR group but not in the OC group. The results also indicate a change in the composition of the LDL and HDL particles, with an altered lipid/protein ratio, during both contraceptive treatments. Despite the impressive relative increase in LDL:HDL ratio in the contraceptive ring group, the average absolute value of this ratio did not reach the mena for healthy men.

Contraception with norplant® implants and NORPLANT®-2 implants (two covered rods): Results from a comparative clinical study in Sweden

Two-hundred-and-forty healthy women, ages 18 to 40 years, were randomized in a ratio of 2:5 to use NORPLANT implants or NORPLANT-2 implants. Through three years of use, no pregnancies were recorded among women using NORPLANT implants and two pregnancies were noted among women using NORPLANT-2 implants resulting in a cumulative net pregnancy rate of 1.3 +/- 0.9 per 100 acceptors (mean +/- SE) by the end of year three. This difference was not statistically significant. During the fourth year, no pregnancies were observed in the NORPLANT group, but 4 pregnancies occurred in the NORPLANT-2 group. The most common reason for terminating the study was bleeding disturbances. During the first year there were significantly more terminations due to bleeding problems in the NORPLANT group than in the NORPLANT-2 group. However, during the second year of use the proportion of women discontinuing for bleeding problems dropped considerably among NORPLANT users and during the third year very few women in either group discontinued because of bleeding problems. The continuation rates after one year were for NORPLANT users 59.4% and for NORPLANT-2 users 77.2%. Corresponding figures after three years of use were 46.1% and 51.7%, respectively. The second most common reason for discontinuation was depression and other mood changes. In both groups we noted a slight increase in weight during the study and a slight decrease in blood pressure and hemoglobin levels with time. In conclusion, both NORPLANT and NORPLANT-2 implants are very effective methods for contraception. The efficacy of NORPLANT-2 implants, however, was not acceptable during the fourth year of use in this study. The latter system could, however, become a suitable three-year contraceptive method, possibly with less bleeding disturbances than NORPLANT in the first year.