Ovarian Hyperandrogenism Research Articles

A Perspective Studies on Herbalism for the Preventive of PCOS

Polycystic ovary syndrome (PCOS) was hypothesized as a result of functional ovarian hyper androgenism (FOH) due to dysregulation of androgen secretion in 1989–1995. When defined as unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyper responsiveness to gonadotropin stimulation. When a Women with PCOS appear to be a higher risk of developing metabolic disorders, hypertension and cardiovascular disorders. Herbal remedies are the greatest significant with effective treatment option for PCOS because they are usually quite gentle on the body and has limited side effects than medication. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions.

Premature Adrenarche.

Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the adrenal cortex, and is a weak androgen agonist thought to be responsible for the clinical signs of pubarche by conversion to more potent androgens, testosterone, and dihydrotestosterone. DHEA's extra-adrenal sulfation product, dehydroepiandrosterone sulfate, is a stable marker for adrenal androgenic activity. Pubarche is the physical manifestation of androgenic hormone production, and includes the development of pubic and axillary hair, adult body odor, and acne. This stage is usually considered premature if it commences before age 8 years in girls or age 9 years in boys. Premature adrenarche is a diagnosis of exclusion, as true centrally mediated precocious puberty, congenital adrenal hyperplasia, exogenous androgen exposure, and androgen-secreting tumors must be ruled out. Premature adrenarche may be associated with a history of an infant who was small for gestational age at birth who then gained weight rapidly thereafter or became obese. In some instances, premature adrenarche may predict functional ovarian hyperandrogenism in adolescence. Management of premature adrenarche is largely aimed at observation, lifestyle adjustments for weight concerns, and monitoring for future possible persistent androgen excess and insulin resistance. [Pediatr Ann. 2018;47(1):e7-e11.].

Clinical Case Seminar: Postmenopausal androgen excess-challenges in diagnostic work-up and management of ovarian thecosis.

Postmenopausal hyperandrogenism can be tumour- or non-tumour-related, with pathology residing either in the ovary or adrenal gland(s). The tempo of investigation is determined by the clinical severity of hyperandrogenism (presence/absence of actual virilisation) and degree of serum testosterone elevation. When clinical or biochemical hyperandrogenism is severe, rapidly developing, or associated with hypercortisolism, screening for adrenocortical or ovarian carcinoma with cross-sectional imaging should be prioritised over detailed biochemical evaluation. Adrenal hyperandrogenism is readily characterised, both biochemically and radiologically. By contrast, even a combination of high-resolution imaging with laboratory evaluation, including dynamic endocrine testing, often cannot distinguish between ovarian hyperthecosis (OH) and virilising ovarian tumour (VOT); a definitive diagnosis usually emerging only after histological examination of excised ovaries. VOTs are typically below the resolution-limit of current imaging modalities and exhibit suppression of gonadotropin-dependent androgen secretion with GnRH-analogue therapy. Thus, for well-characterised ovarian hyperandrogenism, laparoscopic bilateral salpingo-oophorectomy may serve both as a diagnostic and therapeutic procedure. Nevertheless, women unable or unwilling to undergo ovarian surgery can be reassured that malignant VOTs are exceedingly rare and that long-term medical therapy with oral antiandrogens or GnRH-analogues is safe and well-tolerated. OH is strongly associated with insulin-resistance, with hyperinsulinaemia acting synergistically with raised gonadotropin levels to stimulate thecal cell hyperplasia and androgen secretion by the postmenopausal ovary, which lacks granulosa cell aromatase activity and thus cannot convert testosterone to 17 beta estradiol. Thus, features of metabolic syndrome may indicate OH, and significant reductions in androgens can thereby potentially be achieved with lifestyle measures and/or insulin-sensitising drugs.

Ovarian hyperandrogenism in polycystosis which is associated with stress caused by exposure of manganese and nickel

Objective. High concentrations of manganese and nickel in the serum of women with polycystic ovary syndrome (PCOS) have been detected in our previous studies. The aim of this investigation was to study the features of the adrenal hormones metabolism in women with polycystic ovarian syndrome (PCOS) with a high level of manganese and nickel exposure. Material and Methods . Two groups of women were formed for study. The first group consisted of women with PCOS. Patients with Cushing's syndrome were not included in this group. The second group – control group, consisted of healthy women of reproductive age. Serum total testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17-OP), cortisol (C) were identified using ELISA in the early follicular phase. Statistical analysis of the results was performed using Student's test and Mann-Whitney. Results . Women with PCOS had enhanced levels of all studied hormones and metabolites in serum in comparison with the control group (P <0,05). An analysis of reference values frequency exceeding was done. Results showed that most often there was an increase in 17-OP level in 60.0% of cases and DHEAS in 52.38% of cases. Since 17-OP is not synthesized in the ovaries of women with PCOS, we assume that its synthesis is associated with activation of adrenal function. 17-ОР is a precursor for the synthesis of cortisol and androgens. According to the authors, adrenal function activation is associated with stress caused by manganese and nickel toxic concentrations. Cortisol relates to hormonal markers of stress. Women with PCOS had increased levels of C in 30.56%. In conditions of manganese and nickel increased level exposure determining of 17-OP can be useful in the diagnosis of hyperandrogenism. Conclusions . Significantly increased levels of hormones and metabolites predominantly of adrenal origin have been noted in women with PCOS. Revealed violations could be a manifestation of hormonal stress caused by toxic effects of manganese and nickel and are a protective mechanism of organism adaptation to adverse conditions. The process of adaptation to environmental stress is accompanied by dysfunction of the hypothalamic-pituitary-adrenal system.

Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: Aggravated complication of pregnancy.

Polycystic ovary syndrome (PCOS) affects 5–20% of the reproductive age women globally. PCOS is diagnosed by the presence of hyperandrogenism, oligo-anovulation, and polycystic morphology of at least one ovary. Insulin resistance (IR), hyperinsulinemia and associated metabolic abnormalities including metabolic syndrome play a significant role in the development of PCOS. The chances of developing MS in PCOS women was shown to increase by almost 14-fold in patients with increasing body mass index. Even in the absence of overt obesity, a preferential deposition of intra-abdominal fat is noted in PCOS women and this intra-abdominal fat leads to impaired insulin action and functional IR and hyperandrogenism. Functional ovarian hyperandrogenism of ovaries was suggested to be a consequence of IR, which activates androgen synthesizing enzyme, cytochrome p450-c17α-hydroxylase, in ovarian theca cells and causes elevated oxidative stress accompanied by lower antioxidant status in ovaries, which contribute to PCOS pathogenesis. The elevated levels of luteinizing hormone that accompany the early stages of hyperandrogenemia, accelerate ovarian functional deterioration, which is further aggravated by hyperinsulinemia, in PCOS women. The risk of developing gestational diabetes in PCOS women is approximately three times greater, as compared to non-PCOS women, due to IR and hyperinsulinemia. Typical insulin-sensitizing drugs such as metformin, have been used to curtail IR and hyperinsulinemia in pregnant PCOS women, with varying results indicating the complexity of the disease and the need for better controlled studies and additional efforts for PCOS-specific drug discovery.

Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). To investigate the usefulness of an elevated (>40pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. 141 patients with an elevated AMH and body mass index either <20kg/m2 (lean) or >30kg/m2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111±73 vs 56±31, P<0.001) in lean women with FHH compared to those without FHH. PCOS and FHH share common features of elevated AMH levels, oligo-anovulation and polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH.

Which origin for polycystic ovaries syndrome: Genetic, environmental or both?

Polycystic ovaries syndrome (PCOS), the most common female endocrine disorder, affects 7–10% of women of childbearing age. It includes ovarian hyperandrogenism, impaired follicular maturation, anovulation and subfertility. Insulin resistance, although present in most cases, is not necessary for diagnosis. It increases hyperandrogenism and long-term metabolic, cardiovascular and oncological risks. The origin of hyperandrogenism and hyperinsulinemia has a genetic component, as demonstrated by familial aggregation studies and recent identification of associated genomic variants, conferring a particular susceptibility to the syndrome. However, experimental and epidemiological evidences also support a developmental origin via a deleterious foetal environment, concerning the endocrine status (foetal hyperandrogenism), the nutritional level (intrauterine growth retardation), or the toxicological exposure (endocrine disruptors). Epigenetic changes recently reported in the literature as associated with PCOS, enhance this hypothesis of foetal reprogramming of the future adult ovarian function by environmental factors. Better characterisation of these genetic, epigenetic, or environmental factors, could lead to earlier prevention and more efficient treatments.

Free testosterone and dehydroepiandrosterone sulfate serum levels in polycystic ovary syndrome women

Objectives: This study designed to detect the prevalence of ovarian and/or adrenal hyperandrogenism in women with Polycystic Ovary Syndrome (PCOS).Materials: One hundred PCOS women included in this cross sectional study after informed consent and approval of the study by local institute ethical committee. Diagnosis of PCOS based on the Rotterdam ESHRE criteria. Studied women underwent complete physical examination with calculation of body mass index (BMI) and assessment of hirsutism by modified Ferriman Gallway score. Clotted blood sample taken from studied women for measurement of serum total testosterone, sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS) to detect the prevalence of ovarian and/or adrenal hyperandrogenism in PCOS women. Results: 66% of studied PCOS women presented with hirsutism, 22% of studied PCOS women presented with menstrual irregularities (hypomenorrhea, oligomenorrhea) and dysmenorrhea was the presenting symptom in 12%. Free testosterone was elevated in 50 cases of studied women; DHEAS was elevated in 30 cases of studied women while the remaining 20 cases had elevated both free testosterone and DHEAS. Mean free testosterone was 2.6±1.8 pg/ml and mean DHEAS was 5.5±3.8 mg/l. Conclusion: The ovary is the main source of excess androgen in PCOS (50% of studied women) and excess adrenal androgen found in 30% of studied PCOS women, further large studies recommended to confirm this finding.

Discriminating between virilizing ovary tumors and ovary hyperthecosis in postmenopausal women: clinical data, hormonal profiles and image studies.

The presence of virilizing signs associated with high serum androgen levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized postmenopausal women. The differential diagnosis between these two conditions is often difficult. To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. A retrospective study. A tertiary center. Clinical data, hormonal status (T, E2, LH and FSH), pelvic images (transvaginal sonography and MRI) and anatomopathology were reviewed. Thirty-four postmenopausal women with a diagnosis of VOT (13 women) and OH (21 women) were evaluated retrospectively. Clinical signs of hyperandrogenism were more prevalent in the VOT group than the OH group. Although the VOT group showed higher T and E2 levels and lower gonadotropin levels than the OH group, a great overlap occurred among the hormone levels. A pelvic MRI provided an accurate differentiation of these two conditions. In this group of patients, the main features contributing to the differential diagnosis of VOT and OH were serum levels of testosterone and gonadotropins and the presence of an ovarian nodule identified on the MRI. Although the association of clinical, hormonal and radiological features contributes to the differential diagnosis of these two conditions, histopathological analysis remains the gold standard for the diagnosis of ovarian hyperandrogenism in postmenopausal women.

Determination of Source of Hyperandrogenism and Comparisons of Hormonal and Metabolic Profile in Different Phenotype of PCOS: A Hospital Based Study

Objective: Metabolic parameters in polycystic ovary syndrome (PCOS) correlate to their phenotypic presentations and sources of hyperandrogenism. Till date no studies have evaluated the source of hyperandrogenism among phenotypic variants of PCOS. Therefore we determined the sources of hyperandrogenism and compared the metabolic parameters in different phenotypes of PCOS. Material method: Study included 120 PCOS patients and 15 age matched controls. PCOS were diagnosed by revised Rotterdam criteria (2003). Different phenotypic presentations like polycystic ovary (P), ovulatory dysfunction (O) and hyperandrogenism (H) were evaluated and compared for anthropometrical, hormonal and metabolic parameters. They were correlated with the source of androgen excess following post Leuprolide acetate (20 μg/kg) 17-OHP and post synacthen (250 μg) DHEAS measurement. Result: This study had 2 phenotypic presentations i.e. PHO (80%) and OH (20%) out of 4 phenotypic presentations described by Rotterdam among all PCOS (may be due to referral bias). Among obese PCOS 87.5% had PHO and 12.5% had OH phenotypes, while it was 75% and 25% in normal weight PCOS. PHO phenotypes had adrenal and ovarian source of hyperandrogenism. Fasting insulin and HOMA-IR were higher in non-obese PHO than obese PHO but statistically insignificant. Serum DHEAS (delta steroid) had a negative but serum testosterone (keto steroid) had positive correlation with IR in PCOS. Conclusion: Both adrenal and ovarian hyperandrogenism was found in PHO as compared to OH phenotype that had only ovarian hyperandrogenism. Normal weight PCOS had less chance of getting ultrasound abnormalities compared to obese PCOS. PHO phenotypes, who had a greater degree of serum DHEAS had a better metabolic profile despite a greater BMI. So our result suggests that distinction between source of hyperandrogenism and evaluation of different phenotype is beneficial in predicting metabolic risk and future management.

Anti-Müllerian hormone reflects the severity of polycystic ovary syndrome.

To examine the relationship between anti-Müllerian hormone (AMH) and the severity of the phenotype of patients with polycystic ovary syndrome (PCOS) and whether AMH can act as a diagnostic marker for PCOS? A prospective diagnostic utility study of AMH as a marker of PCOS. A consecutive series of women presenting to a tertiary infertility clinic (n = 164) plus a second series of women prepared for assisted conception treatments (n = 89) recruited between June 2012 and May 2013. Polycystic ovary syndrome was diagnosed using the Rotterdam criteria. AMH was measured using the Generation II assay (Beckman Coulter). The diagnostic utility of AMH was established using receiver operator characteristic (ROC) curves. Cut-off values for the individual features of PCOS are proposed. There was a significant difference in serum AMH concentration in women with normal ovaries (13·2 pmol/l), polycystic ovary morphology (PCOM) alone (37·8 pmol/l) and PCOS (53·2 pmol/l). Follicle number, increasing cycle length and evidence of hyperandrogenism were all independently associated with serum AMH concentration (P < 0·01). AMH was significantly affected by the different phenotypic presentations of PCOS with those with all components (PCOM, HA and OA) having the highest mean value [72·7 pmol/l (P < 0·01)]. Serum AMH has the capacity to act as a diagnostic test for PCOS. Moreover, since its value rises with the more marked phenotypes, different cut-off values need to be used to differentiate those patients with polycystic ovarian morphology (PCOM), hyperandrogenism (HA) and oligoanovulation (OA).

The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.

Genetic factors responsible for ovarian hyperandrogenism in women

Genetic factors responsible for ovarian hyperandrogenism in women

Weight loss for women with and without polycystic ovary syndrome following a very low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

BackgroundPolycystic ovary syndrome (PCOS) affects between 2% and 26% of reproductive-age women in the UK, and accounts for up to 75% of anovulatory infertility. The major symptoms include ovarian disruption, hyperandrogenism, insulin resistance, and polycystic ovaries. Interestingly, at least half of the women with PCOS are obese, with the excess weight playing a pathogenic role in the development and progress of the syndrome. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions; however, optimal dietary guidelines are missing. Although many different dietary approaches have been investigated, data on the effectiveness of very low-calorie diets on PCOS are very limited.Materials and methodsThe aim of this paper was to investigate how overweight/obese women with PCOS responded to LighterLife Total, a commercial very low-calorie diet, in conjunction with group behavioral change sessions when compared to women without PCOS (non-PCOS).ResultsPCOS (n=508) and non-PCOS (n=508) participants were matched for age (age ±1 unit) and body mass index (body mass index ±1 unit). A 12-week completers analysis showed that the total weight loss did not differ significantly between PCOS (n=137) and non-PCOS participants (n=137) (−18.5±6.6 kg vs −19.4±5.7 kg, P=0.190). Similarly, the percentage of weight loss achieved by both groups was not significantly different (PCOS 17.1%±5.6% vs non-PCOS 18.2%±4.4%, P=0.08).ConclusionOverall, LighterLife Total could be an effective weight-loss strategy in overweight/obese women with PCOS. However, further investigations are needed to achieve a thorough way of understanding the physiology of weight loss in PCOS.

Hyperreactio Luteinalis: Maternal and Fetal Effects.

Hyperreactio luteinalis is a rare condition in which there is massive cystic enlargement of the ovaries, mimicking malignancy, during pregnancy. When confronted with this condition, the fear of missing a cancer diagnosis often leads the physician to react with unnecessary surgical intervention, potentially resulting in impaired future fertility. The literature on the subject contains mainly case reports and one small case series. A recent review attempted to summarize what is currently known, but there has not yet been a pervasive change in the approach to the management of this condition. In order to define the natural history of the condition and its maternal and fetal effects, we examined all case reports available in the English literature from 1993 to 2014, in addition to another as yet unpublished case report. Our analysis suggests that, despite its impressive presentation with ovarian enlargement and hyperandrogenism, hyperreactio luteinalis tends to be self-limiting, with spontaneous postpartum resolution and without untoward maternal or fetal sequelae. In particular, fetal virilization is rare, and dependent on the timing of hyperandrogenism. Adverse pregnancy outcomes are likely a consequence of the abnormally high hCG levels observed in many of these gestations, and the subset of women with these abnormal values should be considered for enhanced surveillance. Vaginal delivery is preferred, and strategies to sustain the potential for breastfeeding must be introduced while maternal androgen levels fall, allowing lactation to be established. Considering its benign nature and postpartum resolution, management of HL must be conservative, and continued education of health care professionals who may encounter this entity is vital.

Testosterone concentrations in female athletes and ballet dancers with menstrual disorders

Menstrual disorders are common among female athletes and ballet dancers. Endocrine changes, such as high testosterone (HT) levels and high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios, may suggest functional ovarian hyperandrogenism which may induce such dysfunction. The aim of this study was therefore to evaluate endocrine status in female athletes and ballet dancers with menstrual disorders. Their nutritional status and dietary habits were analysed in relation to the testosterone levels. In a cross-sectional approach, 31 female athletes (18.1 ± 2.6 years) and 21 ballerinas (17.1 ± 0.9) with menstrual disorders participated in the study. The levels of serum LH, FSH, progesterone (P), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone, testosterone (T) and sex hormone-binding globulinwere measured to assess hormonal status. In addition, the free androgen index (FAI) was calculated. Nutritional status, total daily energy expenditure and nutritional habits were evaluated. Girls were assigned to one of the following groups: low testosterone (LT) level, normal testosterone level or HT level. There were significant differences between ballerinas and other female athletes in terms of testosterone levels, FAI, age at the beginning of training, length of training period and age at menarche. The PRL level was lowest in the LT group while the FAI index was highest in the HT group. Daily energy and carbohydrate intakes were significantly lower in the HT group. T levels in the study subjects were found to be associated with nutritional factors, energy availability, age at the beginning of training and frequency of training. This is the first report of HT levels being associated with the status of a female ballet dancer, the age of menarche and the length of the training history. Further research is necessary to confirm the results in a larger study group.

Adolescent polycystic ovary syndrome due to functional ovarian hyperandrogenism persists into adulthood.

Menstrual irregularity and above-average testosterone levels in adolescence may presage polycystic ovary syndrome (PCOS) in adulthood but persist in only a minority. Prolonged anovulatory cycles in normal adolescents are associated with increased testosterone levels. Thus, questions have been raised about the accuracy of PCOS diagnosed in adolescents. The purpose of this study was to follow-up hyperandrogenic adolescents with features of PCOS to test the hypothesis that adolescent functional ovarian hyperandrogenism (FOH) persists into adulthood. A series of adults previously reported to have adolescent PCOS, with most documented to have FOH by GnRH agonist or dexamethasone androgen-suppression test criteria, were recalled. Recall occurred >3 years after the initial diagnosis and at the age of >18.0 years. Respondents underwent examination, baseline androgen evaluation, and an oral glucose tolerance test after discontinuing oral contraceptive therapy. Of the adolescent hyperandrogenic patients, 68% (15 of 22) were traceable, and 60% of those traced returned for follow-up, including half (n = 8) of the original FOH group. The baseline characteristics of respondents and nonrespondents were not significantly different. Patients with FOH were reevaluated when their mean age was 23.0 years (range, 18.4-29.4 years), gynecologic age was 10.7 years (range, 5.5-18.4 years), and body mass index was 42.3 kg/m(2) (range, 28.3-52.1 kg/m(2); P = .02 vs adolescence). Serum free testosterone was 24 pg/mL (range, 10-38 pg/mL, normal, 3-9 pg/mL; not significant vs adolescence); all were oligomenorrheic. Whereas 3 of 8 had impaired glucose tolerance as adolescents, at follow-up 6 of 8 had developed abnormal glucose tolerance (2 with type 2 diabetes mellitus). Adolescents with FOH, which underlies most PCOS, uniformly have persistent hyperandrogenism, and glucose tolerance tends to deteriorate. Testing ovarian androgenic function in hyperandrogenic adolescents may be of prognostic value.

Serum HLA-G levels in women with polycystic ovary syndrome

This study was designed to determine serum human leukocyte antigen-G (HLA-G) levels and establish whether serum HLA-G level is related with insulin resistance, oxidative stress, dyslipidemia and ovarian hyperandrogenism in women with polycystic ovary syndrome (PCOS). Twenty-five patients with PCOS and 23 healthy control women were evaluated in this study. Serum HLA-G, lipid fractions, glucose, insulin, malondialdehyde (MDA), glutathione (GSH), white blood cell (WBC), sex hormone-binding globulin (SHBG) and other hormone (gonadotropins and androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Serum luteinizing hormone (LH), total testosterone, fasting insulin, WBC levels and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI) and HOMA-IR values were significantly higher in patients with PCOS compared with healthy women. However, the women with PCOS had considerably lower serum FSH, SHBG, MDA, GSH and HLA-G levels than healthy subjects. HLA-G was inversely related with HOMA-IR, FAI, LH/FSH ratio and WBC, but positively with high-density lipoprotein cholesterol. Decreased serum HLA-G level may be related with insulin resistance, ovarian hyperandrogenism and oxidative stress in women with PCOS. Nevertheless, the exact role of HLA-G in the pathogenesis of the disease remains to be elucidated.

The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum

BackgroundPolycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities. ObjectiveThe objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM. FindingsAdolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state. ConclusionsThere is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed.

Effects of dietary intervention in young female athletes with menstrual disorders.

BackgroundThe aim of this study was to evaluate the influence of three months of dietary intervention on menstrual cycle in young female athletes with amenorrhea or oligomenorrhea.MethodsFrom forty-five female professional athletes with menstrual irregularity that were recruited thirty-one, aged 18.1 ± 2.6 years, completed the study and were analyzed. Hyperprolactinemia, thyroid dysfunction, primary ovarian failure and hyperandrogenism were excluded in the study participants. The subjects started intense training at the age of 11.2 ± 3.5 years and continued during next 6.8 ± 3.3 years. Energy and nutrients intake, total energy expenditure, energy availability and body composition as well as serum concentrations of LH, FSH, 17 – beta estradiol and progesterone were measured at the beginning of the study and after three months of individualized dietary intervention.ResultsFollowing three months of dietary intervention significant increase in energy intake (2354 ± 539 vs. 258 8 ± 557 kcal, P = 0.004) and energy availability (28.3 ± 9.2 vs. 35.8 ± 12.3 kcal/kg FFM/d, P = 0.011) was observed as well as improved energy balance (−288 ± 477 vs. -51 ± 224 kcal/d, P = 0.002). Though no changes in BMI and body composition were noted but significant rise in LH concentrations (3.04 ± 1.63 vs. 4.59 ± 2.53 mIU/ml, P = 0.009) and LH to FSH ratio (0.84 ± 0.56 vs. 0.96 ± 0.52, P = 0.001) was achieved, but no restoration of menstrual cyclicity.ConclusionsThis report provides further support for the role of energy deficiency in menstrual disorders among young female athletes and the benefits of an adequate energy intake and energy availability on hormones concentration. Continuation controlled dietary intervention is needed to assess the extent to which long-term improvement in the nutritional status results in improvements in the hormonal status of female athletes, to an extent that would allow the regulation of the menstrual cyclity.