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The use of biodegradable norethisterone implants as a 6-month contraceptive system.

The effects of a 6-month contraceptive system of biodegradable norethisterone (NET) implants on the menstrual cycle, estradiol and progesterone levels, the presence of side effects, its contraceptive effectiveness, and the NET levels achieved were studied in a group of nine women. There was practically no disruption of the menstrual cycle and no important side effects. Ovulation was inhibited in four subjects, and another four subjects remained ovulatory. In all the subjects a cyclic secretion of estradiol was maintained. No pregnancies occurred. The circulatory levels of NET were very stable throughout the 6-month period of implant use.

Adult↗

Temporal relationships between ovulation and defined changes in the concentration of plasma estradiol-17 beta, luteinizing hormone, follicle-stimulating hormone, and progesterone. I. Probit analysis. World Health Organization, Task Force on Methods for the Determination of the Fertile Period, Special Programme of Research, Development and Research Training in Human Reproduction.

One hundred seventy-seven women have been studied over the periovulatory period, in order to obtain detailed information on temporal relationships between ovulation and defined changes in the concentrations of estradiol-17 beta (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P) in peripheral plasma. Serial samples of blood were taken, the surfaces of the ovaries were examined at laparotomy, and the mature follicle or corpus luteum was removed for histologic examination. The results in 107 cases fulfilled the criteria for statistical analysis, and in 78 the operation was performed after the follicle had ruptured. A probit analysis was undertaken with use of the proportion of women who had ovulated at a given time in relation to the interval from a defined rise or peak in the concentration of a circulating hormone. The median time intervals (in hours) from the hormonal event to ovulation and the 95% confidence limits of the estimates are as follows: 17 beta-estradiol--rise 82.5 (54.0 to 100.5), peak 24.0 (16.9 to 32.1); LH--rise 32.0 (23.6 to 38.2), peak 16.5 (9.5 to 23.0); FSH--rise 21.1 (14.1 to 30.9), peak 15.3 (8.1 to 21.7); progesterone--rise 7.8 (-12.5 to 15.9). From the statistical model for LH it was possible to estimate that ovulation in 90% of the cases had occurred between 16 (+/- 6) and 48 (+/- 6) hours after the first significant rise in the concentration of this hormone and between -3 (+/- 5) and 36 (+/- 5) hours after the peak. An examination of the individual results in every woman gave corresponding ranges of between 24 and 56 hours from the first significant rise in LH and between 8 and 40 hours after the peak. From a practical standpoint, the conclusion is that a defined rise in the concentration of circulating LH is the best indirect parameter of impending ovulation.

Adult↗

[Hypophyseal reaction state during oral contraceptiva (author's transl)].

In 5 normocyclic women, firstly taking a conventional oral contraceptive, Neogynon (50 mcg EE + 250 mcg levo-norgestrel) for 6 months, the levels of LH, 17 beta-E2 and progesterone did not rise after changeover to a dose-reduced pill, Microgynon 30 (30 mcg EE + 150 mcg levo-norgestrel). This fact indicates maintained central suppression. Examination of the hypothalamic-hypophyseal axis by the Gn-RH test (50 mcg) with Microgynon 30 showed negative results during the first treatment cycle in 13 out of 18 women. In the 6th treatment cycle only 7 Gn-RH non-reactive women were observed and after stimulation with 100 mcg Gn-RH only 5 women remained with negative Gn-RH tests. Of the 20 women who took conventional oral contraceptives over a period of 6 months to 6 years (7 took Eugynon: 50 mcg EE + 500 mcg D,L-norgestrel, 5 Lyndiol: 75 mcg mestranol + 2.5 mg lynoestrenol, 8 Neogynon, only one from the Neogynon group showed a positive result. On the other hand there was a positive reaction in 4 out of 7 women using the two step dose-reduced preparation Sequilar (11 tablets of 50 mcg EE + 50 mct levo-norgestrel and 10 tablets of 50 mcg EE + 125 mcg levo-norgestrel).

Adult↗

Long-term intranasal luteinizing hormone-releasing hormone agonist treatment for contraception in women.

Fifty-one female volunteers used a superactive stimulatory luteinizing hormone-releasing hormone (LH-RH) analog for suppression of ovulation for 3 to 12 months. The potent LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was administered intranasally once daily in a dose of 400 or 600 micrograms. No pregnancies occurred during the 283 treatment months. Severe bleeding disturbances were not observed during the long-term treatment. No signs of hyperplastic changes were found in endometrial biopsies. There were no serious side effects. Ovulation promptly returned after cessation of treatment even in women with amenorrhea during treatment periods of 1 year or more. Thus, long-term LH-RH agonist treatment proved to be a safe, effective, and rapidly reversible new method for peptide contraception.

Administration, Intranasal↗

Evaluation of ovarian function after tubal sterilization.

Many women appear to experience menstrual disturbances after tubal sterilization. In this study the ovarian function in such women was investigated. Serial measurements of FSH, LH, estradiol and progesterone were performed throughout the study cycle in 23 previously sterilized patients, 14 with menstrual disturbances (group I--symptomatic) and 9 with normal cycles (group II--asymptomatic). A group of 28 parous women served as controls. Among 23 patients, luteal phase progesterone was elevated in 19, and in 4 it was undetectable (anovulatory). All four anovulatory patients belonged to group I. Anovulatory cycles were also characterized by tonic elevated LH levels. Mean midluteal progesterone values were lower in group I (8.5 ng/ml) than in group II (13.8 ng/ml) and in the controls (16.5 ng/ml). Mean midluteal progesterone was lower than 10 ng/ml in 78% of group I, 44% of group II and 15% of the control patients.

Adult↗

Ovulation detection in the human.

The importance of predicting human ovulation for either optimizing or avoiding conception has been considered from an endocrine, morphological and clinical view point. Of the biochemical markers in peripheral blood, a knowledge of the LH peak is the most clearly defined, with a two to four fold increase above baseline levels for a relatively short 24-30 hour preovulatory period. Ovulation is considered to occur 28-36 hours after the beginning of the LH rise or 8-20 hours after the LH peak. Daily assessment of the rise in preovular oestrogen reflects Graafian follicle development but the rise is less distinct and spread over 3-4 days with marked day to day fluctuations. LH induces a marked reduction in oestrogen production some 12 hours prior to ovulation and at the same time induces a two to three fold increase in progesterone production above baseline levels. While these changes in themselves are not great enough for day to day discrimination, a knowledge of their reciprocal relationship may be. The preovular rise in FSH is relatively small compared to LH and the radioimmunoassay technique has not generally been refined to be as rapid and reliable. Monitoring the day to day growth of the preovular follicle ultrasonically is both linear and potentially predictable but there is a wide range of its final diameter (17-26 mm) prior to ovulation making prediction inaccurate. With further refinements in ultrasonic resolution, detection of intrafollicular changes of the cumulus oophorus and granulosal cell layer configuration and thickness may give a closer prediction of the time of ovulation. At a clinical level a knowledge of menstrual cycle length in association with body messages which herald ovulation are useful and may forewarn that ovulation in terms of days is approaching. Such markers as preovulation pain, the detection of periovular cervical mucus and the change in physical character and position of the cervix are reliable signs of preovulation for many well motivated and informed women for either promoting or avoiding conception. A knowledge of the basal body temperature is not a prospective guide to ovulation, but once the thermal shift is established in association with loss of periovular mucus symptoms, the fertile period can be considered to have passed. Because we do not have a precise and simple marker of human ovulation, it is necessary that the most suitable marker of pre- or postovulation is chosen for the particular need in a given individual.

Body Temperature↗

A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular.

Adolescent↗

Enzyme immunoassay for specific determination of the synthetic estrogen, ethynyl estradiol, in plasma.

In this enzyme immunoassay for ethynyl estradiol, a conjugate of the 3-(O-carboxymethyl)ether with horseradish peroxidase is used as the label and a conjugate of the 6-(O-carboxymethyl)oxime with bovine serum albumin as the immunogen. A solid-phase antibody procedure is used in separating antibody-bound and free steroid. The lower limit of sensitivity of the assay is 2 pg per assay tube. Interference by synthetic progestagens was minimized by extracting the sample with an anti-estrogen serum before assay. Results obtained with a comparison radioimmunoassay and this procedure agreed well (r greater than 0.98).

Contraceptives, Oral↗

Sex hormone levels and intestinal absorption of estradiol and D-norgestrel in women following bypass surgery for morbid obesity.

A report of reduced serum levels of progestins, following oral administration after jejunoileal bypass, promoted the present investigation of the absorption of D-norgestrel and estradiol following different types of intestinal bypass surgery for morbid obesity. A group of non-operated obese patients served as control. Apart from significantly higher gonadotrophin levels, which could be attributed to periovulatory sampling in the non-operated group, there was no significant differences in basal levels of estradiol, estrone, conjugated estrone, androstendione, testosterone, and progesterone. The operation did not influence the pattern of the menstrual cycle. Following a single oral dose of 4 mg micronized estradiol and 125 microgram D-norgestrel, serum levels of estradiol and estrone were equal in the three groups. serum D-norgestrel was equal in the two operated groups, but was significantly higher in the bypass group with 1:3 jejunoileal ratio, compared with the non-operated group. Further, a significant negative correlation between peak levels and weight was found. It is suggested that one year following bypass surgery, obesity - but not intestinal bypass - might be associated with reduced serum levels of exogenous sex steroids following oral administration.

Adult↗

Functional life span of the corpus luteum gravidarum: an estimation from the mode of fluctuation of serum hormones after artificial termination of pregnancy and succeeding exogenous hCG administration.

Concentrations of estradiol (E2), progesterone (P), 17-hydroxyprogesterone (17-OHP), hCG and hPL were measured by radioimmunoassay in sera obtained serially from 35 subjects who received artificial termination of pregnancy and 24 of them were administered 10,000 IU of hCG 3 to 5 days later when endogenous hCG had sufficiently decreased. The subjects were operated respectively at 4-11 weeks (Group A) and 12-23 weeks (Group B) of gestation. In Group B, all the hormones declined promptly showing a hyperbolic pattern. In contrast, E2, P and 17-OHP in Group A revealed a significant delay of decline although hCG and hPL decreased as fast as hormones in Group B. When hCG was administered, P and 17-OHP showed a trend to elevate in Group A, but they showed a trend to decline in Group B. When compared in percentage value, the statistically significant difference is proved in 17-OHP between the two groups. The significant delay of E2, P and 17-OHP and the significant elevation of 17-OHP in Group A as compared with Group B were clearly demonstrated. Since 17-OHP is mainly of luteal origin, these findings seem to confirm that the corpus luteum gravidarum functions as far as 11 weeks of gestation and then involutes.

Abortion, Induced↗

[Excretion of ethinyloestradiol sulfonate in the human milk (author's transl)].

The problem of ethinylestradiol sulphonate excretion in human milk was qualitatively and quantitatively studied. In two women 0.0012 or 0.03000 per cent of total radioactivity were detected within the first nine days from application. Parallel thin-layer chromatography revealed the occurrence of ethinyloestradiol sulphonate in both its depot form and as ethinylestradiol.

Chromatography, Thin Layer↗

Endocrine profile of patients with post-tubal-ligation syndrome.

The endocrine profile of the midluteal phase was assessed in 29 patients with the post-tubal-ligation syndrome, consisting of pain, bleeding and premenstrual tension. Compared to normal controls, the patients had a high serum estradiol and a low serum progesterone level. This abnormal luteal function may be responsible for the symptoms observed and may also explain the failure to conceive following successful reversal of tubal ligation. It is recommended that patients seeking sterilization reversal be screened for abnormal luteal function preoperatively. Selection of sterilization procedures that minimize alteration in luteal function should be given high priority.

Adult↗

[Studies on estradiol occupied and unoccupied receptors in human endometrial cytosol and nucleus: steroid receptors throughout the menstrual cycle and in cases of oral contraceptives administration (author's transl)].

Occupied and unoccupied estradiol (E3) receptors were investigated by exchange assay in cytosol and nuclear extract of human endometrium. Cytosol E2 and progesterone (P) unoccupied receptors and nuclear occupied E2 receptor were measured throughout the menstrual cycle and in the tissues from patients administered oral contraceptives. Sedimentation profiles of these receptors were also studied; and following results were obtained: 1) No occupied E2 receptor was observed in cytosol and almost all of those were of unoccupied type. In nuclear extract, only 0-25% of receptor was of unoccupied type and the other receptor was of occupied type. 2) Highest binding activities of cytosol E2 and P receptors were found in late proliferative phase. Maximum binding sites (Bm) were 630 and 380 f mol/mg protein and dissociation constant (Kd) was 8.9 +/- 0.7 and 4.7 +/- 0.4 x 10(-10) M, respectively. In nuclear extract, binding peaks were observed in late proliferative and late secretory phase. Bm was 1.5 f mole/microgram DNA and Kd was 12.7 +/- 1.0 x 10(-10) M.

Adult↗

Investigations of hormones during early abortion induced by prostaglandin F2alpha and 15(S)-methyl-PGF2alpha.

In early pregnancy up the 7th week of pregnancy PGF2alpha was infused and 15(S)-methyl-PGF2alpha was applied i. m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGF2alpha is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGF2alpha produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnancy.

Abortion, Induced↗