Hyperandrogenism Syndrome Research Articles

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study.

Polycystic ovary syndrome (PCOS) is currently considered a predominantly hyperandrogenic syndrome. In theory, hyperandrogenism can be caused by high level of testosterone (T) as well as by enhanced androgen receptor (AR) activity. C-Terminal binding protein 1 antisense (CTBP1-AS) was a novel long noncoding RNA (lncRNA) to regulate AR activity. In this study, we found that expression level of CTBP1-AS in peripheral blood leukocytes was significantly higher in women with PCOS than that in controls after adjustment for age and body mass index (BMI). Individuals having higher expression of CTBP1-AS had significantly greater disease risk than those having lower expression. We also identified expression of CTBP1-AS as an independent risk factor for PCOS. A positive correlation was observed between the CTBP1-AS expression and the total T (TT) concentration either unadjusted or after adjusting for age, BMI, and homeostatic model assessment insulin resistance. Taken together, our current study presented the first evidence that the lncRNA CTBP1-AS, a novel AR modulator, is associated with PCOS in Chinese population and established the possibility that abnormal CTBP1-AS expression is a risk factor for PCOS and it is a predictor of variability in serum TT level in Chinese women with PCOS.

Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids.

Hyperandrogenic syndrome (HAS) is associated with insulin resistance (IR) and type 2 diabetes. Muscle IR in type 2 diabetes is linked with defects in mitochondrial oxidative capacity. In vivo muscle mitochondrial function has not been studied in HAS, especially in youth, who are early in the disease process. Our goal was to measure muscle mitochondrial oxidative function and peripheral IR in obese youth with HAS. Obese girls without HAS [n = 22, age 15(13,17) yr, BMI Z-score 2.05 ± 0.37] and with HAS [n = 35, age 15(14,16) yr, BMI Z-score 2.18 ± 0.30] were enrolled. Mitochondrial function was assessed with (31)phosphorus MR spectroscopy before, during, and after near-maximal isometric calf exercise, and peripheral IR was assessed with an 80 mU·m(-2)·min(-1) hyperinsulinemic euglycemic clamp. Girls with HAS had higher androgens [free androgen index 7.9(6.6,15.5) vs. 3.5(3.0,4.0), P < 0.01] and more IR [glucose infusion rate 9.4(7.0, 12,2) vs. 14.5(13.2,15.8) mg·kg lean(-1)·min(-1), P < 0.01]. HAS girls also had increased markers of inflammation including CRP, platelets, and white blood cell count and higher serum free fatty acids during hyperinsulinemia. Mitochondrial oxidative phosphorylation was lower in HAS [0.11(0.06,0.19) vs. 0.18(0.12,0.23) mmol/s, P < 0.05], although other spectroscopy markers of mitochondrial function were similar between groups. In multivariate analysis of the entire cohort, IR related to androgens, oxidative phosphorylation, and free fatty acid concentrations during hyperinsulinemia. These relationships were present in just the HAS cohort as well. Obese girls with HAS have significant peripheral IR, which is related to elevated androgens and free fatty acids and decreased mitochondrial oxidative phosphorylation. These may provide future options as targets for therapeutic intervention.

Personality and psychiatric disorders in women affected by polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among fertile women. Studies show reduced quality of life, anxiety, depression, body dissatisfaction, eating disorder, and sexual dysfunction, but the etiology of these disturbs remains still debated. The aim of our study is to verify whether this hyperandrogenic syndrome characterizes a strong psycho(patho)logical personality.Method: Sixty PCOS subjects (mean age 25.8 ± 4.7 years) were evaluated by anthropometric, metabolic, hormonal, clinical, and psychological parameters. After the certainty of the diagnosis of PCOS, the Rorschach test, according to Exner’s comprehensive system (CS) and the Millon Clinical Multiaxial Inventory-III (MCMI-III) were administered to each patient. The control group, on which the comparison was carried out, was composed by 40 healthy and aged compared women who were exclusively administered the Rorschach test according to CS.Results: MCMI-III evidenced axis II DSM-IV personality disorders [4.1% schizoid, depressive, sadistic, negativistic (passive–aggressive), and masochistic, 6.1% avoiding, 12.2% dependent, 20.4% histrionic, 16.3% narcissistic, 2.0% obsessive–compulsive], and axis I DSM-IV psychiatric disorders: 10.2% anxiety, 2.0% somatoform disorder and bipolar disorder, 16.3% major depressive disorder. Finally, we found 44.9% delusional disorder and 4.1% thought disorder. Rorschach test’s results show 53.1% reduced coping abilities and social skills, 55.1% depression, 30.6% perceptual distortion and cognitive slippage, 24.5% constantly alert and worry, 8.1% at risk for suicide, and finally about 50% of our patients had chronic stress.Conclusion: PCOS women have relevant personality and psychiatric disorders, when compared with normal subjects.

Syndrome of hyperandrogenism and thyroid status in women

The article presents a case of adrenogenital syndrome in women, accompanied by a rare manifestation – galactorrhea. A version of the pathogenesis of galactorrhea and a possibility of pathogenetic therapy are discussed.

Long-term efficacy of spironolactone on pain, mood, and quality of life in women with fibromyalgia: An observational case series

ObjectiveNo single drug is broadly efficacious in the long-term treatment of fibromyalgia syndrome (FMS). Spironolactone is known to ameliorate mood and tension headache or migraine in women with premenstrual syndrome or clinical signs of hyperandrogenism. In a case series of women with treatment resistant FMS spironolactone was therefore added to their medication, and they were observed for at least 12 months. Methods31 women with treatment-resistant FMS received spironolactone as add-on medication to various pain modulating drugs. 15 women responded to spironolactone and baseline data were compared with assessments over 12–14 months on treatment with spironolactone (ALDACTONE®) in dose range 100–200mg/day. The efficacy was evaluated by the fibromyalgia impact questionnaire (FIQ) total score and 8 FIQ subtests, a German mood inventory (BSKE-EWL), and further assessments of changes in relevant psychological and physical complaints. 16 women had no effect and stopped the treatment early. ResultsThe subsequent data refer to the 15 responders. The FIQ total score (maximal score=80) decreased from 56.6±10.0 at baseline to 17.1±11.9 (mean±SD) 12–14 months later, and pain intensity on an 11 point numeric rating scale (NRS) decreased from 8.8±1.6 to 2.6±1.9 (mean±SD). Similar changes in FIQ subscores were found for fatigue, morning tiredness, stiffness, anxiety, and depression. Emotional functioning consistently improved: positive mood from 20.0±5.4 to 37.7±5.4 (maximal score=48), and negative mood from 35.4±5.3 to 10.0±4.4 (maximal score=60) (each mean±SD) as well as other mental and physical dysfunctions including non-restorative sleep. All these changes at 4–6 weeks remained on this level for 11–13 months. The drug was well-tolerated and safe, no serious adverse effects were observed. Regular monitoring of serum potassium did not reveal hyperkalemia. All 15 women were able to reduce or discontinue concomitant drugs. ConclusionFifteen of 31 women with otherwise treatment-resistant FMS experienced a number of prolonged beneficial effects from spironolactone on their complex pain-condition. Implications and discussionWe hypothesise that spironolactone affects several central and peripheral neurotransmitter systems such as γ-aminobutyric acid (GABA) activity and dopaminergic transmission. The high rate of non-responsive patients underlines that FMS may represent several subgroups. Pain relief and improvement of associated FHS-symptoms and positive effects on additional diseases or dysfunctions give reasons for marked and sustained improvement in the quality of life.Well-controlled, double-blind, and randomised trials are necessary to confirm our potentially very important observations.

The efficacy of oral isotretinoin versus cyproterone compound in female patients with acne and the triad of cutaneous hyperandrogenism: A randomized clinical trial.

Background:SAHA (Seborrhea, Acne, Hirsutism and Androgenetic Alopecia) syndrome is a dermatologic disorder, with variant response to treatment. Triad of cutaneous hyperandrogenism included nodulocystic or severe acne, female pattern hair loss and hirsutism.Aim:The aim of this study is to compare the effectiveness of isotretinoin and cyproterone compound in the treatment of nodulocystic acne, in patients with SAHA syndrome or triad of cutaneous hyperandrogenism.Materials and Methods:30 female patients with SAHA syndrome were divided randomly into two groups. Group A was treated with cyproterone compound from day 5 of menstrual cycle onwards for 3 weeks and a week without it and group B received isotretinoin, with a dose of 0.75 mg/kg per day from the beginning of menses onwards for 4 months. The results were evaluated by a blind dermatologist using Acne Severity Index (ASI) score at baseline and monthly for 4 months.Results:Despite a continuous reduction in ASI score in both the groups, according to both physician (P = 0.63) and patient (P = 0.25) assessment, cyproterone compound was not statistically more effective than conventional treatment of nodulocystic acne at the end of the study. Side-effects were reported in patients in both groups, generally being mild and tolerable except in two subjects.Conclusion:This study indicates that cyproterone compound is not superior to isotretinoin in the treatment of nodulocystic acne in patient with SAHA syndrome or triad of cutaneous hyperandrogenism. Indeed, other studies are needed to evaluate the effect of cyproterone compound (regardless of androgen level) and isotretinoin in subjects with only nodulocystic acne.

Pathogenesis and treatment of acne at women’s hyperandrogenism syndrome

Аспе is one of most spread people’s disease and is characterized by the piloseboceial complex affection. Acne pathogenesis is a multifactor one, and the hyperandrogenism favors the disease development. The article highlights the acne pathogenesis, discusses methods of the endocrinologic examination and treatment of women’s hyperandrogenism.

Fibrillin-3 in the fetal ovary: can it contribute to polycystic ovary syndrome?

Evaluation of: Hatzirodos N, Bayne RA, Irving-Rodgers HF et al. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 25(7), 2256–2265 (2011).Polycystic ovary syndrome (PCOS), a prevalent hyperandrogenic and anovulatory infertility and metabolic syndrome in reproductive-aged women, is heritable but its etiology is unknown. An allele within an intron of fibrillin-3, a TGF-β pathway regulator, is reliably associated with PCOS, and the epigenome of an early gestation monkey model for PCOS implicates altered TGF-β signaling. In the recent article by Hatzirodos et al., and in contrast to prior findings in mature human ovaries, prominent and transient fibrillin-3 expression is found in human and bovine fetal ovarian stroma during early gestation. Such developmentally constrained ovarian expression of a gene associated with PCOS phenotype has considerable implications for fetal origins of PCOS in women. Further study is needed, however, to determine whether differential expression of fetal ovarian fibrillin-3 results in polycystic ovary morphology, and whether differential fetal expression of fibrillin-3 in non-ovarian tissues enables PCOS-like dysfunction.

Síndrome hiperandrogênica em mulher na pós-menopausa: relato de caso

Hyperandrogenic syndromes include diseases that manifest through an increased biological activity of androgens and that can originate from neoplastic or functional diseases. Androgen-secreting ovarian tumors represent about 1% of ovarian neoplasias. Steroid cell tumors are among the more rare types which account for less than 0.1% of all ovarian tumors. They are usually benign, of small dimensions and unilateral. We report here a rare case of a unilateral steroid cell tumor. A 60-year-old woman was seen after four months of evolution of hirsutism, clitoris hypertrophy and elevation of serum estradiol levels. Her total testosterone and 17-OH-progesterone levels were also increased.

Urinary Prostate-Specific Antigen is Elevated in Female Patients with Cushing’s Syndrome

Background: It has been demonstrated that the expression of prostate-specific antigen (PSA) is known to not be organ or gender specific but rather a steroid hormone mediated response, and the level of PSA is elevated in the serum of women with hyperandrogenic syndromes. The urinary profile of PSA in female subjects is less clear. We investigated the expression of urinary PSA in female subjects with Cushing’s syndrome and the relationship between urinary PSA and 2 steroid hormonal metabolites, 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroids (17-KS). Methods: We classified 97 female patients into 1 of 3 groups: Group A (n=37), patients with Cushing’s syndrome (n=30), or adrenocortical hyperplasia (n=7); Group B (n=29), patients with primary hyperaldosteronism (n=18) or pheochromocytoma (n=11); and Group C (n=31), patients with non-adrenal diseases, including hypertension (n=12) and Type 2 diabetes (n=19). Patients with Cushing’s syndrome or primary hyperaldosteronism were defined by clinical symptoms and laboratory confirmation. Patients with pheochromocytoma were defined by clinical symptoms, laboratory confirmation, and computed tomography or MRI. Patients with non-adrenal diseases were defined by a serum cortisol and plasma adrenocorticotropic hormone (ACTH) level within normal limits. Patients taking any medications in this category were excluded. Biochemical indicators related to the steroid hormonal metabolism, such as 17-OHCS, 17-KS, PSA, and creatinine (Cre) of 24-hour urine in these subjects were measured. The 17-OHCS, 17-KS, and PSA were all adjusted for 24-hour urinary Cre. Results: The 24-hour urinary PSA levels were significantly higher (P 0.01) and 17-KS (0.632, P>0.01), respectively. Conclusions: Urinary PSA was elevated in female patients with Cushing’s syndrome. It indicates that urinary PSA may be an additional parameter for a better definition of female patients suffering from Cushing’s syndrome.

Endocrine and Metabolic Adverse Effects of Psychotropic Drugs in Children and Adolescents

ABSTRACT Much as an increase in the use of psychotropic drugs is observed in children and adolescents over the last decade, the endocrine and metabolic side effects of these drugs can limit their use. Atypical antipsychotics can cause many side effects, which are not suitable for the developmental periods of children and adolescents, such as those related with thyroid, blood sugar, level of sex hormones, growth rate and bone metabolism. Children are under a more serious risk regarding the weight increasing effects of atypical antipsychotics and weight gain that is not proportionate with age is especially important due to the association between glucose or lipid abnormalities and cardiovascular mortality. Aripiprazole and ziprasidone are the least risky antipsychotic drugs when it comes to metabolic side affects. The antipsychotic drug that is associated with weight increase and diabetes in children and adolescents most is olanzapine. Even though there are no comparative long-term data concerning children, it is suggested by the currently available information that metabolic side effects including dyslipidemia and impaired glucose tolerance are at an alarming level when it comes to long-term treatment with antipsychotics. The most risky agents in terms of hyperglycemia and glucosuria development are olanzapine and clozapine. Use of risperidone and haloperidol should be undertaken with caution since it may bring about the risk of hyperprolactinemia. Among the antidepressants associated with weight loss and suppression of appetite are selective serotonin reuptake inhibitors, bupropion and venlafaxine. Thyroid functions can be affected by lithium, carbamazepine and valproate treatments. It is reported that the side effect most frequently associated with valproate is weight increase. The relationship between valproate treatment and the development of hyperandrogenism and polycystic ovary syndrome in young women should also be kept in mind.

Syndrome of hyperandrogenism in girls of pubertal age

Syndrome of hyperandrogenism in women is one of the commonest disease of the adult age. It is associated with a high risk of metabolic disturbances, cardiovascular disorders, and infertility. Taken together, these factors dictate the necessity of in-depth investigations of this pathology. At present, both etiology and pathogenesis of the syndrome of hyperandrogenism remain obscure. As a rule, its clinical manifestations become apparent at puberty. The present review summarizes the data on the development and clinical course of female hyperandrogenism with special reference to its occurrence, diagnostic tools, and therapeutic modalities in adolescent girls.

Hormonal and metabolic characteristics of premenopausal women with a history of preeclamptic pregnancy

To investigate whether women with a history of preeclampsia have more signs of hyperandrogenism and insulin resistance in the premenopausal period than women with history of normotensive pregnancies. Case-control study. University Hospital. Eighteen women with a history of preeclamptic first pregnancy and 19 women with prior normotensive first pregnancy studied 23-24 years after delivery. Diagnosis of metabolic syndrome was based on the International Diabetes Federation (IDF) criteria. Matsuda's whole-body insulin sensitivity index, serum concentrations of follicle-stimulating hormone (FSH), sex hormone-binding globulin, and total and free calculated testosterone were assessed. Polycystic ovary syndrome (PCOS) phenotype was defined using Rotterdam criteria. Insulin sensitivity, metabolic syndrome and signs of hyperandrogenism. Insulin sensitivity and total and free testosterone were similar in the two groups. However, in women with prior preeclampsia and FSH below the median, calculated free testosterone levels were higher than in women with prior preeclampsia and FSH above the median (median 13.4 range (8.0-22.5) vs. 7.1 (5.1-20.5), p = 0.03). Of the women with previous preeclampsia, 17% (3/18) had metabolic syndrome and 11% (2/18) PCOS, versus 11% (2/19) and 0% of the controls, respectively. In women with prior preeclampsia, premenopause was not associated with insulin resistance, but signs of hyperandrogenism were present if FSH was within a premenopausal level.

Proteomic profiles in hyperandrogenic syndromes

Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH) represent the most common causes of hyperandrogenism. Although the etiopathogeneses of these syndromes are different, they share many clinical and biochemical signs, such as hirsutism, acne, and chronic anovulation. Experimental data have shown that peripheral T-lymphocytes function as molecular sensors, being able to record molecular signals either at staminal and mature cell levels, or hormones at systemic levels. Twenty PCOS women and 10 CAH with 21-hydroxylase deficiency, aged between 18-35 yr, were studied. T-cells purified from all patients and 20 healthy donors have been analyzed by 2-dimensional gel electrophoresis. Silver-stained proteomic map of each patient was compared with a control map obtained by pooling protein samples of the 20 healthy subjects. Spots of interest were identified by peptide mass fingerprint. Computer analysis evidenced several peptidic spots significantly modulated in all patients examined. Some proteins were modulated in both syndromes, others only in PCOS or in CAH. These proteins are involved in many physiological processes as the functional state of immune system, the regulation of the cytoskeleton structure, the oxidative stress, the coagulation process, and the insulin resistance. Identification of the physiological function of these proteins could help to understand ethiopathogenetic mechanisms of hyperandrogenic syndromes and its complications.

Progesterone Activates a Progesterone Receptor Membrane Component 1-Dependent Mechanism That Promotes Human Granulosa/Luteal Cell Survival But Not Progesterone Secretion

Objective: We performed this study to test the hypothesis that variation in the lamin a/c gene (LMNA) contributes to milder phenotypes of insulin resistance, hyperandrogenism, and/or metabolic syndrome associated with polycystic ovary syndrome (PCOS). Research Design and Methods: We resequenced the coding region, flanking intronic, and proximal promoter regions of the lamin a/c gene in 43 women with PCOS with evidence of upper-body obesity (waist circumference 88 cm) and identified 56 variants, two of which were nonsynonymous substitutions (lmna11 exon1 E98D; lmna24 exon 7 R455C). We genotyped 53 single-nucleotide polymorphisms (44 identified through resequencing and nine included to maximize informativeness of the entire gene) in 624 index (PCOS) cases and 544 controls of European ancestry. We tested for association between these variants and PCOS. In a subset of individuals, we also tested for association with metabolic syndrome and quantitative traits (body mass index, waist circumference, total testosterone, dehydroepiandrosterone sulfate, fasting glucose and insulin, low-density lipoprotein, and TTG). Results: After correction for multiple testing, none of the variants showed significant evidence for association with PCOS, the metabolic syndrome, or any of the quantitative traits tested. Conclusions: Whereas these studies cannot exclude the role of genetic variation in the lamin a/c gene in isolated cases of PCOS, we can conclude that common variation in the lamin a/c gene does not contribute to the etiology of PCOS in women of European ancestry. Progesterone Activates a Progesterone Receptor Membrane Component 1-Dependent Mechanism That Promotes Human Granulosa/Luteal Cell Survival But Not Progesterone Secretion John J. Peluso, Xiufang Liu, Anna Gawkowska, and Erika Johnston-MacAnanny (J Clin Endocrinol Metab, published May 5, 2009, 10.1210/jc.2009-0147) ABSTRACT Context: Progesterone (P4) promotes its own secretion and the survival of human granulosa/luteal (GL) cells.Context: Progesterone (P4) promotes its own secretion and the survival of human granulosa/luteal (GL) cells. Objective: The objective of these studies was to determine whether progesterone receptor membrane component-1 (PGRMC1) mediates P4’s actions. Design: In vitro studies were conducted on GL cells from women undergoing in vitro fertilization and GL5 cells, which are derived from GL cells. Setting and Patients: GL cells were obtained from women undergoing fertility treatment at a university-based clinic and used for in vitro studies. Main Outcome Measures: PCR, Western blot, and immunocytochemistry were used to detect various progestin binding proteins. H-P4 binding kinetics were assessed on partially purified PGRMC1. Apoptosis was determined after culture by either TUNEL or DAPI staining. P4 was measured by an ELISA assay. PGRMC1 was depleted using small interfering RNA. Results: GL and GL5 cells expressed several P4 binding proteins including the nuclear progesterone receptor (PGR), progestin/ adipoQ receptors (PAQR 7, 8, and 5) and PGRMC1. Ligand binding studies revealed that both P4 and the progestin, R5020, bound PGRMC1 with an EC50 of approximately 10 nM. Interestingly, P4 inhibited apoptosis at concentrations in the 10 nM range, whereas R5020 stimulated P4 secretion at concentrations of at lease 16 M. Depleting PGRMC1 attenuated P4’s antiapoptotic action but failed to influence R5020-induced P4 secretion. T R A N S L A T I O N A L H I G H L I G H T S F R O M J C E M

Hair Loss in Women

Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a progestogen. Antiandrogens such as cyproterone acetate, always accompanied by tricyclic contraceptives, are the best choice of antiandrogens to use in patients with FPHL. Gonadotropin-releasing hormone agonists such as leuprolide acetate suppress pituitary and gonadal function through a reduction in luteinizing hormone and follicle-stimulating hormone levels. Subsequently, ovarian steroid levels also will be reduced, especially in patients with polycystic ovary syndrome. When polycystic ovary syndrome is associated with insulin resistance, metformin must be considered as treatment. Hyperprolactinemic SAHA and alopecia of pituitary hyperandrogenism should be treated with bromocriptine or cabergoline. Postmenopausal alopecia, with previous high levels of androgens or with prostatic-specific antigen greater than 0.04 ng/mL, improves with finasteride or dutasteride. Although we do not know the reason, postmenopausal alopecia in normoandrogenic women also improves with finasteride or dutasteride at a dose of 2.5 mg per day. Dermatocosmetic concealment with a hairpiece, hair prosthesis as extensions, or partial hairpieces can be useful. Lastly, weight loss undoubtedly improves hair loss in hyperandrogenic women.

Body mass index and ovarian function are associated with endocrine and metabolic abnormalities in women with hyperandrogenic syndrome

The aim of this study was to evaluate associations of clinical features, such as hirsutism, polycystic ovaries (PCOs), ovulatory dysfunction, and body mass index (BMI) > or =25 kg/m(2), with metabolic abnormalities in hyperandrogenic women. Hirsutism was based on the modified Ferriman-Gallwey score. Ovulatory function was classified as eumenorrhea, oligomenorrhea and amenorrhea, and PCOs were assessed using the ultrasound criteria recommended in the Rotterdam definition. An oral glucose tolerance test was performed. Different insulin resistance (IR) indices were calculated. Hirsute women had significantly higher BMI, DHEA sulfate (DHEAS) and free androgen index (FAI), and significantly lower values for sex hormone-binding globulin (SHBG). Women with amenorrhea were younger in comparison to women with eumenorrhea and had significantly higher values for fasting insulin (FI) and 1- and 2-h insulin levels; lower values for glucose to insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and SHBG. Women with PCO had significantly higher levels of LH and low-density lipoprotein (LDL), whereas high-density lipoprotein (HDL) levels were significantly lower. Women with a BMI > or =25 kg/m(2) had significantly higher values for age, fasting plasma glucose, FI, and 1- and 2-h glucose and insulin levels, homeostatic model for assessment of IR (HOMA-IR), homeostatic model for assessment of B-cell function (HOMA-B), and FAI, whereas their GIR, insulin sensitivity index, QUICKI, SHBG, and HDL were significantly lower. In women with hyperandrogenic syndrome, BMI> or =25 kg/m(2) and amenorrhea appear to be associated with severe endocrine and metabolic abnormalities.

Polycystic Ovary Syndrome and Oocyte Developmental Competence

Folliculogenesis is a complex process, in which multiple endocrine and intraovarian paracrine interactions create a changing intrafollicular microenvironment for appropriate oocyte development. Within this microenvironment, bidirectional cumulus cell-oocyte signaling governs the gradual acquisition of developmental competence by the oocyte, defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These regulatory mechanisms of follicle growth, controlled in part by the oocyte itself, are susceptible to derangement in polycystic ovary syndrome (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism, insulin resistance, and paracrine dysregulation of follicle development. Consequently, only a subset of PCOS patients experience reduced pregnancy outcome after ovarian stimulation for in vitro fertilization. Recent data implicate functional associations between endocrine/paracrine abnormalities, metabolic dysfunction, and altered oocyte gene expression with impaired oocyte developmental competence in women with PCOS. Therefore, an understanding of how developmentally relevant endocrine/paracrine factors interact to promote optimal oocyte developmental is crucial to identify those PCOS patients who might benefit from long-term correction of follicle growth to improve fertility, optimize follicular responsiveness to gonadotropin therapy, and enhance pregnancy outcome by in vitro fertilization.

The investigation and management of severe hyperandrogenism pre- and postmenopause: Non-tumor disease is strongly associated with metabolic syndrome and typically responds to insulin-sensitization with metformin

Background. An androgen-secreting tumor needs to be excluded in any woman with severe hyperandrogenism. We sought to characterize patients with biochemical hyperandrogenism in respect of tumor versus non-tumor etiologies, explore possible links between non-tumor hyperandrogenism and metabolic syndrome, and ascertain whether metformin therapy can elicit diagnostic reductions in serum testosterone (T).Patients and methods. Seven-year retrospective study of all women referred to a university hospital endocrinology service with baseline T >4.0 nmol/l. Dataset comprised age, menopausal status, body mass index (BMI), presence/absence of hypertension, diabetes, acanthosis or dyslipidemia, along with changes in BMI and serum T following intervention with metformin, oophorectomy or dexamethasone. Non-tumor hyperandrogenism was defined by normalization of serum T or >40% reduction from baseline.Results. Four out of 18 cases had adrenal carcinoma that was clinically obvious at initial presentation (one virilized, three Cushingoid). The remaining 14 were characterized by metabolic syndrome (BMI: 39.9 ± 8.1 kg/m2), serum T of 6.14 ± 1.6 nmol/l, and nadir serum T following intervention of 2.2 ± 1.04 nmol/l. Diagnostic reductions in serum T occurred in 11/12 patients treated with metformin.Conclusions. Non-tumor hyperandrogenism with markedly elevated serum T and associated metabolic syndrome is a defined clinical entity in postmenopause as well as in premenopausal women with polycystic ovary syndrome. This has hitherto been only sparsely documented in the published literature. A fall in serum T level in response to insulin-sensitizing therapy with metformin and lifestyle change may be a reassuring indicator that such women are highly unlikely to harbor an androgen-secreting tumor.

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

The aim of the present study is to assess insulin resistance (IR) in women with hyperandrogenic syndrome, which was suggested to replace the term polycystic ovary syndrome by the Androgen Excess Society, and to evaluate whether sex hormone-binding globulin (SHBG) can be used as a predictive marker of IR in hyperandrogenic women. Clinical, metabolic, and endocrine parameters were measured, and an oral glucose tolerance test was carried out. The women were classified as IR group or non-IR group, in accordance with defined cutoff points for the homeostatic model assessment of IR (HOMA-IR) at > or =2.5, the quantitative insulin sensitivity check index at < or = 0.33, and the Matsuda insulin sensitivity index (ISI) at < or = 5. The women classified as having IR had a significantly higher body mass index (BMI) and free androgen index (FAI) and showed significantly lower SHBG and high-density lipoprotein (HDL) levels, regardless of the indices used. However, with the Matsuda ISI, generally more women were diagnosed as having IR, and this group had significantly higher total testosterone and triglyceride values, as well as a higher incidence of hirsutism. Women who were classified as being insulin resistant using insulin sensitivity indices showed significantly higher BMI and FAI values and lower SHBG and HDL levels. However, the Matsuda ISI may be more favorable for identifying IR in hyperandrogenic women. SHBG may serve as a predictive marker of IR in these women, particularly in those who are obese.