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Medicine Dec 2023Disorders/differences of sex development (DSD) include a diverse group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is... (Review)
Review
RATIONALE
Disorders/differences of sex development (DSD) include a diverse group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is discordant. It involves several variant genes, and one of them is NR5A1. NR5A1 encodes a signal transduction regulator in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal pathway, and pathogenic mutation in this gene is a cause of 46,XY DSD.
PATIENT CONCERNS
A 12-year-old individual raised as a girl was admitted to the hospital due to hirsutism and a deep voice that began at 11 years old. The individual exhibited testicular hypoplasia, clitoral hypertrophy, and female external genitalia.
DIAGNOSES
The patient was diagnosed 46,XY partial gonadal dysgenesis. The cytogenetics revealed a 46,XY karyotype and DNA sequencing shown a variant in NR5A1. Pelvic magnetic resonance imaging showed absence of uterus and ovaries. The abdominopelvic ultrasound revealed bilateral testicle in bilateral groin. Pathology confirmed testes dysgenesis.
INTERVENTIONS
The patient underwent bilateral orchiectomy at age 12 years and was given a feminizing hormonal treatment of 0.5 mg/day of estradiol valerate tablets.
OUTCOMES
The patient recovered well after surgery and hormonal treatment and had a regression in hirsutism and clitoromegaly.
LESSONS
46,XY DSD is a rare disease that the development of chromosomal, gonadal, or anatomical sex is discordant, when diagnosed 46,XY DSD, the identification of an NR5A1 variant should be considered.
Topics: Male; Humans; Female; Child; Testis; Disorder of Sex Development, 46,XY; Hirsutism; Mutation; Gonadal Dysgenesis; Steroidogenic Factor 1; Gonadal Dysgenesis, 46,XY
PubMed: 38206718
DOI: 10.1097/MD.0000000000036725 -
Pediatric Endocrinology, Diabetes, and... 2023Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report... (Review)
Review
BACKGROUND
Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report a case of a patient with symptoms of hypercortisolaemia and androgenization, who was diagnosed with ACC.
CASE PRESENTATION
In a 10-year-old patient with ACC the course of the disease was complicated by 3 recurrences. She was treated with surgery, chemo-, and radiotherapy. Currently, 8 years after the end of treatment, there have been no signs of recurrence.
CONCLUSIONS
A patient after ACC treatment requires regular check-ups and long-term observation. Constant supervision enables early diagnosis of disease recurrence, and the use of treatment improves the prognosis.
Topics: Child; Female; Humans; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Virilism
PubMed: 38031835
DOI: 10.5114/pedm.2023.132131 -
Epigenetics Dec 2023Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic...
Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): -0.080 (0.010); FDR = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.
Topics: Pregnancy; Infant; Humans; Infant, Newborn; Female; Polycystic Ovary Syndrome; Hirsutism; DNA Methylation; Hyperandrogenism; Testosterone
PubMed: 37992405
DOI: 10.1080/15592294.2023.2282319 -
European Review For Medical and... Sep 2023There is insufficient data on which cut-off value must be used to measure the increase in total testosterone (TT) compared to the upper limit of normal (CULN) in the...
OBJECTIVE
There is insufficient data on which cut-off value must be used to measure the increase in total testosterone (TT) compared to the upper limit of normal (CULN) in the diagnosis of androgen-secreting tumor (ASTM) in female individuals with premenopausal hirsutism (FIPH).
PATIENTS AND METHODS
A total of 413 FIPH over 18 years of age who were admitted to the endocrinology clinic between May 2013 and 30 April 2018 were eligible for the study. Hormone profiles of the participants in the follicular phase and other information were obtained from their files. The androgen suppression ratio (ASR) was analyzed after 48 hours of low-dose dexamethasone suppression test (LDDST) in those whose TT CULN (nmol/L) increased two-fold.
RESULTS
Idiopathic hirsutism was found in 193 participants (46.73%) and polycystic ovary syndrome (PCOS) in 200 (48.43%) and other sources of hirsutism; non-classical congenital adrenal hyperplasia (NCCAH) in 10 patients (2.42%), hyperprolactinemia in 6 patients (1.45%), ASTM of ovarian origin in 2 patients (0.48%), Cushing's disease in 1 patient (0.24%), and adrenal ASTM in 1 patient (0.24%). A cut-off value of two-fold CULN increase for TT sensitivity of 100% and a specificity of 99.5% in indicating an ASTM source, and ASR above 49% in LDDST sensitivity of 80% and a specificity of 100% in excluding an ASTM source, was used.
CONCLUSIONS
At the TT level, a two-fold increase CULN in FIPH indicates an ASTM source. In addition, ASR after LDDST is a useful parameter in the exclusion of ASTM sources in the same patient population.
Topics: Humans; Female; Adolescent; Adult; Testosterone; Androgens; Hirsutism; Testosterone Congeners; Neoplasms
PubMed: 37782181
DOI: 10.26355/eurrev_202309_33791 -
Acta Obstetricia Et Gynecologica... Apr 2024This study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma. (Review)
Review
INTRODUCTION
This study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma.
MATERIAL AND METHODS
We retrospectively analyzed patients with pregnancy luteoma admitted to the First Affiliated Hospital of Sun Yat-sen University between January 2003 and December 2022. We recorded their imaging features, clinical characteristics and neonatal outcomes. Additionally, we reviewed relevant studies in the field.
RESULTS
In total, 127 cases were identified, including eight from our hospital and 119 from the literature. Most patients (93/127, 73.23%) were of reproductive age, 20-40 years old, and 66% were parous. Maternal hirsutism or virilization (such as deepening voice, acne, facial hair growth and clitoromegaly) was observed in 29.92% (38/127), whereas 59.06% of patients (75/127) were asymptomatic. Abdominal pain was reported in 13 patients due to compression, torsion or combined ectopic pregnancy. The pregnancy luteomas, primarily discovered during the third trimester (79/106, 74.53%), varied in size ranging from 10 mm to 20 cm in diameter. Seventy-five cases were incidentally detected during cesarean section or postpartum tubal ligation, and 39 were identified through imaging or physical examination during pregnancy. Approximately 26.61% of patients had bilateral lesions. The majority of pregnancy luteomas were solid and well-defined (94/107, 87.85%), with 43.06% (31/72) displaying multiple solid and well-circumscribed nodules. Elevated serum androgen levels (reaching values between 1.24 and 1529 times greater than normal values for term gestation) were observed in patients with hirsutism or virilization, with a larger lesion diameter (P < 0.001) and a higher prevalence of bilateral lesions (P < 0.001). Among the female infants born to masculinized mothers, 68.18% (15/22) were virilized. Information of imaging features was complete in 22 cases. Ultrasonography revealed well-demarcated hypoechoic solid masses with rich blood supply in 12 of 19 cases (63.16%). Nine patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and six exhibited solid masses, including three with multi-nodular solid masses.
CONCLUSIONS
Pregnancy luteomas mainly manifest as well-defined, hypoechoic and hypervascular solid masses. MRI and CT are superior to ultrasonography in displaying the imaging features of multiple nodules. Maternal masculinization and solid masses with multiple nodules on imaging may help diagnose this rare disease.
Topics: Adult; Female; Humans; Infant, Newborn; Pregnancy; Young Adult; Cesarean Section; Hirsutism; Luteoma; Ovarian Neoplasms; Retrospective Studies; Virilism
PubMed: 37710408
DOI: 10.1111/aogs.14672 -
Medicine Sep 2023This study goaled to evaluate the ABO/Rh blood group distribution and its relationship with clinical and biochemical factors in polycystic ovary syndrome (PCOS)...
This study goaled to evaluate the ABO/Rh blood group distribution and its relationship with clinical and biochemical factors in polycystic ovary syndrome (PCOS) patients. ABO/Rh blood group distribution of the patients and the healthy individuals were compared. In addition, the features of clinical and biochemical factors were compared according to the ABO/Rh blood groups. Two hundred and sixty-five patients were involved in the study. At the time of diagnosis, hirsutism (86%) and oligomenorrhea (80.9%) were the most prevalent symptoms. There were 166 (62.6%) patients with baseline ultrasonography results consistent with PCOS. In 111 (41.9%) patients, insulin resistance was found. ABO blood group distributions in the patient (42.6% A, 17% B, 9.4% AB, 30.9% O) and control (42% A, 16% B, 8% AB, 34% O) groups were found to be similar (P = .9). There was no difference between oligomenorrhea, hirsutism, hair loss, acne, obesity, high androgen level, insulin resistance, and ultrasound characteristics according to ABO/Rh blood groups. In this study, ABO/Rh blood group distribution in individuals with PCOS was found to be similar to healthy individuals, and it was determined that ABO/Rh blood group was not a risk factor for PCOS. In addition, no correlation was found between the clinical and biochemical characteristics of the patients at the time of diagnosis and the ABO/Rh blood group.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; ABO Blood-Group System; Insulin Resistance; Oligomenorrhea; Risk Factors; Rh-Hr Blood-Group System
PubMed: 37682192
DOI: 10.1097/MD.0000000000034944 -
European Journal of Pharmaceutical... Nov 2023Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic... (Meta-Analysis)
Meta-Analysis
Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic ovary syndrome (PCOS). However, unclear risk-benefit profiles jeopardize their appropriate clinical applications. This study aimed to quantitatively evaluate the effects of the aforementioned medications and to compare their risk-benefit profiles. Randomized controlled trials published until 14th March 2022 were searched in PubMed and Embase. A model-based meta-analysis was developed to examine the time-effect profiles of each medication. The maximal percentage change of the effect (E) and time to achieve half of E (T) were estimated. Primary outcomes included menstruation, hirsutism score, free androgen index (FAI), body mass index (BMI), insulin sensitivity, and lipid profiles. Overall, 200 studies (9,685 patients and 385 arms) were identified for modeling. OCs performed exceptionally well in improving menstruation (E: 149%; T: 7.44 weeks), hirsutism score (E: 66.2%; T: 26.2 weeks), and FAI (E: 75.7%; T: 0.51 weeks). However, OCs elevated the triglyceride (TG) level (E: 12.6%; T:1.19 weeks). After 12-week OC treatment, the TG level of approximately 30% of patients, whose baselines were normal, exceeded the reference limit. This suggested that OC-induced dyslipidemia should be routinely monitored. The maximal BMI-lowering effect of metformin was similar to that of placebo (E: 3.80%); however, metformin had a shorter T (6.67 weeks versus 12.9 weeks). Further, active lifestyle intervention plus placebo significantly decreased BMI (E: 8.78%). Adding metformin to active lifestyle intervention accelerated the BMI-lowering effect within 24 weeks, whereas with the extension of this addition beyond 24 weeks, BMI did not reduce further, which indicated that benefits were limited from this prolonged addition. AAs were less potent in reducing hirsutism score (E: 40.2% versus 66.2%) and FAI (E: 34.5% versus 75.7%) compared to OCs. OC plus metformin combined OC-derived androgen-suppressing effects and metformin-derived insulin-sensitizing effects, and partially relieved the OC-induced TG increase (E: 9.76%). Baseline dependency was found in most clinical responses, implying that pharmacotherapies tailored based on baselines achieved more clinical improvements. This study presents new quantitative evidence on pharmacotherapies for PCOS. Currently, long-term risk-benefit profiles and emerging therapies are inadequately reported and require more further research.
Topics: Humans; Female; Polycystic Ovary Syndrome; Contraceptives, Oral; Androgen Antagonists; Insulin; Hirsutism; Androgens; Metformin; Hypoglycemic Agents
PubMed: 37666459
DOI: 10.1016/j.ejps.2023.106577 -
Frontiers in Endocrinology 2023Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer,... (Meta-Analysis)
Meta-Analysis
AIMS
Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.
METHODS
We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.
RESULTS
Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.
CONCLUSION
Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Polycystic Ovary Syndrome; Spironolactone; Drug-Related Side Effects and Adverse Reactions; Follicle Stimulating Hormone, Human; Luteinizing Hormone
PubMed: 37635987
DOI: 10.3389/fendo.2023.1223768 -
International Journal of Molecular... Jul 2023Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to... (Review)
Review
Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgen-secreting neoplasms, Cushing's syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVβ3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertility.
Topics: Female; Pregnancy; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Hirsutism; Androgens; Endometrium; Infertility
PubMed: 37569402
DOI: 10.3390/ijms241512026 -
Medicina (Kaunas, Lithuania) Jun 2023Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and... (Review)
Review
Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes. Here, we report a 65-year-old patient with complaints of excessive body hairiness and alopecia. The laboratory investigation showed increased levels of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S). Imaging, including transvaginal ultrasound and pelvic MRI revealed the presence of two masses in the ovaries. The patient underwent a laparoscopic bilateral salpingo-oophorectomy due to the ovarian tumors unknown etiology, and histopathological examination revealed a unilateral benign left ovarian Leydig cell tumor with bilateral ovarian stromal hyperplasia and ovarian hyperthecosis. Making differential diagnosis between ovarian tumors and ovarian hyperthecosis is difficult. Bilateral salpingo-oophorectomy is the treatment of choice in postmenopausal women with benign Leydig cell ovarian tumor, as well as ovarian hyperthecosis, as it offers both a cure and diagnostic confirmation.
Topics: Humans; Female; Aged; Leydig Cell Tumor; Postmenopause; Polycystic Ovary Syndrome; Hyperandrogenism; Hirsutism; Ovarian Neoplasms; Testosterone
PubMed: 37374301
DOI: 10.3390/medicina59061097