Signs Of Hyperandrogenism Research Articles

Case report: Bilateral adrenal macronodular hyperplasia

A 62-year old female presented with weight gain, arterial hypertension and an increased sweating. She received only L-thyroxine for autoimmunthyroidism. The patient was postmenopausal and her menses had been regularly before. Previous testings had shown a normal TSH and urinary cortisol excretion. ACTH was low, and cortisol was inadequately suppressed after 1mg and 8mg dexamethasone. A CT scan revealed bilaterally enlarged adrenal glands (4×3cm and 6×3cm). On clinical examination the woman was obese (BMI 38kg/m2) without typical signs of Cushing's syndrome or hyperandrogenism. ACTH was low (5 ng/l), morning cortisol, aldosterone, renin, the aldosterone/renin ratio, urinary cortisol and catecholamine excretion were normal. Cortisol was 241 nmol/l and 187 nmol/l after a 1mg and 8mg dexamethasone overnight test, respectively. 17-OH-progesterone increased after ACTH to 1569 ng/dl, which raised the possibility of congenital adrenal hyperplasia. No mutation, however, in the CYP21 gene could be detected. A rare condition caused by aberrant adrenal receptor expression (e.g. GIP, vasopressin, β-adrenergic, LH/hCG, 5-HT4, angiotensin) has been shown to cause hypercortisolism and adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH). Further investigations revealed no meal- or orthostasis-induced increase of cortisol ruling out e.g. aberrant GIP, vasopressin, β-adrenergic or angiotensin receptor expression. Furthermore, no cortisol stimulation after LHRH administration was observed. However, metoclopramide, which activates 5-HT4 receptors, yielded a marked increase in cortisol (from 104 to 187 ng/ml) with ACTH being suppressed during the test. Taken together, the most likely diagnosis is AIMAH with subclinical Cushing's syndrome caused by an aberrant expression or overexpression of 5-HT4 receptors in the adrenal tissue. Since AIMAH has not been associated with malignancy and since arterial hypertension could be well controlled by standard treatment, we did not recommend surgery but decided to carefully monitor the patient.

Reduced androgen activation in peripheral blood mononuclear cells in polycystic ovarian syndrome – a compensatory mechanism for hyperandrogenaemia?

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotestosterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990, 335:431; JCE&M 2003, 88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previously shown that PBMCs express SRD5A1 and the androgen receptor (AR) and that SRD5A1 activity is enhanced in age-advanced men (JCE&M 2005, 90:6283). To test the hypothesis whether this represents an adaptive mechanism to the concurrent decrease in circulating androgens, we here sought to analyse SRD5A1 activity in PBMCs from women with PCOS (n=12, age (mean±SEM) 24±1.1yrs, BMI 28±1.5kg/m2) and in healthy controls matched for sex, age and BMI. SRD5A1 activity was assessed in freshly isolated PBMCs by incubation with radiolabelled precursors, measuring the conversion of androstenedione (4-dione) to 5α-androstanedione (5α-dione) and of T to DHT. Global 5α-reductase activity was analysed by measuring the 24-h urinary excretion of 5α-reduced androgen and glucocorticoid metabolites by GC/MS. Circulating 4-dione and free T were significantly higher in PCOS (p<0.001) as were clinical signs of hyperandrogenism (Ferriman-Gallwey score 7.0±1.1 vs. 2.0±0.4, p<0.001). PCOS patients showed an increased urinary excretion of 5α-reduced steroids (p<0.05) confirming systemically enhanced SRD5A1 activity. However by contrast, SRD5A1 activity in PBMCs was significantly decreased in PCOS (4-dione to 5α-dione, p<0.05; T to DHT, p<0.01). These findings suggest that a reduced SRD5A1 activity in PBMCs compensates for increased circulating androgen levels found in PCOS, similar to the converse finding of enhanced SRD5A1 activity in elderly men with a decline in circulating androgens. This might represent an adaptive mechanism that keeps AR activation within lymphocytes at a steady level.

Itchy-Dry Eye Associated with Polycystic Ovary Syndrome

The authors aimed to define the ocular symptomatology of women with polycystic ovaries and hyperandrogenism. Prospective, observational case series. Of the 62 consecutive patients with an ultrasonographic diagnosis of polycystic ovary (PCO), 16 were identified as having clinical and biochemical signs of hyperandrogenism. All women with a history of ocular symptoms (20/62 total patients [32.3%], 15/16 polycystic ovary syndrome (PCOS) patients [93.7%], and 5/46 PCO patients [10.8%]) underwent a complete eye examination with conjunctival impression cytologic sampling. Clinical measurements of tear function (tear film break-up time [BUT], Schirmer I test) were completed along with analysis of conjunctival goblet cell number, conjunctival immunostaining, and reverse-transcriptase polymerase chain reaction for the mucins MUC1 and MUC5AC. Clinical, histologic, and biochemical data of patients with PCOS were compared statistically with that of patients with PCO and with eight age- and gender-matched healthy controls. Eight of the most severely affected patients received systemic antiandrogen therapy and underwent further ocular evaluation four months after systemic therapy. Women with PCOS had greater conjunctival hyperemia (P < .001), dryness (P < .001), itching (P < .001), mucous discharge (P < .001), and contact lens intolerance (P < .001) than patients with PCO. Patients with PCOS had a significant reduction of the tear film BUT accompanied by a significant increase in goblet cell number and conjunctival MUC5AC messenger ribonucleic acid expression compared with both PCO patients and healthy subjects. Evaluation of the ocular surface should be considered in patients with PCO or PCOS. Women with PCOS were more likely to have itchy-dry eyes, decreased tear film BUT, and increased goblet cell density.

The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study

Cinnamon extract has been shown to reduce insulin resistance in in vitro and in vivo studies by increasing phosphatidylinositol 3-kinase activity in the insulin signaling pathway and thus potentiating insulin action. Fifteen women with polycystic ovary syndrome (PCOS) were randomized to daily oral cinnamon and placebo for 8 weeks. Comparisons of post-treatment to baseline insulin sensitivity indices using fasting and 2-hour oral glucose tolerance tests showed significant reductions in insulin resistance in the cinnamon group but not in the placebo group. A larger trial is needed to confirm the findings of this pilot study and to evaluate the effect of cinnamon extract on menstrual cyclicity.

Les lipodystrophies primitives

Primary lipodystrophies represent a heterogeneous group of very rare diseases with a prevalence of less than 1 case for 100.000, inherited or acquired, caracterized by a loss of body fat either generalized or localized (lipoatrophy). In some forms, lipoatrophy is associated with a selective hypertrophy of other fat depots. Clinical signs of insulin resistance are often present: acanthosis nigricans, signs of hyperandrogenism. All lipodystrophies are associated with dysmetabolic alterations with insulin resistance, altered glucose tolerance or diabetes and hypertriglyceridemia leading to a risk of acute pancreatitis. Chronic complications are those resulting from diabetes involving the retina, kidney and nerves, cardiovascular complications and steatotic liver lesions that could result in cirrhosis. Genetic forms of generalized lipodystrophy (or Berardinelli-Seip syndrome) result, in most cases, from recessive mutations in one of two genes: either BSCL2 coding seipin or BSCL1 coding AGPAT2, an acyl-transferase involved in triglyceride synthesis. Acquired generalized lipodystrophy (Lawrence syndrome) is of unknown origin but is sometimes associated with signs of autoimmunity. Partial lipodystrophies can be familial with dominant transmission. Heterozygous mutations have been identified in the LMNA gene encoding nuclear lamin A/C belonging to the nuclear lamina, or in PPARG encoding the adipogenic transcription factor PPARγ. Some less typical lipodystrophies, associated with signs of premature aging, have been linked to mutations in LMNA or in the ZMPSTE24 gene encoding the protease responsible for the maturation of prelamin A into lamin A. Acquired partial lipodystrophy (Barraquer-Simons syndrome) is characterized by cephalothoracic fat loss. Its aetiology is unknown but mutations in LMNB2, encoding the lamina protein lamin B2, could represent susceptibility factors. Highly active antiretroviral treatments for HIV infection are currently the most frequent cause of acquired secondary lipodystrophic syndromes. The genetic diagnosis is performed in specialized laboratories and, in the most severe forms, antenatal diagnosis could be proposed. Treatment of diabetes, dyslipidemia and complications involves the classical intervention strategies. Insulino-sensitizing drugs are useful. Therapeutic trials with recombinant human leptin in patients with very low leptin levels reported good results with respect to the metabolic and liver alterations. The prognosis is linked to the precocity and severity of the diabetic, cardiovascular and liver complications.

Reproductive Outcome of Women With 21-Hydroxylase-Deficient Nonclassic Adrenal Hyperplasia

Many women with 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) carry at least one allele containing a severe mutation of CYP21, and as such are at risk for giving birth to an infant having classic adrenal hyperplasia (CAH). Infants with NCAH typically are asymptomatic at birth, in contrast to those with CAH, but they do develop symptoms of hyperandrogenism later in childhood or as adults. This international multicenter study, conducted both retrospectively and prospectively, was an attempt to determine how often mothers with 21-OH-deficient NCAH bear infants having CAH or NCAH. The 101 women entering the study had a total of 203 pregnancies that could be evaluated. Fourteen tertiary referral centers in nine countries participated in the study. The diagnosis of 21-OH-deficient NCAH was based on a baseline or post-ACTH level of 17-hydroxyprogesterone exceeding 10 ng/mL. Where feasible, the offspring underwent genotypic analysis. Nearly half the women with NCAH presented with oligomenorrhea, and four had primary amenorrhea. More than two-thirds of pregnancies took place before the mother was diagnosed as having NCAH. Spontaneous miscarriages occurred in one-fourth of 138 pregnancies before NCAH was diagnosed but in only four of 65 pregnancies occurring after the diagnosis (6%). The incidence of CAH in 162 live births was 2.5%. Twenty-four children (15%) have been diagnosed as having NCAH. Five other female infants developed signs of hyperandrogenism but did not meet hormonal criteria for a diagnosis of NCAH. Three of the four live-born CAH children were White Jewish or Hispanic, as were two of three NCAH mothers giving birth to a CAH child. In this international study, a woman with NCAH had a 2.5% chance of giving birth to a child having CAH and a 15% chance of having a child with NCAH. Preconception screening for 21-OH-deficient NCAH is especially important for hyperandrogenic or oligoovulatory women who wish to become pregnant. Glucocorticoid therapy before conception and/or before birth may favorably influence the outcome.

Clinical presentation and etiologic factors of hirsutism in premenopausal Iranian women.

Hirsutism is a common clinical condition with different etiologies. Many of these patients have frank or subclinical abnormalities in the adrenal and ovarian steroidogenesis. The disease may be associated with other clinical signs of hyperandrogenism. The objective of this study was to investigate the clinical features of hirsutism and its etiologic factors in premenopausal Iranian women. In a cross-sectional study, 790 consecutive premenopausal women referred to the dermatology Clinics of Hazrat-e Rasool and Firoozgar University Hospitals and three private dermatology clinics during 2001 - 2003 with the clinical diagnosis of hirsutism were studied. All patients underwent detailed clinical assessment and transabdominal ultrasonography of the ovaries. Endocrinologic work-up was performed for 285 patients. Hirsutism was mild in 65%, moderate in 32.5%, and severe in 2.5% of the patients. Positive family history was found in 56.2%. Hormonal studies revealed some abnormalities in 35.2% of the patients. Coexisting medical conditions included acne in 70% of the patients, menstrual irregularity in 38.6%, androgenic alopecia in 21.3%, obesity in 6.5%, acanthosis nigricans in 4.9%, and diabetes in 0.6% of the patients. Etiology of hirsutism was identified as polycystic ovary syndrome (62.53%), idiopathic (35.19%), congenital adrenal hyperplasia (0.38%), prolactinoma (0.13%), and undetermined (1.77%). Polycystic ovary syndrome was diagnosed more frequently in women with menstrual irregularity than eumenorrheic patients (97.70% vs. 40.41%, P < 0.001). Hirsute patients frequently have either elevated androgen levels or clinical conditions associated with hyperandrogenemia. Eumenorrhea does not rule out endocrine abnormality and particularly polycystic ovary syndrome which is a common cause of hirsutism. We recommend performing endocrinologic work up, investigation of coexisting hyperandrogenic states, and evaluation of polycystic ovary syndrome in all patients with hirsutism.

Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome

One of the main criteria to establish a diagnosis of polycystic ovary syndrome (PCOS) is hyperandrogenemia. Recent observations suggest that total testosterone may not be a sensitive marker for the detection of androgen excess. The aim of the present study was to compare the value of different androgen determinations for diagnosis of PCOS. Untreated PCOS patients (n=133; mean age 28 years) and healthy control women (n=54; mean age 28 years) were included in the study. Measurements of total testosterone and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstendione, dehydroepiandrosterone sulfate (DHEAS) and albumin were performed. In addition, the free androgen index (FAI), free and bioavailable testosterone were calculated. Clinical signs of hyperandrogenism were evaluated by physical examination. The area under the receiver operating characteristic curve (AUC-ROC) was used to compare the sensitivity and specificity of different androgen determinations to detect PCOS, defined as clinical hyperandrogenism and irregular cycles compatible with the National Institutes of Health criteria of chronic anovulation and clinical or biochemical hyperandrogenism. All biochemical parameters of hyperandrogenism were significantly higher in PCOS patients than in controls (all p<0.0001). The highest AUC-ROC was found for bioavailable testosterone (0.852) followed by FAI (0.847) and free testosterone (0.837). Lower AUC-ROC was found for SHBG, total testosterone and androstendione (0.765, 0.799 and 0.706, respectively). When FAI=4.97 was taken as a cutoff value, sensitivity was 71.4% and specificity was 85.2%. A cutoff of 0.78 nmol/L for bioavailable testosterone had even higher sensitivity of 75.9%, but slightly lower specificity of 83.3%. FAI and bioavailable testosterone correlated significantly (all p<0.05) with total testosterone, androstendione, LH/FSH ratio and DHEAS. In addition, free testosterone, bioavailable testosterone and FAI correlated significantly with hirsutism scores, and ovarian volume and follicle count. ROC analysis provided evidence that calculated testosterone indices (bioavailable testosterone, FAI, free testosterone) are useful parameters for the discrimination of PCOS patients and healthy controls.

Effects of Treatment With Testosterone Alone or in Combination With Estrogen on Insulin Sensitivity in Postmenopausal Women

Treatment with androgens such as testosterone has a number of salutary effects on postmenopausal women, including greater energy, improved sexual function, preservation of bone mass, and possibly a protective effect on the breast. There is concern, however, that excessive androgen may lead to an insulin-resistant state. This study addressed the issue of insulin sensitivity using testosterone undecenoate (TU), an orally active preparation with only minor liver-related side effects. Participants were 63 naturally postmenopausal women in good general health, 2 of whom were obese. The women were randomly assigned to receive 40 mg testosterone (T) in the form of TU every other day, 2 mg estradiol (E) valerate daily, or both treatments (T+E), all for 3 months. The euglycemic hyperinsulinemic clamp technique served to estimate insulin sensitivity. The 3 groups were similar in age, body weight, bone mass index, blood pressure, serum hormone levels, and a history of using conventional hormone therapy. Diastolic but not systolic blood pressure fell significantly in the T group but, in general, treatment was well tolerated. No hyperandrogenic signs such as acne or hirsutism developed. Total serum testosterone rose to median levels of 35 to 46 ng/dL in both the T and T+E groups-within the normal range for premenopausal women. Fasting blood glucose levels did not change significantly, but plasma insulin levels fell significantly in the E and T+E groups. Basal insulin sensitivity increased significantly in E-treated women only. Steady-state plasma insulin and blood glucose levels were similar in all groups before and after treatment. Whole-body glucose uptake fell significantly by approximately 20% in the T group and also after combined treatment. No significant correlation was found between changes in free T levels and altered anthropometric or metabolic variables. Body weight increased by approximately 1 kg, a small but significant change, in all treatment groups. Total body fat mass and fat distribution remained stable, but total lean body mass increased significantly in the T+E group. Total cholesterol fell significantly by approximately 20 mg/dL in the same group. High-density lipoprotein cholesterol decreased significantly in the T group but increased in the E group. Low-density lipoprotein cholesterol decreased significantly in both E-treated groups. It appears that short-term treatment with TU, alone or combined with estradiol, induces insulin resistance in postmenopausal women and also worsens the serum lipid profile. Treatment may, however, increase lean body mass. More work is needed to appreciate the clinical significance of these findings.

Inhibitory Effect of Obesity on Gonadotropin, Estradiol, and Inhibin B Levels in Fertile Women

To examine whether obesity and insulin resistance have an independent effect on the gonadotropin, estradiol, and inhibin B serum levels and follicle count in the early follicular phase of fertile women with a wide range of BMI and without signs of hyperandrogenism. Twenty-two overweight and obese (BMI > or =25.0 kg/m(2)) women and 10 normal-weight (BMI <25.0 kg/m(2)) women, all having apparently normal fertility, were studied. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin B, and insulin, level of insulin resistance (estimated by homeostasis model assessment for insulin resistance), and follicle count were measured during the early follicular phase (Days 2 to 5 of the menstrual cycle). Overweight women showed lower FSH (p < 0.001), LH (p < 0.001), and inhibin B (p < 0.05) levels compared with normal-weight women, whereas estradiol concentrations and follicle count were not significantly different between the two groups. When normal-weight and overweight women were examined as a group and multiple regression analyses were performed, estradiol showed a negative association with BMI (or waist circumference) (p < 0.05) and a positive correlation with LH (p < 0.05) and FSH (p < 0.05); inhibin B maintained a positive association only with estradiol (p < 0.05); and FSH and LH showed a negative correlation with BMI (or waist circumference) (p < 0.001 and p < 0.01, respectively). Overweight and obese fertile women have lower FSH, LH, inhibin B, and estradiol levels in the early follicular phase, with a possible direct inhibitory effect of body mass on gonadotropin and estradiol production, independently of age, insulin (concentrations and sensitivity), and other hormones. By contrast, the number of ovary follicles does not seem to be influenced by insulin and body mass in these patients.

Stress in Women

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome that is characterized from oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries. Clinical expression is determined by genetic as well as environmental factors. Women with PCOS are a specific group of women which have several aspects of metabolic syndrome (MBS). Concomitantly MBS could be part of metabolic abnormalities present in PCOS. Stress has been linked to aggravate the metabolic abnormalities present in MBS. An interaction seems to exist between stress, environmental, as well as genetic factors, starting from the prenatal age and continuing to the adult life. This results in specific endocrinological and metabolic disorders which are shared by women with PCOS and women with MBS.

Is the PCOS diagnosis solved by ESHRE/ASRM 2003 consensus or could it include ultrasound examination of the ovarian stroma?

The clinical heterogeneity of polycystic ovary syndrome (PCOS) is mirrored by the unceasing debate on the most appropriate diagnostic criteria. To highlight differences and inconsistencies between NIH and ESHRE/ASRM criteria, we applied them to 375 patients with oligo/amenorrhoea and signs of hyperandrogenism. Among them, we identified 273 women with PCOS according to NIH, whereas up to 345 patients fulfilled ESHRE/ASRM criteria. The 72 patients, constituting the gap between the two classifications, exhibited a lower expression of clinical signs compared with the 273 patients matching both criteria. To the whole group, we then applied the ESHRE/ASRM criteria modified to include an easily reproducible ultrasound examination of the ovarian stroma (UCSC criteria). In this way, we identified 30 women who were healthy according to all criteria, 37 affected by PCOS according only to the ESHRE/ASRM Consensus, 35 affected according only to the UCSC and ESHRE/ASRM criteria and 273 who were considered to have PCOS by all criteria. These groups showed a progressively increasing expression of PCOS features. In the grey area between NIH and ESHRE/ASRM classifications, UCSC criteria could identify a subgroup of women, missed by NIH criteria, with more pronounced stigmas than those identified by ESHRE/ASRM criteria alone, and who may profit more from a targeted therapy.

Alopecia androgénica prematura en un varón con déficit de 21-hidroxilasa no clásico. Nueva mutación grave (Y336X) del gen CYP21A2 en 2 hermanos afectados

Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency mainly manifests with symptoms and signs of hyperandrogenism, which are usually obvious in women and sometimes obvious in children or adolescents, but are rarely observed in adult men especially with increasing age. Male pattern alopecia is considered an androgenetic and age-related symptom. However, its early appearance should raise the suspicion of an underlying endocrinological disease, and biochemical screening should be done.Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia.Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X).Given the high prevalence of carriers with severe mutations, we discuss the risk for such patients of conceiving a child with a classical disease and the need for a reliable molecular diagnosis in order to provide accurate genetic counselling.

Up-to-date Definition of the Polycystic Ovary and Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is common in the general population. In this paper the author presents the up to date definition of PCOS and PCO. At a joint ASRM/ESHRE consensus meeting, a refined definition of the PCOS was agreed, in which two out of the following are required: (1) oligomenorrhoea or amenorrhoea; (2) clinical and/or biochemical signs of hyperandrogenism; (3) polycystic ovaries, once appropriate tests have been performed to exclude other causes of androgen excess and menstrual disturbance. The definition of a polycystic ovary (PCO) should have at least one of the following: either 12 or more follicles measuring 2–9 mm in diameter or increased ovarian volume (&gt;10 cm3). If there is a follicle &gt;10 mm in diameter, the scan should be repeated at a time of ovarian quiescence in order to calculate volume and area. The presence of a single PCO is sufficient to provide the diagnosis. The distribution of follicles and a description of the stroma are not required in the diagnosis.

Diagnosis and management of the dermatologic manifestations of the polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex phenotypic spectrum of primarily hyperandrogenic signs and symptoms. PCOS is the most common endocrine disturbance to affect women of reproductive years. Although patients affected are often very disturbed by the cutaneous manifestations, including acne, hirsutism, alopecia, obesity, and acanthosis nigricans, the clinical manifestations of PCOS ramify far beyond the skin. PCOS frequently causes menstrual abnormalities and infertility. Insulin resistance is both pathogenic and a cause of numerous serious health consequences. The accurate diagnosis and recognition of cutaneous hyperandrogenism in PCOS are discussed. The differential diagnosis is reviewed. The work-up and approach to evaluation of patients with PCOS is presented. Although no uniform treatment approach for the management of the cutaneous manifestations of PCOS has been agreed upon, the data on various treatment options and the author's treatment approach to these patients are presented.

Mild androgen phenotypes

Mild androgen phenotypes are found in 30-40% of patients referred to an endocrine clinic because of suspected hyperandrogenic syndrome. These disorders are characterized by clinical or biological signs of hyperandrogenism in women with normal ovulatory menstrual cycles. Three main mild androgen disorders may be distinguished: ovulatory polycystic ovarian syndrome (PCOS), idiopathic hyperandrogenism, and idiopathic hirsutism. Ovulatory PCOS includes ovulatory hyperandrogenic patients presenting with polycystic ovaries. Using ESHRE/ASRM criteria for diagnosis of PCOS, this disorder is now part of PCOS spectrum. While in vivo and in vitro studies have confirmed the similarities between the two forms of PCOS, ovulatory PCOS presents clinicians with some unique problems. In fact, fertility is not a problem, but insulin resistance is present, and although milder than in classic PCOS it may be associated with an increased cardiovascular and metabolic risk. Because of this, an ovarian sonography should be performed in all ovulatory hyperandrogenic patients, and when polycystic ovaries are found cardiovascular and metabolic risk should be carefully evaluated. Ovulatory PCOS patients with altered glucose tolerance and/or with dyslipidaemia may need treatment with insulin-sensitizing agents. Idiopathic hyperandrogenism regroups ovulatory patients with increased androgen levels and normal ovaries, while idiopathic hirsutism includes ovulatory patients presenting with hirsutism but normal circulating androgens and normal ovaries. The differentiation between these two disorders may be difficult because commercial assays of androgen levels are generally unreliable. While idiopathic hyperandrogenism may be associated with insulin resistance, neither disorder is associated with an increased cardiovascular risk. The main clinical problem is hirsutism, and this may be approached by aesthetic or pharmacological therapies.

Comparison of clinical and laboratory characteristics of cases with polycystic ovarian syndrome based on Rotterdam’s criteria and women whose only clinical signs are oligo/anovulation or hirsutism

This study was an attempt to determine whether the hormonal and clinical profiles of polycystic ovarian syndrome (PCOS) or non-PCOS cases whose only admission signs were oligo/anovulation or hirsutism. This retrospective study comprised a total number of 118, age-matched, young Turkish women with initial admission signs and symptoms of menstrual disorders (MD) like oligo/anovulation or hirsutism. Of these, 66 cases were diagnosed as PCOS, based on 2003 Rotterdam criteria [presence of two of first three criteria such as oligo- and/or anovulation, signs of clinical hyperandrogenism (HA-c) and/or biochemical signs of hyperandrogenism (HA-b) and polycystic ovaries on ultrasonography after exclusion of specific identifiable disorders]. Fifty-two women were diagnosed as cases of oligo/anovulation or hirsutism before the era of PCOS Rotterdam's consensus criteria. These two PCOS and non-PCOS cases were evaluated in terms of body mass index (BMI), waist-to-hip ratio, serum FSH, LH, estradiol (E2), dehydroepiandrosterone sulphate (DHEAS), androstendione (A) 17 hydroxyprogesterone (17-HP), fasting insulin, C-peptide levels, sex hormone-binding globulin (SHBG) and finally, ultrasonographic ovarian morphology. PCOS cases with unilateral and bilateral polycystic ovarian morphology on ultrasound scan were analyzed based on Rotterdam criteria. No statistically significant difference was detected among two groups, in terms of BMI, waist-to-hip ratio, serum FSH, LH, E2, fasting insulin, C-peptide levels (P > 0.05). However, blood levels of DHEAS, A and 17-HP were higher, whilst SHBG levels were remarkably lower (P = 0.008) in PCOS cases. Among PCOS group, hormonal and clinical characteristics did not differ, irrespective or uni- or bilaterality of ovarian morphology on ultrasonographic scan. Percentages of cases with androgenic alopecia, oily skin/acnea and increased ovarian volume were higher in PCOS group; whereas Ferriman-Gallwey score >/= 8 were similar between two groups. Total but not free testosterone remained high in PCOS group (P < 0.01). In both PCOS and non-PCOS cases, a linear correlation was apparent between BMI and insulin levels (r (s )= 0.69 and 0.32, P < 0.05, respectively). Among PCOS group, MD + HA-b + HA-c (n = 40) was present in 60.6% of subjects, MD + HA-b (n = 12) in 18.2%, and MD + HA-c (n = 14) in 21.2%. The three phenotypes did not differ in mean BMI, waist-to-hip ratio and biochemical characteristics. To conclude, non-PCOS women with only sign or symptom of oligo/anovulation or hirsutism had a more favorable endocrine milieu. These cases should be followed in vigilance in an aim to confront the development of short- and long-term adverse effects of impending PCOS in the future. Furthermore, different phenotypes of PCOS cases were clinically or biochemically similar in characteristics.

Polymorphisms of the peroxisome proliferator–activated receptor-γ and its coactivator-1α genes in Chinese women with polycystic ovary syndrome

The polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and its coactivator-1 (Gly482Ser) genes were investigated among 201 Chinese Han women with polycystic ovary syndrome (PCOS) and among 147 regularly cycling women as control subjects. We did not find statistically significant differences with peroxisome proliferator-activated receptor-gamma2 Pro12Ala and peroxisome proliferator-activated receptor-gamma-1alpha Gly482Ser polymorphism distributions between Chinese women with PCOS and controls, or with body mass index and reproductive hormones among various genotypic groups of PCOS, suggesting that these genetic mutants did not have an effect on the susceptibility to PCOS.

Hormonal therapy of acne

The antiandrogen agents most frequently used in acne treatment are all systemic and are especially useful in the presence of other signs of peripheral hyperandrogenism, in extensive acne and in any type of acne resistant to conventional treatments. However, they can only be used in women, contraception is essential, they are only suppressive and recurrence occurs after treatment is stopped, and they may cause side effects and drug interactions. Antiandrogens are classified as steroids, which affect the production of androgens, or non-steroids, which have only peripheral effects. The main steroid antiandrogens used in acne treatment are those with diuretic actions (spironolactone), those with progestagenic actions (usually given with estrogen in contraceptive formulations) and estrogens. The main non-steroid agent is flutamide.

Diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature

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. 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. 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. 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.