Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism.
Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women. (+info)
Dexamethasone supplementation to gonadotropin stimulation for in vitro fertilization in polycystic ovarian disease.
PURPOSE: This study was conducted to determine whether glucocorticoid supplementation for patients with polycystic ovarian disease during ovulation induction with gonadotropins for in vitro fertilization (IVF) therapy is beneficial. METHODS: Seventy-one cycles of patients undergoing first attempts at IVF, with classical polycystic ovarian disease and hyperandrogenemia, who enrolled in the IVF-embryo transfer program, were evaluated retrospectively. In 20 cycles (20 patients) glucocorticoid supplementation was noted and compared to 51 cycles (51 patients) without glucocorticoid as adrenal androgen suppression. Ovaries were stimulated by gonadotropin releasing hormone agonist, human menopausal gonadotropin, and dexamethasone. Ovarian responsiveness and IVF-embryo transfer outcome were analyzed and included the number of follicles > 17 mm in diameter, serum estradiol concentration on the day of human chorionic gonadotropin administration, number of human chorionic gonadotropin ampoules administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate, and number of clinical pregnancies and their outcome. RESULTS: The results showed that the pregnancy rate in patients who received glucocorticoid was 22.1%, compared to 26% in the controls (statistically insignificant). The IVF cycle variables studied revealed no statistically significant differences. CONCLUSIONS: Our observations did not support the notion that adrenal androgen suppression by glucocorticoid, or as an adjuvant therapy, is beneficial to patients with polycystic ovarian disease who enrolled in an IVF-embryo transfer program. (+info)
Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study. (+info)
Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status.
OBJECTIVE: To study the incidence of 21-hydroxylase deficiency in Slovenian hyperandrogenic women, at the gene level. Previous endocrine studies indicated large differences in the incidence of 21-hydroxylase deficiency in hyperandrogenic women. The predictive values of the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation and of HLA typing in screening for carrier status were re-evaluated. DESIGN: Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women. MEASUREMENTS: Cortisol and 17-OHP concentrations were measured at baseline and 60 min after ACTH stimulation. Basal adrenal androgen concentrations were also measured. RESULTS: None of 83 hyperandrogenic patients was affected with non-classical 21-hydroxylase deficiency, but 12 of 81 patients (14.8%) had high concentrations of 17-OHP after stimulation, indicative of carrier status. The increase in 17-OHP concentrations could be explained by a carrier status for CYP21 gene mutations in only three of 12 patients (25%), whereas seven of 69 patients (10. 1%) with normal concentrations of 17-OHP after stimulation were found to be carriers of CYP21 gene mutations, indicating low positive predictive values of ACTH stimulation as a screening test for carriers of 21-hydroxylase deficiency. In total, 11 carriers were identified among 83 patients: seven CYP21 gene deletions/conversions, two Gln(318)Stop and one Val(281)Leu mutation and one gene conversion extending from exon 4 to exon 7 were found. The association between Val(281)Leu mutation and HLA-B14 antigen was confirmed in this Slovenian population. CONCLUSIONS: Basal or ACTH-stimulated 17-OHP concentrations are not a good indicator of the carrier status for 21-hydroxylase deficiency among Slovenian hyperandrogenic patients. Reliable screening for carriers of 21-hydroxylase deficiency is possible only by molecular analysis of the CYP21 gene. (+info)
Clearance of acanthosis nigricans associated with the HAIR-AN syndrome after partial pancreatectomy: an 11-year follow-up.
We describe a woman with the syndrome characterised by hyperandrogenism, insulin resistance and acanthosis nigricans (the HAIR-AN syndrome), and an associated insulinoma (islet B-cell tumour), whose signs and symptoms cleared after partial pancreatectomy. (+info)
Clinical presentation of PCOS following development of an insulinoma: case report.
A 24 year old woman presented with a prolonged clinical history of fasting and exertional hypoglycaemia, and was subsequently diagnosed with an insulinoma. Concurrent symptoms of oligomenorrhoea and hyperandrogenism of similar duration were noted. Biochemically, hyperinsulinaemia was observed in association with a raised serum luteinizing hormone (LH), raised testosterone and androstendione concentrations. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS) but minimal change was observed in the ovarian ultrasound appearances. This case demonstrates the role of insulin in mediating the hypersecretion of both LH and androgens in women with polycystic ovaries. We suggest that hyperinsulinaemia converted occult 'polycystic ovaries' to become clinically manifest as 'polycystic ovary syndrome'. This paradigm has clear implications for women with insulin dependent diabetes mellitus who presumably have systemic hyperinsulinaemia. (+info)
Use of a long-acting gonadotrophin-releasing hormone analogue in a postmenopausal woman with hyperandrogenism due to a hilus cell tumour.
OBJECTIVE: The aim of this study was to prove the utility of GnRH analogues for the suppression of androgen secretion in a postmenopausal woman with a suspected virilizing ovarian tumour. DESIGN AND METHODS: We present a case of a 72-year-old woman with virilization of recent onset. Hormonal studies revealed a fourfold increase in serum testosterone levels, normal dehydroepiandrosterone sulphate concentrations and high levels of serum 17-hydroxyprogesterone levels. Computed axial tomography scan of the ovaries was normal and the adrenal glands showed a discrete enlargement. The long-acting GnRH analogue, triptorelin, was injected initially (3.75mg i.m.) and serum hormone levels were measured weekly throughout one month. RESULTS: GnRH produced a decrease in serum testosterone levels to normal values, in parallel with the suppression of serum LH and FSH concentrations. The patient was treated for three months with triptorelin and she experienced an amelioration of the hyperandrogenic symptoms. In order to achieve a diagnosis, the patient was submitted to a laparotomy that revealed a small hilus cell tumour in the left ovary. CONCLUSION: GnRH analogues may offer a good therapeutic option in some states of gonadotrophin-dependent hyperandrogenism of ovarian origin. (+info)
The best correlation of the new index of hyperandrogenism with the grade of increased body hair.
OBJECTIVE: Hyperandrogenemia is the most frequent endocrine disorder in fertile women causing a variety of negative metabolic disturbances. Establishing the diagnosis of androgen overproduction has important implications for the follow-up and treatment of patients. The aim of our study was to identify the optimal laboratory marker of androgen production by correlating the markers to the presence or grade of increased body hair as a clinical sign of hyperandrogenism. DESIGN: Prospective observational study. METHODS: A total of 62 women with acne were included into the study. The serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were evaluated. The index of free testosterone (IFT) and a new index of hyperandrogenism (IHA) were calculated. The monitored laboratory markers were correlated to the presence or grade of increased body hair using several statistical methods. RESULTS: The statistical significance of differences between the average levels of laboratory markers between hirsute and non-hirsute women decreased in the following order: IHA, androstenedione and DHEA. Of all the above laboratory markers, only increased IHA was present significantly more often in hirsute women. The significance of correlation between the grade of increased body hair and the tested variables decreased in the following order: IHA, IFT, DHEA, androstenedione, DHEAS and testosterone. CONCLUSIONS: The clinical marker of hyperandrogenism correlates most closely to IHA, reflecting the levels of all commonly determined androgens or androgen precursors and SHBG. Its simple calculation makes IHA a suitable tool for determining total production of androgens in clinical practice, especially in cases with borderline elevations of values. (+info)