0000000000018991
AUTHOR
Rogerio A. Lobo
Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet.
BACKGROUND The study aim was to determine differences in body mass in two populations of women (USA and Italy) with polycystic ovary syndrome (PCOS), and to assess the effect of diet on body mass and cardiovascular risk factors. METHODS Pools of women with PCOS from the USA (n = 343) and Italy (n = 301), seen between 1993 and 2001, were available for assessment. From these populations, 20 women who were seen consecutively in 2001 at each site had detailed analyses of diet and cardiovascular risk factors. RESULTS In the entire group, American women had a significantly higher body mass compared with Italian women (P < 0.01). Also, the 20 women consecutively evaluated in the USA had a signific…
The importance of diagnosing the Polycystic Ovary Syndrome
The polycystic ovary syndrome (PCOS) is an extremely common disorder that occurs in 4% to 7% of women of reproductive age. Although PCOS is known to be associated with reproductive morbidity and increased risk for endometrial cancer, diagnosis is especially important because PCOS is now thought to increase metabolic and cardiovascular risks. These risks are strongly linked to insulin resistance and are compounded by the common occurrence of obesity, although insulin resistance and its associated risks are also present in nonobese women with PCOS. Women with PCOS are at increased risk for impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Cardiovascular disease is believ…
Ovine corticotropin-releasing factor and dexamethasone responses in hyperandrogenic women
Eighteen hyperandrogenic, hirsute women received ovine corticotropin-releasing factor (CRF; 1 microgram/kg) as well as a dexamethasone (DEX) suppression test. Nine of the 18 hirsute women exhibited increased DEX sensitivity. Plasma adrenocorticotropic hormone (ACTH) responses after ovine CRF were significantly lower in the DEX-sensitive subgroup, but serum androstenedione was higher. Baseline serum androgen levels could not predict DEX responses. A significant negative correlation existed between the suppression of androgens after DEX and the increase in ACTH after ovine CRF. The suppression of androgen correlated with the ratio of the increase in androgen to the increase in ACTH after ovin…
Physiological Estrogen Replacement May Enhance the Effectiveness of the Gonadotropin-Releasing Hormone Agonist in the Treatment of Hirsutism
GnRH agonists (GnRH-A) have been used for the treatment of hirsutism in women with ovarian hyperandrogenism. However, significant side-effects, including vasomotor symptoms and bone loss, have prevented the long term use of this therapy. In this study, we evaluated the effects of low dose (physiological) estrogen replacement on the side-effects and clinical and hormonal parameters of 22 hirsute women with ovarian hyperandrogenism when treated with a long-acting GnRH-A, Decapeptyl. Ten patients with Ferriman-Gallwey (FG) scores averaging 13.4 +/- 1.5 were randomly assigned to be treated with Decapeptyl alone (3.75 mg, im, every 28 days for 6 months), and 12 other patients with FG scores aver…
Characterization of metabolic changes in the phenotypes of women with polycystic ovary syndrome in a large Mediterranean population from Sicily.
Objective To better characterize the metabolic alterations in various phenotypes of polycystic ovary syndrome (PCOS) in a large homogeneous (Sicilian) Mediterranean population with a low prevalence of obesity. Design Retrospective study. Patients A total of 1215 consecutively evaluated women with PCOS divided into four Rotterdam phenotypes (A, B, C and D) and in 108 matched ovulatory, nonhyperandrogenic women. Measurements BMI, fasting glucose, total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol and an oral glucose tolerance test. Results The overall prevalence of obesity was 31%, metabolic syndrome 6.6%, diabetes 2.1%, altered glucose metabolism 13.1%, and abnormal lipid pro…
Mullarian-inhibiting substance reflects ovarian findings in women with polycystic ovary syndrome better than does inhibin-B
Objective: To investigate Müllerian-inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS), as well as relationships to ovarian morphology, levels of inhibin B, and other reproductive hormones. Design: Prospective clinical study. Setting: Academic endocrinology centers in Palermo, Italy and New York. Patient(s): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls. Intervention(s): Fasting blood was obtained in all subjects in the early follicular phase (days 5–6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed. Main Out…
The diagnosis of polycystic ovary syndrome in adolescents
In women, the definition of polycystic ovary syndrome (PCOS) has become broad and includes several possible phenotypes. Because several features of PCOS may be in evolution in adolescents, we suggest that only firm criteria should be used to make a diagnosis of PCOS during adolescence. Hyperandrogenism, oligomenorrhea, and ovarian morphology change during adolescence and are discussed individually. Adolescents with incomplete criteria for a firm diagnosis of PCOS should be followed up carefully and may be diagnosed at a later time.
Pituitary-adrenal responses to corticotropin-releasing factor in late onset 21-hydroxylase deficiency
Intravenous corticotropin-releasing factor (CRF) and adrenocorticotropin hormone (ACTH) were administered in patients with adult onset 21-hydroxylase deficiency to compare their diagnostic capability as well as to investigate hypothalamic-pituitary-adrenal function in this disorder. Responses of 17-hydroxyprogesterone, which were markedly elevated compared with controls, were identical with CRF and ACTH. However, intravenous ACTH resulted in higher androstenedione levels in comparison to CRF. Adrenocorticotropin hormone also resulted in decreased cortisol responses, confirming a defect in steroidogenesis, a finding that was not evident with CRF. Plasma ACTH responses to CRF were similar in …
Altered Regulation of Insulin-Like Growth Factor Binding Protein-I in Patients With Polycystic Ovary Syndrome
Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women. We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 ± 1 and 22 ± 1 years, respectively). All subjects were studied after an overnight fast between days 5–8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of …
The ratio of androstenedione: 11β-hydroxyandrostenedione is an important marker of adrenal androgen excess in women
To determine if the ratio of serum androstenedione (A):11 beta-hydroxyandrostenedione (OHA) would be helpful in differentiating adrenal from ovarian hyperandrogenism.Prospective study of outpatients being evaluated for hyperandrogenism.Normal women (n = 27), those with hyperandrogenic chronic anovulation (n = 25), and 7 with adult onset of congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency.Fasting serum between 8:00 A.M. and 9:00 A.M. Patients with hyperandrogenic chronic anovulation and CAH received dexamethasone (DEX) 2 mg for 7 days.Serum testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), A, and 11 beta-OHA by radioimmunoassay.Serum 11 beta-OHA an…
Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin.
Objective: Metabolic syndrome (MBS) is a significant health care problem in postmenopausal women and is driven largely by obesity. We wished to assess the prevalence of insulin resistance (IR), diagnosed using practical methods, and whether several adipocyte factors (adiponectin, leptin, resistin) or the gastric peptide ghrelin, associated with cardiovascular risk, might be abnormal and may relate to IR. Study design: We evaluated 37 obese postmenopausal women with MBS and 34 matched obese premenopausal controls, as well as 14 non-obese premenopausal controls. We measured fasting glucose and insulin, performed 75g 2 hr oral glucose tolerance and intravenous insulin tolerance tests to assess…
Does metformin induce ovulation in normoandrogenic anovulatory women?
Objective: This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyperandrogenism and classic polycystic ovary syndrome. Study design: A randomized trial of metformin (1500 mg daily) and placebo in 24 anovulatory women was undertaken for 3 months. Assessments of changes in hormone levels and insulin sensitivity were carried out. Abnormal ormonal values were defined by levels exceeding the range in normal ovulatory controls. Results: Anovulatory women had normal androgen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls. Over 3 months, there were 16 ovulatory cycles…
Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women
Objective To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism. Design Prospective outpatient study of 36 hyperandrogenic women and controls divided into groups based on the presence or absence of significant hirsutism and the presence or absence of moderate to severe acne. Serum levels of adrenal and ovarian derived androgens were elevated but similar in all patient groups. Interventions Measurement of serum androgens including metabolites of 5 α -reductase activity: 3 α -androstanediol glucuronide and sulfate and androsterone (A) glucuronide and sulfate. Results 3 α -androstanediol glucuronide and sulfate were e…
Does ovarian blood flow distinguish between ovulatory and anovulatory patients with polycystic ovary syndrome?
The purpose of this study was to determine whether parameters of ovarian blood flow distinguish between women with polycystic ovary syndrome (PCOS) who ovulate and those who are anovulatory.This was a prospectively enrolled trial, carried out as a cross-sectional comparison of 12 ovulatory patients with PCOS and 20 matched subjects with classic PCOS and 10 healthy control subjects. Hormonal parameters and ovarian blood flow by color flow Doppler imaging were obtained in the early follicular phase.Characteristic elevations in luteinizing hormone (LH) and androgens were found in both groups with PCOS compared with control groups. Women with anovulatory PCOS had high insulin levels and lower Q…
Correlates of increased lean muscle mass in women with polycystic ovary syndrome.
ObjectiveMuscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed.DesignProspective investigation.MethodsNinety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated.ResultsIn PCOS, waist circumference and insulin were high…
Increasing adiposity in normal ovulatory women affects adipocytokine expression in subcutaneous and visceral abdominal fat
Abstract Objective To determine which adipocytokines are differentially expressed as a function of body mass index (BMI), to compare expression of adipocytokines in abdominal subcutaneous and omental fat, and to correlate these findings with serum levels, BMI, and parameters of insulin resistance. Methods Serum and subcutaneous (sc) and omental (om) tissue were obtained from lean and obese ovulatory women undergoing gynecologic surgery. We determined adipocytokine expression in sc versus om abdominal fat and related this to increasing BMI. Results Serum leptin was higher and adiponectin lower in overweight subjects. Adipocytokines had higher expression in sc abdominal versus om adipose tiss…
AMH MEASUREMENT VERSUS OVARIAN ULTRASOUND IN THE DIAGNOSIS OF POLYCYSTIC OVARY SYNDROME IN DIFFERENT PHENOTYPES.
This study was designed to assess the value of serum anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) in various phenotypes and to assess ovarian ultrasound parameters.We performed a retrospective matched controlled study of 113 females with various PCOS phenotypes and 47 matched controls. The diagnostic utility of AMH measurement and ovarian ultrasound were compared. Using receiver operating characteristic (ROC) curve analyses, the threshold for AMH (4.7 ng/mL) and ultrasound parameters (follicle number per ovary [FNPO]22 and ovarian volume [OV]8 cc) were established.In the entire cohort, AMH had a low sensitivity of 79%; while FNPO and OV were 93% and 68%,…
Reassessment of adrenal androgen secretion in women with polycystic ovary syndrome
Objective To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary syndrome (PCOS). Methods Thirty women with PCOS and ten ovulatory controls were evaluated. Serum dehydroepiandrosterone (DHEA) sulfate and 11β-hydroxyandrostenedione were measured before and after 3 and 6 months of GnRH agonist (GnRH-A) therapy. All controls and 15 women with PCOS received intravenous ACTH before and after GnRH-A therapy. Results Twenty-one (70%) of the women with PCOS had elevations of DHEA sulfate, and 16 (53%) had elevations in 11/3-hydroxyandrostenedione. Only two women with PCOS had normal values of both adrenal androgens. After GnRH-A therapy, only 11 subjects (37%…
A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women
Summary objectives To compare the relative effectiveness of two newer antiandrogens (flutamide and finasteride) with cyproterone acetate (CPA), at both low and high doses in the treatment of moderate to severe acne in hyperandrogenic women. subjects and design Forty-eight hyperandrogenic women were prospectively randomized to the following treatments for 1 year: CPA 2 mg with 35 µg ethinylestradiol; CPA 50 mg with 25 µg ethinylestradiol (reverse sequential regimen); flutamide 250 mg daily; and finasteride 5 mg daily. Assessment of Cook scores was the primary end-point of the trial. Blood for androgens was obtained at baseline in these women and 30 ovulatory age-matched controls. results Ser…
Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome
To determine the prevalence of insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) using baseline fasting blood measurements of glucose and insulin. Prospective clinical study. Academic endocrinology unit in Palermo, Italy. Two hundred and sixty-seven women with PCOS, consecutively evaluated, and 50 consecutively selected ovulating controls. Fasting blood was obtained for glucose and insulin measurements from all women. For 60 women with PCOS and 20 controls an insulin tolerance test (ITT) was also performed. Assessment of normal and abnormal values for fasting insulin, glucose/insulin ratio, and the calculated indices of the homeostasis model assessment (HOMA), quantitat…
Assessment of Cardiovascular Risk and Prevention of Cardiovascular Disease in Women with the Polycystic Ovary Syndrome: A Consensus Statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society
Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD.An expert panel in PCOS and CVD reviewed literature and presented recommendations.Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, co…
Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women
Abstract Objective: Although serum leptin is principally influenced by body mass, to understand the role of insulin and androgens in the regulation of serum leptin in normal weight women. Design: Prospective observational study. Setting: Academic practice in reproductive endocrinology. Patient(s): Twenty-one women with polycystic ovary syndrome (PCOS) of normal body weight, 8 apparently normal women with polycystic-appearing ovaries (PAO), and 21 normal women. Intervention(s): Fasting blood levels of luteinizing hormone, follicle-stimulating hormone, testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), insulin, insulin growth factor–binding protein-1 (IGFBP-1), and leptin. M…
Treatment of hyperandrogenic alopecia in women
Many women with androgenic alopecia have normal circulating androgen levels. Increased scalp sensitivity to androgens may account for these cases. Even when androgen levels are increased, no particular pattern has emerged. Classical anti-androgen measures have proved disappointing, in contrast to the results obtained in women with hirsutism or acne. This study evaluated flutamide and finasteride in 36 premenopausal, hyperandrogenic women presenting with androgenic alopecia. Frontal hair thinning was assessed in photos of the frontoparietal region using the Ludwig grading system. Thirty ovulatory women matched for age and body weight served as a control group. Groups of 12 subjects received …
Subcutaneous and omental fat expression of adiponectin and leptin in women with polycystic ovary syndrome
Objective To assess message expression of adiponectin and leptin in visceral and SC fat in women with polycystic ovary syndrome (PCOS) and in control women. Design Prospective clinical trial. Setting Academic medical centers in Mexico City, Mexico and New York, New York. Patient(s) Women with PCOS and control women. Intervention(s) Surgical biopsies of visceral (omental) and subcutaneous (SC) adipose tissue, fasting blood samples, and ultrasound measurements of visceral and SC fat. Main Outcome Measure(s) Messenger RNA assessment of adiponectin and leptin in adipose tissue samples; serum measurements of adiponectin, leptin, glucose, insulin, and hormone levels; measurements of fat quantity …
Consensus On Women'S Health Aspects Of Polycystic Ovary Syndrome (Pcos)
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females with a high prevalence. The etiology of this heterogeneous condition remains obscure and its phenotype expression varies. Two, widely cited, previous ESHRE/ASRM-sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008). The present third PCOS consensus paper summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, preg…
Ovarian size and blood flow in women with polycystic ovary syndrome (PCOS) and their correlations with some endocrine parameters
Objective: To determine how common polycystic ovarian morphology may be in women given the clinical diagnosis of polycystic ovary syndrome (PCOS) based on chronic anovulation and hyperandrogenism and whether certain hormonal factors correlate with ovarian morphology and blood flow. Design: Prospective study. Setting: Two academic endocrinology centers in Italy. Patient(s): Three hundred twenty-six women with PCOS and 50 age-matched and weight-matched ovulatory women. Intervention(s): Ultrasound assessment of ovarian morphology in patients and controls and ovarian blood flow and fasting hormone levels in a subset of 50 patients and matched controls. Main Outcome Measure(s): Ovarian morpholog…
Alterations in the sensitivity of serum insulin-like growth factor 1 and insulin-like growth factor binding protein-3 to octreotide in polycystic ovary syndrome
Objective To determine if the somatostatin analog, octreotide, affects insulin and related peptides and, hence, androgen levels differently between polycystic ovary syndrome (PCOS) patients and controls. Design Prospective controlled trial. Setting Reproductive endocrinology clinic of our medical center. Patients Eleven women with PCOS and six matched ovulatory controls. Interventions Octreotide (100 μg) was administered subcutaneously in the midfollicular phase. Serum was obtained before and at 60, 120, 180, and 240 minutes after octreotide. Main Outcome Measures Fasting insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), T, androstenedion…
Not all women diagnosed with PCOS share the same cardiovascular risk profiles
Although definitive and confirmatory data are lacking, women with polycystic ovary syndrome (PCOS) are considered to be at increased risk for cardiovascular and metabolic disease. In recent years, the diagnosis of PCOS has broadened considerably to result in several phenotypes. Here we review the evidence for cardiovascular and metabolic risks in PCOS in the classic disorder and the various phenotypes. We conclude that not all women with PCOS should be considered as being similar in terms of cardiovascular risk profiles.
Evidence for altered adipocyte function in polycystic ovary syndrome.
Background: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. Methods: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin,…
Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome.
Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin.
Ovarian suppression reduces clinical and endocrine expression of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Objective To determine the effectiveness of GnRH-agonist (GnRH-a) treatment in women with late onset congenital adrenal hyperplasia. Design Prospective assessment of GnRH-a treatment in six women with documented late-on-set congenital adrenal hyperplasia who were not preselected. Comparisons were made to previous responses in the same patients receiving dexamethasone. Eight age- and weight-matched ovulatory women served as controls. Setting Academic medical center. Intervention Baseline blood determinations before and after IV ACTH, before and after 6months of GnRH-a treatment. Estrogen and progestin replacement was begun in all women after the 3rd month of treatment. Main Outcome Measures …
Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee.
OBJECTIVE To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss (FPHL), a common form of hair loss in women that is characterized by the reduction of hair density in the central area of the scalp, whereas the frontal hairline is generally well conserved. PARTICIPANTS An expert task force appointed by the Androgen Excess and PCOS Society, which included specialists from dermatology, endocrinology, and reproductive endocrinology. DESIGN Levels of evidence were assessed and graded from A to D. Peer-reviewed studies evaluating FPHL published through December 2017 were reviewed. Crite…
Alterations in androgen conjugate levels in women and men with alopecia.
Objective To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists. Design Prospective study in various groups of women and men. Setting Reproductive Endocrine Clinic at our university medical center. Patients Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgeni…
Endothelial dysfunction in PCOS. role of obesity and adipose hormones
PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponect…