Predictive value of the FSH:LH ratio on follicular and luteal phase characteristics of the human menstrual cycle.

A prospective study was designed to assess the predictive value of gonadotropin measurements obtained during the early follicular phase upon the hormonal characteristics of the subsequent cycle. The data obtained in 12 normal cycles were used to compute the mean and confidence interval (mean +/- 2 SEM) of the FSH:LH ratio, FSH and LH plasma levels. The limits of the confidence intervals for these different parameters were used to classify the patients. Data of 204 patients were analysed. Low FSH:LH ratios (less than 1.34) are associated with an increase in follicular phase length (+2.4 days), a lower ovulatory rate, but neither luteal phase length nor progesterone levels differ between these two groups. When patients are classified according to FSH levels, our results show that low FSH levels (less than 2.94 mIU/ml) are associated with longer follicular (+2.6 days) and shorter (-1.1 days) luteal phase lengths, but ovulatory rate and progesterone levels in the luteal phase of the ovulatory cycles are similar to those obtained in patients of the normal or high FSH group. High LH levels (greater than 3.15 mIU/ml) are associated with a decreased ovulation rate but follicular and luteal phase characteristics are similar to those obtained in patients in the normal or low LH group. In conclusion, low FSH: LH ratios and low FSH plasma levels measured in the early follicular phase of the cycle are associated with longer follicular phase lengths; but basal gonadotropin measurements have limited predictive value on luteal phase characteristics.

[Paradoxic improvement of glucose intolerance in 8 females using estrogen-progestagen contraceptives containing norgestrel and ethinyl-estradiol]. / Amélioration paradoxale de l'intolérance au glucose chez 8 femmes sous contraception oestroprogestative contenant du norgestrel et de l'éthinyl-oestradiol.

Sixty females, aged 20 to 35, received an oral contraceptive pill (Norgestrel 0.5 mg and Ethinyloestradiol 50 micrograms/day) during one year. Group I was formed by 41 normal patients before and after 12 months. Group II was formed by 11 patients, normal before and with impaired oral glucose tolerance after 12 months. Group III was formed by 8 patients with impaired glucose tolerance before treatment and normal oral glucose tolerance after 12 months. All patients were submitted to 3 oral glucose tolerance tests, the first one at the 16th day of the control cycle, the second and the third at the 16th days of the 6th and 12th cycles during treatment. No significative modification of glycemia, insulinemia or weight was noted in group I. In group II the impaired oral glucose tolerance was associated with an increase of weight. In group III the improvement of glucose tolerance was marked by hyperinsulinemia.

[Does prolactin have a role in the physiopathology of luteal insufficiency?]. / La prolactine a-t-elle un rôle dans la physiopathologie de l'insuffisance lutéale?

A TRH-test was performed in 305 normoprolactinemic patients with gynecological disorders in order to appreciate the possible relationship between luteal defect, anovulation, galactorrhea and prolactin. The basal prolactin mean values of each group (normal cycle, pure luteal defect, luteal defect with persistent estrogenic influence, anovulation: with or without galactorrhea) were not different. However, some patients with luteal defect with persistent estrogenic influence and galactorrhea had an exaggerated response to TRH, and women with oligomenorrhea or amenorrhea had a low one. Unapparent hyperprolactinemia appears infrequent in normoprolactinemic patients.

RU 16117, an orally active estriol-like weak estrogen.

RU 16117, the 11 alpha-methoxy derivative of ethynyl estradiol, is an orally active weak estrogen potentially effective in the treatment of estrogen-deficiency in postmenopausal women (climacteric symptoms and severe osteoporosis). Biochemical studies have shown that RU 16117, like estriol, possesses the properties characteristic of a partial estrogen agonist/antagonist. RU 16117 binds to the cytosol estrogen receptor (ER) to form a complex which dissociates much faster than the estradiol complex. This explains its lower nuclear uptake. Furthermore, the nuclear RU 16117 complex also dissociates faster than the estradiol complex. Consequently, although low doses of RU 16117 can induce the majority of the effects of estradiol (increased polymerase A and B activities, cytosol ER replenishment, progestin receptor induction, increased uterine weight), these effects are long-lived only if the dose is considerably increased or if the compound is administered repeatedly or continuously. Since RU 16117 transiently occupies available estrogen binding sites, it can prevent the full response of estradiol. Thus, under appropriate kinetic conditions, it acts as an estrogen antagonist on the above parameters and also on DMBA-induced mammary tumors in the rat. At a daily dose of 24 micrograms for a period of 4 weeks RU 16117 led to 65% reduction in the number of already-established tumors. RU 16117 inhibits basal gonadotropin secretion and decreases the LH response to LHRH. Injection of 5 micrograms s.c. to the rat in estrus markedly inhibited the spontaneous peaks of LH, FSH and PRL measured on the afternoon of expected proestrus. Low doses which block ovulation by 100% had no detectable effect on vaginal cornification, thus suggesting a greater sensitivity at the hypothalamo-pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding of steroids by proteins in follicular fluid of the human ovary.

Steroid-protein interactions were studied in the antral fluid of preovulatory follicles of the human ovary. Two high affinity binding systems are described. These steroid-binding proteins do not differ from those identified in the plasma of women (transcortin and sex binding protein), as indicated by similar specificity, binding affinity, and electrophoretic pattern. Their concentrations in the fluid are either similar to or lower than those in plasma. Since the steroid concentrations in antral fluid are approximately 20- to 100-fold higher than the binding capacities of the specific steroid binders, the buffer role that many authors attribute to the proteins which bind steroids is unlikely in antral fluid.

Clinical investigation of the menstrual cycle. III. Clinical, endometrial, and endocrine aspects of luteal defect.

This study was intended to correlate different clinical and biologic parameters to better define luteal insufficiency (LI) and to contribute to a better understanding of its origin. Endometrial patterns were used as the basis for classification of clinical cases. Of 328 outpatients with menstrual disorders and/or infertility, 88 were considered to have LI. Their cycles were compared with 79 normal cycles. Two different principal endometrial patterns of LI are described: pure LI, when the endometrium is more than 2 days out of phase; and LI with persistent estrogenic influence, when the histologic estrogenic stigmata are excessive during the luteal phase. Basal body temperature charts demonstrated menstrual cycle disturbances: either ovulation delay or a slow increase in temperature (longer than 2 days). Plasma steroid concentrations also demonstrated a perturbation of the entire menstrual cycle: progesterone levels were statistically significantly lower in LI than in normal cycles and this defect was worse when the estrogenic influence was persistent; the preovulatory estradiol peak was disturbed in all circumstances, as was the concentration of endometrial steroid receptors. These simultaneous abnormalities strongly suggest a central origin of LI.

Protein-bound and free plasma phenytoin during pregnancy.

In a clinical study using low doses of phenytoin as an ovulation inducer, the plasma levels and the binding percentages of this drug and the plasma level of its main metabolite, p-hydroxyphenytoin, were monitored. The results show that during pregnancy, plasma levels of both remain stabile and low as compared with those observed in epilepsy treatment. This could be one explanation for the absence of teratogenic effects observed in this and other studies using phenytoin for the same therapeutic aim.

Uterine receptors and fertility regulation.

PIP: This review of the role of uterine receptors in fertility regulation concerns itself with the physiology of receptors at the cellular levels and their role in fertility. The biology of steroid hormone receptors shows that they share common properties; they are acidic proteins which contain no sugar or lipid. They are heat denaturable. Steroid receptor activity is interpreted as any steroid hormone binding to the receptor site with high affinity. Then transduction is effective in coupling the hormone binding to the executive site which may then interact with another macromolecule or catalyze a reaction. When this executive effect is switched on, the hormone leaves. Subcellular concentrations of estradiol and progesterone receptors are presented tabularly along with some specific characteristics of the 2 receptor types. Various methodologies for measuring receptor content, usually requiring ligand binding of radioactivity, are briefly outlined. Steroid receptors occur cyclically and their appearance is important in the normal menstrual cycle and probably in the determination of implantation time of fertilized ovum. Hence, new methods of fertility control can be based on interference with the cyclic variations of receptor concentration, particularly progesterone receptor. For example, administration of progesterone at midcycle would lead to set a premature negative effect on progesterone receptor and lead to abnormal secretory transformation of the endometrium.^ieng

Estradiol and progesterone receptors in human endometrium: normal and abnormal menstrual cycles and early pregnancy.

Estradiol and progesterone receptor sites (empty or filled with endogenous hormone)have been measured in the cytoplasm and nuclei of human endometrium. Receptor changes have been observed throughout the normal menstrual cycle. During the preovulatory phase the cytoplasmic estradiol receptor sites do not change while the nuclear receptor sites more than double. Cytoplasmic estradiol receptor sites decrease very early in the secretory phase, whereas the decrease in nuclear sites occurs later. Cytoplasmic progesterone receptor sites more than double during the preovulatory phase and show a large decrease immediately after ovulation, when the concentration of nuclear receptor is at its highest. Thus the total cellular concentrations of both estradiol and progesterone receptors are lowest in the late secretory phase. It was found that they are positively correlated with the concentration of plasma estradiol only during the proliferative phase. The concentration of cytoplasmic progesterone receptor is negatively correlated with 17 beta-hydroxysteroid oxidoreductase activity during the secretory phase. In anovulatory cycles the concentrations of estradiol and progesterone receptors are high, similar to those of the late proliferative phase. "luteal insufficiency" is characterized by a very low concentration of estradiol receptor. Early pregnancy endometrium (8 to 10 weeks' gestation) is characterized by a large concentration of progesterone receptor, exceeding those of any period of the menstrual cycle.

PIP: In the present study receptor measurements have been obtained in 101 cases of normal menstrual cycles, and receptor changes correlated with microsomal 17-beta-hydroxysteroid-dehydrogenase activity and the concentration of plasma estradiol. During preovulatory phase estradiol receptor sites do not change, while they decrease very early in the secretory phase. Progesterone receptor sites more than double during preovulatory phase, and decrease immediately after ovulation. Cellular concentrations of both estradiol and progesterone are positively correlated with the concentration of plasma estradiol during the proliferative phase. Anovulatory cycles are characterized by high concentrations of estradiol and progesterone receptors. A large concentration of progesterone receptors characterizes early pregnancy endometrium.

[Late gestation amniocentesis: value and risk assessment (author's transl)]. / Amniocentèse en fin de gestation: intérêt, appréciation du risque.

Over a 6-year period, 2165 amniocenteses were performed in 1168 women between the 32nd and 42nd weeks of gestation. There was no injury to the foetus. Premature rupture of the membranes was observed in 11.13% of the cases, which is less than the risk of spontaneous rupture (12.5%). The incidence of premature delivery was 2.8% during the first 3 years of the study and 2.6% during the next 3 years; these figures are lower than in women who do not undergo amniocentesis. The risks of amniocentesis are therefore quite acceptable, particularly when weighed against the benefits of data on foetal maturity and foetal distress obtained by the procedure. During the last 4 years no respiratory distress syndrome nor post-maturity were observed.

Physicochemical properties of non-activated and activated renin from human amniotic fluid.

The main physicochemical and enzymic properties of non-activated and activated human amniotic renin (EC 3.4.99.19) were studied in order to clarify the relationships between the two enzymes. Human amniotic renin was activated by dialysis against acidic buffer (pH 3.3), direct acidification or trypsin treatment. All procedures produced similar activation. The physicochemical characteristics of non-activated and activated renin were compared to those of human renal renin. Non-activated renin had a molecular weight of 45,500. A similar molecular weight was obtained by gel eluate activation and by acid treatment of renin prior to gel filtration. Similar isoelectric points were also found for non-activated and activated renin. One major renin peak focused at pH 6.6, whereas no similar renin peak was detected in extracts from normal human kidney. In addition, non-activated and activated renin forms were found to have the same optimal pH, the same Km and the same inhibiting pepstatin concentrations.

The iodine content of amniotic fluid and placental transfer of iodinated drugs.

Determinations of total iodine content, levels of thyroxine (T4) and triiodothyronine (T3), and protein concentrations were made on amniotic fluid. A total of 218 samples obtained at various stages of pregnancy, from both normal and pathological pregnancies, were studied. Normal values for the iodine and hormone concentrations are presented. Several amniotic fluid samples showed greatly elevated iodine levels, thought to be the result of maternal iodine intake. This study demonstrated that such elevated levels can be produced by urography with an iodinated medium, by thyroid extract therapy, and by vaginal therapy with an iodinated agent. Levels of T4 and T3 in amniotic fluid decreased slightly from the second to the third trimester and were unrelated to the total iodine levels. Despite reports in the literature of fetal hypothyroidism produced by amniography with a fat-soluble medium, no thyroid defect was observed in this series in the presence of elevated amniotic fluid iodine levels or when a water-soluble iodinated medium was used for amniography.

[Luteal insufficiency. Histoclinical and biological correlations]. / L'insuffisance lutéale. Corrélations histocliniques et biologiques.

Luteal insufficiency, an entity accepted with difficulty, is responsible for 3.5 p. 100 of cases of infertility and 35 p. 100 of early abortions. This study, carried out in 328 women with an average age of 29 years, involved clinical and histological features, as well as the estimation of plasma levels and endometrial receptors of ovarian steroids. Three broad histological patterns emerged:--luteal insufficiency associated with oestrogenic insufficiency indicative of overall ovarian deficiency;--luteal insufficiency with functional dysmaturation indicative of deficient or delayed luteal function, with or without persistence of excessively high oestrogen activity,--luteal insufficiency related to the short life of the corpus luteum which stops on the 20th day. Relationships between histological findings, the measurement of receptors and plasma estimations are discussed and precise analysis of endometrial biopsies must be considered as one of the best test of luteal insufficiency.

Clinical investigation of the menstrual cycle. II. Neuroendocrine investigation and therapy of the inadequate luteal phase.

Nonhormonal drugs--diphenylhydantoin and nialamide, which act on the central nervous system and have no known endocrine activity--were given to two groups of women with distinct types of electroencephalographic patterns in an effort to regulate menstrual disorders. Equalization of the lengths of both the follicular phase and the luteal phase to the normal range was observed during the drug therapy. Forty-five per cent of the pregnancy rate was achieved in 36 of the 80 infecund patients within 4 months of treatment. The mode of action of these drugs is still unknown.

[Effect of ergot alkaloid derivatives on milk secretion in the immediate postpartum period]. / Effet de dérivés des alcaloïdes de l'ergot de seigle sur la sécrétion lactée dans le post-partum immédiat.

30 women received an intramuscular injection of 0.2 mg of methylergobasine immediately after delivery and then 3 tablets of 1 mg of ergotamine tartrate per mouth daily for 6 days post-partum. 28 women received no treatment after delivery. The selection of the two groups was random. The treatment with rye ergot derivatives did not have a significant effect on the quantity of milk that the infant took, nor on the infant's weight gain in the 6 first days of life.