Hormonal and metabolic changes induced by elevated plasma free fatty acids in term pregnancy. I. Effect on maternal blood glucose, insulin and human placental lactogen circulating levels.

The influence of plasma free fatty acid (FFA) concentration on the secretion of human placental lactogen (hPL) was investigated in 16 normal young women during the last month of gestation, in order to determine whether hPL secretion is influenced in the same way as human growth hormone (hGH) during plasma FFA elevation. Maternal blood glucose (BG), plasma triglycerides (TG), FFA, immunoreactive insulin (IRI) and hPL levels were measured during and after a lipid emulsion infusion for 75 min (10 cases). The intravenous injection of 5,000 U of heparin at the 15th min of the lipid infusion was followed by a decrease in plasma triglyceride levels and by an accompanying rise in plasma FFA (rom 468 plus or minus 52 to 2,478 plus or minus 310 mueq/liter). In control experiments lipid infusion alone (3 cases) resulted in a moderate increase in FFA (718 plus or minus 157 to 1,046 plus or minus 255 mueq/liter), and separate iv heparin administration (3 cases) elevated the FFA levels from 728 plus or minus 50 to 1,649 plus or minus 153 mueq/liter). No significant change in either IRI or hPL levels was discernible in any of the tests performed. A tendency of blood glucose to increase was observed after heparin administration. It was concluded that a marked and sustained plasma FFA elevation, achieved through intravenous lipid and heparin infusion cannot alter hPL circulating levels in term human pregnancy.

Immunofluorescent localization of placental lactogen, chorionic gonadotrophin and its alpha and beta subunits in organ cultures of human placenta.

Localization of human placental lactogen (HPL), chorionic gonadotrophin (HCG) and its free alpha and beta subunits in mature and immature placental villi before and during organ culture was examined with an 'indirect' immunofluorescent technique using highly specific antisera. HPL fluorescence was strictly localized to the syncytiotrophoblast and the intensity of this fluorescence increased with gestational age and decreased with the time of culture. Undissociated HCG and HCG beta immunofluorescence was localized to the syncytiotrophoblast. Maximum intensity was observed in immature placentae and was not significantly affected by the duration of culture. However, irregular and patchy HCG and HCG beta immunofluorescence was seen in the cytotrophoblasts under conditions of extensive syncytiotrophoblastic damage. HCG alpha immunofluorescence was localized in the syncytiotrophoblast of immature placentae and was more intense in mature placentae. Beginning the third day of culture, HCG alpha fluorescence increased and was also present in the cytotrophoblast. On the basis of these observations and additional data, the possibility is discussed that cytotrophoblastic cells, better preserved than the syncytiotrophoblast in case of restricted energy and oxygen supply, may actively synthesize free HCG alpha, in addition to syncytiotrophoblastic production of this subunit. By contrast, HPL, undissociated HCG, and HCG beta are mainly or exclusively eleborated in the syncytiotrophoblastic layer.

Effects of a 1-year treatment with a low-dose combined oral contraceptive containing ethinyl estradiol and cyproterone acetate on glucose and insulin metabolism.

OBJECTIVE: To study the effects of the slightly estrogen-dominant monophasic low-dose oral contraceptive (OC) Diane-35 (Schering AG, Berlin, Germany) (35 micrograms ethinyl estradiol [EE2] + 2 mg cyproterone acetate, a 17 alpha-hydroxyprogesterone derivative [17-OHP]) on glucose and insulin metabolism. DESIGN: Seven healthy young women were investigated by using the euglycemic hyperinsulinemic glucose clamp technique (insulin delivery rate = 100 mU/kg per hour for 120 minutes). This test was performed, after an overnight fast, during the last 7 days of a spontaneous cycle and within the last 5 days of pill intake during the sixth and twelfth cycle of a continuous treatment with Diane-35 in each subject. RESULTS: The three indexes measuring the insulin-induced glucose disposal during the clamp (glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels) were not significantly affected by Diane-35. In contrast, the metabolic clearance rate of the exogenous insulin infused during the clamp tended to be slightly increased with Diane-35 (significant after 6 but not after 12 cycles). CONCLUSION: These results suggest that a 1-year treatment with the OC Diane-35, which contains EE2 + a 17-OHP rather than a 19-nortestosterone derivative as the progestogen compound, does not significantly alter peripheral (presumably muscular) insulin sensitivity but slightly increases insulin (presumably hepatic) clearance.

PIP: To investigate the effects on glucose and insulin metabolism of the slightly E-dominant, monophasic, low-dose oral contraceptive (OC) Diane-35, which contains 35 mcg ethinyl estradiol and 2 mg cyproterone acetate, a 17 alpha-hydroxyprogesterone derivative, the euglycemic hyperinsulinemic glucose clamp technique test was performed in 7 health young women after a one-year trial. The 7 subjects had a mean age of 22 years, a body mass index of 20.4 kg/m sq., had either never used OCs or had discontinued use at least 8 weeks before the study, were not taking medication, had no history of obesity or diabetes, and had normal glucose tolerance. The metabolic test was performed within the last 7 days before the presumed onset of menstruation during the last pretreatment cycle and within the last 5 days of OC intake during the sixth and twelfth cycle of continuous treatment with the OC. It was found that the glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels were not significantly affected by the OC. The metabolic clearance rate of the exogenous insulin infused during the clamp technique test was significantly increased after 6 cycles but not after 12. It was concluded that a 1-year treatment with Diane-35 does not alter peripheral (and presumable muscular) insulin sensitivity significantly, but increases insulin (presumably hepatic) clearance slightly.

Carbohydrate metabolism in women who used oral contraceptives containing levonorgestrel or desogestrel: a 6-month prospective study.

Blood glucose and pyruvate, plasma insulin, and glucagon levels as well as erythrocyte insulin receptors were measured during an oral glucose tolerance test in 38 normal women before and after 6 months' use of one of three new oral contraceptives containing low doses of 19 nortestosterone-derived progestogens, levonorgestrel, and desogestrel. A slight deterioration of glucose tolerance was observed, with the area under the glucose curve increasing by only 7%, 9%, and 12% after Ovidol (Aaciphar SA, Brussels, Belgium), Marvelon (Organon, SA, Brussels, Belgium), and Trigynon (Schering SA, Brussels, Belgium) administration, respectively. We did not find any argument in favor of the development of a state of insulin resistance in women using these compounds, because erythrocyte receptor binding was not modified and plasma insulin responses to glucose were decreased. The glucose-induced suppression of plasma glucagon levels seemed less effective for treatment with the desogestrel-containing preparations than with the levonorgestrel-containing oral contraceptives.

Clinical experience with a triphasic oral contraceptive ('Trinordiol') in young women.

Seven hundred and fifty cycles of treatment with a new triphasic oral contraceptive (WL-49(50). 'Trinordiol') containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years), 70% of whom had regular, normal cycles. Sixty-five percent had not used contraception before; the others had previously been on combined or progestagen-only oral contraceptives or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. No pregnancy was recorded during the 750 cycles of treatment. Fifteen (20%) women dropped out of the study for medical reasons, essentially breast tenderness, weight increase, spotting and nausea, in decreasing order of frequency. Mastalgia was present in 21% of the women (8.9% of the cycles) during triphasic oral contraception, but this symptom disappeared in more than half of the cases within 3 months of continued use. Other side-effects were less frequent: vaginal discharge (4.4% of the cycles), nausea (3.7%), abdominal and leg cramps (2.8%), headaches (3.2%) and weight increase (3%). Spotting and breakthrough bleeding were reported during only 1.9% of the cycles, a remarkably low frequency. No absence of withdrawal bleeding was noted. Weight and blood pressure changes were minimal and never reached statistical significance. Hypertension developed during triphasic medication in 1 predisposed individual. Complaints of oestrogen-related symptoms such as breast tenderness and digestive disorders were probably due to the reduced progestagen content of the preparation compared with combined low fixed daily dose oral contraceptives. However, no increases in dysmenorrhoea and/or premenstrual tension were noted. It is concluded that the triphasic preparation provides effective contraception with excellent cycle control and minimal side-effects, which should help to increase the acceptability of low-dose combined oral contraceptives.

PIP: 750 cycles of treatment with a new triphasic oral contraceptive (OC), (WL-49(50), Trinordiol), containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years). 70% of all young women had normal, regular menstrual cycles. 65% had not used contraception previously, and the others had previously taken combined or progestogen only OCs or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. Routine clinical evaluation, including gynecological examination, weight and blood pressure measurement, assessment of cycle events, and recording of spontaneously reported side effects, was performed every 3 months. Cycle control during triphasic OC use was very good. There was a statistically significant trend of the cycles toward more regularity than prior to this type of contraception, with an increased frequency of 28-day cycles. Duration of menses was significantly reduced and menstrual volume was more frequently rated by the women as normal. Spotting and breakthrough bleeding showed a very low frequency, the latter accounting for less than 10% of intermenstrual bleeding during triphasic OC medication. Frequency of side effects was 53.3% (40 women) during triphasic OC use. 20% of the population reported side effects among the reasons for stopping triphasic OC use. Breast tenderness was the most frequent side effect recorded in almost 9% of the total number of treatment cycles. It affected 21% of the women under study, a significantly more frequent occurrence than before triphasic OC use in these individuals. The tendency of this symptom to improve was observed in more than half of the cases within 3 months use of triphasic OC use. Other signs of estrogenic dominance such as gastrointestinal disturbances, vaginal discharge, pelvic congestion, and leg cramps were also present but much less prominent than breast tenderness. 16 (21.3%) patients presented with breast tenderness for 67 (8.9%) cycles. Nausea and vomiting were experienced by 6 (8%) patients for 28 (3.7%) cycles. Vaginal discharge was present in 10 (13.3%) patients for 33 (4.4% cycles). Spotting and breakthrough bleeding occurred in 6 (8%) women for 14 (1.9% cycles). Absence of change in weight was recorded in 1/3 of the women studied; another 1/3 experienced a weight reduction of 1-4 kg and the last 1/3 gained 1-4 kg. There were no statistically significant variations in either systolic or diastolic blood pressure values.

Postmenopausal changes of lipid and glucose metabolism: a review of their main aspects.

In postmenopausal women, partly in relation to advancing age and partly due to oestrogen deficiency, there is a frequent increase in body weight, and more specifically, in android fat distribution. In addition, loss of ovarian function is associated with the development of a more atherogenic profile with increased triglycerides, LDL-cholesterol and its smaller dense subfractions, decreased HDL- and HDL2-cholesterol and, potentially, an irregular increase in Lp(a). Not only does oestrogen therapy counteract all these changes towards a definitely less atherogenic profile but oestrogens seem also implicated in reducing LDL oxidative products, in favouring a higher ratio of prostacyclin to thromboxane and, potentially, of endothelium derived relaxing factor to endothelin, and also in acting as a calcium antagonist in the vessel wall. All of these favourable vascular effects are not solely attributable to lipid-related oestrogen effects. Excess weight and central obesity, diet changes and lack of exercise, more frequent with advancing age, all concur to alter glucose tolerance and increase insulin resistance during the postmenopause. Impaired glucose tolerance and diabetes mellitus may be found in nearly 20% of women aged 55 to 65 years. In addition, oestrogen deficiency may be further responsible for decreased pancreatic insulin secretion and alteration of its metabolic clearance rate-changes that can be reversed toward improved insulin secretion and sensitivity by oestrogen treatment in small dosages. By contrast, synthetic androgenic progestins can counteract these effects of oestrogens more than progesterone derivatives do, and they may partly help to promote insulin resistance and hyperinsulinism.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian function is effectively inhibited by a low-dose triphasic oral contraceptive containing ethinylestradiol and levonorgestrel.

For various metabolic and clinical reasons, it has been strongly advocated to reduce the dose of both the estrogen and progestogen components of oral contraceptives (OCs). In this study, we compared after 6 months of treatment, the action on various hormonal parameters of a standard-dose combined OC containing ethinylestradiol (EE) 0.050 mg and levonorgestrel (LNg) 0.250 mg and a low-dose triphasic combination containing a 59% reduced amount of the same steroids. Hormonal measurements in the last 3 days of OC intake indicated that basal levels of FSH and LH were less inhibited by the low-dose preparation, while PRL levels were unchanged. However, gonadal function was effectively inhibited by both high and low dose OCs, as demonstrated by equally low levels of E2, E1, P and 17-P. Consequently, no residual gonadal function could be anticipated from the observed low steroid concentrations. These results corroborated other studies (reviewed in this paper) in which serial hormonal measurements also revealed a complete lack of follicular maturation during low-dose triphasic OC treatment. Moreover, inhibition of circulating levels of A, DHEA, DHEAS, free T and DHT was similarly obtained with both preparations. Collectively, these data indicate that ovarian function is as effectively inhibited by a low-dose triphasic preparation as by a higher, standard-dose OC containing the same steroids.

PIP: For various metabolic and clinical reasons, it has been strongly recommended that the dose of both the estrogen and progestogen components of oral contraceptives (OCs) be reduced. In this study, the authors compared, after 6 months of treatment, the action on various hormonal parameters of astandard-dose combined OC containing ethinyl estradiol (EE) 0.050 mg and levonorgestrel (LNg) 0.250 mg and a low-dose triphasic combination containing a 59% reduced amount of the same steroids. Hormonal measurements in the last 3 days of OC intake indicated that basal levels of FSH and LH were less inhibited by the low-dose preparation, while prolactin (PRL) levels were unchanged. However, gonadal function was effectively inhibited by both high and low dose OCs, as demonstrated by equally low levels of E2, E1, P, and 17-P. Thus, no residual gonadal function could be anticipated from the observed low steroid concentrations. These results corrborated other studies (also reviewed in this paper) in which serial hormonal measurements also revealed a complete lack of follicular maturation during low-dose triphasic OC treatment. Moreover, inhibition ofcirculating levels of A, DHEA, DHEAS, free T and DHT was similarly obtained with both preparations. Collectively, these data indicate that ovarian function is as effectively inhibited by a low-dose triphasic preparation as by a higher, standard-dose OC containing the same steroids.

Absence of antisteroid antibodies in oral contraceptive users presenting with vascular events.

Previous reports speculated that vascular events could be related to the development of antibodies against synthetic steroids contained in oral contraceptives or other hormonal treatments. This study describes original immunoassays designed to detect antisynthetic steroid antibodies. In a first step, the assays were characterized and validated using animal-raised antisteroid antibodies. In a second step, a population of 88 oral contraceptive users, 47 of them having developed a vascular thrombosis during synthetic steroid use and 41 serving as healthy control users, were tested. Detection of antibodies against ethinylestradiol, levonorgestrel, norethisterone, cyproterone acetate, and gestodene showed that the values obtained in normal oral contraceptive users as well as thrombosis patients are very low, and show no statistically significant difference between the two groups tested. Taken together, these data indicate that the "immunological hypothesis" related to antisteroid antibodies is unlikely to explain the pathogenesis of vascular events in oral contraceptive users.

Antisteroid immune complexes and vascular thrombosis during steroid hormone therapy.

To test an immunological hypothesis proposed to explain the pathogenesis of cerebrovascular thrombosis in steroid users, circulating immune complexes were assayed in the sera from 6 control subjects, 14 ever users of oral contraceptive having developed a neurological ischaemic accident, and 7 patients with the same clinical history during use of other sex steroid not containing ethinylestradiol. Beaumont's ammonium sulfate and polyethylene glycol precipitation methods, together with a specific method of isolation of circulating immune complexes using affinity chromatography on Protein A, were used. Radioactivity from labeled ethinylestradiol added to the sera before precipitation was monitored in the precipitates to detect anti-ethinylestradiol antibodies. There were no significant differences for these parameters in the three groups. However, protein content and 3H-EE activity in the precipitates were equally and dramatically reduced after affinity chromatography in the three groups. These latter results do not support the presence of antibodies against ethinylestradiol in steroid users with cerebrovascular thrombosis. Moreover, our data suggest a lack of specificity of Beaumont's method for the isolation of immune complexes containing anti-ethinylestradiol antibodies.

Serum lipid and lipoprotein changes induced by new oral contraceptives containing ethinylestradiol plus levonorgestrel or desogestrel.

Changes in serum lipid and lipoprotein levels were evaluated in a randomized prospective study conducted in matched healthy young women before and after 6 months' use of three oral contraceptives (OCs): Trigynon (preparation A, n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) and levonorgestrel (LNG); Marvelon (preparation B, n = 14), a monophasic OC containing low doses of EE + Desogestrel (DOG, a new progestogen derived from LNG); and Ovidol (preparation C, n = 11), a sequential OC containing higher doses (50 micrograms) of EE + DOG. After 6 months of use, total triglyceride levels were non-significantly increased by preparations A (+ 29% from basal values) and B (+21%), and very significantly increased by preparation C (+90%). Total cholesterol and phospholipids were unchanged by preparations A and B, whereas phospholipids were significantly increased by preparation C. However, HDL-cholesterol, LDL-cholesterol and their epidemiologically important ratios (HDL-chol:total-chol; LDL-chol:HDL-chol) were kept unchanged by all preparations tested. Apolipoprotein A-1 (Apo A-1) was slightly but significantly increased by all three preparations whereas apolipoprotein B (Apo B) was significantly decreased by preparation B. All ratios Apo A-1:Apo B were accordingly ("favorably") increased, especially during treatment with preparation B. In conclusion, the triphasic OC containing low doses of LNG does not induce obvious, clinically significant, alterations of lipid metabolism, and it is also the case for the low-dose monophasic combination of EE + DOG. The higher-dose sequential preparation of EE + DOG behaves as a more estrogenic compound, increasing total triglyceride concentrations above the normal range.

PIP: Changes in serum lipid and lipoprotein levels were evaluated in a randomized prospective study conducted in matched healthy young women before and after 6 months' use of 3 oral contraceptives (OCs): Trigynon (preparation A, n=13), a triphasic OC containing low doses of ethinylestradiol (EE) and levonorgestrel (LNG); Marvelon (preparation B, n=14), a monophasic OC containing low doses of EE + Desogestrel (DOG, a new progestogen derived from LNG); and Ovidol (preparation C, n=11), a sequential OC containing higher doses (50 mcg) of EE + DOG. After 6 months of use, total triglyceride levels were non-significantly increased by preparations A (+29% from basal values) and B (+21%), and very significantly increased by preparation C (+90%). Total cholesterol and phospholipids were unchanged by preparations A and B, whereas phospholipids were significantly increased by preparation C. However, HDL-cholesterol, LDL-cholesterol and their epidemiologically important ratios (HDL-chol:total-chol; LDL-chol:HDL-chol) were kept unchanged by all preparations tested. Apolipoprotein Apo A-1) was slightly but significantly increased by all 3 preparations whereas apolipoprotein B (Apo B) was significantly decreased by preparation B. All ratios Apo A-1:Apo B were accordingly ("favorably") increased, especially during treatment with preparation B. In conclusion, the triphasic OC containing low doses of LNG does not induce obvious, clinically significant, alterations of lipid metabolism, and it is also the case for the low-dose monophasic combination of EE + DOG. The higher-dose sequential preparation of EE + DOG behaves as a more estrogenic compound, increasing total triglyceride concentrations above the normal range.

Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel.

The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): TrigynonR (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); MarvelonR (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and OvidolR (n = 10), a sequential OC containing higher doses (50 micrograms) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol greater than Marvelon greater than Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged. Collectively, these data indicate that (a) all three OCs are effective ovulation inhibitors, (b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, (c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and (d) free testosterone levels are equally well suppressed by all three Ocs.

[Evaluation of the cardiovascular impact of hormonal replacement therapy in menopausal women]. / Evaluation de l'impact cardiovasculaire du traitement hormonal substitutif chez la femme ménopausée.

Cardiovascular diseases (CVD) are a major cause of female mortality. The occurrence of menopause and estrogen deficiency is a well defined risk factor for CVD. Both retrospective and prospective epidemiological studies indicate that estrogen as well as estrogen-progestin hormone replacement therapy is associated with a reduced incidence of mortality and morbidity due to myocardial infarction or (probably) to stroke by about 50% without any obvious change in venous thromboembolism, when compared to absence of hormone use. A favorable effect of estrogens on the lipid profile could explain about 1/3 of this reduction of risk. Among other potential non-lipid effects of estrogens associated with a positive cardiovascular action, an improvement of insulin secretion together with a decrease in insulin resistance have been noted, this effect being however less obvious if the progestin used has androgenic properties. An improvement of the coagulation-fibrinolysis balance is plausible under treatment, as well as direct action of estrogen on the arterial wall (alteration of both endothelium-dependent and endothelium-independent factors such as a calcium-antagonist effect), leading to an improvement of arterial flow at the coronary, cerebral and peripheral levels. Hormone replacement therapy would be a primary and-potentially-secondary prevention of cardiovascular diseases. However, large prospective, controlled and randomized therapeutic trials that are now underway, are mandatory to definitively establish the cardioprotective effect of hormone replacement therapy.

[Raloxifene: a selective modulator of estrogen receptors]. / Le raloxifène: un modulateur sélectif du récepteur aux oestrogènes.

It has been demonstrated that postmenopausal hypoestrogenia induces numerous complications including osteoporosis and increased risk of cardiovascular disease. Oral or transdermal administration of estrogens can reduce these risks, but induces adverse effects. Recently, raloxifene, a new molecule from the benzothiophene family, has been demonstrated to prevent postmenopausal bone loss. It does not induce endometrial stimulation, and recent studies show that it could reduce breast cancer incidence. Its mode of action, consisting of mixed agonist and antagonistic estrogenic actions on different organs and systems, allows to classify it into the selective estrogen receptor modulator (SERM) family. In this review article, we will describe the characteristics of the molecule, its mode of action and the potential indications of its clinical use.

[Comparison of contrast hysterosonography and transvaginal ultrasonography for uterus imaging]. / Comparaison de l'hystérosonographie de contraste et de l'échographie vaginale en imagerie utérine.

AIM OF THE STUDY: To evaluate the efficacy of transvaginal sonography and saline infusion hysterosonography, as imaging tools, for the diagnosis of uterine abnormalities. METHODS: Two hundred seventy five patients were examined using transvaginal sonography (TVS) and saline infusion sonography (SIS), and the results were compared. RESULTS: Saline infusion sonography was performed in 88.4% of the cases. The most frequent cause of SIS failure was the presence of a stenotic cervix. In case of normal TVS, SIS allowed to visualize a polypoid lesion that was not demonstrated by TVS in 20.4% of the cases (n = 29/142). Saline infusion sonography confirmed the diagnosis of focal lesion suspected after TVS in all cases (n = 36). Finally, the localization of intramyometrial or submucous myomas was improved by SIS: myomas diagnosed by TVS as intramyometrial were demonstrated by SIS to be submucous in 41% of the cases (n = 23/56). CONCLUSIONS: Our results confirm that saline infusion sonography is a useful complementary tool for transvaginal sonography in the diagnosis of focal endometrial lesions and for the localization of fibromyomas.

[Free salivary steroids and plasma hormones in women]. / Stéroïdes salivaires et hormones plasmatiques libres chez la femme.

The use and limitations of steroid assay in saliva are presented and discussed. Salivary cortisol was well correlated with unbound cortisol plasma, the only biological active fraction of total cortisol. Assay of salivary cortisol is particularly useful in patients taking oral contraceptives or during pregnancy. Indeed, in these patients, because of the marked increase in plasma cortisol binding globulin concentration (from 41 to 100 mg% or more), plasma total cortisol concentration increases from 18 +/- 4 micrograms% to 40 +/- 10 micrograms% whereas plasma unbound cortisol usually remains within the normal range. During the menstrual cycle, salivary progesterone rises from 5.4 +/- 1.8 to 15.1 +/- 3.6 ng%. As it is well correlated with plasma unbound progesterone concentration, salivary progesterone may be considered as a convenient and reliable index of luteal function. Because of its very low concentration, salivary estradiol is difficult to assay with routinely available techniques and, at present, is of limited interest for clinical investigation.

[Contrast hysterosonography: an efficient means of investigation in gynecology. Review of the literature]. / L'hystérosonographie de contraste: un moyen d'investigation contributif en gynécologie. Revue de la littérature.

Contrast-enhanced vaginosonography constitutes a new way of imaging the uterine cavity. Real time transcervical injection of sterile saline in the uterine cavity (saline infusion sonography, SIS) allows to precisely visualize numerous intrauterine pathologies such as endometrial polyps, myomas, intrauterine adhesions and various anatomical malformations. We introduced the technique of saline infusion sonography in October 1996 for the evaluation of endouterine pathologies. In this review article, we will describe the technique of contrast sonography, its indications, contraindications and semiology, the practical problems to be solved and its performances.

[Contrast hysterosonography: indications and technic]. / L'hystérosonographie de contraste: indications et technique.

Contrast-enhanced sonography constitutes a new way of visualizing the uterine cavity. Indeed, real-time transcervical instillation of sterile saline inside the uterine cavity during transvaginal sonography (saline infusion sonography, SIS) allows a precise diagnosis of various intrauterine pathologies such as endometrial polyps, submucous myomas, intrauterine adhesions and various anatomical malformations. The aim of this article is to detail the technique of saline infusion sonography, its indications, contra-indications and semiology.

Metabolic effects of oral contraceptives.

Combination oral contraceptives (OCs) are probably not an independent risk factor for cardiovascular disease but through their metabolic actions, may partly amplify the effects of known risk factors for cardiovascular disease. This review of the literature and our own data indicate that use of high-dose, progestogen-dominant OCs induces a potentially atherogenic lipoprotein profile (high low-density lipoprotein-cholesterol:high-density lipoprotein-cholesterol ratio), mostly attributable to the antiestrogenic action of the progestogen content of these OCs. In contrast, lower-dose combination OCs with reduced amounts of progestogens and slight estrogen dominance, either monophasic or multiphasic, produce strikingly fewer adverse effects on lipoproteins. Moreover, use of low-dose, as opposed to high-dose, OCs results in almost unchanged glucose tolerance, marginally increased or unchanged insulin and glucagon responses to glucose, and probably unchanged levels and activity of peripheral insulin receptors. Further in-depth studies of low-dose OC formulations are mandatory to ascertain reduced metabolic risk of these OCs.

Metabolic effects of two low-dose triphasic oral contraceptives containing ethinyl estradiol and levonorgestrel or gestodene.

A well-known triphasic oral contraceptive (OC) containing ethinyl estradiol (EE) plus levonorgestrel (LNG) was compared with a triphasic containing the same dose of EE in combination with a 14% smaller dose of a new progestogen gestodene (GTD), in a prospective study of 24 and 20 healthy young women, respectively. Serial determinations of lipids, lipoproteins, and carrier proteins, and repeated standardized oral glucose tolerance tests (OGTTs) were conducted during 12 months of OC use. All lipid concentrations recorded before and during both treatments were strictly within the normal range. After 12 months, no significant fluctuations were observed in levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and apolipoprotein A1; concentrations of total triglycerides, phospholipids, and apolipoprotein B were slightly but significantly increased; the epidemiologically important ratios of HDL-cholesterol:total cholesterol and apolipoprotein A1:apolipoprotein B were not significantly changed, while the ratio of LDL-cholesterol:HDL-cholesterol was significantly decreased at 12 months of use of the GTD triphasic. SHBG levels (+ 100% over basal during use of the LNG-OC and + 200% with the GTD-OC) and transcortin (+ 100% over basal) increased early and remained stable. During use of the LNG-OC, glucose tolerance was strictly unchanged, while insulin response to a 75-g glucose load was transiently increased at 6 months (area under the curve [AUC] + 29%) before returning to normal at 12 months. During GTD-OC treatment, glucose tolerance was slightly impaired (AUC + 14%) at 6 months but back to normal at 12 months, while insulin response during OGTT was completely unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)