Multifollicular Ovaries Research Articles

Neonatal diabetes mellitus and polycystic ovaries in a child with severe insulin resistance caused by a variant in the INSR gene. Description of the clinical case

Rare severe insulin resistance syndromes such as Donohue syndrome, RabsonMendenhall syndrome, and type A insulin resistance are caused by mutations in the insulin receptor (INSR) gene. Donohue and RabsonMendenhall syndromes are caused by biallelic mutations in the - and / or -subunits of INSR, are characterized by a severe course with severe clinical symptoms and an unfavorable prognosis. The difficulty of managing and treating these patients is associated with a low incidence, lack of practice in managing such patients, as well as a lack of experience in surgical interventions in these patients.
 All insulin resistance syndromes are characterized by a significant increase in the level of insulin in the blood plasma in the absence of obesity, progressive diabetes mellitus and an excess of androgens. Polycystic ovary syndrome or stromal hyperthecosis develops in adult patients with syndromic forms of insulin resistance.
 We present a rare clinical case of a complicated course of Donohue syndrome, diagnosed in a 2-month-old patient. A feature of this clinical case was the giant growing multifollicular ovaries, which became an absolute indication for organ resection surgery.
 The experience of treatment and observation of this patient reflects the importance of early verification of the diagnosis, timely appointment of adequate therapy, allows you to objectively assess the effectiveness of the treatment, helps in choosing medical tactics and predicting the course and outcome of the disease.

PMON281 PERSISTENT VIRILIZATION AND VASOMOTOR SYMPTOMS IN A TRANSMAN 5-YEARS POST TESTOSTERONE WITHDRAWAL

Abstract Introduction Polycystic ovarian syndrome (PCOS) is one of the most common reproductive abnormalities, characterized by irregular menses, hirsutism, and polycystic ovaries (PCO). In cisgender females is associated with insulin resistance and increased risk of metabolic and CV disease. Management of PCOS in transmen has not been established. Case Presentation Twenty-three-year-old transman referred for evaluation of heat intolerance, upper body flushing, sweating, and nausea. Symptoms were severe, non-responsive to lifestyle modifications. He denied change in size of hats, rings or shoes, no easy bruising, no muscular weakness but increased facial hair even after 5-year testosterone withdrawal. He had a normal puberty, menses, breast growth and distribution of fat for assigned female at birth. Testosterone gender affirming care started at age 14 to age 18 but discontinued secondary to irritability and rage. Progesterone and etonogestrel implant were used without success of suppression of menses, requiring hysterectomy with retention of ovaries, to relieve gender dysphoria (GD), in addition to gender affirming bilateral mastectomy. Physical exam is notable for normal vital signs, weight 111 Kg, BMI 33, +male pattern alopecia, terminal facial hair, full beard, acne, supraclavicular fat deposition, and pink thin abdominal stria. Total testosterone and DHEA were elevated at 58.7 ng/dl (13.84-53.35 ng/dL) and 501 ug/dl (18-391 ug/dL) respectively; random estradiol 63 pg/ml; SHBG, LH, FSH, TSH, free T4, T3, IGF1, prolactin, 24-hour urine cortisol and 5-HIAA were normal. Repeat labs were similar, and free testosterone was 26 pg/ml (1-18 pg/mL). Pelvic US showed multi follicular ovaries. A trial of low dose oral estradiol resulted in total resolution of symptomatology. Discussion PCOS was diagnosed based on hirsutism and PCO. He was not bothered by virilization; testosterone was declined as his GD was relieved by gender affirming surgical interventions. We hypothesize that mood disturbances may have been secondary to high endogenous and exogenous androgen levels, as symptomatology resolved upon testosterone withdrawal. We postulate that climacteric symptoms relieved by low dose estradiol may have been the result of an alteration in hormonal feedback. Decreased feedback of testosterone to the hypothalamus has been described during antiandrogen therapy for prostate cancer, as the cause of hot flashes and nausea. Our patient did not have low androgen levels; however, it is possible that drastic fluctuations in androgens, caused "relative hypogonadal" status resulting in his symptomatology. There are no clear guidelines on evaluation and treatment of PCOS in transmen; as virilization is usually not bothersome, however more research is needed on the metabolic effects and CV risk in this population. Our case emphasizes the importance of obtaining baseline hormonal levels before initiation of hormonal affirming care. Transmen are to be screened for PCOS and work up of unexplained hirsutism pursued to treat metabolic and CV risk factors aggressively. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Ultrasound in Polycystic Ovarian Syndrome: What? When? How? Why? Who?

Assessment of the ovarian morphology is one of the most commonly performed ultrasound examinations. Polycystic ovarian syndrome (PCOS) is a multifactorial, multifaceted, polygenic disorder with varying phenotypes. It defines a labyrinthine symptomatology including menstrual cycle irregularities, hormonal imbalance, and metabolic disturbance. Historically, this syndrome has been diagnosed clinically with supportive lab parameters. However, the role of ultrasound has mutated from identifying, to mis-defining and finally to re-classifying PCOS. At present it seems that the ultrasound identification of the ‘string of pearls’ has cemented this disease with a misleading name. A supposed increase in the detection of polycystic ovarian morphology on ultrasound has been accredited to advances in technology allowing better visualisation of the ovaries/stroma/follicles by higher frequency probes with the possibility of endovaginal imaging. Nevertheless, there is a disparity in what the ultrasound shows, how the clinician interprets the report, and what the patient understands about her diagnosis. Identification of the multifollicular ovary is still quite frequently ascribed to PCOS, while ovarian ultrasound remains ambiguous to the different phenotype of PCOS. Whether morphological disparities represent a normal variation in ovarian anatomy or true precursors of PCOS remains debatable. The absence of definition of a ‘normal’ ovary with respect to volume and follicular number, makes the diagnosis of PCOS more challenging.

Clinical and ultrasound characteristics of the health status of fertile aged women, who smoke and have metabolic syndrome

Objectives: to identify clinical and ultrasound indicators that can determine the need for further examination of fertile aged women who smoke and have metabolic syndrome (MS) regarding the risk of developing somatic pathology or diseases of the reproductive system.Materials and methods. 2 groups of women of fertile age were examined: the first group consisted of 20 women who smoked with MS, the second group included 20 women who smoked without MS. All women were interviewed using a specially designed general and reproductive health questionnaire. Ultrasound examination of the abdominal cavity and pelvic organs was performed using convex and transvaginal sensors according to existing examination protocols.Results. Women of the first group had a higher body mass index and other obesity parameters, which is typical for MS. Women of the second group smoked more cigarettes per day. The identified early onset of menstrual function in women with MS may be a manifestation of hormonal homeostasis disorders at the end of puberty with a predominance of estradiol secretion and insufficient progesterone synthesis in the second phase of the menstrual cycle. A significant amount of blood loss during menstruation and painful menstruation in women of the first group may be a manifestation of adenomyosis, which confirms by echo-positive and echo-negative inclusions in the myometrium and thickening of the uterine walls. In most patients with MS ultrasound showed multifollicular ovaries, which may point at polycystic ovary syndrome, given changes in body mass index and ovarian structure as a response on hyperestrogenemia. Prolonged manifestation of MS also negatively affected the abdominal organs, as evidenced by echo-positive inclusions in the liver and pancreas parenchyma, which is a manifestation of inflammatory diseases of these organs.Conclusions. The combination of prolonged smoking and metabolic syndrome leads to more pronounced changes in the reproductive system and abdominal organs, which in turn expands the range of recommended methods of instrumental examination for such women.

Polycystic Ovarian Syndrome: A Narrative Review Article on Serum Markers in Pcos

PCOD is a heterogeneous illness characterized by clinically or biochemically excess androgen, dysfunction in ovulation, and polycystic ovaries that is caused by a complicated hereditary disease.
 Poly-cystic ovary syndrome (PCOS), affecting 10 to 20% of premenopausal females, is a common heterogeneous disorder depending on diagnostic criteria of high serum levels of androgen concentrations, and infertility, irregular menstruation, provided that precise diagnosis such as hyperprolactinemia and inbred adrenal hyperplasia have been debarred. In recent years, the international agreement has favored the adoption of the Rotterdam criteria for mature women's diagnosis. During pubertal development, non-uniform menses, chronic anovulatory cycles, multi-follicular ovary shape, and moderately increased blood androgen concentrations are common.
 It's difficult to establish a diagnosis in adolescent females since there's a lot of overlap between typical pubertal milestones and PCOS clinical characteristics. Insulin resistance, hyperinsulinemia, and obesity are all typical symptoms of PCOS, however, they aren't diagnostic.
 Impaired glucose tolerance, which leads to insulin-dependent diabetes mellitus, insulin resistance, dyslipidemia, increased blood pressure, endometrial cancer, hyperinsulinemia, obesity, alcoholic independent fatty liver, and sleep apnea are among the comorbidities linked with PCOS. Depression and poor conditions of life are also prevalent problems. Preliminary detection of PCOS in teenage females is critical.
 The goal of this article is to offer a summary of serum indicators and evidence for several serum markers used to diagnose PCOS.

Testosterone and androstenedione are positively associated with anti-Müllerian hormone in premenopausal women.

To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women. Community-based, cross-sectional study. Eastern states of Australia. Women aged 18-39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal. AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11-oxygenated C19 steroids, measured by liquid chromatography-tandem mass spectrometry. Data were available for 794 women, median age of 33 years (range: 18-39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho = .29, p < .001) androstenedione (rho = .39, p < .001) and DHEA (rho = .10, p = .005) but not 11-ketoandrostenedione or 11-ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79-28.03; p < .001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76-8.03; p < .001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21-1.90] vs. 0.36 nmol/L [range: 0.13-0.87]; p = .001) in women with self-reported polycystic ovary syndrome. The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review.

Pathogenesis of Reproductive and Metabolic PCOS Traits in a Mouse Model.

Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder; however, the etiology and pathogenesis of PCOS are poorly understood and current management is symptom-based. Defining the pathogenesis of PCOS traits is important for developing early PCOS detection markers and new treatment strategies. Hyperandrogenism is a defining characteristic of PCOS, and studies support a role for androgen-driven actions in the development of PCOS. Therefore, we aimed to determine the temporal pattern of development of PCOS features in a well-characterized dihydrotestosterone (DHT)-induced PCOS mouse model after 2, 4, and 8 weeks of DHT exposure. Following 2 weeks of treatment, DHT induced the key PCOS reproductive features of acyclicity, anovulation, and multifollicular ovaries as well as a decrease in large antral follicle health. DHT-treated mice displayed the metabolic PCOS characteristics of increased body weight and exhibited increased visceral adiposity after 8 weeks of DHT treatment. DHT treatment also led to an increase in circulating cholesterol after 2 weeks of exposure and had an overall effect on fasting glucose levels, but not triglycerides, aspartate transaminase (AST) and alanine transaminase (ALT) levels, or hepatic steatosis. These data reveal that in this experimental PCOS mouse model, acyclicity, anovulation, and increased body weight are early features of a developing PCOS phenotype whereas adiposity, impaired glucose tolerance, dyslipidemia, and hepatic steatosis are later developing features of PCOS. These findings provide insights into the likely sequence of PCOS trait development and support the addition of body weight criteria to the early diagnosis of PCOS.

Ultrasonographic Changes of the Uterus and Ovaries in Female Infants with Congenital Adrenal Hyperplasia: Pseudo-Testicular Sign

Background: Congenital Adrenal Hyperplasia (CAH) is one of the main causes of ambiguous genitalia. The unusual appearance of internal genitalia in CAH patients is similar to many other conditions which are classified in Disorders of Sex Development (DSD). This study aimed to accurately describe diagnostic ultrasonic features of the uterus and ovaries in CAH patients in order to distinguish it from other causes of ambiguous genitalia. Methods: This cross-sectional study was performed in Akbar Children Hospital, Mashhad University of Medical Sciences, Mashhad, Iran, from 2017 to 2020. Ultrasound findings of the uterus and ovaries of 22 female infants (2-60 days of age) with CAH due to 21-hydroxylase deficiency and 47 healthy infants with a similar age were recorded and eventually analyzed in this study. Results: All the healthy infants in the control group had a normal prominent cervix, except for two neonates (95%). In the case group, only 9 (41%) infants had a normal prominent cervix, and other 13 newborns had nearly equal sizes of fundus and cervix. There was a significant difference between the two groups in the fundus-to-cervix ratio (P=0.009). The 77% patients had no follicles in both ovaries, while 28% healthy infants in the control group had no follicles, and the rest had unilateral or bilateral multi-follicular ovaries. After two months following treatment, bilateral multi-follicular ovaries were observed in all patients. The sign of non-follicular ovaries (pseudo-testicular appearance) was significantly more prevalent in the case group (P=0.004). Furthermore, half of infants showed normal pelvic lymph node that mimic a testicular-like appearance due to its uniform hyper-echoic texture. Conclusion: The testicular-like appearance of normal pelvic lymph nodes and non-follicular ovaries in a female infant with CAH. Attention to these usual findings can prevent misdiagnoses of cryptorchidism and time loss to perform other laboratory tests and karyotyping.

PROBABILITY OF MISDIAGNOSIS IN POLYCYSTIC OVARY SYNDROME

The purpose of this article was to convey information about polycystic ovary syndrome (PCOS), to reveal the information about the diagnosis of this syndrome and methods of treatment under various circumstances and reproductive plans. PCOS is now being diagnosed very often. However, frequently this is performed only on the basis of ultrasound diagnostics of the pelvic organs, which is not entirely correct. The picture of multi-follicular ovaries is just one of the symptoms of this syndrome, which may also indicate the presence of other disorders in the body.&#x0D; This is the main reason why the wrong treatment is prescribed. After all, the wrong diagnosis is the key to the wrong treatment. It is important to understand that even with true PCOS, the most important thing is a woman's reproductive plans. When a woman has reproductive plans, COC therapy is out of the question. The realities of today are such that everyone needs to understand at least a little bit about the anatomy and physiology of their own body. This helps a lot to avoid misdiagnosis and, as a result, incorrect treatment, and also speeds up the search for the true cause of the problem. If misdiagnosed, the underlying problem is ignored, which can serve as a trigger for its aggravation and, as a result, its symptoms.&#x0D; That is why everyone in our time needs to understand everything about it. So, for example, few people understand such things as: what is the menstrual cycle, how it should take place, what is its normal duration, what is the rate of discharge and in what periods of the menstrual cycle, is the pain normal at one time or another, and so on. Very often doctors of the old school prescribe, for example, COCs. Most importantly, this is often unnecessary. Also, in our society, after completing the COC course, the concept of "cancellation effect" was formed, which is not true.&#x0D; Evidence-based medicine believes that eggs have several stages of growth and development, and only one of them is regulated by hormones. The rest of the stages proceed continuously and without stopping, and no exogenous or endogenous hormones can stop this. That is, the eggs always die regardless of whether you take COCs or not - this is an axiom. No method is able to prolong the childbearing age, since the ovarian reserve ends, it stops. The only thing that can save eggs is cryo-freezing. This method can be a solution for those who want to have their own children, but at the moment, for one reason or another, fertilization does not occur.&#x0D; Yes, not all diseases can be cured, but even with those that are incurable, you need to learn to live and adapt, remove their manifestations and, if possible, reduce discomfort.&#x0D; Even in the absence of complete recovery from a particular disease, it is necessary to understand that there are methods of physical therapy, diet and conventional drug therapy that can partially improve the condition. Recently, diet therapy has been actively discussed, namely the presence of a complete, balanced and rational diet for all, without exception.&#x0D; In recent decades, fractional nutrition has shown its effectiveness. A balanced fractional nutrition allows you to provide the body with a sufficient amount of energy, to normalize the intestines, to ensure the normal functioning of the hormonal and nervous systems, etc.&#x0D; What is PCOS and the main health problems in women associated with this syndrome? Can true PCOS be completely cured? The correct and complete diagnosis of PCOS and the main nuances of its "treatment" are offered.

2-D and 3-D ultrasonographic characteristics of the ovary in women with PCOS and multifollicular ovaries

In this prospective study, seventy-six patients (PCOS group; n = 36, multifollicular ovary group; n = 40) were evaluated by 2-D and 3-D ultrasonography. VOCAL programme, echogenicity, number of follicles and blood flow parameters were evaluated. The patients with PCOS had a higher total ovarian volume, mean stromal volume and stromal echogenicity (18.6 ± 4.75 to 10.2 ± 3.4 p < .01; 12.23 ± 2.53 to 5.02 ± 2.44 p = .02; score 1:28 to 10 p < .01, respectively). There was no statistically significant difference in terms of mean RI and PI values between the groups (p > .05). 3 D power Doppler parameters included VI, FI, and VFI values of the patients with PCOS were higher when compared to those of the patients with multifollicular ovary (3.82 ± 2.65 to 1.78 ± 1.2, p < .01; 50.76 ± 4.45 to 40.6 ± 3.64, p = .03; and 2.34 ± 1.02 to 1.12 ± 0.65, p = .02, respectively). Our results revealed that total ovarian volume, stromal volume and echogenicity; VFI, VI, and FI could be useful for differential diagnosis in women with PCOS and multifollicular ovaries. Impact statement What is already known on this subject? Ultrasonography is considered the new diagnostic tool for PCOS. Enlarged ovaries with multiple small follicles peripherally located around increased ovarian stroma with increased stromal echogenicity are the sonographic features of polycystic ovaries. What do the results of this study add? 3-D Doppler ultrasonography may be more specific in the determination of multifollicular and polycystic ovaries when compared to RI and PI in 2-D Doppler ultrasonography. Moreover, 3-D power Doppler ultrasonography could be useful for differential diagnosis in women with PCOS and multifollicular ovaries. What are the implications of these findings for clinical practice and/or further research? In clinical practice, the differentiation of multifollicular ovaries and polycystic ovaries (PCO) is difficult with the use of 2-D sonography alone. Therefore, 3-D ultrasound and power Doppler may also be used in addition to 2-D ultrasound for the differentiation of multifollicular ovaries and PCO.

Identifying genes associated with the development of human polycystic ovary syndrome.

The pathophysiology of polycystic ovary syndrome (PCOS) is confusing until today as it is a multifactorial endocrine disorder. It is presented with altered gonadotropin levels, bulky multi-follicular ovaries, infertility, and obesity. This complex pathophysiology is linked with insulin resistance and hyperandrogenism. Hyperandrogenemia significantly contributes towards cosmetic anomalies including hirsutism, acne, and alopecia in the PCOS women. The preexisting insulin resistance in women with PCOS is likely to aggravate the increased levels of androgen. The review findings have shown that in the steroidogenic pathway, ovarian steroidogenesis patterns classify mainly towards the hypertrophy of theca cells along with alteration in the expression of key enzymes. The association of polymorphisms in genes encoding the process of an intricate cascade of steroidogenesis is delineated. The emergence of an unanimously accepted genetic marker for susceptible PCOS was affected based on inconsistent findings. The present study has provided a comprehensive summary of the impact of polymorphisms among the common androgen-related genes to govern the genetic predisposition.

MON-202 Changes in the Expression of Epigenetic Enzymes Induced by Prenatal Testosterone Excess May Underlie the Antral Follicular Defects in the Sheep Model of PCOS

Prenatal testosterone (T) excess leads to oligo/anovulation and multifollicular ovary in sheep, characteristics of women with PCOS. Persistence of antral follicles - the result of reduced atresia, follicular growth arrest and premature luteinization, contribute at least in part to the multifollicular ovarian morphology. Decrease in aromatase (CYP19) in granulosa cells and 17alpha-hydroxylase (CYP17) in theca cells and increase in anti-Mullerian hormone (AMH) in granulosa cells may contribute to the antral follicular persistence. Observations that histone H3K9 hypermethylation decreases cumulus cell CYP19 (Journal of Assisted Reproduction and Genetics 33: 1105-1113, 2016), AMH gene hypermethylation reduces granulosa cell AMH (Oncotarget 6: 3627-3643, 2015), and inhibition of histone deacetylation reduces theca cell CYP17 expression (PloS One 7: e49553, 2012) suggest that epigenetic changes are involved. We hypothesized that prenatal T excess induced changes in expression of CYP17, CYP19 and AMH are facilitated by changes in expression of key epigenetic enzymes. Granulosa / theca cells were isolated via laser capture microdissection from antral follicles of 21 months-of-age control (n=5) and prenatal T-treated (100mg im. twice weekly from gestational day 30 to 90; term: 147 days; n=6) sheep. Expression of methylation / demethylation and / or acetylation / deacetylation enzymes were determined by real time PCR and data analyzed by Student’s t-test and Cohen’s effect size analysis. Prenatal T excess decreased (p < 0.05) histone demethylase KDM1A in granulosa and theca cells, histone acetylase (HDAC) 3 in theca cells, and increased histone methyltransferase SMYD3 in the theca cells. Prenatal T excess also induced large magnitude (1) increases in DNA methyltransferase (DNMT) 1, histone methyltransferases EZH2 and SUV39H1, and histone deacetylase HDAC1 in granulosa cells; (2) decrease in DNA methyltransferase DNMT3B, KDM1A, and HDAC3 in granulosa cells; (3) increase in SMYD3 and HDAC1 in theca cells, and (4) decrease in KDM1A and HDAC3 in theca cells. While decrease in KDM1A and increase in SUV39H1 leading to H3K9 hypermethylation may account for reduced granulosa cell expression of CYP19, downregulation of HDAC3 may underlie the decrease in thecal cell expression of CYP17. Decreased DNMT3B expression may contribute to hypomethylation of AMH gene and consequent increase in AMH expression in granulosa cells. These findings suggest that changes in expression of key genes involved in the development of multifollicular phenotype are likely mediated via granulosa and theca cell specific changes in epigenetic enzyme expression. Because the ovarian attributes of prenatal T-treated sheep parallel that seen in PCOS women, these observations may be of translational relevance. Supported by NIH PO1HD44232.

SA53RISK COMMUNICATION IN PSYCHIATRIC GENETIC COUNSELLING: HOW OFTEN DO PATIENTS WANT TO DISCUSS SPECIFIC CHANCES FOR ILLNESS, HOW ARE THESE CHANCES PERCEIVED, AND HOW DO THEY IMPACT PATIENT OUTCOMES?

Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder often emerging during the peri-pubertal years concomitantly with the onset of gonadarche and adrenarche. Both gonadarche and PCOS reflect functional changes in the hypothalamic–pituitary––ovarian axis. During this transition, normal girls manifest features consistent with PCOS such as irregular menses, mild hyperandrogenism, and multifollicular ovary morphology. Themes common to puberty and PCOS, neuroendocrine features, androgen exposure, and insulin sensitivity, will be considered to address the possibility that PCOS interferes with the normal pubertal transition.

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology.

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals

ObjectiveFemale-to-male transition remains a specific clinical indication for long-term testosterone administration. There is a limited number of studies dealing with the effect of androgen treatment on their female receptive targets (mainly breast and uterus) and the knowledge in this field is scarce and, sometimes, contradictory. Materials and MethodsWe performed a prospective study including 12 patients aged between 20 years and 32 years, with a diagnosis of gender dysphoria, treated with parenteral testosterone administration before sexual reassignment surgery. ResultsEndometrial histology revealed the presence of active endometrium in 10 cases and secretive endometrium in two cases. Multifollicular ovaries were observed in all cases of active endometrium, while corpus luteum was present in the two cases of secretory endometrium. Fibroids or hypertrophic myometrium were observed in 58% of the patients. Estrogen receptor was very high (59%) in the endometrial epithelial cells and low (17%) in the myometrium. Androgen receptor expression was modest in endometrial epithelial cells (24%) and sustained in myometrium (69%). Ki67 expression is steadily present in all uterine compartments, varying from 8% in epithelial endometrium to 2% in the myometrium. ConclusionOur data suggest that long-term testosterone administration to female-to-male patients during reproductive age induces a low proliferative active endometrium, associated with some hypertrophic myometrial changes.

Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a commonly encountered endocrine disorder that is characterized by a combination of hyperandrogenism, menstrual disturbances (predominantly oligomenorrhea), and a classic sonographic polycystic ovarian morphology. Additional sequelae associated with PCOS include infertility and enhanced risk of developing type 2 diabetes mellitus and cardiovascular disease. The prevalence of depressive disorders and obstructive sleep apnea is disproportionately higher in women with PCOS, and this population is at increased risk for endometrial hyperplasia and endometrial cancer. This chapter reviews the definition, epidemiology, etiology and genetics, pathophysiology, diagnosis (including history, physical examination, and laboratory tests), differential diagnosis, and management of PCOS. Syndromes and diseases associated with PCOS are discussed. Tables describe the three approaches to PCOS, conditions mimicking PCOS, diagnosis of the metabolic syndrome in women using the National Cholesterol Education Program criteria, workup for PCOS, comprehensive care for PCOS patients, and the multistep approach to treatment of PCOS-related anovulatory infertility. Figures include transvaginal ultrasound images of a normal ovary and a multifollicular ovary in a woman with PCOS, the Ferriman-Gallwey scoring system for quantifying hirsutism, acanthosis nigrans on the neck of a woman with PCOS and insulin resistance, the relationship between body mass index and basal luteinizing hormone levels, oral glucose challenge results in nonobese women with PCOS, and an algorithm for treatment decision making. This review contains 6 highly rendered figures, 6 tables, and 120 references.

Developmental programming: prenatal steroid excess disrupts key members of intraovarian steroidogenic pathway in sheep.

Prenatal testosterone (T) excess disrupts ovarian cyclicity and increases circulating estradiol levels as well as follicular recruitment and persistence culminating in multifollicular ovary similar to women with polycystic ovary syndrome. We tested whether prenatal T excess, by androgenic or estrogenic action, disrupts the steroid biosynthetic machinery in sheep in a cell-, follicle stage-, age-, and treatment-specific manner consistent with the ovarian disruptions and increased estradiol release. Impact of T/dihydrotestosterone (DHT) treatments from days 30-90 of gestation on steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P-450 17α-hydroxylase/C17, 20-lyase (CYP17A1), and cytochrome P-450 aromatase (CYP19A1) were examined on fetal day 90, 140 and 10 months (postpubertal), and 21 months (adult, no DHT group) of age by immunohistochemistry. All 4 markers changed in a cell-, follicle stage-, and age-specific manner. Both treatments increased steroidogenic acute regulatory protein expression in preantral follicles of postpubertal and adult females. Effects of prenatal T and DHT on 3β-hydroxysteroid dehydrogenase differed in a follicle- and age-specific manner. CYP17A1 was reduced in the theca interna of antral follicles by T, but not DHT, in 10- and 21-month-old females. CYP19A1 was reduced by both T and DHT at all ages barring an increase on fetal day 140. Reduced granulosa CYP19A1 and thecal CYP17A1 in adults likely disrupt the intrafollicular androgen/estrogen balance contributing to follicular persistence. The reduced thecal CYP17A1 expression suggests that the hyperandrogenic ovarian phenotype may originate from increased enzyme activity or alternatively via a different isoform of CYP17. The reduced CYP19A1 in antral follicles of adults indicates that the increased circulating estradiol release likely arises from the increased number of persisting follicles.

Ovarian torsion in children: Management and outcomes

BackgroundThe purpose of this study is to evaluate the clinical symptoms, diagnosis, management, and outcomes in children with ovarian torsion. MethodsThe charts of 50 patients with 53 cases of ovarian torsion treated between January 1989 and March 2012 were reviewed retrospectively. Long term follow up was available for 20 girls who had their ovaries left in the abdominal cavity after detorsion. ResultsIn 22 cases ovaries were removed, and in 31 cases the torsion was relieved and the ovaries left in the abdominal cavity. Twenty-five of the salvaged ovaries were black-bluish and 10 bluish in color. Since 2005, after a change in preferred treatment, all ovaries treated by detorsion were left in the abdominal cavity. The long term results were observed clinically and by ultrasound in 20 girls. Multifollicular ovaries were found in 17 girls. One girl had a normal size paucifollicular ovary, a one-year-old girl had a normal size ovary with microfollicles, and one girl had no ovarian material detectable by ultrasound. ConclusionsLong term analysis of the treatment of ovarian torsion revealed that ovaries treated by detorsion and left in the abdominal cavity preserved their normal anatomy and function. Conservative surgical treatment proved to be safe. None of the girls had thromboembolism or peritonitis, and no malignant tumors were found in the operated ovaries.

Polycystic ovary–like syndrome in adolescent competitive swimmers

To investigate the potential effects of intensive swimming on clinical and hormonal pubertal development in adolescent girls and to determine whether hyperandrogenism contributes to menstrual disorders. Cross-sectional study. Endocrinology and gynecology pediatric units of academic hospitals. Eighteen competitive swimmers and 18 age-matched control subjects with breast stages IV or V. None. Clinical, biologic, and ultrasonographic investigations. A high number of cases of hyperandrogenism was seen in swimmers compared with control subjects (n = 11 vs. n = 5 with T level >0.5 ng/mL), as well as a higher LH/FSH ratio (1.5 vs. 0.9) and SHBG level (58.4 vs. 39.5 nmol/L) and more oligomenorrhea (n = 9 vs. n = 4). Half of the swimmers with hyperandrogenism presented pauci- or multifollicular ovaries determined by pelvic ultrasound. Free T was not significantly different between the two groups. Hyperandrogenism and oligomenorrhea may be part of the spectrum of polycystic ovary syndrome in elite swimmers. Our findings suggest that hyperandrogenism may have preceded the intensive training of these swimmers and may have predisposed the choice of sport for these girls. Intensive swimming may in turn have attenuated the clinical expression of their hyperandrogenism. Follow-up after the cessation of intensive activity would be helpful to evaluate the endocrine and metabolic profiles of these swimmers.

Cystic ovaries in women affected with hereditary angioedema.

Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic-pituitary) abnormality, including high plasma beta-endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (HANE) during attacks as well as during symptom-free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HANE who were not on oral contraceptives. We have found PCO in 5/13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.