Body mass index is a good predictor of metabolic abnormalities in polycystic ovary syndrome.

AIM: To assess which parameters among hyperandrogenism (total testosterone-tT-or free androgen index-FAI), sex hormone binding globulin (SHBG) or body mass index (BMI) could better predict a worse metabolic profile in women with polycystic ovary syndrome (PCOS). METHODS: Five hundred and eighty-six women with PCOS and clinical or biochemical hyperandrogenism were included. Receiver Operating Characteristics (ROC) curves with tT, FAI, SHBG and BMI were performed for metabolic parameters and a cut-off with sensitivity and specificity was obtained for each parameter. The women were then divided into three groups and compared according to their BMI. RESULTS: Based on the ROC curves, tT proved not to be a good predictor of metabolic alterations. FAI and SHBG resulted to be good predictors of some markers of metabolic damage. The area under the curves (AUC) of SHBG were greater than those of FAI. SHBG levels affects the values of homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, high density lipoproteins (HDL), low density lipoproteins (LDL), and total cholesterol also when corrected for BMI. However, the highest AUCs of the ROC curves were observed when BMI was used, which was significantly related to all the metabolic parameters analyzed. Dividing women according to their BMI, BMI between 25.00 and 30.00 kg/m2 had a worse metabolic profile but still in a normal range, while BMI ≥ 30 kg/m2 women had a significant metabolic derangement. DISCUSSION: BMI is a good predictor factor of metabolic changes in PCOS women at any age, and obesity is associated to the appearance of metabolic complications. Overweight and obese PCOS women should be addressed to perform a complete metabolic assessment.

Thyroid autoimmunity in different phenotypes of polycystic ovary syndrome: a single-center experience.

PURPOSE: Polycystic ovary syndrome (PCOS) has been associated with Hashimoto's thyroiditis (HT) and 4 phenotypes have been described in this syndrome. The aim of this work was to investigate the frequency of anti-thyroid antibodies (TAb) and thyroid function in the 4 phenotypes of PCOS. PATIENTS: This study included 448 patients with PCOS: 260 (58.0%) with phenotype A, 119 (26.6%) with phenotype B, 38 (8.5%) with phenotype C and 31 (6.9%) with phenotype D. RESULTS: TAb positivity was detected in 90/448 patients (20.1%) and was statistically significant higher (p = 0.03) in the grouped phenotypes A-B (83/379, 21.9%) than in phenotypes C-D (7/69, 10.1%). Positive anti-thyroglobulin antibodies (TgAb) were detected in 74/448 (16.5%) patients and positive anti-thyroperoxidase antibodies (TPOAb) in 66/448 (14.7%) patients. Both TgAb and TPOAb positivity was higher but not statistically significant in phenotype A-B than phenotype C-D. High titer TgAb (> 100 UI/ml) frequency was significantly higher (p = 0.005) in grouped phenotypes A-B (39/379, 10.3%) than in phenotypes C-D (0/69, 0.0%), while no significant difference was observed for low titer TgAb (≤ 100 UI/ml). According to a binary logistic regression analysis hypothyroidism was significantly associated with TAb positivity (OR 4.19; CI 2.25-7.79; p < 0.01) but not with PCOS phenotype. Androgen profile was not associated with TAb positivity. CONCLUSION: A higher frequency of positive TAb and of high titer TgAb and TPOAb have been detected in PCOS women with phenotypes A and B, probably in relation to the greater imbalances between estrogen and progesterone levels present in these phenotypes.

Comparison of PCOS phenotypes in adolescent and young adult Mediterranean women with possible PCOS.

PURPOSE: During adolescence, PCOS features are supposed to be in evolution. Because of this, the diagnosis of PCOS in adolescence is often unclear and few studies have compared adolescent and adult PCOS phenotype distribution and features. The aim is to compare phenotypes in adolescents and young adults with PCOS. METHODS: 109 girls aged from 13 to 19 years were retrospectively studied. All patients had a gynecological age > 2 years. 63 patients were adolescents (3-5 years beyond menarche) while 46 patients were young adults (6-9 years beyond menarche). Diagnosis of different PCOS phenotypes (A, B, C, D) was made according to the Rotterdam criteria. Clinical data (menstrual cycles, BMI, presence of hirsutism), androgen circulating levels (total testosterone, androstenedione, dehydroepiandrosterone sulphate) and ovarian morphology by ultrasound were assessed. RESULTS: 109 patients presented PCOS according to the Rotterdam criteria. Phenotype A was by far the most common phenotype (73.4%) followed by phenotype B (21.1%). Only few patients had phenotype C (4.6%) or phenotype D (0.9%). When patients were divided in two groups (adolescent and young adult patients), no significant difference in prevalence and features of the different phenotypes was observed. CONCLUSION: In this cohort of adolescent and young adult women with PCOS, the progression of age does not change the prevalence and the features of main PCOS phenotypes. It suggests that the Rotterdam criteria might be used also in adolescents, at least in those with 2 or more years of gynecological age, for the diagnosis of PCOS.

Effect of aging on clinical features and metabolic complications of women with polycystic ovary syndrome.

PURPOSE: To assess the distribution of clinical features and metabolic abnormalities of polycystic ovary syndrome (PCOS) women according to their age. METHODS: Retrospective study on 602 women (mean age 23.9 ± 6.2 years), diagnosed according to International PCOS Network Guidelines criteria as having PCOS in a University-based Hospital. Anthropometric features, hormonal and metabolic parameters were measured and compared between the different age groups (group A ≤ 20 years; group B 21-30 years; group C > 30 years). RESULTS: Patients in group A were more often hyperandrogenic, while in group C hypertension, dyslipidemia, obesity, impaired fasting glucose, and insulin resistance (IR) were more prevalent. After adjusting for BMI, age correlated positively with sex hormone-binding globulin (SHBG), IR, total- and LDL-cholesterol, and negatively with DHEAS, insulin, and free androgen index (FAI). SHBG was significantly associated with IR and atherogenic dyslipidemia, while FAI levels were linked to hypertension, independently of other factors considered. Furthermore, the regression analysis showed a stronger relationship between BMI and metabolic outcomes, regardless of age. CONCLUSION: Polycystic ovarian syndrome (PCOS) phenotype changes with age. Clinical and biochemical hyperandrogenism are a major concern in young PCOS women, while metabolic burden tends to increase with aging. Some of the cardiovascular risk factors are dependent on FAI and SHBG levels, whereas BMI confirms its key role in the genesis of most of the metabolic sequelae in PCOS, independently of age.

Tailored hormonal approach in women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is probably one of the most devastating diagnoses for women of reproductive age. The major implications for fertility, climacteric symptoms, and quality of life, the great impact of long-term consequences such as bone loss and cardiovascular health, and the lack of a coherent and shared clinical approach make the choice for the right hormonal therapy challenging. In this review we propose an integrated and patient-based hormonal approach for women with POI, from puberty to late reproductive age.

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition.

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.Methods: A 52-year-old woman with a 2 months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173 ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.

Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemiaMaterials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.

[Oral contraceptive pill and thrombotic risk: epidemiological studies]. / Pillola e rischio trombotico: gli studi wpidemiogici.

The venous thromboembolism (VTE) is a rare event during childbearing age and during the assumption of combined oral contraceptive. The absolute risk of VTE in users of combined oral contraceptives is 20-30 per 100000 women years. A number of case-control studies published in recent years have shown an apparent increase in the risk of VTE among users of oral contraceptives (OCs) containing desogestrel, gestodene, drospirenone and cyproterone, relative to the use of levonorgestrel. The data derived from these recent studies is of borderline statistical significance because any important factors are not considered to evaluate the real correlation between the assumption of OCs and risk of venous thromboembolism. Among the factors that should be considered, there are: EE dose, duration of use, coexistance of other risk factors of venous thromboembolism (age, BMI, familiarity, surgical interventions) and other prescription bias. The lack of these factors is likely to contribute to the increased risk of venous thromboembolism observed in users of third-generation OCs when compared to that in users of second-generation OCs. To date, because of the inadequacy of epidemiological studies, the data about the correlation between OCs and TVE, are not conclusive and it will be necessary to carry out other studies to clarify this debating point, definitively.

Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia.

CONTEXT: Because many women with 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) carry at least one allele affected by a severe mutation of CYP21, they are at risk for giving birth to infants with classic adrenal hyperplasia (CAH). OBJECTIVE: Our objective was to determine the frequency of CAH and NCAH infants born to mothers with 21-OH-deficient NCAH. DESIGN AND SETTING: We conducted an international multicenter retrospective/prospective study. PATIENTS AND METHODS: The outcome of 203 pregnancies among 101 women with 21-OH-deficient NCAH was reviewed. The diagnosis of 21-OH-deficient NCAH was established by a basal or post-ACTH-stimulation 17-hydroxyprogesterone level of more than 10 ng/ml (30.3 nmol/liter). When possible, genotype analyses were performed to confirm CAH or NCAH in the offspring. RESULTS: Of the 203 pregnancies, 138 (68%) occurred before the mother's diagnosis of NCAH and 65 (32%) after the diagnosis. Spontaneous miscarriages occurred in 35 of 138 pregnancies (25.4%) before the maternal diagnosis of NCAH, and in only four of 65 pregnancies (6.2%) after the diagnosis (P < 0.002). Four (2.5%; 95% confidence interval, 0.7-6.2%) of the 162 live births were diagnosed with CAH. To date, 24 (14.8%; 95% confidence interval, 9.0-20.6%) children, 13 girls and 11 boys, have been diagnosed with NCAH. The distribution of NCAH children and their mothers varied significantly by ethnicity (P < 0.0001, for both). CONCLUSIONS: The risk of a mother with 21-OH-deficient NCAH for giving birth to a child affected with CAH is 2.5%; at least 14.8% of children born to these mothers have NCAH.

Effects of finasteride, a 5 alpha-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women.

An oral 5-mg dose of finasteride, a 5 alpha-reductase inhibitor, was administered for 3 months to 10 hirsute women to determine the effect on gonadotropin secretion, on basal and stimulated androgen secretion, and on hair growth. Hair growth was assessed by the Ferriman-Gallwey score. All of the above determinations were evaluated before and after 1 and/or 3 months of finasteride treatment. Basal and GnRH-stimulated gonadotropin secretions were not affected. Indeed, finasteride did not modify the pulsatility of LH secretion. No change was seen in estradiol, PRL, free testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin concentrations. Serum concentrations of cortisol (F) were significantly reduced after 1 month of finasteride treatment. The F levels returned to pretreatment levels after 3 months. Plasma levels of dihydrotestosterone and 3 alpha-androstanediol glucuronide significantly decreased during finasteride treatment. A significant increase in testosterone concentrations was observed after 3 months. Finasteride did not modify the responses of testosterone, androstenedione, and dehydroepiandrosterone sulfate to ACTH-(1-24) injection. Conversely, finasteride blunted the F response to corticotropin stimulation. Three months of finasteride treatment significantly decreased the Ferriman-Gallwey score. In conclusion, finasteride significantly decreased dihydrotestosterone and hair growth in hirsute women without negatively affecting gonadotropin secretion.

The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome.

Adrenal hyperandrogenism is a common feature of patients with polycystic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivity to ACTH. Because enhanced ovarian androgen secretion does not appear to explain this phenomenon, we explored the role of estrogen in inducing enhanced adrenal sensitivity, in that a state of relative hyperestrogenism exists in PCO. Eight patients with PCO and seven matched controls received ovine corticotropin-releasing hormone (oCRH; 0.1 micrograms/kg) iv before and after hypoestrogenism was induced by leuprolide acetate (LA; 1 mg, sc, each day). In patients with PCO, a third oCRH test was repeated after transdermal estradiol (E2; 0.1 mg) had been applied for a week, during which time LA was continued. At baseline, patients with PCO had increased responses of 11 beta-hydroxyandrostenedione and dehydroepiandrosterone (P < 0.03 and P < 0.02) and increased delta maximal ratios of androstenedione (A4)/ACTH and dehydroepiandrosterone/ACTH (P < 0.01) after oCRH treatment. After LA administration to patients with PCO, these ratios were significantly suppressed (P < 0.01) and returned to baseline after E2 was added. There were no changes in controls. Steroid ratio responses to oCRH suggested that 17,20-desmolase activity (delta maximum change in the ratio of A4/17-hydroxyprogesterone) was lowered with estrogen suppression and increased again after transdermal E2 administration. There was a significant positive correlation between changes in E2 levels and delta maximum change in the ratios of A4/17-OHP after oCRH treatment, signifying 17,20-desmolase activity (r = 0.58, P < 0.02). In conclusion, these data provide evidence that estrogen is at least one factor that influences adrenal androgen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome.

High testosterone levels of ovarian origin affect adrenal steroidogenesis?

Androgens of ovarian origin have been suggested to affect adrenal enzymatic activity. To investigate this possibility, the 17-hydroxyprogesterone (17-OH P) and cortisol (F) responses to an ACTH stimulation test (0.25 mg iv, bolus) were evaluated in 10 normal women and in 39 hyperandrogenic women with normal (14 subjects) or high (25 subjects) testosterone (T) levels. The 17-OH P release and the ratio between 17-OH P and F release in response to the ACTH stimulation test were significantly higher (P less than 0.05) in hyperandrogenic women with high T levels than in normal subjects. Eight hyperandrogenic women with high T received intranasal GnRH agonist (Buserelin, 1200 micrograms/day) for 4 weeks, and the 17-OH P and F release in response to the ACTH stimulation was reassessed after agonist treatment. At the end of GnRH agonist administration the mean circulating levels of T were significantly reduced (P less than 0.05). The F response to the ACTH test was not modified by pretreatment with the GnRH agonist. The 17-OH P response to the ACTH stimulation test after the GnRH agonist was unchanged in comparison with control tests, as well as the ratio between 17-OH P and F responses to the ACTH test. These data do not seem to confirm, as previously suggested, that high T levels of ovarian origin affect adrenal steroidogenesis.

The effects of the gabaergic drug, sodium valproate, on prolactin secretion in normal and hyperprolactinemic subjects.

To find out whether the gamma-aminobutyric acid (GABA)ergic system affects PRL secretion in humans, sodium valproate (DPA or Na-dipropyl-acetate), a drug inducing increase of endogenous GABA, was administered to 20 normal and 15 hyperprolactinemic subjects. PRL circulating levels were measured by RIA in the samples obtained after acute oral treatment with 400 mg DPA. A significant decrease (P less than 0.01) in comparison with basal levels was observed in normal women from 30-180 min after drug administration. DPA treatment also lowered blood PRL levels in hyperprolactinemic subjects (seven females) without evidence of pituitary tumor. A decrease very similar to the one found in normal subjects (P less than 0.05 vs. basal levels) was observed within 180 min from drug ingestion. Conversely, no significant changes were found after the same treatment in hyperprolactinemic patients with evidence of prolactinoma (seven females and one male). Taken together, these data seem to demonstrate that pharmacological enhancement of endogenous GABAergic tone is followed by inhibition of PRL secretion. They also suggest that GABA may exert an inhibitory control on PRL release in humans. In hyperprolactinemic subjects, this GABAergic control appears to be present only when a pituitary tumor cannot be demonstrated.

Pharmacological activation of gamma-aminobutyric acid-system blunts prolactin response to mechanical breast stimulation in puerperal women.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system participates in the control of PRL secretion during the puerperium, different doses of sodium valproate (DPA), a drug that increases endogenous GABA activity, were administered orally to puerperal women who did not wish to breast feed their infants. Two groups of five women were each given DPA in doses of 400 and 800 mg, respectively. PRL levels were measured in plasma samples collected before and after drug administration. Another group of five puerperal women was treated with 800 mg DPA 60 min before mechanical breast stimulation using an electric breast pump for 15 min. Circulating PRL levels were measured in samples obtained before, during, and after breast stimulation. No drug-associated side effects were observed. After placebo administration, no significant variations in plasma PRL levels occurred in any subject. The lower dose of DPA (400 mg) induced a slight decrease in plasma PRL levels, but 800 mg of the drug induced a significant fall (P less than 0.05 vs. baseline values) in PRL, with a maximum percent decrease (68.2 +/- 4%) 180 min after DPA treatment. Mechanical breast stimulation performed after placebo treatment induced a significant increase (P less than 0.01) in plasma PRL levels, with peak values (37 +/- 10% above baseline values) 10 min after the onset of stimulation. When DPA was administered to the same women, a significant decrease (23 +/- 3%) in plasma PRL occurred during breast stimulation. Thereafter, PRL values continued to fall in spite of breast stimulation. PRL levels were significantly decreased after DPA treatment compared to both basal values (P less than 0.01) and the levels found in the same patients during control tests (P less than 0.05). These results demonstrate that enhancement of endogenous GABAergic tone induced by DPA significantly decreases basal PRL levels and blunts PRL release after mechanical breast stimulation. In agreement with animal data, a possible physiological role of GABA in the control of PRL release during puerperium may be suggested.

Inhibitory effect of the dopamine agonist bromocriptine on the postcastration gonadotrophin rise in women.

Basal or stimulated gonadotrophin plasma levels were measured after bilateral ovariectomy in untreated and bromocriptine (BCT)-treated normal women. BCT was orally administered from the 7th to the 14th day after ovariectomy at a dose of 3.75 mg/day. BCT significantly (P less than 0.05) inhibited LH release, both basally and after LRF stimulation. Plasma FSH levels were also reduced in treated subjects, but this decrease did not reach statistical significance relative to controls. The blunted postcastration gonadotrophin rise found with BCT administration suggests that pituitary gonadotropin secretion is, in part, under dopaminergic inhibitory control.

Platelet-vessel wall interactions with third-generation oral contraceptives: no evidence of detrimental effects.

Because of the association of oral contraceptives (OC) and cigarette smoking with an increased thrombotic risk, we evaluated thromboxane (TX) and prostacyclin urinary (u) metabolites, as in vivo indices of platelet-vessel wall interactions, in women assigned to third generation OC. Twenty-eight women (15 smokers) underwent a 6-month trial of 30 microg ethinylestradiol plus 0.150 mg desogestrel. Cotinine plasma levels were elevated only in persons classified as smokers and serum TXB2 determination confirmed the absence of cyclooxygenase inhibition throughout the study. u-TXB2 and 11-dehydro-TXB2 were higher in smokers than in non-smokers. OC decreased u-11-dehydro-TXB2 both in smokers (from (pg/micromol creatinine) 35.1+/-6.9 to 15.8+/-2.8; P<0.025) and non-smokers (from 31.7+/-9.8 to 20.6+/-4.8, P = N.S.). u-6-keto-prostaglandin(PG)F1alpha excretion, also higher in smokers compared to non-smokers, was also reduced after OC in smokers (from (pg/micromol creatinine) 24.3+/-5.2 to 14.8+/-2.3; P<0.05). Smokers also had a trend to higher u-2,3-dinor-6-keto-PGF1alpha, marginally reduced by OC. Thus, the OC regimen used here improves - if anything - platelet vessel wall interactions as assessed by prostanoid production in vivo. The prothrombotic tendency associated with the use of OC in smokers does not appear to be mediated by changes in platelet-vessel wall interactions.

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

OBJECTIVE: To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. DESIGN: Controlled clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. PATIENT(S): Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. INTERVENTION(S): Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). MAIN OUTCOME MEASURE(S): Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). RESULT(S): Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. CONCLUSIONS: Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Use of sulprostone for induction of preoperative cervical dilation or uterine evacuation: a comparison among the effects of different treatment schedules.

Sulprostone was administered to 144 pregnant women to induce either preoperative cervical dilation or uterine evacuation. A comparison was performed to select the drug treatment schedule showing the greatest effects with the lowest incidence of side effects. As for preoperative cervical dilation, the local (intracervical/intramural) injection of 50 + 50 micrograms and the intramuscular treatment with 500 micrograms of sulprostone showed the most favorable effects on the cervix after 12 and 6 hours, respectively. The cervix dilated 8 mm or more in 82.6% of subjects treated locally and in 85.7% of those treated intramuscularly. No patient experienced a serious side effect, but two displayed vomiting after receiving 500 micrograms of the drug. Uterine evacuation was induced by both repeated intramuscular injections (500 micrograms every 4 hours) and continuous intravenous infusion (2.8 micrograms/minute for 6 hours) of sulprostone in more than 90% of the patients with intact pregnancy, missed abortion, or fetal death. The efficacy of the drug was not influenced by gestational age or parity. Gastrointestinal symptoms were the only recorded side effects, with negligible incidence and intensity for both routes of sulprostone administration.

Ovarian influence on adrenal androgen secretion in polycystic ovary syndrome.

OBJECTIVE: To determine whether the ovary influences adrenal androgen secretion in polycystic ovary syndrome (PCOS). DESIGN: The adrenal androgen secretion was evaluated before and during ovarian suppression with a long-acting GnRH agonist. SETTING: Department of Obstetrics and Gynecology, Pisa, Italy. PARTICIPANTS: Women with PCOS and high (10 subjects) and normal (12 subjects) DHEAS levels and 6 normal women. INTERVENTIONS: After 1 mg dexamethasone, an ACTH-(1-24) stimulation test was performed in the early follicular phase of the menstrual cycle. The test was repeated after two injections of a long-acting GnRH analogue (GnRH-a). MAIN OUTCOME MEASURES: Basal plasma levels of gonadotropins, E2, T, androstenedione (A), 17 alpha-hydroxyprogesterone (17-OHP), DHEAS, and cortisol (F) were evaluated before the evening administration of dexamethasone. Serum A, T, 17-OHP, DHEAS, and F were measured 9 hours after dexamethasone and in samples collected 60 and 120 minutes after ACTH IV injection. RESULTS: In the high DHEAS group the maximum increases in T, A, 17-OHP, and DHEAS in response to ACTH were significantly higher than in normal DHEAS PCOS women and in normal women. The GnRH-a modified the A and T responses to ACTH in the high DHEAS group. CONCLUSIONS: Ovarian steroids, or other extra-ovarian factors, seem to be responsible for the increased A and T responses to the corticotropin stimulation demonstrated in some PCOS women.

Clinical and endocrine effects of flutamide in hyperandrogenic women.

OBJECTIVE: To investigate the clinical and endocrine effects of the antiandrogen flutamide in hirsute women. DESIGN: Hirsutism was assessed before and after 3 months of treatment with flutamide 500 mg/d. Endocrine evaluations were performed before and during the 2nd month of treatment with flutamide 500 mg or 750 mg/d. SETTING: Department of Obstetrics and Gynecology, Pisa, Italy. PARTICIPANTS: Eighteen hirsute women were studied: nine women were hyperandrogenic, and the other 9 had an idiopathic hirsutism. INTERVENTIONS: Women were randomly treated with flutamide 500 mg/d (9 patients) or 750 mg/d (9 patients) for 3 and 2 months, respectively. Six received placebo 1 month before flutamide treatment. MAIN OUTCOME MEASURES: Hirsutism was assessed by measuring hair diameter. Follicle-stimulating hormone and LH responses to GnRH were evaluated. Basal plasma levels of T, androstenedione (A), 17-hydroxyprogesterone (17-OHP), DHEAS, cortisol (F), and sex hormone-binding globulin (SHBG) were evaluated. The same hormones were determined after a single dose of flutamide (250 or 500 mg) or placebo throughout a 12-hour period and in samples collected 60 and 120 minutes after ACTH intravenous injection. RESULTS: Hair diameter was reduced by 30%. Both dosages of flutamide did not change basal and stimulated gonadotropin, T, A, 17-OHP, F, and SHBG levels. Both dosages reduced stimulated DHEAS levels. CONCLUSIONS: Flutamide may have a beneficial effect on hirsutism. This effectiveness is mainly due to its peripheral antiandrogen action. However, an effect on the adrenal gland seems to be present.