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JCEM Case Reports Jun 2024Isolated 17,20-lyase deficiency (ILD) is a partial form of 17α-hydroxylase/17,20-lyase deficiency that typically presents with infertility and lack of pubertal...
Isolated 17,20-lyase deficiency (ILD) is a partial form of 17α-hydroxylase/17,20-lyase deficiency that typically presents with infertility and lack of pubertal development. Successful live births have been achieved using assisted reproductive techniques. We present a case of spontaneous pregnancy in an 18-year-old female with ILD without reproduction treatments or glucocorticoid use. She presented to our clinic with absence of pubarche and oligomenorrhea and had typical external genitalia and complete breast development. Follicular phase progesterone and estradiol were within reference values, and androgen levels were undetectable. Corticosterone was increased, and cortisol responded partially to the ACTH-stimulation test. This profile raised a suspicion for ILD, which was confirmed by the finding of the homozygous p.R347H variant in the gene. Sex steroid replacement and glucocorticoid use during stress were prescribed. She returned 2 years later 20 weeks pregnant. Her gestation was uneventful, and a full-term healthy male was born. This phenomenon could be partially explained by sufficient estrogen synthesis via residual 17,20-lyase enzymatic activity. Intermittent estradiol use may have favored uterine development and fine-tuned the pituitary-gonadal axis rhythm. Normal progesterone levels may have permitted an adequate endometrial "implantation window" without glucocorticoid use. Finally, elevated corticosterone may have compensated for the partial cortisol deficiency.
PubMed: 38933733
DOI: 10.1210/jcemcr/luae100 -
Annals of the Academy of Medicine,... Dec 2023Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary... (Review)
Review
INTRODUCTION
Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary syndrome (PCOS). This has prompted the re-examination of the features that characterise this common condition. Current definitions have led to great heterogeneity in the prevalence of PCOS and have contributed to inconsistent treatment protocols and assessment of therapeutic outcomes. Diagnosis is further complicated by the lack of universal agreement on threshold cut-offs for ovarian dysfunction and ethnic differences in hirsutism; both of which are key features in the definitions that are commonly used currently. These challenges often result in dissatisfaction with medical care among PCOS patients and their physicians.
METHOD
Our factor analysis mathematically identified anti-Mullerian hormone (AMH), associated polycystic ovarian morphology (PCOM) and serum testosterone as the only significant cluster associated with menstrual cycle length variability.
RESULTS AND CONCLUSION
As such, we propose a simplified criteria wherein the presence of at least 2 of the 3 features below would be sufficient to define PCOS: (1) chronic oligo-ovulation or anovulation as indicated by oligomenorrhea (cycle lengths >35 days) or amenorrhea; (2) PCOM: raised AMH ≥37.0 pmol/L instead of transvaginal ultrasound assessment of ovaries; and (3) Androgen excess, or raised serum androgens above the laboratory reference for women. Further studies are required to examine whether the proposed criteria would reduce diagnostic confusion and improve care and outcomes, especially among patients of East Asian ethnicities.
Topics: Humans; Polycystic Ovary Syndrome; Female; Testosterone; Phenotype; Anti-Mullerian Hormone; Asian People; Hirsutism; Oligomenorrhea; Anovulation; Factor Analysis, Statistical; Amenorrhea; Menstrual Cycle; Ovary; East Asian People
PubMed: 38920160
DOI: 10.47102/annals-acadmedsg.202369 -
Journal of Clinical Lipidology May 2024Polycystic ovary syndrome (PCOS) is a common endocrinopathy worldwide with a heterogeneous clinical presentation including reproductive, metabolic, and endocrine... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrinopathy worldwide with a heterogeneous clinical presentation including reproductive, metabolic, and endocrine elements. However, the assessment and management of PCOS remains inconsistent, with many women undiagnosed and untreated. We now also understand that the management of PCOS should extend throughout a woman's lifespan as many elements of the syndrome persist after menopause. Management has traditionally focused on the treatment of hyperandrogenism and oligomenorrhea. Women with PCOS often have dyslipidemia, hypertension, obesity, and metabolic syndrome, which may be worsened by the hormonal abnormalities, and are therefore at higher risk for cardiovascular disease morbidity and mortality, a risk that increases after menopause. While treatment with hormonal therapy, in particular combined oral contraceptives, may improve cardiovascular risk factors, management plans should incorporate specific diagnosis and management of these factors, if present, because of the strong contribution to the risk for atherosclerotic cardiovascular disease (ASCVD). Given the complexities of the syndrome, optimal management often requires a multi-disciplinary approach including the lipid and cardiometabolic specialist to provide counseling and support for lifestyle modification along with pharmacologic therapy as indicated to address the full range of any reproductive, endocrine, and cardiometabolic abnormalities.
PubMed: 38908968
DOI: 10.1016/j.jacl.2024.04.131 -
Steroids Jun 2024Polycystic ovary syndrome (PCOS) represents major endocrine and metabolic disorder among women largely characterized by hyperandrogenism and oligomenorrhea precipitates... (Review)
Review
Polycystic ovary syndrome (PCOS) represents major endocrine and metabolic disorder among women largely characterized by hyperandrogenism and oligomenorrhea precipitates serious complications such as type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. Several etiological theories were proposed to define the exact cause of the PCOS, which is characterized, by the hypothalamic-pituitary axis, ovarian morphology, and release of adrenal steroid hormones, metabolic syndrome, and hereditary factors. The review explored the role of dysbiosis and the mechanisms through which microbial dysbiosis can affect PCOS development. In recent time, various research groups highlighted the role of microbial gut dysbiosis associated with obesity as potential etiological factor for the PCOS. In the present review, we reviewed the mechanisms attributed to the microbial dysbiosis and treatment approaches to deal with the situation.
PubMed: 38876407
DOI: 10.1016/j.steroids.2024.109455 -
F&S Science Jun 2024To study the association between altered vitamin D profiles and different indices and clinical features of polycystic ovary syndrome (PCOS), including anti-mullerian...
OBJECTIVE
To study the association between altered vitamin D profiles and different indices and clinical features of polycystic ovary syndrome (PCOS), including anti-mullerian hormone (AMH) levels, phenotypes [A {hyperandrogenism (HA)+ ovulatory dysfunction (OD)+ polycystic ovarian morphology (PCOM)}], B (HA+OD), C (HA+PCOM), and D (OD+PCOM)], insulin resistance (IR), oligomenorrhea, hyperandrogenism, obesity indices, and stress biomarkers in the ethnic population of West Bengal.
DESIGN
Case-control observational study.
SETTING
Outpatient department of gynaecology and obstetrics, Medical College, Kolkata-700073, and environing Kolkata, West Bengal, India.
PARTICIPANTS
(Patients and Control): Sample size: case group (PCOS, n=160), age: 16-38 years, and their gender, age, and ethnicity-matched healthy control (n=160).
INTERVENTIONS
In this observational study, a structured questionnaire for menstrual status and to determine the scores of cutaneous manifestations, a bioelectrical impedance analyser for measurement of anthropometric indices, relevant biochemical assessments (vitamin D, AMH, insulin, glucose and other associated hormonal profiles), statistical software for the social sciences, and Microsoft Office Excel were used to evaluate and analyze different indices (significant at P<0.01 and P<0.05).
MAIN OUTCOME MEASURES
Study of the association of vitamin D deficiency with differential manifestations of PCOS such as phenotypes of the syndrome, altered AMH levels, and risk of insulin resistance. An attempt has been made to determine the cut-off value of AMH of the PCOS patients belonging to the ethnic population of West Bengal using receiver operating characteristic (ROC).
RESULTS
Vitamin D deficiency was found to be directly correlated (P=0.000) with AMH in PCOS phenotype A (67%), oligomenorrhea, and PCOM, along with a substantial (P<0.01) agonistic relationship with insulin resistance in the PCOS population under study. In the PCOS phenotype B, the AMH level was highest, with a cut-off value of 5.27 ng/ml (asymptotic sig.=0.000, 95% CI: 8.37-9.95, derived by receiver operating characteristic-ROC analysis, with area under the ROC curve-AUC=0.949, sensitivity=0.882, and specificity=0.880). Oligomenorrhic PCOS women possess significantly (P=0.000) higher values of AMH (8.70±3.66>3.09±1.86) than the regular menstrual rhythm within the same group. PCOS patients had significantly (P<0.01 and 0.05) less skeletal muscle mass and greater subcutaneous fat content than the control group.
CONCLUSIONS
25-hydroxy-vitamin D might be intermeshed with the underlying pathophysiology and severity of PCOS, and associated metabolic disorders like IR. The AMH level is finely tuned by most of the plausible effectors of PCOS and contends to be a promising biomarker for the diagnosis and prognosis of PCOS.
PubMed: 38876205
DOI: 10.1016/j.xfss.2024.06.002 -
International Journal of Sport... May 2024Despite the increased popularity of female elite road cycling, research to inform the fueling requirements of these endurance athletes is lacking. In this case study, we...
Despite the increased popularity of female elite road cycling, research to inform the fueling requirements of these endurance athletes is lacking. In this case study, we report for the first time the energetics of a female world-tour cyclist competing in the 2023 Tour de France Femmes, an 8-day race of the Union Cycliste Internationale. The 29-year-old athlete presented with oligomenorrhea and low T3 before the race. Total daily energy expenditure assessed with the doubly labeled water technique was 7,572 kcal/day (∼4.3 physical activity levels), among the highest reported in the literature to date for a female. Crank-based mean maximal power was consistent with female world-tour cyclists (5 min, mean 342 W, 4.8 W/kg; 20 min 289 W, 4.1 W/kg). The average daily energy intake measured with the remote food photography method (Stage Days 1-7) was 5,246 kcal and carbohydrate intake was 13.7 g/kg (range 9.7-15.9 g/kg), and 84 g/hr during stages, and an average fat intake of 15% of daily energy intake. An estimated 2,326 kcal/day energy deficit was evidenced in a 2.2 kg decrease in body mass. Notwithstanding the high carbohydrate intake, the athlete was unable to match the energy requirements of the competition. Despite signs of energy deficiency preexisting (oligomenorrhea and low T3), and other further developing during the race (weight loss), performance was in line with that of other world-tour cyclists and a best personal performance was recorded for the last stage. This case study emphasizes the need for further research to inform energy requirements for female athletes' optimal performance and health.
PubMed: 38796175
DOI: 10.1123/ijsnem.2023-0275 -
Medicina (Kaunas, Lithuania) May 2024: This study aims to evaluate the association between the use of oral isotretinoin and menstrual irregularities in acne patients with previously regular menstrual... (Observational Study)
Observational Study
: This study aims to evaluate the association between the use of oral isotretinoin and menstrual irregularities in acne patients with previously regular menstrual cycles. : A prospective observational study was conducted on 58,599 female patients aged 14 to 36 at King Abdullah University Hospital in Irbid, Jordan. The patients were followed for a period of 4.5 to 8 months during treatment and for 2 months post-treatment. Menstrual cycle changes were documented, and statistical analysis was performed to identify any significant associations. : A total of 111 (37.1%) patients, who were previously known to have regular menstrual cycles, complained of menstrual changes while using oral isotretinoin. Ninety-nine of those patients who complained of menstrual changes had their cycles back to normal post-treatment. There is a significant difference in the total accumulative dose between those with changes in menses and those without; -value [0.008]. The most common change that occurred was amenorrhea ( < 0.001), followed by oligomenorrhea and menorrhagia ( < 0.001 and = 0.050, respectively). The duration of treatment was a significant predictor of menstrual irregularities, with an odds ratio (OR) of 5.106 (95% CI: 1.371-19.020, = 0.015), indicating a higher likelihood of menstrual changes with increased treatment duration. The total accumulative dose was also significantly associated with menstrual irregularities (OR = 0.964; 95% CI: 0.939-0.990; = 0.006). Additionally, a family history of PCOS significantly increased the odds of menstrual irregularities (OR = 3.783; 95% CI: 1.314-10.892; = 0.014). : The study identified that 37.1% of the participants experienced changes in their menstrual cycles while undergoing isotretinoin therapy, with the vast majority (89.2%) returning to normal within two months post-treatment. Our logistic regression analysis pinpointed the duration of isotretinoin treatment, the total accumulative dose, and a family history of PCOS as significant predictors of menstrual irregularities.
Topics: Humans; Female; Isotretinoin; Prospective Studies; Adult; Menstrual Cycle; Menstruation Disturbances; Jordan; Adolescent; Young Adult; Administration, Oral; Acne Vulgaris; Dermatologic Agents
PubMed: 38793015
DOI: 10.3390/medicina60050832 -
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 -
Journal of Reproductive Immunology May 2024Premature Ovarian Insufficiency (POI), also known as Premature Ovarian Failure (POF), is a heterogeneous disorder characterized by the cessation of ovarian function... (Review)
Review
Premature Ovarian Insufficiency (POI), also known as Premature Ovarian Failure (POF), is a heterogeneous disorder characterized by the cessation of ovarian function before age 40. Clinical symptoms include menstrual disorders: amenorrhea/oligomenorrhea or symptoms of estrogen deficiency. This review aims to provide the most important summary of the immunophenotypic profile of premature ovarian failure syndrome, along with a review of the latest reports on the usefulness of inflammatory markers. The inflammatory microenvironment in POI applies to many levels. Concomitants of autoimmune ovarian inflammation and impaired cellular immune response may be a picture of impaired regulation in autoimmune ovarian disease. The serum concentration of pro-inflammatory cytokines, like IL-6, IL-8, IL-17, tumor necrosis factor α (TNF-α), and interferon-gamma (IFN-γ), tend to increase, whereas levels of the anti-inflammatory cytokine, IL-10, tend to decrease. In our review, we focus on whether the measured immunological parameters could help in the diagnosis and prognosis of the syndrome. Among the inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) is noteworthy, as it is decreased in patients with POI. It is important to stress that besides case series, we need properly powered studies with randomization to answer which treatment is effective, and how to deal with concurrent autoimmunity. In this review, we emphasize the importance of the premature ovarian failure syndrome immunoprofile for a proper understanding of the complexity of this syndrome, potential diagnostic points, and therapeutic targets.
PubMed: 38776714
DOI: 10.1016/j.jri.2024.104253