Cardiovascular findings in women suffering from Turner syndrome requesting oocyte donation.

BACKGROUND: Through oocyte donation (OD), women with Turner syndrome (TS) may achieve motherhood. However, this population has a high prevalence of cardiac malformations and carry a risk for aortic dissection that is increased by pregnancy. Until recently, the necessity for a specialized cardiac evaluation before pregnancy was underestimated as was the need for follow-up through adulthood. The aim of this study was to evaluate the follow-up (mainly cardiovascular) of women with TS requesting OD. METHODS: Disease monitoring since diagnosis and prior cardiac evaluations conducted out of our centre were assessed in 25 women with TS who requested OD. New cardiac evaluations using echocardiography and magnetic resonance imaging were performed by our specialized cardiologist in 18 of these patients. RESULTS: We observed that the medical follow-up of women with TS was often deficient throughout adulthood. Most of the prior cardiac evaluations performed by cardiologists not accustomed to women with TS, either before (n = 8) or when starting OD (n = 12), were considered normal. However, when revaluated by a cardiologist who is familiar with TS, seven women were diagnosed with a bicuspid aortic valve and thus excluded from OD. In addition, when appropriate screening was conducted by our referent cardiologist before OD no cardiac complication was observed during pregnancy or delivery. CONCLUSIONS: Careful follow-up, including cardiac evaluation, should be recommended for women diagnosed with TS, before and after puberty. Moreover, assessment of cardiovascular parameters by a cardiologist familiar with TS should be routinely repeated before undertaking OD.

Should physicians prescribe metformin to women with polycystic ovary syndrome PCOS?

1. Metformin is not efficient enough in order to regulate menstrual cycles. 2.Metformin is not efficient enough in order to treat hyperandrogenism. 3. Metformin should not be used as a first-line treatment in order to treat infertility. Clomiphene citrate (CC) is the reference treatment. 4. Metformin in addition to CC is not recommended as a second line treatment, after the failure of CC alone. 5. Metformin should not be used during pregnancy in non diabetic women with PCOS, in order to prevent the risk of gestational diabetes. 6. Metformin should be prescribed to PCOS women when they are diabetic, in order to prevent their cardiovascular risk, after lifestyle modification. 7. Metformin should not be used in PCOS non diabetic women in order to lose weight. Metformin should not be used in order to treat dyslipidemia in women with PCOS. 8. In PCOS women, without diabetes, but with fasting hyperglycemia or carbohydrate intolerance, metformin should be prescribed if: BMI>35.

Impaired sexual and reproductive outcomes in women with classical forms of congenital adrenal hyperplasia.

OBJECTIVES: The objectives of the study were 2-fold: 1) a detailed description of sexual and reproductive outcomes in adult women with congenital adrenal hyperplasia (CAH) of different phenotypic severity at birth; and 2) comparisons of these outcomes among CAH subtypes and between CAH women and non-CAH control women. DESIGN: This was a cross-sectional study using a face-to-face interview, a written questionnaire, the Female Sexual Function Index, and a gynecological examination. PATIENTS: Patients included 35 women with CAH, representing Prader stages I-V at birth, aged 18-43 yr, who had been treated from birth to adolescence in the same pediatric endocrine clinics. Sixty-nine non-CAH healthy control women were selected from hospital-staff families. RESULTS: None of the CAH women expressed doubts about their gender assignment. Twenty percent (seven of 35) had homosexual inclinations; 23% (eight of 35) were married; three reported a complete lack of sexual activity; and 37% (13 of 35) said they never had heterosexual intercourse with vaginal penetration. Sexual functioning as assessed by the Female Sexual Function Index was much lower in CAH women than controls and lowest in CAH women with high Prader stages. Eighty-one percent (18 of 22) experienced pain during vaginal penetration. Only eight women became pregnant, and 17% (six of 35) had children. CONCLUSIONS: Despite expert medical and surgical care by physicians dedicated to this rare disease, women with CAH still suffer major limitations in their sexual function and reproductive life.

Heterogeneity of fetal growth in type 1 diabetic pregnancy.

OBJECTIVE: To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia. MATERIAL AND METHODS: Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model. RESULTS: The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index. CONCLUSIONS: The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

[Dysthyroidism in patients treated with interferon alpha]. / Dysthyroïdies chez les malades traités par interféron alpha.

In addition to their initially recognized antiviral activity, interferons are known to have a number of effects on the immune system. The role of alpha-interferon (alpha-IFN) has been evaluated in 8 studies, including 573 patients, aimed at determining the prevalence, clinical course and predictive factors of autoimmune dysthyroidism in patients treated with alpha-IFN. Two major categories of patients were treated with alpha-IFN: those with cancer and those with chronic viral hepatitis. Two types of interferon were used: human leukocyte IFN and recombinant IFN. Among the 542 patients in which thyroid function was evaluated, 47 (8.7%) had clinical or biological dysthyroidism: hypothyroidism in 25 (53%), hyperthyroidism in 13 (28%) and biphasic hyper-hypothyroidism in 9 (19%). The delay to onset was known in 44 patients (mean 9 months, range 1.5 to 23 months). Dysthyroidism was temporary in certain patients and did not require treatment, but antithyroid drugs were required in others. The prevalence of antithyroglobulin and/or antimicrosomal antibodies varied from 0 to 20% (mean 13.7%). The prevalence of antithyroid stimulating hormone receptor antibodies appeared to be lower than that of antithyroid antibodies. The pathogenic mechanism of dysthyroidism in patients given alpha-IFN remains unknown, but could result from the induction of antithyroid antibodies or an increase in pre-existing levels. Abherent expression of HLA-DR antigens on the surface of the thyrocytes has been proposed as a possible factor, although gamma-IFN and not alpha-IFN leads to the expression of class II antigens. It has also been shown that alpha-IFN induces the expression of class I antigens on thyrocytes, indicating that the observed dysthyroidism might result from an over-expression of class I antigens which would facilitate direct activation of cytotoxic T cells. In summary, alpha-IFN can induce dysthyroidism in about 1 out of 10 patients, probably by the induction or stimulation of autoimmune phenomena. The positive predictive value of antithyroid antibodies is modest, about 60%, but the negative predictive value is high at 93%. Thyroid function should be monitored closely in patients given alpha-interferon.

Evidence of oestradiol-induced changes in gonadotrophin secretion in men with feminizing Leydig cell tumours.

To study the sex steroid-gonadotrophin relationship, plasma oestradiol (E2), testosterone and gonadotrophin-releasing hormone (GnRH)-induced (100 micrograms iv) gonadotrophin response were measured in 42 male partners of infertile couples with normal sperm count (group I) and in 21 men with Leydig cell tumour (LCT, group II) in which a basal evaluation was repeated after tumour removal. Plasma free alpha-subunit (FAS), immunoreactive alpha-inhibin and luteinizing hormone (LH) pulse analysis were assessed in 10 LCT before and in six of them after surgery. Testosterone was significantly (p < 0.01) lower whereas E2 was significantly (p < 0.001) higher in group II than in group I. Gonadotrophin data were similar in both groups. The mean FAS was higher in group II than in group I and alpha-inhibin was higher than the normal range in 6/10 LCT. In group II, E2 levels were significantly (p < 0.01) and negatively correlated with testosterone, FSH, GnRH-induced gonadotrophin rise and LH pulse amplitude but not frequency. Significant (p < 0.001) changes were observed after surgery: E2 and alpha-inhibin fell; testosterone, LH and FSH rose; whereas FAS did not change significantly. The LH pulse amplitude but not frequency increased significantly (p < 0.05). In conclusion E2 oversecreted by LCT decreased LH and testosterone levels concomitantly. The GnRH-induced gonadotrophin level rose and the LH pulse amplitude decreased when the plasma E2 level rose, whereas the pulse frequency remained unaffected. A concomitant increase in alpha-inhibin and E2 is likely to be responsible for the drop in plasma FSH levels. These data support an action of excessive amounts of E2 at pituitary level, perhaps by decreasing the sensitivity of gonadotrophs to GnRH.

Somatostatin receptor imaging in non-functioning pituitary adenomas: value of an uptake index.

Somatostatin receptor imaging (SRI) was performed in five patients with known non-functioning pituitary adenomas. To determine whether the pituitary uptake correlates with response to octreotide therapy, an uptake index (UI) was calculated. Pituitary adenomas were detected in all five patients. The UI was, respectively, 15.1, 3.7, 2.2, 2.2 and 2.2 (the UI calculated in 12 normal subjects was between 1 and 1.9). Only the patient with the highest UI (15.1) had a dramatic improvement in tumour volume and visual function in response to octreotide therapy. The UI might be a good predictive parameter of octreotide therapy efficacy in non-functioning adenomas.

Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect.

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 micrograms per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

Development of fetal rat ovaries responsiveness to LH during organ culture.

The responsiveness of fetal neonatal rat ovaries to LH was investigated in vitro using three complementary approaches. First, steroid production was assessed after culture. In control media, detectable levels of estrogens (estradiol and estrone) and progesterone were only observed from day 6 postpartum and during the second week of life respectively. In the presence of LH (100 ng/ml) ovaries produced both estrogens and progesterone from day 4 postpartum and the response to LH was enhanced with IBMX supplementation in the medium. Second, 3 beta-HSD activity was measured with either LH or (Bu)2 cAMP (1mM). Irrespective to the time-period studies (Bu)2 cAMP stimulated this enzyme whereas the stimulation with LH occurred only from day 5 postpartum Third, specific hCG binding was assessed and we found that it occurred only on days 7 and 10. However, when fetal ovaries were pretreated for 48 h with (Bu)2 cAMP, a specific hCG binding could be detected and progesterone production was enhanced in response to LH. An effect of the nucleotide via a stimulation of the neuraminidase activity did not seem to be involved. Lastly treatment of 18-day-old fetal ovaries with cholera toxin (10nM) or forskolin (1 microM) was found to stimulate progesterone production and VIP (0.1 to 1 microM) stimulated both the 3-HSD activity and the estradiol production. These data suggest that the absence of steroidogenic response to LH before day 4 postpartum could be explained by the absence of receptors, though the LH transmembrane signal-transduction system is functional in fetal ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the new dopaminergic agonist CV 205-502 on plasma prolactin levels and tumour size in bromocriptine-resistant prolactinomas.

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of 3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal rat ovary.

3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) was examined in rat fetal ovaries. The enzymatic activity was determined by measuring the conversion of radiolabeled pregnenolone to progesterone. 3 beta-HSD, present in 14-day old fetal ovaries showed a regular increase in the course of development. Pretreatment with dcAMP for 48 h enhanced the apparent maximal velocity of the enzyme by about 5-fold without increase in the apparent Km. The increase in 3 beta-HSD activity was not due to the synthesis of pregnenolone observed after dcAMP pretreatment, but it was dependent on protein synthesis. The present results indicate that (1) 3 beta-HSD activity is present in fetal female gonads and the absence of steroid biosynthesis cannot be related to a defect in this enzyme (2) 3 beta-HSD activity is enhanced in the presence of dcAMP. The absence of gonadotropic receptors in the rat ovary before birth could explain the low level of the enzymatic activity measured in fetal ovaries.