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Ricardo Azziz

Publications and source records attributed to Ricardo Azziz.

At least 19 recordsLinked to original sources
PubMed2026

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗
PubMed2006

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California. PATIENT(S): Participants included 285 white women with PCOS and 187 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes. RESULT(S): The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T. CONCLUSION(S): Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.

Adolescent↗
PubMed2006

Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement.

OBJECTIVE: The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. PARTICIPANTS: The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. EVIDENCE: Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. CONSENSUS PROCESS: The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. CONCLUSIONS: Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.

Chemistry, Clinical↗
PubMed2006

Heritability of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their sisters.

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) secretion is an inherited trait in PCOS and that serum DHEAS concentrations, as a marker of AA secretion, will be correlated between women with PCOS and their sisters. DESIGN: Prospective case-control. SETTING: Tertiary care center. PATIENT(S): Sixty-two PCOS probands and 69 sisters. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DHEAS concentrations and clinical phenotypes were obtained. Familial correlation between sisters was estimated. A variance components model was used to estimate the heritability (h(2)) of the DHEAS levels. Body mass index (BMI)-adjusted DHEAS levels were used in all of the analyses. RESULT(S): There was no difference in age between the proband and sister groups (28.7 +/- 8.1 years vs. 28.0 +/- 8.8 years, P=.65), and probands had higher BMI values (33.4 +/- 7.6 kg/m(2) vs. 27.9 +/- 7.0 kg/m(2), P<.001). Sixteen of the 69 (23.2%) sisters were affected by PCOS. The sister-sister correlation of DHEAS level was 0.28 +/- 0.12 for the whole group (P<.05), and this correlation was higher, at 0.38 +/- 0.14 (P< or =.05), after excluding 31% of the affected sisters and 34% of the unaffected sisters who received hormonal therapy at or within 3 months of the time of the study. The h(2) estimates of DHEAS were 0.43 (P=.037) and 0.44 (P=.062) when all sisters and only untreated sisters, respectively, were included in the analysis. CONCLUSION(S): The correlation of serum DHEAS levels between PCOS probands and their sisters suggests a familial component in the regulation of DHEAS levels and possibly AA production in PCOS. The h(2) estimates of 0.43-0.44 for BMI-adjusted DHEAS suggest that genetic factors account for between 40% and 50% of the overall variation in DHEAS levels in these women. Our results support the hypothesis that circulating AA levels represent an inherited trait in PCOS.

Adult↗
PubMed2006

Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.

OBJECTIVE: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. PARTICIPANTS: Participants included expert investigators in the field. EVIDENCE: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. CONSENSUS PROCESS: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. CONCLUSIONS: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.

Androgens↗
PubMed2006

Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women.

CONTEXT: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. DESIGN: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: A total of 287 White women with PCOS and 187 controls participated. MAIN MEASUREMENTS: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. RESULTS: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. CONCLUSIONS: This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

Reproducibility of the adrenal androgen response to adrenocorticotropic hormone stimulation.

Eleven healthy, eumenorrheic, nonhirsute women underwent acute adrenal stimulation testing at monthly intervals in order to measure the responses of cortisol (F), DHEA, and androstenedione, to a 60-minute acute stimulation with 1.0 mg ACTH (1-24). When the women were subdivided into either high or low responders to ACTH stimulation (relative to the group median), the relative adrenocortical response within individual subjects was found to be highly constant over time.

Adrenal Glands↗
PubMed2006

Difference in dietary intake between women with polycystic ovary syndrome and healthy controls.

OBJECTIVE: To test the hypothesis that the dietary intake and dietary composition of women with polycystic ovary syndrome (PCOS) is associated with indices of glycemic status. We hypothesized that women with PCOS would consume a diet higher in total energy, fat, and specific foods with a high glycemic index than would healthy, control-group women and that dietary composition would be associated with indices of insulin resistance and secretion among women with PCOS. DESIGN: Cohort study. SETTING: Research center on a university campus. PATIENT(S): Thirty women with PCOS and 27 healthy, age-, race-, and body mass index (BMI)-matched control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Nutrient intake data were collected from a food questionnaire and a 4-day food record. Fasting sera were analyzed for concentrations of insulin and glucose; estimates of insulin resistance were calculated. RESULT(S): Consumption of total energy, macronutrients, micronutrients, and high glycemic index foods was similar between the groups. However, the PCOS group consumed significantly more white bread (7.9 +/- 4.4 vs. 5.5 +/- 2.9 servings over 4 days) and tended to consume more fried potatoes than did the control group (1.0 +/- 1.5 vs. 0.4 +/- 0.7 servings over 4 days). The PCOS group had a significantly greater fasting insulin concentration (22.5 +/- 14.9 vs. 15.1 +/- 8.3 muIU/mL) and a significantly lower glucose-to-insulin ratio (4.7 +/- 2.1 vs. 7.6 +/- 5.2) than the control group. Within the PCOS group, HOMA-IR and HOMA-%beta-cell function were significantly associated with BMI. The HOMA-IR, HOMA-%beta-cell, fasting insulin, and glucose-to-insulin ratio were not positively associated with measures of diet composition. CONCLUSION(S): Compared with matched control women, women with PCOS exhibited a dietary pattern that was marked by consumption of a greater amount of specific foods with a high glycemic index; however, diet composition was not associated with the greater fasting insulin concentration or with lower glucose-to-insulin ratio that was observed in the PCOS group.

Adult↗
PubMed2006

Family size in women with polycystic ovary syndrome.

Given that polycystic ovary syndrome (PCOS) is associated with oligo-ovulatory infertility and is an inherited trait, we hypothesized that the families of patients with PCOS are smaller than those of matched controls. However, our study of 106 white patients with PCOS, ages 18-45, and 53 healthy eumenorrheic nonhirsute white controls did not indicate a difference in family size between the groups; these results have important implications for the design of prospective studies of the heritability and genetics of PCOS.

Adolescent↗
PubMed2006

Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism.

CONTEXT: Hirsutism (i.e. facial and body terminal hair growth in a male-like pattern in women) is the principal clinical sign of hyperandrogenism, although its definition remains unclear. OBJECTIVE: The purposes of the present study were to define 1) the degree of facial and body terminal hair, as assessed by the modified Ferriman-Gallwey (mFG) score, in unselected women from the general population; 2) the effect of race (Black and White) on the same; and 3) the normative cutoff values. DESIGN AND SETTING: We conducted a prospective observational study at a tertiary academic medical center. PATIENTS/PARTICIPANTS: Participants included 633 unselected White (n = 283) and Black (n = 350) women presenting for a preemployment physical exam. INTERVENTIONS: Interventions included history and physical examination. MAIN OUTCOME MEASURES: Terminal body hair growth was assessed using the mFG scoring system; nine body areas were scored from 0-4 for terminal hair growth distribution. RESULTS: The mFG scores were not normally distributed; although cluster analysis failed to identify a natural cutoff value or clustering of the population, principal component and univariate analyses denoted two nearly distinct clusters that occurred above and below an mFG value of 2, with the bulk of the scores below. Overall, an mFG score of at least 3 was observed in 22.1% of all subjects (i.e. the upper quartile); of these subjects, 69.3% complained of being hirsute, compared with 15.8% of women with an mFG score below this value, and similar to the proportion of women with an mFG score of at least 8 who considered themselves to be hirsute (70.0%). Overall, there were no significant differences between Black and White women. CONCLUSIONS: Our data indicate that the prevalence and degree of facial and body terminal hair growth, as assessed by the mFG score, is similar in Black and White women and that an mFG of at least 3 signals the population of women whose hair growth falls out of the norm.

Adult↗
PubMed2006

Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature.

CONTEXT: Polycystic ovary syndrome (PCOS) is defined most commonly according to the proceedings of an expert conference sponsored by the National Institutes of Health (NIH) in April 1990, which noted the disorder as having 1) hyperandrogenism and/or hyperandrogenemia, 2) oligoovulation, and 3) exclusion of known disorders. Alternatively, another expert conference held in Rotterdam in May 2003 defined PCOS, after the exclusion of related disorders, by two of the following three features: 1) oligo- or anovulation, 2) clinical and/or biochemical signs of hyperandrogenism, or 3) polycystic ovaries. In essence, the Rotterdam 2003 expanded the NIH 1990 definition creating two new phenotypes: 1) ovulatory women with polycystic ovaries and hyperandrogenism, and 2) oligoanovulatory women with polycystic ovaries, but without hyperandrogenism. OBJECTIVE: The objective of this study was to ascertain the validity of using the Rotterdam 2003 criteria rather than the NIH 1991 criteria for the diagnosis of PCOS. INTERVENTION(S): Interventions included the use of the Rotterdam 2003 criteria for diagnosing PCOS and, in particular, the proposal to define two new phenotypes as PCOS. POSITIONS: Available data suggest that hyperandrogenic ovulatory women with polycystic ovaries tend to have mild insulin resistance and mild evidence of ovarian dysfunction, although significantly less than women with anovulatory PCOS. However, whether these women will have an increased risk of infertility or metabolic complications, such as type 2 diabetes, remains to be determined. Alternatively, the risk of insulin resistance and long-term metabolic risks of oligoovulatory women with polycystic ovaries is even less well characterized and may be nonexistent. CONCLUSIONS: Because of the paucity of data on the two new phenotypes and their long-term implications and the potential negative impact on research, clinical practice, and patient insurability, the adoption of the Rotterdam 2003 criteria for defining PCOS should be considered premature. However, because polycystic ovaries are a frequent feature of PCOS, a modification of the NIH 1990 criteria is proposed. Additional research characterizing the phenotypes and associated morbidities of PCOS is urgently required.

Female↗
PubMed2006

Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, and its definition remains fluid and controversial. PCOS is characterized by clinical and/or biochemical hyperandrogenism, and is frequently accompanied by ovulatory dysfunction and polycystic ovaries. PCOS is a diagnosis of exclusion, with other androgen excess and related disorders to be excluded. The prevalence of PCOS is 6.5-8.0% of unselected women of reproductive age, using the NIH 1990 criteria. Genetically, PCOS is a common, complex disorder. Despite repeated attempts to identify the putative gene or genes responsible for this disorder, the PCOS gene(s) remain elusive.

Adolescent↗
PubMed2006

A twenty-first century research agenda for polycystic ovary syndrome.

Notwithstanding the significant progress made in our understanding of polycystic ovary syndrome (PCOS), the field remains ripe for further discovery and more intensive translational research. Immediate priorities include developing evidence-based criteria for diagnosing PCOS and for assessing the response to the various treatments available. The basis for the identification of PCOS remains mainly expert opinion, and the lack of universally accepted evidence-based criteria limits the generalizability of research studies on PCOS. Additional important areas requiring intensive investigation include the natural history and etiology and the long-term sequelae and prevention of the disorder. Overall, this disorder is a prototype for the benefits of translational science and a transdisciplinary approach to understanding the pathophysiology and therapy for anovulatory infertility.

Evidence-Based Medicine↗
PubMed2006

Role of diet in the treatment of polycystic ovary syndrome.

OBJECTIVE: To determine whether eucaloric diets either enriched with monounsaturated fatty acids (MUFA; 17% energy) or low in carbohydrates (Low CHO; 43% energy) would increase insulin sensitivity (Si) and decrease circulating insulin concentrations, relative to a standard diet (STD; 56% CHO, 31% fat, 16% protein), among women with polycystic ovary syndrome (PCOS). DESIGN: Crossover. SETTING: Academic research environment. PATIENT(S): Healthy women with PCOS not on hormonal or insulin-sensitizing therapy. INTERVENTION(S): Subjects consumed three, 16-day, eucaloric diets, each separated by a 3-week washout period. A frequently sampled, intravenous, glucose tolerance test was administered at baseline and following each diet. MAIN OUTCOME MEASURE(S): Fasting glucose, insulin, the acute insulin response to glucose (AIRg), Si, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, A4, total cholesterol, high-density lipoprotein cholesterol (HDL-C), tryglycerides (TG), and free fatty acids (FFA). RESULT(S): Fasting insulin was lower following the Low CHO diet relative to the STD diet; AIRg was lower following the Low CHO diet relative to the MUFA diet. Fasting glucose, Si, and the circulating concentrations of reproductive hormones were not significantly affected by the intervention. CONCLUSION(S): A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS, which, over time, may improve reproductive/endocrine outcomes.

Adult↗
PubMed2006

Diagnosis, phenotype, and prevalence of polycystic ovary syndrome.

New diagnostic criteria for polycystic ovary syndrome (PCOS) suggested three main phenotypes: classic (hyperandrogenism and anovulation), ovulatory, and normoandrogenic. However, it is unclear whether the normoandrogenic phenotype actually represents PCOS. Overall, 6% to 8% of reproductive-aged women suffer from PCOS, making this disorder one of the most common endocrine abnormalities.

Anovulation↗
PubMed2006

Report on the Third Annual Meeting of the Androgen Excess Society, San Diego, California, June 3, 2005.

The third annual meeting of the Androgen Excess Society, held in San Diego, California, June 3, 2005, reported on new developments in the field, including intrafollicular steroidogenesis, intrathecal biochemistry, mechanisms of insulin signal and resistance of polycystic ovary syndrome, and novel aspects of androgen signaling. The experience of the 21-OH-deficient Nonclassical Adrenal Hyperplasia (NCAH) Multicenter Study Group was also discussed, along with a keynote presentation on the molecular aspects of 3beta-HSD-deficient NCAH.

Adrenal Hyperplasia, Congenital↗
PubMed2005

Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) and the metabolic syndrome have many features in common and may share the same pathogenesis. OBJECTIVE: This study was performed to determine the prevalence and predictors of the metabolic syndrome in PCOS. DESIGN: The clinical, hormonal, and oral glucose tolerance test results were analyzed in 394 PCOS women who were screened for participation in a multicenter trial to evaluate the effects of troglitazone on ovulation and hirsutism. SETTING: A multicenter clinical trial is presented. PATIENTS OR OTHER PARTICIPANTS: The subjects were women with PCOS who had or lacked the metabolic syndrome. MAIN OUTCOME MEASURES: Waist circumference, fasting glucose, high-density lipoprotein cholesterol and triglyceride concentrations, and blood pressure were the main outcome measures. RESULTS: Twenty-six (6.6%) subjects had diabetes; among the 368 nondiabetics, the prevalence for individual components comprising the metabolic syndrome were: waist circumference greater than 88 cm in 80%, high-density lipoprotein cholesterol less than 50 mg/dl in 66%, triglycerides greater than or equal to 150 mg/dl in 32%, blood pressure greater than or equal to 130/85 mm Hg in 21%, and fasting glucose concentrations greater than or equal to 110 mg/dl in 5%. Three or more of these individual criteria were present in 123 (33.4%) subjects overall. The prevalence of the metabolic syndrome did not differ significantly between racial/ethnic groups. The prevalence of the metabolic syndrome from lowest to highest quartile of free testosterone concentration was 19.8, 31.3, 46.9, and 35.0%, respectively [P = 0.056 adjusted for body mass index (BMI)]. None of the 52 women with a BMI less than 27.0 kg/m2 had the metabolic syndrome; those in the top BMI quartile were 13.7 times more likely (95% confidence interval, 5.7-33.0) to have the metabolic syndrome compared with those in the lowest quartile. Thirty-eight percent of those with the metabolic syndrome had impaired glucose tolerance compared with 19% without the metabolic syndrome (P < 0.001). CONCLUSIONS: The metabolic syndrome and its individual components are common in PCOS, particularly among women with the highest insulin levels and BMI. Hyperinsulinemia is a likely common pathogenetic factor for both PCOS and the metabolic syndrome.

Adult↗