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Journal of Pediatric Endocrinology &... Apr 2024Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired activity of the enzyme required for cortisol and aldosterone...
OBJECTIVES
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired activity of the enzyme required for cortisol and aldosterone production, resulting in increased adrenal androgen synthesis. Factors affecting fertility in CAH patients include ambiguous genitalia and their complications, excessive androgen secretion, adrenal progesterone hypersecretion, and various psychosocial factors. Serum anti-Müllerian hormone (AMH) level is used to assess ovarian reserve in women. A few data on serum AMH levels in CAH patients are available in the literature. The aim of the study was to evaluate ovarian reserve in a group of post-menarche females diagnosed with CAH by measuring serum AMH level and assessing the number of antral follicles sonographically.
METHODS
A case-control study was conducted on 17 post-pubertal CAH females and 17 age-matched healthy female controls; the mean age of the patient group was 15.09 ± 3.55 years ranging from 11 to 24 years, while the mean age of the control group was 16.04 ± 3.72 years ranging from 12 to 25 years, the mean post-menarchal age of the patients group was 3.29 ± 1.37 years ranging from 1 to 6 years while the mean post-menarchal age of the control group was 4.13 ± 1.62 years ranging from 1 to 9 years. The degree of hirsutism was compared between the two groups according to the modified Ferriman-Gallwey score, clitoral length was assessed using a digital caliber. Serum levels of adrenal androgens in addition to basal levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and serum AMH were measured in both groups.
RESULTS
Patients had smaller uterine volumes, and smaller ovarian volumes but a comparable number of antral follicles and comparable serum AMH levels relative to controls.
CONCLUSIONS
Good compliance with treatment in patients with CAH results in good hormonal control, low risk of PCOS, good fertility parameters, and a good ovarian reserve.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Infant; Child, Preschool; Ovarian Reserve; Androgens; Case-Control Studies; Progesterone; Adrenal Hyperplasia, Congenital; Fertility; Follicle Stimulating Hormone; Anti-Mullerian Hormone
PubMed: 38459773
DOI: 10.1515/jpem-2023-0462 -
The Journal of Sexual Medicine Apr 2024Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular...
BACKGROUND
Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results.
AIM
To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database.
METHODS
The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years).
OUTCOMES
We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh.
RESULTS
When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls.
CLINICAL IMPLICATIONS
Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women.
STRENGTHS AND LIMITATIONS
The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors.
CONCLUSIONS
We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Adult; Testosterone; Cardiovascular Diseases; Databases, Factual; Adolescent; Young Adult; Propensity Score; Pulmonary Embolism; Hirsutism; Venous Thrombosis; Androgens
PubMed: 38459625
DOI: 10.1093/jsxmed/qdae032 -
Endocrine Reviews Mar 2024From 1965-2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary...
From 1965-2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology; insulin resistance, hyperinsulinism, type 2 diabetes mellitus; folliculogenesis; androgen secretion; obesity; phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicates that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and pro-inflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in one-quarter of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.
PubMed: 38457123
DOI: 10.1210/endrev/bnae007 -
Journal of the West African College of... 2023Leydig cell tumors are rare but are the most common nongerm cell gonadal tumors. They are mostly benign but malignant variants have been reported. Leydig cells...
Leydig cell tumors are rare but are the most common nongerm cell gonadal tumors. They are mostly benign but malignant variants have been reported. Leydig cells constitute the main androgen-synthesizing compartment in adult males but are also capable of estrogen production. This can manifest with clinical features of excessive hormone elaboration. We report a case of a 39-year-old man with abnormal bilateral breast development, reduced libido, and weak erection of 3 years' duration. He never noticed any testicular swelling before presentation. Examination revealed well-developed breasts bilaterally and a mass in the lower pole of the left testis. Scrotal ultrasound confirmed a hypoechoic tumor measuring 2 × 3 cm in the lower pole of the left testis and hormonal evaluation revealed a markedly elevated estradiol level. A diagnosis of estrogen-secreting testicular tumor was made. He had a testis-sparing excision of the scrotal lesion as well as liposuction and excision of glandular tissues of the breasts. He had an uneventful postoperative recovery and was discharged a day after surgery. Histology of excised testicular lesion revealed a benign Leydig cell tumor. Four months following surgery, there was an improvement in libido, erection, and sperm concentration of the patient. The patient was also very satisfied with the cosmetic outcome of the excision of the bilateral gynecomastia. We recommend self-examination of testicles as an important step for early diagnosis of testicular tumors.
PubMed: 38449551
DOI: 10.4103/jwas.jwas_54_23 -
Endocrinology Feb 2024Macromastia is an excessive, rapid, or slow growth of breast tissue in 1 or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder,...
Macromastia is an excessive, rapid, or slow growth of breast tissue in 1 or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder, back, and neck pain, poor posture, infections, and loss of nipple sensation. The pathogenesis of macromastia or hypertrophy of mammary tissue remains poorly understood. The purpose of this study is to investigate the immunohistochemical expression of several hormone receptors that may potentially influence the growth of breast tissue in women with macromastia. Immunohistochemical studies performed on representative sections of breast tissue from 63 patients diagnosed with macromastia included estrogen receptor, progesterone receptor, androgen receptor (AR), prolactin receptor, growth hormone receptor, and vascular endothelial growth factor. The expression of each stain was evaluated separately in the glandular epithelium and adipose tissue and calculated as an H-score. We observed that AR expression in breast glandular and adipose tissue in women with macromastia was significantly lower than benign, nonhypertrophic breast tissue of a control group. Although the analyses were controlled for the age, the fact the mean age and hormonal status differed between the patients and the controls could have affected the results. Additional large studies will be required to further verify this finding and increase the knowledge about the etiology of this condition and then guide pharmacological treatment of juvenile and/or idiopathic gigantomastia.
Topics: Female; Humans; Vascular Endothelial Growth Factor A; Mammaplasty; Breast; Hypertrophy
PubMed: 38437158
DOI: 10.1210/endocr/bqae026 -
Food & Function Mar 2024Sex hormones play a pivotal role in the growth and development of the skeletal, neurological, and reproductive systems. In women, the dysregulation of sex hormones can... (Review)
Review
Sex hormones play a pivotal role in the growth and development of the skeletal, neurological, and reproductive systems. In women, the dysregulation of sex hormones can result in various health complications such as acne, hirsutism, and irregular menstruation. One of the most prevalent diseases associated with excess androgens is polycystic ovary syndrome with a hyperandrogenic phenotype. Probiotics have shown the potential to enhance the secretion of ovarian sex hormones. However, the underlying mechanism of action remains unclear. Furthermore, comprehensive reviews detailing how probiotics modulate ovarian sex hormones are scarce. This review seeks to shed light on the potential mechanisms through which probiotics influence the production of ovarian sex hormones. The role of probiotics across various biological axes, including the gut-ovarian, gut-brain-ovarian, gut-liver-ovarian, gut-pancreas-ovarian, and gut-fat-ovarian axes, with a focus on the direct impact of probiotics on the ovaries the gut and their effects on brain gonadotropins is discussed. It is also proposed herein that probiotics can significantly influence the onset, progression, and complications of ovarian sex hormone abnormalities. In addition, this review provides a theoretical basis for the therapeutic application of probiotics in managing sex hormone-related health conditions.
Topics: Female; Humans; Gonadal Steroid Hormones; Polycystic Ovary Syndrome; Hirsutism; Menstruation Disturbances
PubMed: 38433710
DOI: 10.1039/d3fo04345b -
Problemy Endokrinologii Feb 2024Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids...
Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.
Topics: Adolescent; Humans; Receptors, Glucocorticoid; Glucocorticoids; Adrenal Glands; Metabolism, Inborn Errors; Rare Diseases
PubMed: 38433539
DOI: 10.14341/probl13321 -
Chemical Research in Toxicology Mar 2024Pyraclostrobin and cyprodinil are broad-spectrum fungicides that are used in crops to control diseases. However, they are excessively used and, as a result, end up in...
Pyraclostrobin and cyprodinil are broad-spectrum fungicides that are used in crops to control diseases. However, they are excessively used and, as a result, end up in the environment and threaten human health and ecosystems. Hence, knowledge of their mechanisms of action is critical to revealing their environmental fate and negative effects and regulating their use. In the present study, we conducted a comprehensive study to show the adverse effects of pyraclostrobin, cyprodinil, and their mixture using zebrafish larvae and different cell lines. Several end points were investigated, including mortality, development, gene expression, reporter assays, and molecular docking simulations. We found that both compounds and their mixture caused developmental delays and mortality in zebrafish, with a higher effect displayed by pyraclostrobin. Both compounds altered the expression of genes involved in several signaling pathways, including oxidative stress and mitochondrial function, lipid and drug metabolisms, the cell cycle, DNA damage, apoptosis, and inflammation. A noteworthy result of this study is that cyprodinil and the mixture group acted as NFκB activators, while pyraclostrobin demonstrated antagonist activity. The AHR activity was also upregulated by cyprodinil and the mixture group; however, pyraclostrobin did not show any effect. For the first time, we also demonstrated that pyraclostrobin had androgen receptor antagonist activity.
Topics: Animals; Humans; Zebrafish; Molecular Docking Simulation; Ecosystem; Strobilurins; Pyrimidines
PubMed: 38419406
DOI: 10.1021/acs.chemrestox.3c00371 -
The Journal of Obstetrics and... May 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its... (Review)
Review
AIM
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its pathogenesis remains largely unknown. This review focuses on how androgen excess influences the molecular basis of energy metabolism, mitochondrial function, and mitophagy in granulosa cells and oocytes, summarizes our current understanding of the pathogenesis of PCOS, and discuss perspectives on future research directions.
METHODS
A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review.
RESULTS
Female offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5'-triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS.
CONCLUSION
In conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy-apoptosis axis.
Topics: Polycystic Ovary Syndrome; Female; Humans; Mitophagy; Apoptosis; Animals; Mitochondria
PubMed: 38417972
DOI: 10.1111/jog.15916 -
JCEM Case Reports Mar 2024Nonclassic congenital adrenal hyperplasia (NCCAH) is characterized by mild cortisol deficiency, excess androgens and adrenocorticotropin (ACTH) production, and often...
Nonclassic congenital adrenal hyperplasia (NCCAH) is characterized by mild cortisol deficiency, excess androgens and adrenocorticotropin (ACTH) production, and often with various features of dysmetabolic syndrome. Elective bariatric surgery is one of the most effective long-term management strategies for severe obesity. Our case presents a 34-year-old woman with symptomatic NCCAH and class III obesity who status post Roux-en-Y gastric bypass (RYGB) had significant weight loss with metabolic resolution of NCCAH, and no longer required glucocorticoid (GC) therapy. At 11 months post operation and off GC therapy, she had a weight deficit of approximately 160 pounds (72.57 kg) with continued metabolic resolution of NCCAH markers including ACTH, 17-hydroxyprogesterone, and androstenedione. Presently, GC therapy remains one of the few available treatments for symptomatic NCCAH; however, long-term GC therapy has the potential for various complications and side effects. Our case presents elective bariatric surgery as a potential and unique treatment option for patients with NCCAH with associated class III obesity. The exact pathophysiologic basis for this effect and its potential role in long-term management of appropriate NCCAH patients requires further study.
PubMed: 38404690
DOI: 10.1210/jcemcr/luae018