-
[show abstract]
[hide abstract]
ABSTRACT: Context:The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established.Objective:The objective of the study was to determine the normal relationship of pubertal hormone responses to sleep and to GnRH agonist (GnRHag) challenge across the female pubertal transition.Design/Setting:This was a prospective study in a General Clinical Research Center.Participants:Sixty-two healthy 6- to 13-year-old volunteer girls participated in the study.Interventions:Interventions included overnight blood sampling followed by GnRHag (leuprolide acetate) injection.Primary Outcome Variables:The primary outcome variables included LH, FSH, and estradiol.Results:LH levels rose steadily during sleep and after GnRHag throughout the prepubertal years. The LH response to sleep and GnRHag correlated well across groups (eg, r = 0.807, peak vs 4 h post-GnRHag value); however, this correlation was less robust than in boys (r = 0.964, P < .01). Sleep peak LH of 1.3 U/L or greater had 85% sensitivity and 2.1 U/L or greater 96% specificity for detecting puberty (thelarche). The LH 1-hour post-GnRHag value of 3.2 U/L or greater had 95% sensitivity and 5.5 U/L or greater 96% specificity for detecting puberty. Girls entered puberty at lower LH levels than boys. FSH levels rose day and night during the prepubertal years to reach 1.0 U/L or greater during puberty but discriminated puberty poorly. Estradiol of 34 pg/mL or greater at 20-24 hours after GnRHag was 95% sensitive and 60 pg/mL or greater was 95% specific for puberty. Thirty-six percent of overweight early pubertal girls had meager hormonal evidence of puberty.Conclusions:These data suggest that sleep-related pubertal hormone levels critical for puberty are normally reflected in the responses to GnRHag testing across the normal female pubertal transition. Inconsistencies between clinical and hormonal staging may arise from peripubertal cyclicity of neuroendocrine function and from excess adiposity.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function.
Prospective case-control study.
General clinical research center.
Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18).
Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test.
Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test.
AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A.
AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool.
Fertility and sterility 04/2012; 98(1):242-9. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A).
Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4-7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all.
Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671-0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, P< 0.01). Glucose intolerance was absent in PCOS-A, but present in 30% of PCOS-T (P < 0.001). Most of the PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese.
Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.
Human Reproduction 09/2011; 26(11):3138-46. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: P450c17 deficiency is an uncommon steroidogenic disorder that typically presents as a sexually infantile adolescent phenotypic female with hypertension and hypokalemia. Although cortisol synthesis is impaired, elevated corticosterone and deoxycorticosterone ordinarily prevent adrenal insufficiency. Thus, diagnosis prior to puberty is rare. We report novel clinical features of an infant with complete P450c17 deficiency due to two novel mutations in CYP17A1.
A 10-week-old, 46,XY phenotypic female presented with hypotension, developed hypokalemic hypertension post-resuscitation, then hyperkalemic hyponatremia upon weaning salt supplements. All CYP17A1 exons of the proband and parents were PCR-amplified and sequenced. Cosyntropin, GnRH agonist, and hCG tests were performed.
Sequencing demonstrated compound heterozygosity for two novel CYP17A1 mutations, C327dupT and C362G>A (W121X), both generating premature stop codons in exon 2 and predicting non-functional enzymes. Plasma corticosterone was very elevated, deoxycorticosterone normal, cortisol detectable, and aldosterone low-normal at baseline. Responses to cosyntropin of corticosterone and progesterone were elevated, deoxycorticosterone and aldosterone normal, cortisol subnormal, and 17α-hydroxycorticosteroid intermediates undetectable. GnRH agonist/hCG testing showed no androgenic response.
This is the first report of P450c17 deficiency presenting in a 46,XY female infant with hypotensive shock, a state exacerbated by the atypical absence of deoxycorticosterone elevation.
Hormone Research in Paediatrics 08/2011; 76(6):434-41.
-
Pediatrics in Review 07/2011; 32(7):281-92. · 0.55 Impact Factor
-
Pediatrics in Review 06/2011; 32(6):223-9. · 0.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lipoprotein delivery of fatty acids and cholesterol is linked with peroxisome proliferator-activated receptor (PPAR) activation in adipocytes and macrophages. We postulated that similar interactions exist in sebaceous epithelial cells (sebocytes) in which PPAR activation induces differentiation. High-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) markedly enhanced sebocyte differentiation above that found with PPAR agonists and were more potent than explicable by their lipid content. The PPARγ antagonist GW5393 reduced sebocyte differentiation to all PPAR isoform agonists, HDL and VLDL, suggesting that the lipoprotein effect on differentiation occurs partially through activation of PPARγ. Furthermore, we found that sebocytes expressed a unique pattern of lipogenic genes. Our results demonstrate that HDL and VLDL are the most potent inducers of sebocyte differentiation tested to date, and these actions are partially inhibited by PPAR antagonists. This suggests that substrates provided by lipoproteins are targeted to sebocytes and affect their own disposition via PPAR activation.
Journal of nutrition and metabolism 01/2011; 2011:163631.
-
[show abstract]
[hide abstract]
ABSTRACT: Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty.
Brain research 12/2010; 1364:186-97. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine if intermittent, low-dose, short-acting gonadotropin-releasing hormone agonist (GnRH-agonist) administration sufficiently up-regulates pituitary-gonadal function in gonadotropin deficiency to be of diagnostic or therapeutic value.
Case-control study.
General clinical research center.
Normal adult volunteers and gonadotropin-deficiency patients.
Low-dose leuprolide acetate administered subcutaneously at 4- to 5-day intervals up to 1 year.
Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid responses.
In normal men and women, low-dose GnRH-agonist repetitively transiently stimulated gonadotropins in a gender-dimorphic manner. In congenitally gonadotropin-deficient men (n = 6) and women (n = 1), none of whom had a normal LH response to an initial GnRH-agonist test dose, this regimen consistently stimulated LH to the normal baseline range within 2 weeks. Long-term GnRH-agonist administration to a partially gonadotropin-deficient man did not alleviate hypogonadism, however. Women with hypothalamic amenorrhea (n = 2) responded normally to a single GnRH-agonist injection; however, repeated dosing did not seem to induce the normal priming effect.
The subnormal LH response to GnRH-agonist in patients with congenital gonadotropin deficiency normalized in response to repetitive intermittent GnRH-agonist administration but not sufficiently to improve hypogonadism. Hypothalamic amenorrhea patients lacked the priming response to repeated GnRH-agonist but otherwise had normal hormonal responses to GnRH-agonist. We conclude that intermittent administration of a short-acting GnRH-agonist is of potential diagnostic value in distinguishing hypothalamic from pituitary causes of gonadotropin deficiency.
Fertility and sterility 12/2010; 94(7):2697-702. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hexose-6-phosphate dehydrogenase (H6PD) inactivating mutations cause cortisone reductase deficiency, which manifests with hyperandrogenism unexplained by commonly used tests and, thus, mimics polycystic ovary syndrome (PCOS). The aim of this study was to screen for mutations of H6PD gene in PCOS patients with biochemical hyperandrogenemia.
Direct DNA sequencing of the entire H6PD coding sequence was performed in 74 PCOS patients and 31 healthy controls. Results were confirmed by PCR-restriction fragment length polymorphism assay to determine the genotypic frequency of the variants.
Multiple novel missense variants were detected in the study. Two exon 2 variants (acccaggc deletion proximal to the start codon and D151A) and two exon 5 variants (R453Q and P554L) were common, occurring in 23.8%, 17.1%, 35.2%, and 16.1%, respectively. There was significant linkage disequilibrium between the exon 2 and exon 5 variants. No significant differences were observed in the genotype, allele distributions, or adrenal function tests of the variants between cases and control groups. We did not detect any reported inactivating mutations in our study.
Although the H6PD gene is very polymorphic and missense variants are common, coding variants rarely (<1.5%) are responsible for hyperandrogenemic PCOS. We suggest that genetic studies be reserved for patients with dexamethasone-suppressible adrenal hyperandrogenism who have a discrepancy between urinary 17α-hydroxycorticoid and cortisol excretion.
Steroids 11/2010; 76(1-2):135-9. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background. Excess adiposity and premature adrenarche (PA) are risk factors for the development of polycystic ovary syndrome (PCOS). Methods. Girls with slowly progressive precocious breast development, who were overweight and had PA (SPPOPA, 6.2-8.2 years, n = 5), overweight PA (6.6-10.8 years, n = 7), and overweight premenarcheal controls (OW-PUB, 10.6-12.8 years, n = 8) underwent hormonal sleep testing and GnRH agonist (GnRHag) and ACTH tests. Results. Despite an insignificant sleep-related increase in LH and prepubertal baseline hormone levels, SPPOPA peak LH and estradiol responses to GnRHag were intermediate between those of PA and OW-PUB, the LH being significantly different from both. Conclusions. GnRHag tests indicate that SPPOPA is a slowly progressive form of true puberty with blunted LH dynamics. These results argue against the prepubertal hyperandrogenism of excess adiposity or PA enhancing LH secretion or causing ovarian hyperandrogenism prior to menarche. Excess adiposity may contribute to both the early onset and slow progression of puberty.
International Journal of Pediatric Endocrinology 01/2010; 2010.
-
[show abstract]
[hide abstract]
ABSTRACT: Kruppel-like factor 15 (KLF15) is a newly discovered transcription factor that plays an important role in glucose homeostasis and lipid accumulation in cells. We present evidence for KLF15 as a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene (HSD17B5) and its potential role in the pathogenesis of hyperandrogenism.
The aim was to investigate the molecular mechanism of HSD17B5 regulation.
Diverse molecular biology techniques were used.
We identified a KLF15 binding site in the HSD17B5 promoter by using luciferase promoter constructs, EMSA, and chromatin immunoprecipitation assays. Overexpression of KLF15 increased HSD17B5 promoter activity and testosterone formation at least 3-fold in cultured H295R cells. Insulin increased KLF15 mRNA expression according to real-time RT-PCR and increased HSD17B5 promoter activity according to luciferase assays. KLF15 overexpression in combination with insulin, glucocorticoid, and cAMP stimulated adipogenesis in H295R cells. In silico and RT-PCR analyses showed that the KLF15 gene promoter undergoes alternative splicing in a tissue-specific manner. Comparison of the HSD17B5 promoter in seven different species revealed that the KLF15 binding site has no human homolog in species other than orangutans.
KLF15 is potentially a novel link between the regulation of testosterone production and fat stores by insulin in humans.
The Journal of clinical endocrinology and metabolism 04/2009; 94(7):2594-601. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to determine the ovarian function of asymptomatic volunteers with a polycystic ovary (V-PCO).
Non-hirsute eumenorrheic V-PCO (n = 32) and volunteers with ultrasonographically normal ovaries (V-NO) (n = 21) were compared with one another and with polycystic ovary syndrome (PCOS) patients who met National Institute of Health criteria (n = 90). DESIGN/SETTING/INTERVENTIONS: GnRH agonist (GnRHag), ACTH, and oral glucose tolerance tests were prospectively performed in a General Clinical Research Center.
The distribution of 17-hydroxyprogesterone (17OHP) responses to GnRHag of V-PCO formed a distinct population intermediate between that of V-NO, the reference population, and PCOS. Nevertheless, the V-PCO population was heterogeneous. There were 53% (seventeen of 32) that were functionally normal, with 17OHP responses and free testosterone levels like V-NO. A total of 25% (eight of 32) had an elevated free testosterone, thus meeting Rotterdam criteria for PCOS; one third of these had 17OHP hyperresponsiveness to GnRHag testing. The remaining 22% (seven of 32) had 17OHP hyperresponsiveness to GnRHag, but normal free testosterone. Of PCOS, 69% had elevated 17OHP hyperresponsiveness to GnRHag. Ovarian volume correlated significantly with 17OHP responses only in PCOS, accounting for just 10% of the variance.
Many asymptomatic volunteers have a PCO. They are a distinct, but heterogeneous, population with respect to ovarian function, ranging from normal (53%) to occult PCOS by Rotterdam criteria (25%). Nearly one quarter (22%) had the typical PCOS type of ovarian dysfunction without hyperandrogenemia, termed a "dysregulated PCO"; they or their offspring may be at risk for PCOS. Ovarian ultrasonographic characteristics must be considered when establishing norms for ovarian function.
The Journal of clinical endocrinology and metabolism 03/2009; 94(5):1579-86. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The typical polycystic ovary syndrome (PCOS) phenotype includes 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHag) testing. Functionally atypical PCOS lacks this feature.
The hypothesis was tested that the typical PCOS ovarian dysfunction results from intrinsically increased sensitivity to LH/human chorionic gonadotropin (hCG) due to a flaw in FSH action. PARTICIPANTS/DESIGN/INTERVENTIONS/MAIN OUTCOME MEASURES: After phenotyping a cohort of 60 women, steroid and inhibin-B responses to gonadotropins were evaluated in representative typical (n = 7) and atypical (n = 5) PCOS and healthy controls (n = 8). Submaximal hCG testing before and after an FSH test dose was performed in random order before and after prolonged ovarian suppression by depot GnRHag.
The study was performed at a Clinical Research Center.
Of our PCOS cohort, 68% were the typical type. Typical PCOS had 17OHP hyperresponsiveness and, unlike controls, significant androgen and estradiol responses to hCG. FSH increased inhibin-B and did not inhibit free testosterone or enhance estradiol responsiveness to hCG, all unlike controls. After ovarian suppression, 17OHP, androstenedione, and inhibin-B responsiveness to gonadotropin testing persisted. Atypical PCOS had significantly higher body mass index but lower ovarian volume and plasma free testosterone than typical PCOS. Steroid responses to hCG were insignificant and similar to controls. FSH suppressed free testosterone but stimulated inhibin-B. The estradiol level after combined hCG-FSH was subnormal. Free testosterone was less GnRHag suppressible than in typical PCOS.
Typical PCOS is characterized by intrinsic ovarian hypersensitivity to hCG to which excessive paracrine FSH signaling via inhibin-B may contribute. Atypical PCOS is due to a unique type of ovarian dysfunction that is relatively gonadotropin hyposensitive.
The Journal of clinical endocrinology and metabolism 03/2009; 94(5):1587-94. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The early onset of puberty may be related to obesity, so there is a need to know the prevalence of early pubertal milestones in nonoverweight children. OBJECTIVE. We compared attainment of stage 2 breasts, stage 3 (sexual) pubic hair, and menarche in the Third National Health and Nutrition Examination Survey sample of children with normal BMI with those with excessive BMI (> or =85th percentile).
The ages at which 5%, 50%, and 95% of youth had attained key pubertal stages were estimated by probit models. Logit models were then fit to compare attainment of these milestones in children of excessive and normal BMI.
Pubertal signs occurred before 8.0 years of age in <5% of the normal-BMI general and non-Hispanic white female population. However, pubertal milestones generally appeared earlier in normal-BMI non-Hispanic black and Mexican American girls; thelarche occurred before age 8.0 in 12% to 19% of these groups, and the 5th percentile for menarche was 0.8 years earlier for non-Hispanic black than non-Hispanic white subjects. Pubarche was found in < or =3% of 8.0-year-old girls with normal BMI of all of these ethnic groups but was significantly earlier in minority groups. Pubarche appeared before 10.0 years in <2% of normal-BMI boys. Girls with excessive BMI had a significantly higher prevalence of breast appearance from ages 8.0 through 9.6 years and pubarche from ages 8.0 through 10.2 years than those with normal BMI. Menarche was also significantly more likely to occur in preteen girls with an elevated BMI.
Prevalence estimates are given for the key pubertal milestones in children with normal BMI. Breast and sexual pubic hair development are premature before 8 years of age in girls with normal BMI in the general population. Adiposity and non-Hispanic black and Mexican American ethnicity are independently associated with earlier pubertal development in girls.
PEDIATRICS 02/2009; 123(1):84-8. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to determine whether excessive adiposity is associated with alteration of the normal hormonal changes of early pubertal girls.
Healthy 6.4- to 9.5-yr-old, prepubertal (PRE, n = 20) and 9.4- to 13.0-yr-old pubertal premenarcheal volunteers (PUB, n = 20) were divided into excessive-weight (EW) or normal-weight (NW) groups according to the 85th percentile body mass index. INTERVENTIONS AND SETTING: Overnight blood sampling; GnRH agonist (GnRHag), low-dose ACTH, oral glucose tolerance tests, and pelvic ultrasonograms were performed in our Clinical Research Center.
EW girls were similar in age and baseline and ACTH- and GnRHag-stimulated androgen levels to stage-matched NW girls. However, the sleep-related LH rise was blunted in EW-PUB girls compared with NW-PUB girls. The sleep-related rise of mean LH in EW-PUB [0.68 +/- 0.35 (sem) U/liter] was insignificant, less than that of NW-PUB (2.1 +/- 0.45, P < 0.05) and not significantly different from that of PRE girls (0.08+/-0.03). EW-PUB had slower LH pulse frequency and a lower rise in LH pulse amplitude during sleep than NW-PUB girls (both P < 0.05). Overnight FSH patterns paralleled LH patterns, whereas estradiol levels were similar in stage-matched NW and EW groups, differing between stages as expected. Early morning and peak LH, FSH, and estradiol responses to GnRHag were similar in EW-PUB and NW-PUB and significantly greater than those of PRE girls.
Healthy EW-PUB girls have significantly blunted sleep-related LH production. These data suggest that excess adiposity, in the absence of sex steroid excess, may subtly suppress hypothalamic-pituitary-gonadal function in premenarcheal pubertal girls.
The Journal of clinical endocrinology and metabolism 02/2009; 94(4):1168-75. · 6.50 Impact Factor
-
Robert L Rosenfield
[show abstract]
[hide abstract]
ABSTRACT: The current regulatory environment, designed to protect children, imposes barriers to research in children that are a deterrent to high-quality clinical research in minors. This article summarizes the special procedures necessary to obtain approval for research in healthy children that poses more than minimal risk according to the code of federal regulations (45 CFR 46.407 and 21 CFR 50.54). The operational realities of the process are illustrated by the case of the most recent research protocol to be reviewed under these rules. The current process poses obstacles to future studies of complex research questions in children and adolescents that require unaffected controls, such as the relationship of adolescent anovulatory disorders to adult illness. It is concluded that current regulatory procedures, while protecting children, increase the potential for the neglect of important research needs of children and are a disincentive to pursuit of a career in clinical research for young clinicians. Suggestions are made for improving the balance between the need for research in children and adolescents and its regulation.
Annals of the New York Academy of Sciences 07/2008; 1135:287-95. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to develop clinical practice guidelines for the evaluation and treatment of hirsutism in premenopausal women.
The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, two methodologists, and a medical writer. The Task Force received no corporate funding or remuneration.
Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations, and "suggest" for weak recommendations.
Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the Task Force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes.
We suggest testing for elevated androgen levels in women with moderate or severe hirsutism or hirsutism of any degree when it is sudden in onset, rapidly progressive, or associated with other abnormalities such as menstrual dysfunction, obesity, or clitoromegaly. For women with patient-important hirsutism despite cosmetic measures, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For women who choose hair removal therapy, we suggest laser/photoepilation.
Journal of Clinical Endocrinology & Metabolism 05/2008; 93(4):1105-20. · 6.50 Impact Factor
-
Robert L Rosenfield
[show abstract]
[hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) appears to arise as a complex trait with contributions from both heritable and nonheritable factors. Polygenic influences appear to account for about 70% of the variance in pathogenesis. In view of this evidence for congenital contributions to the syndrome, childhood manifestations may be expected.
The objective has been to review the evidence that risk factors for PCOS can be recognized in childhood.
This study consisted of screening of the PCOS literature for articles pertaining to potential childhood and adolescent antecedents.
Congenital virilizing disorders; above average or low birth weight for gestational age; premature adrenarche, particularly exaggerated adrenarche; atypical sexual precocity; or intractable obesity with acanthosis nigricans, metabolic syndrome, and pseudo-Cushing syndrome or pseudo-acromegaly in early childhood have been identified as independent prepubertal risk factors for the development of PCOS. During adolescence, PCOS may masquerade as physiological adolescent anovulation. Asymptomatic adolescents with a polycystic ovary occasionally (8%) have subclinical PCOS but often (42%) have a subclinical PCOS type of ovarian dysfunction, the prognosis for which is unclear.
Identifying children at risk for PCOS offers the prospect of eventually preventing some of the long-term complications associated with this syndrome once our understanding of the basis of the disorder improves.
Journal of Clinical Endocrinology & Metabolism 04/2007; 92(3):787-96. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypogonadotrophic hypogonadism results in the absence of puberty and if left untreated leads to infertility. Mutations in KAL1 are known to account for some of the cases of Kallmann syndrome. The aim of this study was to determine the prevalence of KAL1 mutations in a large number of patients with idiopathic hypogonadotrophic hypogonadism (IHH). One hundred and thirty eight patients (109 males and 29 females) with IHH were studied for mutations in KAL1. DNA from these patients was subjected to denaturing gradient gel electrophoresis or single strand conformation polymorphism to identify mutations. Sequencing was performed to confirm mutations detected. Four mutations were found in 109 males (3.7%). All four mutations were in anosmic/hyposmic men making the prevalence 4/63 (6.3%) in this group of patients. No mutations were found in the 29 female patients. KAL1 mutations are an uncommon cause of Kallmann syndrome.
Molecular Human Reproduction 04/2007; 13(3):165-70. · 3.85 Impact Factor
