Clinical Signs Of Hyperandrogenism Research Articles

The Relationship Between Platelet Indices, Hormonal Status, and Insulin Resistance in Adolescents with Polycystic Ovary Syndrome: A Retrospective Case-Control Study

Aim: This study aimed to investigate the relationship between polycystic ovary syndrome in adolescents, a disease caused by inflammation and insulin resistance that is associated with metabolic disorders, and platelet indices, which provide information about platelet activity. Materials and methods: Patients with oligoovulation, hyperandrogenemia, or clinical signs of hyperandrogenism (hirsutism, acne, etc.) and polycystic appearance with ≥ 20 small follicles ≥ 2∼ 9 mm in diameter in both ovaries on ultrasound according to the newly updated Rotterdam criteria were included in the study with a diagnosis of polycystic ovary syndrome and formed PCOS group. Patients with similar age groups and body mass index (BMI) values who presented to the clinic for non-PCOS symptoms (vaginitis, dysmenorrhea, cystitis), whose complete blood count was checked during hormone testing, and who did not meet the Rotterdam criteria were selected as the control group. Platelet indices found in routine blood count parameters (platelet large cell ratio (P-LCR), platelet distribution width (PDW) and mean platelet volume (MPV)) were analyzed between the two groups. In addition, the relationship between these indices and hormone status and insulin resistance in PCOS patients was analyzed. Patients with diabetes mellitus, hypertension, malignant diseases, cardiovascular diseases, essential thrombocytopenia or other blood diseases and patients taking medication were excluded. Results: In the study of 123 patients, there was no statistically significant difference between the groups in terms of age and body mass index (p:>0.05). When hemogram parameters were compared between the groups, hemogram parameters such as P-LCR (p: 0.002), PDW (p: 0.011) and MPV (p: 0.007), which indicate platelet activity, were statistically significantly higher in the PCOS group. When the data of PCOS patients were analyzed, platelet indices were found to be higher in the group with high insulin resistance (p:

A Comparative Study of Fresh versus Frozen Embryo Transfer and their Outcomes in Patients with Polycystic Ovarian Syndrome

Background: In in vitro fertilization (IVF)/assisted reproductive technology, fresh embryo transfer is generally preferred over frozen embryo transfer (FET). Still, some research shows that FET could increase the childbirth rate which reduces the amount of ovarian hyperstimulation syndrome (OHSS) and pregnancy problems in females with polycystic ovarian syndrome (PCOS). There is a high risk of aberrant pregnancies, incorrect placentation, and other issues when a fresh embryo is transferred. They are more likely to get OHSS. Fresh embryo transfer reduces the chances to get pregnant as the stimulatory effect will be there for long time, and the endometrium is less receptive for the embryos and vice versa in the case of FET. For IVF, the transfer of fresh embryos is typically preferred over the transfer of frozen embryos. However, some research suggests that the transfer of frozen embryos may increase the live birth rate and decrease the rates of OHSS and pregnancy complications in women with polycystic ovary syndrome. One of the most prevalent endocrine illnesses in women of reproductive age is PCOS. Chronic anovulation, hyperandrogenemia, and clinical signs of hyperandrogenism are hallmarks of polycystic ovary syndrome in the absence of additional diseases such as congenital adrenal hyperplasia, androgen-producing tumors, or Cushing syndrome. Despite the fact that some patients are discovered to be clomiphene citrate (CC) resistant, CC is still the first line of treatment for anovulatory infertility caused by PCOS. Numerous treatments, such as the usage of metformin, ovarian drilling, and gonadotropin therapy, may be taken into consideration in these people. Materials and Methods: Fifty women in all ranging in age from 25 to 45 participated in the study. Half of the study participants are from Wardha, and the other half are from rural areas close to Wardha. Participants were chosen from patients who sought medical attention for issues relating to infertility. We have taken consent from all the patients with the mutual understanding that their medical is being used for a comparative study. All the patients in our study are subjected to IVF following embryo transfer. We have taken n = 50 in which all the patients are PCOS patients with AMH noticeably higher than others. Out of them, we have taken 25 patients who are allocated for fresh Day 5 transfer and 25 of them are allocated for Day 5 FET. We have collected data for a total of 50 patients and compared the β-human chorionic gonadotropin values whether it is positive or negative in each case. We have done a comparative study by comparing the results of patients undergoing fresh versus FET with their ages ranging from 25 to 45 years. Results: The data of fresh Day 5 embryo and frozen Day 5 transfer and their outcome were noted. We concluded that FET has good results compared to fresh embryo transfer.

Impaired Glucose Tolerance in Patients with Polycystic Ovarian Syndrome

Background: Polycystic ovary syndrome first described by Stein and Leventhal, is a complex genetic trait of unclear etiology characterized by Oligomenorrhea or anovulation, biochemical or clinical hyperandrogenism and polycystic ovarian morphology on ultrasonography. Women with polycystic ovarian syndrome have an increased risk of developing impaired glucose tolerance and type 2 diabetes mellitus. This study aims to determine the prevalence of impaired glucose tolerance in patients with polycystic ovary syndrome. Study Design: Cross-sectional study Study Duration: This study was conducted in the Department of Endocrinology Ayub Teaching Hospital Abbottabad from 1st Nov 2021 to 30th April 2022. Materials and Methods: All patients with age range 16 to 40 years who were diagnosed with polycystic ovarian syndrome were included in the study. Age, ovarian volume, clinical signs of hyperandrogenism, menstrual abnormalities, serum testosterone, blood glucose at baseline and following 75g of oral glucose load, Body mass index etc. were recorded. Data was analyzed using SPSS-23. Results: Among 139 patients, 35(25.2%) were in the age range 16-25 years while 104(74.8%) were in the age range 26-40 years. Mean age was 28.6(SD±4.2) years. 69(49.6%) patients had BMI> 30 Kg/m2, 60(43.2%) had BMI between 25-29.9 Kg/m2, while only 10(7.2%) patients had their BMI within normal range (18.5-24.9). Mean BMI was 30.7 Kg/m2 (SD±4.4). 47(33.8%) patients had ovarian volume less than 25ml while, 92(66.2%) had ovarian volume greater than 25ml. Mean ovarian volume was 25.5(SD±6.7). 106(76.3%) patients had serum testosterone less than 70ng/dl while, 33(23.7%) had serum testosterone greater than 70ng/dl. Mean serum testosterone was 48.8(SD±26.4). Hirsutism and Acne was observed in 92 (66.2%) and 91(65.5%) patients respectively. 75 (54%) women had positive family history of Diabetes, 56 (40.3%) had family history of polycystic ovary syndrome and 71 (51.1%) patients had past or current history of oral contraceptive pills. Impaired glucose tolerance was found in 52(37.4%) patients. Post stratification results were statistically significant. Conclusions: The prevalence of impaired Glucose tolerance with polycystic ovary syndrome can be as high as 37.4%. Increasing age and Body Mass Index, raise serum testosterone level and increasing ovarian volume are significant predictors for developing impaired glucose tolerance in women with polycystic ovary syndrome. Keywords: Polycystic Ovarian Syndrome, Impaired Glucose Tolerance, Predictive Factors.

Practical approaches to the use of markers of biochemical hyperandrogenism in women

Hyperandrogenism (HA) remains an actual problem that raises a large number of questions, in particular, in cases of discrepancy between the clinical signs of HA and biochemical parameters. This review includes an analysis of recent studies of androgen synthesis and metabolism in healthy women of reproductive age; management of pathologies accompanied by HA; as well as contemporary approaches to the principles of prescribing and evaluating the results of the main available markers of biochemical HA. There are сoncepts of clinical and biochemical HA. Biochemical HA is an increase in the levels of various circulating androgens. The concept of clinical HA includes hirsutism as assessed by the modified Ferriman–Gallwey scale. The most common causes of HA include polycystic ovary syndrome, non-classical forms of congenital adrenal hyperplasia, other endocrine disorders. It is necessary to carry out a differential diagnosis of these conditions with more rare causes as a primarily tumor pathology. The choice and evaluation of laboratory markers of biochemical HA should be made taking into account clinical data such as puberty history, anovulation, polycystic ovarian morphotype, obesity; presence and degree of hirsutism and/or other androgen-associated dermatopathies, the characteristics of the course of clinical HA (sudden onset, rapid progression), presence of other endocrinopathies, liver and kidney dysfunction; diabetes mellitus. The objectives of the laboratory assessment of HA are determination of HA severity; determination of the source of excess androgen synthesis (ovaries, adrenal glands); assessment of the free fraction of circulating active androgens; in some cases, assessment of the formation of active androgens in the skin. The following indicators are used to solve the tasks in laboratory diagnostics: total testosterone, free testosterone, free androgen index, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, dihydrotestosterone. A comprehensive assessment of these indicators allows not only assessing the presence of HA and its severity, but also the nature of its leading and secondary components, which determine the presence and prognosis of metabolic risks and allow individualizing therapeutic approaches.

Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression.

Clinical manifestations of polycystic ovary syndrome: a modern view

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the urgent problems of gynecological endocrinology. The main signs of PCOS include a violation of menstrual and/or ovulatory function and clinical and/or biochemical hyperandrogenism, as well as polycystic ovarian morphology according to the ultrasound results. PCOS leads to infertility, obesity, and cardiovascular system diseases. PCOS is an important symptom complex in the diagnosis, which directly affects the reproductive function of females, hence the percentage of fertility. This study aimed to analyze the features of clinical, laboratory, and instrumental parameters in females with a previously established PCOS diagnosis referred for surgical treatment. The obtained results were studied from the point of view of the clinical guidelines of the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology (2003), International PCOS Network (2018), and the Ministry of Health of the Russian Federation (2021).
 MATERIALS AND METHODS: The study included 121 females who were admitted to hospitals in Moscow for surgical treatment. Among the gynecological surgical hospitals, the following medical institutions were allocated: the city clinical hospital, the research center, and the commercial clinic we conditionally divided into three levels.
 The city clinical hospital had 54 females (1st group) aged 2137 years, the research center with 48 females (2nd group) aged 2242 years, and the commercial clinic with 19 females (3rd group) aged 2541. Before the ovarian surgery for PCOS, all patients underwent an additional examination, including the collection of anamnesis, particularly, features of menstrual and generative function, anthropometric indicators, body weight, and height study. Based on these parameters, the body mass index (BMI) was calculated, the clinical signs of hyperandrogenism (acne, excessive hair growth on the body and face, and the degree of hirsutism) were assessed, and the hormonal profile was determined to detect biochemical hyperandrogenism (free testosterone). Additionally, the level of glucose and insulin in the blood plasma was determined in all patients, and a pelvic ultrasound examination (ultrasound) was performed.
 RESULTS: Menstrual irregularities were revealed, of which complaints were presented by a total of 49.5% of patients. The results of the preliminary selection of patients with PCOS for surgical treatment revealed that 108 (89.2%) had primary and secondary infertility, of whom 64 (52.9%) had BMI within the normative values, 29 (23.9%) were overweight, and 25 (20.6%) were obese. Clinical manifestations of hyperandrogenism were present in 61 (50.4%) patients included in the study. The level of free testosterone above the normative values (2.85 pg/ml) was diagnosed only in 9 (7.4%) patients out of 121 who are included in the study. Additionally, this parameter was within the upper limit of the norm (average value of 2.780.36 pg/ml) in 112 females but was combined with clinical manifestations of hyperandrogenism. Black acanthosis was noted in 6 (5.0%) patients with free testosterone levels in 3.013.64 pg/ml. Increased blood glucose levels were combined with obesity in 3 (5.5%) patients of 1st group and 1 (2.1%) in 2nd group. Insulin levels significantly exceeded the upper limit of the norm in 6 (5.0%) patients. The ultrasound result in all patients (n=121) revealed the presence of echographic signs of PCOS in PCOS was confirmed by ultrasound in 54 females in 1st group, 48 females in 2nd group, and 19 females in 3rd group.
 CONCLUSION: Our results suggest an unreasonably broad interpretation of PCOS diagnosis. Therefore, PCOS diagnosis should be primarily remembered as a diagnosis-exception. Only repeated, extended, thorough, and comprehensive examination of patients with a presumed PCOS diagnosis will allow you to better navigate the individual characteristics of patients and offer adequate methods for correcting the symptom complex to improve the overall health, fertility, and quality of life.

HIPERREAÇÃO LUTEÍNICA EM GESTAÇÃO SIMPLES NORMAL: RELATO DE CASO

Hyperreactio luteinalis (HL) is a very rare and benign condition related to pregnancy, in which there is a massive and functional increase in ovaries, occupied by multiple benign theca lutein cysts. It generally does not affect pregnancy course and can be observed and diagnosed incidentally in third trimester. The cysts and, consequently, the ovaries regress spontaneously after delivery due to decrease in hCG. This report describes a case of HL in a 29-year-old primiparous woman with dyspnea, pelvic pain and clinical signs of hyperandrogenism, with the ovaries enlarged on transvaginal ultrasound. The conduct was expectant and, during delivery, a biopsy was performed, which confirmed the diagnosis. The knowledge of benign and self-limited disease defends a conservative treatment and helps in differentiation between HL and other malignant diseases. It is, therefore, essential that obstetricians are familiar with HL to guide the correct management and avoid unnecessary iatrogenic procedures.

Sexual Function in Chinese Women with Polycystic Ovary Syndrome and Correlation with Clinical and Biochemical Characteristics

To investigate sexual function in Chinese women with polycystic ovary syndrome (PCOS) and to explore the correlation with clinical and biochemical characteristics. A cross-sectional study was designed in 1000 PCOS women, aged 18–45 years, via the Chinese version of Female Sexual Function Index (FSFI) evaluating sexual function, with additional questions possibly related to sexual life. Clinical and biochemical characteristics likely to affect sexual function were determined, including anthropometric indicators, serum levels of hormones, luteinizing hormone to follicle-stimulating hormone ratio (LH/FSH ratio), prolactin (PRL), total testosterone (TT), free androgen index (FAI), sex-hormone-binding globulin (SHBG), glucose, and lipid metabolism indicators. Nine hundred ten PCOS women participated in the study, 685 patients were included after screening, and 211 were suitable to detect correlations of clinical and biochemical characteristics with sex function parameters. The mean total FSFI score was 24.19 ± 2.8; 79.56% of the women were at risk of female sexual dysfunction (FSD). Women doing regular aerobic exercise and use of contraception had higher FSFI scores, while those with a desire to conceive and clinical signs of hyperandrogenism had lower FSFI scores. There were negative associations of FSFI scores with age and body fat distribution. No significant associations between FSFI scores and hormonal factors (surprisingly including SHBG) were found, except for total testosterone and satisfaction (OR = 0.976, p = 0.002). HOMA-IR was significantly related to reduced desire score (OR = 0.914, p = 0.004) and lubrication score (OR = 0.964, p = 0.044). PCOS was associated with a high risk of FSD (defined according to FSFI) in about 80% of the women in our study, and clinical characteristics play a more important role.

Polycystic ovary Syndrome in Adolescents: Pitfalls in Diagnosis and Management.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder during a woman's reproductive lifespan, with well-documented diagnostic criteria and therapeutic strategies in adults; the same is not necessarily true for adolescents. The purpose of this review was to identify frequent pitfalls in PCOS diagnosis and management during adolescence. Although there is no global consensus on the definition, most experts converge to the presence of both oligo/amenorrhea and (clinical and/or biochemical) hyperandrogenism, as a prerequisite for diagnosis in adolescents. The former criterion includes: (a) consecutive menstrual intervals > 90 days even in the first year after menarche; (b) menstrual intervals persistently < 21 or > 45 days for ≥ 2 years after menarche; or (c) lack of menses by the age of 15 or 2-3 years after pubarche. However, these menstrual irregularity patterns may overlap with other common entities in adolescents, such as frequent or infrequent uterine bleeding or anovulation due to immaturity of the hypothalamic-pituitary-ovarian axis. Clinical signs of hyperandrogenism are obscure, without well-validated criteria. Finally, the criterion of polycystic morphology cannot be safely used in adolescents, mostly due to technical limitations of the transabdominal ultrasound. Except for the efficacy of lifestyle intervention in overweight and obese adolescents with PCOS, limited and low-quality data exist regarding the available medications, such as oral contraceptives, metformin, and anti-androgens. Individualized management, guided by clinical experience and research data and close monitoring appear the most effective approach in this PCOS population for optimal control of its reproductive and metabolic outcomes. Research focusing on PCOS genetic and molecular mechanisms may elucidate what diagnostic and therapeutic strategies will be most appropriate in adolescents with PCOS in the future.

Spironolactone for treatment of female pattern hair loss

Spironolactone for treatment of female pattern hair loss

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8–12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Nouveautés dans l’hyperplasie congénitale des surrénales: New insights in congenital adrenal hyperplasia

Congenital adrenal hyperplasia is an autosomal recessive disease due to functional abnormalities of adrenal steroid enzymes. The most common form of the disease is due to a 21-hydroxylase deficiency. The classical forms (most severe) are characterized by a deficiency in cortisol and sometimes in aldosterone, which may compromise the vital prognosis of neonates, and by an increase in androgen synthesis, leading to the virilization of girls’ external genitalia at birth, followed by clinical signs of hyperandrogenism during childhood and adolescence. Neonatal screening has improved management and reduced morbidity and mortality in the neonatal period, but its performance could be broadly optimised by adjusting the assay techniques or the biomarkers used. The genetic diagnosis is difficult owing to the large genetic heterogeneity of the 6p21.3 region, which contains the CYP21A2 gene, especially with respect to the use of new-generation techniques of sequencing. Prenatal diagnosis is now possible as early as 6 weeks of gestation, but prenatal treatment remains controversial, awaiting results from prospective cohorts evaluating its long-term impact. Since conventional therapies have limitations, new therapies are currently being developed to allow better control of androgen synthesis and a substitutive treatment that respects the physiological rhythm of cortisol secretion, which would limit the development of long-term complications.

Interventions for hirsutism (excluding laser and photoepilation therapy alone).

Interventions for hirsutism (excluding laser and photoepilation therapy alone).

Testicular feminization syndrome as rare cause of tumoral elevation of testosterone in women

The aim of our work was to evaluate the number and final diagnosis of women with an elevation of total testosterone ≥ 1.6 ng/ml measured by direct RIA assay (normal range: 0.2–0.8 ng/ml). From the database of the lab (between 2004 and 2013), we analyzed data from 130 women. The distribution showed that over half patients had total testosterone 3 ng/ml, diagnosis were: unknown because of unavailable data (n = 3), men misclassified as women by data processing (n = 2), pregnancy with normal free testosterone index (n = 2), transgender patients (n = 2), androgen therapies in post-menopausal women (n = 3), congenital adrenal hyperplasia (n = 3), adrenocortical tumor (n = 1) and androgen insensitivity syndrome (n = 1). This last 24-year-old woman was initially referred for pelvic IRM because of suspicion of Mayer-Rokitansky-Kuster-Hauser syndrome. The patient had a normal female phenotype with breast development, no clinical signs of hyperandrogenism or virilization but primary amenorrhea. IRM showed absence of Mullerian structures (uterus, fallopian tubes) and presence of two gonads in the abdomen. Biology showed elevated total testosterone (8.4n = ng/ml) with normal SHBG conferring elevated free testosterone index, low oestradiol and normal LH and FSH. Karyotype analysis demonstrated a male chromosomal sex (46XY) confirming the diagnosis of complete androgen insensitivity. Finally, FISH analysis by using a SRY gene probe confirmed the presence of SRY gene on Y chromosome. In conclusion, a systematic analysis of the lab database was a tool to detect an external case for which both academic and multidisciplinary follow-up may be helpful.

Long-term efficacy of spironolactone on pain, mood, and quality of life in women with fibromyalgia: An observational case series

ObjectiveNo single drug is broadly efficacious in the long-term treatment of fibromyalgia syndrome (FMS). Spironolactone is known to ameliorate mood and tension headache or migraine in women with premenstrual syndrome or clinical signs of hyperandrogenism. In a case series of women with treatment resistant FMS spironolactone was therefore added to their medication, and they were observed for at least 12 months. Methods31 women with treatment-resistant FMS received spironolactone as add-on medication to various pain modulating drugs. 15 women responded to spironolactone and baseline data were compared with assessments over 12–14 months on treatment with spironolactone (ALDACTONE®) in dose range 100–200mg/day. The efficacy was evaluated by the fibromyalgia impact questionnaire (FIQ) total score and 8 FIQ subtests, a German mood inventory (BSKE-EWL), and further assessments of changes in relevant psychological and physical complaints. 16 women had no effect and stopped the treatment early. ResultsThe subsequent data refer to the 15 responders. The FIQ total score (maximal score=80) decreased from 56.6±10.0 at baseline to 17.1±11.9 (mean±SD) 12–14 months later, and pain intensity on an 11 point numeric rating scale (NRS) decreased from 8.8±1.6 to 2.6±1.9 (mean±SD). Similar changes in FIQ subscores were found for fatigue, morning tiredness, stiffness, anxiety, and depression. Emotional functioning consistently improved: positive mood from 20.0±5.4 to 37.7±5.4 (maximal score=48), and negative mood from 35.4±5.3 to 10.0±4.4 (maximal score=60) (each mean±SD) as well as other mental and physical dysfunctions including non-restorative sleep. All these changes at 4–6 weeks remained on this level for 11–13 months. The drug was well-tolerated and safe, no serious adverse effects were observed. Regular monitoring of serum potassium did not reveal hyperkalemia. All 15 women were able to reduce or discontinue concomitant drugs. ConclusionFifteen of 31 women with otherwise treatment-resistant FMS experienced a number of prolonged beneficial effects from spironolactone on their complex pain-condition. Implications and discussionWe hypothesise that spironolactone affects several central and peripheral neurotransmitter systems such as γ-aminobutyric acid (GABA) activity and dopaminergic transmission. The high rate of non-responsive patients underlines that FMS may represent several subgroups. Pain relief and improvement of associated FHS-symptoms and positive effects on additional diseases or dysfunctions give reasons for marked and sustained improvement in the quality of life.Well-controlled, double-blind, and randomised trials are necessary to confirm our potentially very important observations.

Relation of antimullerian hormone with the clinical signs of hyperandrogenism and polycystic ovary morphology

The relation of antimullerian hormone (AMH) levels with the clinical and biochemical markers of polycystic ovary syndrome (PCOS) could be different. A total of 463 PCOS patients were evaluated in this cross-sectional study. Groups were constructed according to polycystic ovarian morphology (PCOM) and menstrual cycle-length. The relation of serum AMH with androgenic hormones, menstrual cycle-length and clinical signs of PCOS were investigated. A powerful positive relation was found between the PCOM and AMH levels (odds ratio = 2.49). There was a negative correlation between age and AMH level (p < 0.001, r[correlation coefficent] = −0.155). Positive correlations were found between luteinizing hormone (LH) and AMH (p < 0.001, r = 0.25) and also between cycle length and AMH (p < 0.01, r = 0.27). We found a negative week correlation between AMH and follicle-stimulating hormone (FSH) (p = 0.01, r = −0.19). After controlling main androgenic hormones, AMH was found to be correlated with the Ferriman–Gallway score (p = 0.03, r = 0.18). There was a positive relationship between hirsutism and AMH (odds ratio = 1.43), but no correlation between AMH and other parameters of clinical hyperandrogenism like hair-loss, acne and seborrhea were identified. The strongest relation was presented between the AMH levels and PCOM. Also, cycle-length correlated well with the AMH levels. The relationship between hirsutism and AMH is found to be independent from androgenic hormones.

Hyperandrogenism secondary to topical testosterone exposure

Topical testosterone gels are now a widely used method of testosterone replacement therapy and have been shown to be convenient and effective[1]. The unintentional transfer of testosterone gel to children or partners by skin contact is a rare but significant adverse effect[2]. A 3-year-old well girl was referred for assessment of precocious puberty. Pubic hair had been first noted by her mother 9 months earlier. Examination revealed a tall girl (>99.9th centile) with no breast development but Tanner stage III pubic hair and cliteromegaly. Testosterone levels were elevated at 2.5nmol/l, as was her Androstenedione level at 1.1nmol/l. 17 OH P was normal and tumour markers were negative. Urine steroid profile was quantitatively normal but there was a modest increase in androgen metabolites. Bone age was advanced by 16 months. Ultrasound and MRI imaging of her ovaries and adrenals did not reveal a source of androgen production. Upon further direct questioning, her father revealed he was using topical testosterone replacement therapy. Her father was advised of measures to reduce secondary exposure. Her repeat testosterone level fell to <0.7 nmol/l upon retesting 4 months later and the cliteromegaly resolved. At follow up a further six months later, testosterone level had risen to 2.5nmol/l. Switching to the use of IM preparations was encouraged. Follow-up testing after these measures were adopted revealed normal undetectable testosterone levels (<0.7nmol/l). Once daily application of testosterone gels to the skin results in relatively stable and physiological testosterone levels in most users[3]. It is often favoured above the other methods of delivery of testosterone as it is painless, discrete and convenient to use. Even small quantities of transferred testosterone may result in clinical signs of hyperandrogenism. When reviewing children with evidence of virilization, we must remember to question parents about the potential for exogenous androgen exposure.

Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors

The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism. A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism. Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5-14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7-2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6-7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3-5.4). Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopausal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.

Androgen deficiency in women and possibilities for its hormonal diagnostics

The authors describe the distribution patterns of free testosterone concentrations in the saliva of women who previously underwent ovariectomy, in postmenopausal women, in those presenting with clinical signs of hyperandrogenism, and in healthy women in the follicular phase of the menstrual cycle. The level of salivary free testosterone in postmenopausal women and after ovariectomy was lower than in younger premenopausal patients. Women with clinical signs of hyperandrogenism showed higher free testosterone levels than the age-matched young healthy subjects. The salivary free testosterone levels in 60-75% of the ovariectomzed, postmenopausal, and hyperandogenic women remained within their normal range in young healthy women. It is concluded that high analytical sensitivity of the chemiluminescent method for the measurement of free testosterone in the saliva makes possible its application to the screening for androgen status of the women at risk of testosterone deficiency.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome

Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.