-
Annals of Clinical and Laboratory... Mar 2024Testosterone is the principal male sex hormone and is secreted primarily by the testes. In most clinical laboratories testosterone is routinely measured for diagnosis of... (Comparative Study)
Comparative Study
Significant Positive Bias in Lower Concentrations but Negative Bias in Higher Concentrations in Testosterone Measurement Using Beckman Access Immunoassay Compared to a Liquid Chromatography-Tandem Mass Spectrometry Reference Method.
OBJECTIVE
Testosterone is the principal male sex hormone and is secreted primarily by the testes. In most clinical laboratories testosterone is routinely measured for diagnosis of male hypogonadism or androgen excess in females using FDA approved immunoassays. We compared testosterone values measured by Beckman access immunoassay with those measured by a reference LC-MS/MS method.
METHODS
Testosterone was measured in 36 patients using left over serum or plasma specimens by both Beckman immunoassay on the DXI 800 analyzer and a reference LC-MS/MS method.
RESULTS
We observed overall significant negative bias of approximately 31.9 % when testosterone values obtained by the reference LC-MS/MS method were plotted in the x-axis and the corresponding testosterone values using the immunoassay in the y-axis, as regression equation was y=0.6887x+38.81 (n=36). The corresponding Deming regression was y=0.6639x+34.7163. However, in eight specimens with low testosterone concentrations, immunoassays significantly overestimated testosterone concentrations.
CONCLUSIONS
Immunoassays may underestimate the true testosterone concentration in males but overestimate in females with low testosterone concentration. Therefore, for diagnosis of hypogonadism in males and androgen excess in females, testosterone values obtained by Beckman Access immunoassay on the DXI 800 analyzer should be interpreted with caution.
Topics: Humans; Testosterone; Tandem Mass Spectrometry; Immunoassay; Male; Chromatography, Liquid; Female; Bias; Reference Standards
PubMed: 38802160
DOI: No ID Found -
Investigating GABA Neuron-Specific Androgen Receptor Knockout in two Hyperandrogenic Models of PCOS.Endocrinology May 2024Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links...
Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signaling in GABAergic neurons is critical in PCOS pathogenesis in 2 well-characterized hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic peripubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to gonadotropin-releasing hormone (GnRH) neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy, and impaired glucose homeostasis, was not different between GABARKO and wild-type (WT) mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinizing hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signaling in GABA neurons is largely not required for the development of PCOS-like traits in androgenized models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signaling in GABA neurons.
Topics: Animals; Polycystic Ovary Syndrome; Female; Receptors, Androgen; Mice, Knockout; Mice; Disease Models, Animal; GABAergic Neurons; Hyperandrogenism; Ovary; Androgens; Pregnancy; Gonadotropin-Releasing Hormone; Prenatal Exposure Delayed Effects
PubMed: 38788194
DOI: 10.1210/endocr/bqae060 -
Lancet (London, England) Jun 2024Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea.
METHODS
In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711).
FINDINGS
Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths.
INTERPRETATION
Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women.
FUNDING
The Jon Moulton Charity Trust.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adult; Bariatric Surgery; Ovulation; Obesity; Oligomenorrhea; Treatment Outcome; Amenorrhea; Young Adult; Gastrectomy; Infertility, Female
PubMed: 38782004
DOI: 10.1016/S0140-6736(24)00538-5 -
Current Medical Research and Opinion Jun 2024Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is... (Review)
Review
Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is drastically increasing in the Indo-Asian ethnicity over the recent years. According to Rotterdam criteria, PCOS is characterized by clinical or biochemical excess androgen and polycystic ovarian morphology; however, it has been established in the recent years that PCOS exacerbates to further serious metabolic conditions on the long term. This is a narrative literature review and not systematic review and is based on PubMed searches with relevant keywords "Polycystic ovarian syndrome AND acarbose OR metformin OR myoinositol; PCOS AND metabolic syndrome OR cardiovascular disease OR menstrual irregularity OR infertility OR chronic anovulation OR clinical hyperandrogenism" used in the title and are limited to articles published in English language with no time limits. A prominent aspect of PCOS is hyperandrogenaemia and hyperinsulinemia. About 50-70% of afflicted women have compensatory hyperinsulinemia and close to one tierce suffer from anovulation and infertility. Insulin resistance leads to metabolic complications and works with luteinizing hormone in increasing the ovarian androgen production. This excess androgen leads to clinical manifestations, irregular menstrual cycles and infertility. There isn't an entire cure, only the symptomatic clinical factors are considered rather than focusing on the underlying long-term complications. Therefore, the article focuses on a potent alpha glucosidase inhibitor, acarbose which suppresses the post meal glucose and insulin by delaying the absorption of complex carbs. It exhibits cardio-metabolic and hormonal benefits and is well tolerable in the south asian population. This review highlights the safety, effectiveness of acarbose in ameliorating the long-term complications of PCOS.
PubMed: 38771729
DOI: 10.1080/03007995.2024.2358237 -
Frontiers in Endocrinology 2024Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced... (Review)
Review
Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced Perceptual Functioning model explains the connection between ASC, savant traits, and giftedness more seamlessly, and their co-emergence with atypical sexual differentiation. Overexcitability of primary sensory inputs generates a relative enhancement of local to global processing of stimuli, hindering the abstraction of communication signals, in contrast to the extraordinary local information processing skills in some individuals. Weaker inhibitory function through gamma-aminobutyric acid type A (GABA) receptors and the atypicality of synapse formation lead to this difference, and the formation of unique neural circuits that process external information. Additionally, deficiency in monitoring inner sensory information leads to alexithymia (inability to distinguish one's own emotions), which can be caused by hypoactivity of estrogen and oxytocin in the interoceptive neural circuits, comprising the anterior insular and cingulate gyri. These areas are also part of the Salience Network, which switches between the Central Executive Network for external tasks and the Default Mode Network for self-referential mind wandering. Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases. It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations.
Topics: Humans; Androgens; Estrogens; Autism Spectrum Disorder; Male; Sex Differentiation; Klinefelter Syndrome; Perception; Brain
PubMed: 38752176
DOI: 10.3389/fendo.2024.1343759 -
Journal of Cutaneous and Aesthetic... 2024Hirsutism is the presence of excessive terminal hair on androgen-dependent sites of the body. Lasers like Alexandrite, diode, and Nd:Yag lasers have been used for hair...
BACKGROUND
Hirsutism is the presence of excessive terminal hair on androgen-dependent sites of the body. Lasers like Alexandrite, diode, and Nd:Yag lasers have been used for hair reduction with varying efficacy. Trichoscopy of hair is a simple noninvasive method of hair assessment. However, it has not been used in the assessment of diode laser hair reduction.
OBJECTIVES
This study aimed to assess the efficacy and safety of diode laser hair reduction in skin color with the help of clinical and trichoscopic assessment.
MATERIALS AND METHODS
This prospective observational study included 73 patients of hirsutism recruited in 18-month period. All participants received sessions of 805 nm diode laser at monthly intervals up to six sessions. Clinical and trichoscopic evaluation along with photographs were obtained at each visit. Side effects, if any, were noted in every sitting.
RESULTS
All patients were females of Fitzpatrick skin types III-V. All clinical parameters showed statistically significant hair reduction when compared with baseline. Trichoscopic parameters of hair reduction like total hair count, terminal hair count, and terminal/vellus hair ratio showed reduction compared to baseline which was statistically significant ( < 0.05). The most common side effect noted in our study was pain followed by erythema and perifollicular edema.
CONCLUSIONS
Diode laser is an effective and safe procedure for the reduction of unwanted facial hair, even in darker skin types. We also wish to emphasize that trichoscopy for the assessment of laser hair reduction is a recent, noninvasive, simple, and underutilized tool. No serious adverse events were noted in our study.
PubMed: 38736858
DOI: 10.4103/JCAS.JCAS_63_23 -
Endocrinology May 2024Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the...
Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.
Topics: Animals; Female; Follicle Stimulating Hormone; Mice; Ovarian Follicle; Transcriptome; Dose-Response Relationship, Drug; Oocytes; Oogenesis; Signal Transduction; Granulosa Cells; Cyclic AMP
PubMed: 38735763
DOI: 10.1210/endocr/bqae054 -
Acta Paediatrica (Oslo, Norway : 1992) Jul 2024
Topics: Humans; Polycystic Ovary Syndrome; Female; Adolescent; Contraceptives, Oral, Combined; Hyperandrogenism; Androgens
PubMed: 38727034
DOI: 10.1111/apa.17271 -
Frontiers in Endocrinology 2023The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an... (Review)
Review
The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Phytotherapy; Phytochemicals; Animals; Plant Extracts
PubMed: 38725974
DOI: 10.3389/fendo.2023.1294406