Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis.

PROBLEM: The aim of this study was to verify whether anti-thyroid antibodies are present in the follicular milieu of euthyroid infertile women with thyroid autoimmunity undergoing in vitro fertilization (IVF) and whether IVF outcome is different in affected women with respect to negative controls. A secondary endpoint was to check whether there are changes in thyroid hormone levels during the IVF cycle. METHOD OF STUDY: Anti-thyroglobulin and anti-thyroperoxidase levels were measured in both follicular fluid and serum on the day of oocyte retrieval in women with thyroid autoimmunity. Serum TSH, FT3, and FT4 levels were measured in all patients before treatment initiation, on the day of oocyte retrieval and of pregnancy test. IVF outcome parameters were recorded in all women. RESULTS: Oocyte fertilization, grade A embryos, and pregnancy rates were lower in women with thyroid autoimmunity than in negative controls, while early miscarriage rate was higher. Anti-thyroid antibodies were measurable in follicular fluid in all affected women and were strongly correlated with serum levels. No significant changes in thyroid hormone levels were recorded in any women. CONCLUSION: The presence of anti-thyroid antibodies in ovarian follicles, as demonstrated for the first time in this study, may play a critical role in female infertility related to thyroid autoimmunity.

Comparison of effects of 3 mg drospirenone plus 20 µg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 µg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, open-label clinical trial. SETTING: Academic medical clinic. PATIENT(S): Forty-eight hirsute women with PCOS. INTERVENTION(S): Patients were randomized to treatment with DRP/20EE or with DRP/20EE plus metformin (1,500 mg/d) or with DRP/20EE plus CPA (12.5 mg/d, 10 days per cycle) for 6 months. MAIN OUTCOME MEASURE(S): Blood pressure, lipid profile, and indexes of glucose tolerance and insulin sensitivity were assessed before and after 6 months of treatment. RESULT(S): Body mass index and blood pressure were not modified by any treatment. Treatment with DRP/EE20 did not change the lipid profile; DRP/EE20 plus metformin significantly increased high-density lipoprotein cholesterol concentrations; DRP/EE20 plus CPA significantly increased triglycerides and total cholesterol. The area under the curve for insulin was significantly decreased by DRP/EE20 and DRP/EE20 plus metformin, but it was significantly increased by DRP/EE20 plus CPA. Treatment with DRP/EE20 plus CPA significantly increased the homeostasis model assessment of insulin resistance index and significantly reduced the glucose to insulin ratio index. Treatment with DRP/EE20 significantly increased the glucose to insulin ratio index. CONCLUSION(S): Treatment with DRP/EE20 improved insulin sensitivity in hirsute women with PCOS, with no deterioration of lipid profile. This effect was not ameliorated by the addition of metformin. The positive metabolic effects of DRP are abolished by the concomitant use of CPA.

Hyperandrogenemia influences the prevalence of the metabolic syndrome abnormalities in adolescents with the polycystic ovary syndrome.

OBJECTIVE: The prevalence of the metabolic syndrome (MBS) abnormalities in Italian adolescents with polycystic ovary syndrome (PCOS) was evaluated. DESIGN: Retrospective chart review. SETTING: University outpatient clinic. PARTICIPANTS: Fifty-three adolescents with PCOS. INTERVENTIONS: Subjects underwent a physical evaluation. Fasting blood samples were taken for the evaluation of metabolic parameters. MAIN OUTCOME MEASURES: The prevalence of MBS abnormalities according to de Ferranti criteria was assessed. RESULTS: 9.4% of adolescents with PCOS had the MBS (three abnormalities). Twelve girls (22.7%) had two abnormalities. Seventeen (32.1%) of PCOS girls have no MBS abnormalities. PCOS adolescents with the MBS were more obese, insulin resistant and they had significantly higher levels of total and free testosterone. The number of metabolic abnormalities correlated with free, total testosterone, free androgen index (FAI) and body mass index (BMI). Groups with two or three abnormalities were not differentiated by BMI, insulin, lipids, blood pressure, but they were differentiated by total and free testosterone and FAI. Adolescents with the MBS have higher total and free testosterone and FAI than girls with two MBS abnormalities. CONCLUSIONS: The MBS and its components are present in some adolescents with PCOS, placing them at increased risk for cardiovascular disease early in adulthood. Hyperandrogenemia is a risk factor for MBS independent of obesity.

Body mass index and body composition in adolescents treated with gonadotropin-releasing hormone analogue triptorelin depot for central precocious puberty: data at near final height.

BACKGROUND/AIM: In children with central precocious puberty (CPP), gonadotropin-releasing hormone (GnRH) analogue treatment has been associated with an increase in body mass index (BMI). We evaluated BMI and body composition in adolescents treated with GnRH analogue at their near final height to assess the long-term effects of therapy on these parameters. PATIENTS AND METHODS: We studied 20 patients (14.8 +/- 1.6 years; 17 females) previously treated with triptorelin depot for CPP (3.75 mg/28 days) from 8.1 +/- 0.8 to 11.5 +/- 0.8 years. 23 healthy adolescents with normal onset of puberty (14.7 +/- 2.1 years, 19 females) were the controls. BMI and body composition (dual-energy x-ray absorptiometry) were assessed. RESULTS: Patients reached their near adult height (-0.5 +/- 1.1 standard deviation score (SDS)); the girls were menstruating and the majority (15/17) had regular cycles, the boys showed normal testicular function. BMI was unchanged from the start of GnRH analogue therapy (0.4 +/- 1.0 SDS) to near adult height (0.2 +/- 1.0 SDS, p = NS vs. 0). Total fat mass (TFM) was significantly increased (16,144 +/- 8,065 g; controls 10,712.1 +/- 4,120.4 g, p < 0.02); glucose homeostasis and lipid profile corresponded to reference ranges. CONCLUSIONS: GnRH analogue therapy did not show long-term detrimental effects on BMI, but it may increase TFM, suggesting that body composition should be monitored till adulthood.

Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels.

OBJECTIVE: To evaluate the metabolic profiles of adolescents with different phenotypes of polycystic ovary syndrome (PCOS). DESIGN: Observational study. SETTING: University outpatient clinic. PATIENT(S): Adolescents with PCOS (n = 120) were divided into four groups: oligomenorrhea and hirsutism (O-H, n = 50), oligomenorrhea, hirsutism, and polycystic ovaries (PCO-O-H, n = 22), oligomenorrhea, hirsutism, and hyperandrogenemia (A-O-H, n = 28), oligomenorrhea, and hirsutism, hyperandrogenemia, and polycystic ovaries (PCO-A-O-H, n = 20). A control group of age-matched adolescents (n = 30) was included. INTERVENTION(S): Subjects underwent physical and ultrasound evaluations; fasting blood samples were taken for the measurement of endocrine and metabolic parameters. MAIN OUTCOME MEASURE(S): The endocrine and metabolic profiles were evaluated. RESULT(S): Adolescents with PCOS showed reduced insulin sensitivity and dyslipidemia. Triglycerides, and total and low-density lipoprotein cholesterol were higher in the phenotypes with hyperandrogenemia. Insulin resistance and body mass index were not significantly different between PCOS phenotypes. Triglyceride positively and high-density lipoportein cholesterol levels negatively correlated with free testosterone and free androgen index. CONCLUSION(S): The risk of metabolic alterations may vary in adolescent PCOS patients with different phenotypes. Hyperandrogenemia is a risk factor for dyslipidemia. This information may be of relevance in counseling adolescents with PCOS.

Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome.

OBJECTIVE: Evaluation of clinical and endocrine effects of naltrexone administration in obese women with PCOS. DESIGN: Open, controlled, clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. PATIENT(S): Ten PCOS women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/day) for 6 months. MAIN OUTCOME MEASURE(S): Body mass index and the menstrual cyclicity during naltrexone treatment were assessed. Basal levels of LH, FSH, 17beta-estradiol (E(2)), 17-hydroxyprogesterone, total and free T, androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding globulin were evaluated before treatment and every 3 months. Progesterone levels were measured in the luteal phase during the sixth month. Gonadotropin response to GnRH administration (10 microg) and a 75-g oral glucose tolerance test were performed before and every 3 months. RESULT(S): Body mass index significantly decreased from 29.94 +/- 1.04 to 26.07 +/- 0.81 during treatment. The menstrual cyclicity improved in 80% of PCOS women: the mean cycle length was 40-360 days before treatment and ranged between 25 and 120 days and 28-120 days after 3 and 6 months of treatment. Plasma levels of free T, androstenedione, dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting glucose-to-insulin ratio improved in women with insulin resistance. CONCLUSION(S): Naltrexone may have a beneficial effect on the clinical and endocrine-metabolic disturbances of obese PCOS women. Whether these effects are the consequences of weight loss or are due to changes in opioidergic tone is debatable.