[Diagnosis and treatment of polycystic ovary syndrome]. / Diagnostic et traitement du syndrome des ovaires polykystiques.

Obesity, ultrasonic ovarian morphology, serum LH levels and LH/FSH ratio are inconstant symptoms of the polycystic ovary syndrome (PCOS) and are thus no longer essential for diagnosis. PCOS is diagnosed today by the finding of chronic anovulation and hyperandrogenism characterized by a high serum level of "free" testoterone. The other causes of hyperandrogenism, as well as anovulations due to hyperprolactinemia, high levels of FSH and abnormal thyroid function have to be ruled out. PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I). From in vitro and vivo studies and treatment of hyper I, it has been shown that the hyper I of PCOS stimulates androgen production. Hyper I of PCOS increases the activity of androgens: by first provoking an important decrease of the sex hormone binding globulin (SHBG) thus increasing the "free", bioactive testosterone level. and then by activating the cytochrome P 450 c 17 alpha enzymatic system that controls androgen production. Subsequent to metformin administration, the reduction of hyper I and androgen serum levels creates a favorable condition for the resumption of ovarian function and clomiphene citrate action. This explains the high percentage of ovulations and pregnancies.

[Pre-ovulatory peaks of gonadotropins. Recent data]. / Pic préovulatoire des gonadotropines. Données récentes.

From recent data we know that: The duration of the LH peak seems to be more important than its amplitude for the induction of ovulation. Ovulation induction by hCG is not physiological; the absence of an FSH surge, and the long duration of LH activity would contribute to some of the luteal phase abnormalities. Recombinant hLH, on the other hand could give better results provided its action last about 48 hours. The results, however, are not as expected, probably because of the type of isoforms injected. The circulating FSH and LH isoforms found during the preovulatory peak of gonadotropins have a much higher in vitro biological activity than those found at other periods of the cycle. The production of FSH and LH recombinant of different biological activity is in process. The mechanism of the preovulatory peak of gonadotropins is still not fully understood. The respective role of GnRH and of the ovarian steroids has yet to be precisely determined in the human being. Ovarian peptides very probably also play a role.

[The biological activity of luteinizing hormone (LH)]. / Activité biologique de lutropine (LH).

In vitro bioassay (BIO) is a very specific and sensitive method for determining levels of luteinizing hormone (LH). It provides a means of evaluating the values obtained with routine radioimmunoassays (RIA). Serum levels with bioassay are higher than those obtained with radioimmunoassay. The LH BIO/LH RIA ratio measures the difference between the two methods and gives a means of evaluating the quality of the LH secreted. The LH BIO/LH RIA ratio is significantly higher at the summit than at the nadir of the LH serum pulses. This ratio also increases after administration of GnRH. The differences in the quality of the LH can be explained by micro-heterogenicity. Immunofluorometric assay of LH (LH FIA) is much more sensitive than either the LH BIO or the LH RIA assays. Unlike the LH BIO/LH RIA ratio, the LH BIO/LH FIA ratio remains unchanged during LH pulses and after administration of GnRH. This difference can be explained by the lack of sensitivity but also by the lack of specificity of the LH RIA. LH RIA is not reliable when the serum levels of LH are low. However, RIA is valid when the serum levels of LH are increased as occurs in polycystic ovary syndromes.

[Functional hypothalamic amenorrheas. I. Physiopathology]. / Aménorrhées hypothalamiques fonctionnelles. I. Physiopathologie.

Functional hypothalamic amenorrhea are very probably due to a decrease of the frequency of the secretory pulses of LH, ie of GnRH. This decrease could be the consequence of a chronic hypersecretion of the corticotropin releasing hormone (CRH). CRH seems to act on the hypotalamic pulse generator of GnRH through the effect of the endogenous opioid peptides of the central nervous system. Opioid receptor antagonists restore normal pulse frequency of LH in most cases. Research is being done to try to elucidate the cause of the failure to such treatment: dopamine in among other mechanisms, supposed to play an essential role.

[Functional hypothalamic amenorrheas. II. Clinical aspects]. / Aménorrhées hypothalamiques fonctionnelles. II. Clinique.

The most important causes of the functional hypothalamic amenorrhea (FHA), that are psychological stress, physical stress and weight loss, are associated with a decrease of the frequency of the LH secretory pulses and with a state of hypercortisolism. The slowing down of the LH pulse frequency is difficult to demonstrate in clinical practice. The classical symptoms of FHA which are low gonadotropin levels, and hypogonadism are not very specific. The diagnosis of FHA is therefore one of exclusion. Recent physiopathological studies have individualised new symptoms that are hypercortisolism, hypoprolactinaemia and an important increase in the night serum levels of melatonine, all of which could help to confirm the diagnosis. FHA is relatively frequent and its treatment with pulsatile GnRH administration or naltrexone is very successful.

[The corpus luteum and progesterone secretion]. / Corps jaune et sécrétion de progestérone.

The pulsatility of LH secretion has been known only since 1970. The pulsatility of progesterone secretion has now also been shown. The frequency and amplitude of these pulses vary during the three phases of the luteal period. The first or early luteal (EL) phase lasts four days starting from the peak of LH. There is no pulsatility of progesterone during EL. The frequency of LH pulsatility is 103 +/- 8 minutes. The second or mid luteal (ML) phases, from +6 to +9 days after the peak of LH, is characterised by pulses of LH and of progesterone, most often in positive crossover correlation and with 7 to 14 pulses per 24 hours. The frequency of LH pulsatility is 166 +/- 33 minutes according to Filicori. The amplitude of LH secretion is 4 to 40 ng/ml. The third or late luteal (LL) phase, occurring at +11 days before the menstrual period, has the same characteristics in terms of quality but shows variations in frequency and amplitude towards a decrease. Thus the amplitude of progesterone secretion is 2.8 to 9 ng/ml (Veldhuis). In the opinion of clinicians, the corpus luteum is independent up to LH+ 5 days. The injection of hCG during this time is ineffective. A single progesterone level is sufficient if the result is 10 ng/ml or more. The problem remains complex concerning results below 10 ng/ml. The solution suggested for the present is that described by Olive: during ML and/or LL, three samples in the morning at hourly intervals and two endometrial biopsies during two consecutive cycles.

[Premature failure of the ovaries]. / Défaillance prématurée des ovaires.

The premature ovarian failure syndrome has been reviewed on the basis of existing data. The frequency, clinical picture and diagnostic procedures of premature ovarian failure are discussed. The disorder is characterized by secondary amenorrhea with constant estrogen deficiency and elevated gonadotropin levels in the post-menopausal range. Differential diagnosis is to be made with pituitary adenomas secreting gonadotropin, circulating gonadotropin antibodies, and biological profiles typical of the peri-menopausal years. Histopathology distinguishes two principal forms of premature ovarian failure: the premature menopause with complete follicular depletion of the ovaries, and the insensitive ovary syndrome. A correct ovarian biopsy is important for this diagnosis and can also help to point toward an immunological etiology. The following causes of premature menopause are analysed: chromosomal abnormalities, autoimmune disorders, viral infections and galactosemia. The toxic and iatrogenic causes are not developed. The factors eventually implicated in the insensitive ovary syndrome are discussed: deficient biological activity of gonadotropins, the presence of inhibitor substances preventing hormone action and the presence of antibodies toward FSH receptors. In the management of premature ovarian failure, a possible autoimmunization has to be considered. When an immunological disorder is suspected, other autoimmune glandular failures, that may develop secondarily, have to be detected. From the 26 pregnancies reported after a diagnosis of the insensitive ovary syndrome, only two occurred after a correct ovarian biopsy. Those cases seem to indicate that reducing endogenous gonadotropins to normal levels is important before considering induction of ovulation.

[Risk factors in cancer of the endometrium]. / Les facteurs de risque du cancer de l'endomètre.

The authors evaluate the incidence of the main risk factors in endometrial cancer by comparing a continuous series of 101 patients with a matched reference series. Among these factors, obesity and multiparity are significantly more frequent in patients with endometrial cancer. All of these risk factors are related to a hyperestrogen level. Their knowledge may contribute to a policy of prevention of endometrial cancer, but does not permit its screening by limiting to women presenting these risk factors.

[Value and indications for nipple stimulation in obstetrics]. / Intérêt et indications de la stimulation mamelonnaire en obstétrique.

The authors have evaluated the effect of stimulation of the breast on uterine tone in a series of 25 patients at term where induction of labour was indicated for obstetric reasons. In 64% of cases breast stimulation carried out for 30 minutes was followed by uterine contractions. In 20% of these cases the authors found that the uterus contracted strongly and in two patients so strongly as to cause fetal heart slowing. Breast stimulation matures the cervix slightly but this is not statistically significant for Bishop's score. In 16% of case breast stimulation provoked labour. Analysing these results and studying the literature shows that the effect is linked to the degree of cervical maturity at the onset and the effect of stimulation depends also on the length of time the stimulation was carried out. In practice the use of breast stimulation is limited because of the risks of hypertonic contractions and this is turn requires careful fetal heart monitoring.

[Interpretation of the blood level of a steroid]. / Interprétation du taux sanguin d'un stéroïde.

The authors define the conditions under which the steroid circulate in the blood : free, bound to albumin or bound to their specific binding proteins. Based on the physiology of steroids, the authors try to define the value of the serum levels in the evaluation of steroid production and, more particularly, the variations in this production. The biological activity seems to be directly related to the free circulating fraction.

[Cytological detection of cancer of the cervix uteri]. / Le dépistage cytologique du cancer du col utérin.

In spite of the apparent simplicity in detection of dysplasias (cervical intraepithelial neoplasias or CIN I, II, or III) and cancer of the cervix, numerous epidemiologic, biochemical, cytologic and socioeconomic problems are involved. The purpose of this early detection is unquestionably sound, even if the efficiency seems not to achieve high levels in accordance to expectations concerning results and if the cost of reiterated cervical and vaginal scraping smears seems exorbitant. The financial constraints and some cost-effectiveness analyses have promulgated use of longer intervals between cytologic exams (Pap tests). Such an attitude is only acceptable if an improvement in quality and sensitivity of detection is likewise established: other factors such as variable biologic development of epithelial lesions of the cervix must be taken into account; and consideration of cytologic sensitivity of early detection with the difficulties encountered in definition and identification of groups of women at risk. The longer spread between Pap smears exposes some women to the danger of non-detection of certain dysplasias (CIN I, II, or III), rapidly developing carcinomas, and so they lose out on the benefits of an early diagnosis, limited, effective, and less expensive treatment.

[Pregnancy provoked by pulsatile administration of gonadotropin- releasing hormone in 2 women with oligomenorrhea]. / Grossesses provoquées par l'administration pulsatile de gonatrophine releasing hormone chez deux femmes oligoménorrhéiques.

Pulsatile administration of gonadotropin releasing hormone (GnRH) at a rythm of 1 microgram/min during 6 minutes every 2 hours restored ovulatory cycles and subsequently pregnancy was obtained in 2 patients who presented with oligomenorrhea and sterility.

[The effects of the pulsatile administration of naloxone on the secretion of gonadotrophins in a case of hypothalamo-hypophyseal amenorrhea]. / Effets de l'administration pulsatile de naloxone sur la sécrétion des gonadotrophines dans un cas d'aménorrhée d'origine hypothalamo-hypophysaire.

12 mg of Naloxone were given using an intravenous pulsatile pump at the rate of 0.4 mg/minute every 8 minutes over a period of 4 hours in a woman of 28 years of age who had secondary amenorrhea of hypothalamic origin. The levels of L.H., F.S.H. and Prolactin were calculated every half hour during and after the perfusion. These was a progressive rise in the amplitude of L.H. peaks but no changes in F.S.H. and Prolactin levels. Intermittent inhibition of endogenous opioids seems to re-establish the pulsatile secretions of the hypothalamo-pituitary axis.

[Protein binding of steroids]. / Les liaisons protéiniques des stéroïdes.

The role of protein-binding in the physiology of steroids is of great complexity. The following are envisaged: the types of protein, methods of binding and the affinity of steroids for proteins, and the variations in free fraction according to plasma protein levels; the functions of binding proteins on the activity and clearance of steroids as well as on the peripheral conversion of androgens; the factors which influence variations in binding protein levels and in particular the influence of circulating levels of natural hormones and the influence of hormone treatment.

[Changes in LH, FSH, PRL and estradiol after perfusion with naloxone in normal and amenorrheic women]. / Variations de L.H., F.S.H., P.R.L. et de l'estradiol après perfusion de naloxone chez les femmes normales et aménorrhéiques.

Naloxone is antagonistic to endogenous opioids. Giving it shows that these opioids act as controlling mechanisms in the secretion of LH and FSH by the hypothalamic, pituitary system and probably of Gn-RH by the hypothalamus. Endogenous opioids and particularly beta endorphin, which is itself under the control of oestradiol, play an inhibitory role on the secretion of Gn-RH and alter the pulsatile mode of Gn-RH secretion. We could not demonstrate PRL action which has been described by other authors.

[Hemoglobin A1c and its variations in pregnancy]. / L'hémoglobine A1c et ses variations au cours de la grossesse.

Variations in haemoglobin A1c were studied at different stages of pregnancy in 306 non-diabetic women, using a specific method. It was found that HbA1c levels progressively decreased during the first 25 weeks of pregnancy, then remained stable. No correlation was noted between carbohydrate metabolis and Hb A1c levels. The new assay provides additional information on glucose tolerance in pregnant women and could be used to detect gestational diabetes.

[Exfoliatin in neonatal staphylococcal infections]. / L'exfoliatine dans les staphylococcies néonatales.

An outbreak of staphylococcal skin infection in neonates was investigated clinically, bacteriologically and epidemiologically with the following findings: (1) In 8 out of 13 cases, exfoliatin-producing staphylococci were present in the bullae, which is unusual with bullous lesions occurring at other ages; (2) exfoliatin producing staphylococci were present in all children with bullous lesions, as well as in carriers; (3) 39% of the phage II group staphylococci studied produced exfoliatin; (4) purulent lesions due to phage II staphylococci which did not produce exfoliatin were observed. The contaminating agent could be identified in most cases.