Widespread Distribution of Luteinizing Hormone/Choriogonadotropin Receptor in Human Juvenile Angiofibroma: Implications for a Sex-Specific Nasal Tumor.

Juvenile angiofibroma (JA) is a rare, sex-specific, and highly vascularized nasal tumor that almost exclusively affects male adolescents, but its etiology has been controversial. The G protein-coupled hormone receptor LHCGR [luteinizing hormone (LH)/choriogonadotropin (hCG) receptor] represents a promising new candidate for elucidating the underlying mechanisms of sex specificity, pubertal manifestation, and JA progression. We used highly sensitive RNAscope technology, together with immunohistochemistry, to investigate the cellular expression, localization, and distribution of LHCGR in tissue samples from JA patients. Our results provide evidence for LHCGR expression in subsets of cells throughout JA tissue sections, with the majority of LHCGR+ cells located in close vicinity to blood vessels, rendering them susceptible to endocrine LH/hCG signaling, but LHCGR+ cells were also detected in fibrocollagenous stroma. A majority of LHCGR+ cells located near the vascular lumen co-expressed the neural crest stem cell marker CD271. These results are intriguing as both LH and hCG are produced in a time- and sex-dependent manner, and are known to be capable of inducing cell proliferation and angiogenesis. Our results give rise to a new model that suggests endocrine mechanisms involving LHCGR and its ligands, together with autocrine and paracrine signaling, in JA vascularization and cell proliferation.

Mechanism of elevated LH/FSH ratio in lean PCOS revisited: a path analysis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-20% of reproductive-age women. However, the treatment of PCOS is mainly based on symptoms and not on its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in PCOS patients, was thought to be the central mechanism of the syndrome, especially in lean PCOS. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is the main regulator of GnRH secretion, whereas neurokinin B (NKB) and dynorphin regulate kisspeptin secretion in KNDy neurons. This study aims to deepen the understanding of the neuroendocrine disorder in lean PCOS patients and its potential pathophysiology-based therapy. A cross-sectional study was performed at Dr. Cipto Mangunkusumo Kencana Hospital and the IMERI UI HRIFP cluster with 110 lean PCOS patients as subjects. LH, FSH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Bivariate and path analyses were performed to determine the relationship between variables. There was a negative association between dynorphin and kisspeptin, while NKB levels were not associated with kisspeptin. There was no direct association between kisspeptin and the LH/FSH ratio; interestingly, dynorphin was positively associated with the LH/FSH ratio in both bivariate and pathway analyses. AMH was positively correlated with the LH/FSH ratio in both analyses. Path analysis showed an association between dynorphin and kisspeptin levels in lean PCOS, while NKB was not correlated with kisspeptin. Furthermore, there was a correlation between AMH and the LH/FSH ratio, but kisspeptin levels did not show a direct significant relationship with the LH/FSH ratio. HOMA-IR was negatively associated with adiponectin levels and positively associated with leptin and FAI levels. In conclusion, AMH positively correlates with FAI levels and is directly associated with the LH/FSH ratio, showing its important role in neuroendocrinology in lean PCOS. From the path analysis, AMH was also an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. Interestingly, this study found a direct positive correlation between dynorphin and the LH/FSH ratio, while no association between kisspeptin and the LH/FSH ratio was found. Further research is needed to investigate AMH and dynorphin as potential therapeutic targets in the management of lean PCOS patients.

The LH:FSH Ratio in Functional Hypothalamic Amenorrhea: An Observational Study.

BACKGROUND: In functional hypothalamic amenorrhea (FHA), luteinizing hormone and follicle-stimulating hormone levels show high interindividual variability, which significantly limits their diagnostic value in differentiating FHA from polycystic ovary syndrome (PCOS). Our aim was to profile the LH:FSH ratio in a large sample of patients with well-defined FHA. METHODS: This observational study included all consecutive patients with FHA presenting to the Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, between January 2017 and August 2023. The main parameters of interest were the LH level, the FSH level, and the LH:FSH ratio. In a subgroup analysis, we compared the LH:FSH ratio of patients with PCO morphology (PCOM) on ultrasound with that of patients without PCOM. RESULTS: A total of 135 patients were included. Only a minority of patients revealed FSH and LH levels ≤ 2.0 mIU/mL (13% and 39%, respectively). Most patients (81.5%) had an LH:FSH ratio ≤ 1.0, while a minority (2.2%) had a ratio ≥ 2.1. The LH:FSH ratio was similar in patients with and without PCOM. CONCLUSION: In a well-defined FHA sample, the LH:FSH ratio was ≤ 1 in most patients. The LH:FSH ratio may prove useful in distinguishing FHA from PCOS but needs further investigation.

Efecto de la metformina sobre los niveles de zinc y magnesio en mujeres con síndrome de ovario poliquístico

Fundamento: el síndrome de ovario poliquístico implica oligomenorrea y/o anovulación por exceso de testosterona o LH, además de trastornos metabólicos que pueden resultar en una disminución de los niveles de vitaminas y minerales importantes, incluidos los niveles de zinc y magnesio. Objetivo del estudio: mostrar si el tratamiento con metformina para mujeres de ovario poliquístico puede cambiar los niveles de zinc y magnesio en esas mujeres. Materiales y métodos: este estudio involucra a 23 mujeres de ovario poliquístico diagnosticadas temprano que no toman metformina y 16 mujeres ováricas poliquísticas que toman metformina 850 mg dos veces al día durante al menos tres meses. FSH, LH, testosterona, estradiol, prolactina, SHBG, insulina en ayunas, glucosa en ayunas, magnesio y zinc se miden en el segundo día del ciclo. Resultados: los pacientes sin metformina mostraron aumentos significativos en la relación LH, FSH y testosterona libre en valores de p de 0,03, 0,037 y 0,009 respectivamente. El zinc mostró una correlación directa con el estradiol en pacientes que no recibieron metformina y una correlación indirecta con el índice de masa corporal en pacientes en tratamiento con metformina. Conclusión: el zinc es un elemento importante para la fertilidad femenina, ya que puede mejorar el nivel de estradiol puede deberse a su actividad antioxidante que disminuye la reacción inflamatoria en la región pélvica y mejora la función del ovario. El aumento en el nivel de zinc tiene un efecto inverso en el índice de masa corporal. Sin embargo, el tratamiento con metformina en este estudio no mostró ningún efecto sobre el nivel de magnesio y zinc en mujeres ováricas poliquísticas.

Background: polycystic ovary syndrome involves oligomenorrhea and/ or anovulation due to excess testosterone or LH, in addition to metabolic disorders that may result in decreased levels of important vitamins and minerals, including Zinc and Magnesium levels. Aim of the study: To show if metformin treatment for polycystic ovarian women can change zinc and magnesium levels in those women. Subjects and methods: this study involves 23 early-diagnosed polycystic ovarian women not on metformin and 16 polycystic ovarian women on metformin 850 mg twice daily for at least three months. FSH, LH, testosterone, estradiol, prolactin, SHBG, fasting insulin, fasting glucose, magnesium and zinc are measured on the second day of the cycle. Results: the patients without metformin showed significant increases in LH, LH: SH ratio, and free testosterone at P-values of 0.03, 0.037 and 0.009 respectively. Zinc showed a direct correlation with estradiol in patients not on metformin and an indirect correlation with body mass index in patients on metformin treatment. Conclusion: Zinc is an important element for female fertility as it may enhance estradiol level may be due to its antioxidant activity which decreases the inflammatory reaction in the pelvic region and enhance ovary function. The increase in zinc level has an inverse effect on body mass index. However, metformin treatment in this study showed no effect on the level of magnesium and zinc in polycystic ovarian women.

Effect of Prebiotic Dietary Supplement Acacia senegal on Hormonal and Metabolic Markers in Polycystic Ovary Syndrome Patients: A Pilot Study.

Background The most prevalent endocrine condition affecting women of reproductive age is polycystic ovarian syndrome (PCOS), which is linked to a variety of metabolic abnormalities. Although the pathogenesis of PCOS is not fully understood, it is known that oxidative stress, altered gut microbiome, and increased gonadotrophin-releasing hormone play a significant role. Gum arabic (GA) is an edible, dried, gummy exudate from the Acacia senegal tree, well-known for its prebiotic and antioxidant effects. The main objective of the study was to assess the changes in hormonal and metabolic profiles in PCOS patients after the ingestion of gum arabic. Method This was a clinical trial conducted on fifteen patients suffering from PCOS, with a mean age of 27.8 years (20-39 years). All patients experienced irregular cycles. Hormonal and metabolic markers (follicular stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), fasting insulin, total cholesterol (TC), and glycosylated hemoglobin (HBA1c) were measured before and after the ingestion of gum arabic (30 g/day of GA dissolved in 250 ml water for eight weeks) on the second day of the menstrual cycle after granting ethical approval from the National Medicine and Poisons Board and from the participants of the study. Results The study demonstrated a significant decrease in the luteinizing hormone level, FSH/LH ratio, and cholesterol pre- and post-gum arabic ingestion (p-values 0.001, 0.013, and 0.007, respectively). Follicular stimulating hormone slightly reduced post-ingestion with no significant difference (p-value 0.414). No significant changes were seen in the testosterone, insulin, or HBA1c levels. Conclusion The study concluded that gum arabic ingestion for eight weeks decreases the luteinizing hormone and LH/FSH ratio and improves the metabolic profile by reducing the cholesterol level in PCOS patients.

An interplay of Progesterone, Leukemia Inhibitor Factor and Interleukin-6 in the window of implantation; Impact on fertility.

BACKGROUND: The process of implantation is crucial for the initiation of conception and hence fertility. In addition to a number of factors, it is regulated by a cross talk of gonadotrophins [Luteinizing Hormone (LH), Follicle Stimulatory Hormone (FSH)], ovarian steroids [Estrogen (Et), Progesterone (Pt)] and cytokines [Leukemia inhibitory factor (LIF) and Interleukin 6 (IL6)]. These biomarkers are chief players of implantation. OBJECTIVE: We aimed to explore the role of gonadotrophins (LH, FSH, LH/FSH ratio), ovarian steroids (Et, Pt) and cytokines (LIF, IL6) in the implantation process. This aim was achieved by comparing these hormones and cytokines in the fertile and infertile groups [Polycystic ovaries (PCOs), endometriosis, unexplained infertility (Uex-IF)] and finding their association in all study groups. METHODS: A case control study conducted from October 2020-March 2023. A total of 135 infertile women (with PCOs, Uex-IF, and endometriosis) and 177 fertile women (matched for age and BMI) were selected. Levels of 'Et', 'Pt', 'LIF' and, 'IL6' were estimated using Enzyme Linked Immunosorbent Assay (ELISA). LH and FSH values were obtained from hospital desk records. The Independent Student'st-test was used to compare fertile and infertile groups. One-way ANOVA test was used to compare more than two groups, and Pearson's chi-square (χ2) test was employed to compare percentages of variables. Pearson correlation analysis was performed to assess the associations and correlations. A p value < 0.05 was considered statistically significant. RESULTS: Significantly higher levels of LIF and IL6 were observed in fertile women compared to infertile women. Pt levels were significantly greater in the fertile group than in the infertile group. The FSH/LH ratio was significantly higher in the fertile group. Among infertile women, PCOs (71%) and Uex-IF (91%) exhibited lower Pt levels than the fertile controls (p < 0.01), but these levels remained within the reference range (RR). Among the fertile group (81%), levels of LIF within the RR were significantly higher compared to those with Uex-IF (49%) and females with endometriosis (37%). Moreover, the highest number of participants (57%) with Uex-IF exhibited IL6 levels significantly below the RR in comparison to the fertile group and infertile groups (PCOS and endometriosis). However, lower levels of IL6 were observed in women with Uex-IF. In the control group, LIF exhibited a significant positive correlation with IL6 (r = 0.370), Pt (r = 0.496), Et (r = 0.403), and LH (r = 0.428). Among women with PCOs, LIF showed a significant positive correlation with IL6 (r = 0.443), Pt (r = 0.607), and LH (r = 0.472). In cases of Uex-IF, LIF demonstrated a significant positive correlation with IL6 (r = 0.727). Females with endometriosis displayed a significant positive correlation between LIF and IL6 (r = 0.535) as well as Pt (r = 0.605). In fertile women, a positive correlation was observed between LH and IL6 (r = 0.197, p = 0.009), LIF (r = 0.428, p = 0.000), Pt (r = 0.238, p = 0.001), and Et (r = 0.356, p = 0.000). Furthermore, a positive correlation was found between LH and LIF (r = 0.472, p = 0.000) in women with PCOs. CONCLUSION: Elevated levels of Pt were found to increase the production of LIF in fertile females. However, infertile females with PCOs and Uex-IF exhibited deficient levels of Pt, supporting its role as a biomarker for successful implantation in infertile women. These females showed decreased levels of gonadotropins as well as reduced LH/FSH ratio and diminished secretion of receptivity marker LIF, in addition to reduced Pt secretion. This suggests that reduced gonadotropin levels contribute to a lower LH/FSH ratio, resulting in decreased Pt secretion and ultimately leading to low levels of LIF, thereby causing impaired implantation in women with PCOs and Uex-IF. The exploration of low levels of LIF in patients with endometriosis requires further investigation. The significantly low levels of IL6 in the Uex-IF group elucidate the role of this cytokine in association with decreased Pt and LIF synthesis within this group.

Diagnostic Performance of Anti-Müllerian Hormone, Luteinizing Hormone to Follicle-Stimulating Hormone Ratio, Testosterone, and Prolactin to Predict Polycystic Ovary Syndrome Among Sudanese Women.

Background: Polycystic ovary syndrome (PCOS) is one of the most important contributing factors to infertility. The diagnosis of PCOS is not an easy procedure, as the signs and symptoms are heterogeneous and of undefined etiology. There are only a few published studies that address the diagnostic performance of anti-Müllerian hormone in diagnosis of PCOS in sub-Saharan Africa including Sudan. Objective: This study aims to assess anti-Müllerian hormone (AMH), luteinizing to follicle-stimulating hormone ratio (LH: FSH), total testosterone (TT), and prolactin (PRL) levels among PCOS. In addition, we determine if AMH can be used as a predictor of PCOS among Sudanese women. Methods: There were 600 women enrolled in this observational cross-sectional study, 300 of whom had PCOS, and 300 of whom healthy women; PCOS was diagnosed using the Rotterdam criteria. On days 2-4 of the menstrual cycle, serum LH, FSH, AMH, TT, and PRL levels were measured for all participants. Diagnostic performance of these parameters for PCOS was determined by receiver operating characteristic (ROC) curve. Results: Significantly higher means among PCOS regarding their BMI, AMH; LH: FSH ratio; TT; PRL, whereas significantly inverse in FSH compared with normal ovulatory women. On ROC analysis, AMH had the largest operating characteristic curve at cut-off >3.95 ng/mL; AUC = 0.999 with Youden's index 0.99%, followed by LH: FSH ratio at cut-off 0.749; AUC=0.932; Youden's index 0.813%, TT cut-off 0.82 mIU/L, AUC=0.852 with Youden's index 0.58, while PRL showed the lowest AUC=0.627 with cut-off 15.3 ng/mL, Youden's index was 0.18%, P. value<0.001. Conclusions: Sudanese women with PCOS had higher serum AMH level, LH:FSH ratio, and TT level. Moreover, AMH level has better discriminative power and good diagnostic potency for the diagnosis of PCOS among Sudanese.

Serum LH/FSH ratios in 87 infants with differences of sex development.

The ratio between luteinizing hormone (LH) and follicle-stimulating hormone (FSH) has previously been described as an excellent marker of sex in healthy infants. However, LH/FSH remains not fully described in patients with differences of sex development (DSD). The aim was therefore to describe LH/FSH in infants with DSD. This was a retrospective study of DSD patients, all aged 0-1.2 years. In total, 87 infants with DSD and at least one serum sample per infant were included. Longitudinal samples from single patients were included whenever possible. Serum LH/FSH ratios in these patients were plotted against recently published age-related and sex-dimorphic cutoffs. Overall, LH/FSH sometimes corresponded to assigned sex without any obvious pattern in terms of diagnoses. LH/FSH corresponded to the biological sex in all patients with Turner or Klinefelter syndrome. In patients with 46,XX or 46,XY DSD (except congenital adrenal hyperplasia (CAH)), the ratios did not correspond to the assigned sex in all cases and were interchangeably within the male and female range. In patients with CAH, the ratio corresponded to biological sex (based on sex chromosomes) in some cases but also ranged across the cutoffs. In the 15 patients with 45,X/46,XY mosaicism, the LH/FSH ratios corresponded to the assigned sex in all cases (12 were raised as males, 3 as females) and at all time points in cases with multiple sampling. While this study describes LH/FSH in infants with DSD, the exact clinical role of the ratio in the management of these patients remains to be further elucidated.

Elevated baseline LH/FSH ratio is associated with poor ovulatory response but better clinical pregnancy and live birth in Chinese women with PCOS after ovulation induction.

Background: What is the association between elevated baseline LH/FSH ratio and reproductive outcomes, especially ovulatory response, among Chinese women with polycystic ovary syndrome (PCOS) after ovulation induction. Methods: This was a secondary analysis of a multicenter randomized trial in 1000 women with PCOS from 21 sites (27 hospitals) in Mainland China. LH and FSH levels before ovulation induction and the main outcomes including ovulation, biochemical pregnancy, clinical pregnancy, miscarriage, and live birth were measured. A linear regression model, logistic regression models and Cox proportional hazard regression model were used to estimate the association between LH/FSH ratios and reproductive outcomes in PCOS. Results: LH/FSH ratio was significantly associated with age, body mass index (BMI), total testosterone (TT), estradiol (E2), free testosterone (FT), and antimullerian hormone (AMH). Anovulatory women had significantly higher LH/FSH ratio than ovulatory women (P = 0.003), especially in women with young age (P = 0.023), high BMI (P = 0.002), low E2 (P = 0.002), FT (P = 0.010), TT (P < 0.001) and AMH(P = 0.032). Women with elevated LH/FSH ratio were associated with lower ovulation (LH/FSH≥1 OR = 0.42, 95% CI, 0.26-0.68; LH/FSH≥2 OR = 0.32, 95% CI, 0.20-0.54; LH/FSH≥3 OR = 0.40, 95% CI 0.21-0.74) when compared with LH/FSH<1. The association was held after adjustment for treatment with or without the confounding factors. Although no association between LH/FSH ratio and biochemical pregnancy, women with 1 ≤ LH/FSH<2 were associated with higher clinical pregnancy (OR = 1.71; 95% CI, 1.09-2.67) and live birth (OR = 1.73; 95% CI, 1.09-2.75) compared to women with LH/FSH<1. Women with 2 ≤ LH/FSH<3 were associated with lower miscarriage rate (OR = 0.38; 95% CI, 0.16-0.93). Conclusions: Elevated baseline LH/FSH ratio in women with PCOS was associated with poor ovulatory response, but women were more likely to achieve clinical pregnancy and live birth than women with normal LH/FSH. It suggests LH and FSH in women with PCOS may play a role in successful pregnancy despite of negative impact in ovulation.

ANTI-THYROID ANTIBODIES AND THE GONADOTROPHINS PROFILE (LH/FSH) IN EUTHYROID POLYCYSTIC OVARIAN SYNDROME WOMEN.

Context: The current study aimed to determine association of anti-TPO with LH/FSH in PCOS women. Design: Current case control study included 33 diagnosed PCOS women and 32 age matched healthy women and were analysed for body mass index (BMI) and waist to hip ratio (WHR), fasting blood glucose (FBG), free T3 (FT3), free T4 (FT4), Thyroid stimulating hormone (TSH), dehydroepiandrostenedione (DHEA-S), total testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and anti thyroperoxidase antibodies (anti-TPO). Data was statistically analysed by Student's t - test and Pearson's correlation analysis. Results: Of the total PCOS women, 45% were obese and 34.37% had raised anti-TPO. The biochemical profile of obese PCOS women showed significantly raised FBG (p<0.0001), LH (p<0.0001), Testosterone (p<0.0001) and DHEA-S (p=0.0021) as compared to non-obese PCOS women. The LH/FSH ratio was significantly raised in PCOS women as compared to control (p<0.0001). Pearson's correlation analysis showed a significant association of anti-TPO with FBS, testosterone, LH and LH/FSH in obese PCOS and with Testosterone and LH in non-obese PCOS women using SPSS 21. Conclusion: The current study shows a high prevalence of AITD in euthyroid PCOS women and suggests a strong link of euthyroid obese PCOS women to autoimmunity due to the hyper-anderogenism and a higher LH/FSH ratio.

Association of Angiotensin-Converting Enzyme gene polymorphism in Pakistani women with the atypical steroidogenesis in Polycystic ovarian syndrome: A case-control study.

BACKGROUND: Polymorphism in the angiotensin-converting enzyme gene (ACE) is responsible for elevated ACE concentrations in plasma. High ACE levels induce insulin resistance and hyperandrogenism, which are the main attributes of polycystic ovary syndrome (PCOS). Therefore, it was hypothesized that I/D polymorphism plays a role in the pathogenesis of PCOS. OBJECTIVE: A case-control study was designed to investigate the association of I/D polymorphism of the ACE gene with PCOS in Pakistani women of reproductive age. METHODS: ACE I/D polymorphism was assessed in 252 women of age group 16-40 years. For genotypic analysis, PCR amplification of genomic DNA was carried out. Statistical analysis was performed to interpret the results using SPSS software. RESULTS: Our study showed that PCOS women were more likely to have a high body mass index and waist circumferences. Most PCOS patients had menstrual irregularities 99.3%, hirsutism 75.2% and cysts in ovaries 66.6%, along with other hyperandrogenic conditions (P-value = 0.001). The genotypic and allelic frequencies were significantly different between patients and controls. There was a significant association of three genotypes with the ratio of LH: FSH among PCOS patients (P = 0.05). Anthropometric characters, comorbidities, clinical symptoms, and PCOS conditions showed no statistical significance with ACE polymorphism. CONCLUSIONS: ACE I/D polymorphism was not found associated with clinical conditions of PCOS in women of reproductive age. However, it was associated with atypical steroidogenesis. So, it indicates that ACE I/D polymorphism aggravates the pathogenesis of PCOS.

The LH/FSH ratio is not a sex-dimorphic marker after infancy: data from 6417 healthy individuals and 125 patients with Differences of Sex Development.

STUDY QUESTION: What is the course of the LH/FSH ratio from infancy into adulthood in healthy individuals and in patients with Differences of Sex Development (DSD)? SUMMARY ANSWER: The LH/FSH ratio had a marked overlap between the sexes after infancy and onwards throughout adulthood in healthy individuals and it was not a marker of hypogonadism in DSD patients. WHAT IS KNOWN ALREADY: The LH/FSH ratio is a distinct marker of sex during minipuberty. No study has evaluated the LH/FSH ratio from infancy into adulthood. STUDY DESIGN, SIZE, DURATION: This was a combined study of prospective longitudinal and cross-sectional cohorts of healthy individuals totaling 6417 males and females aged 0-80 years. Retrospective data from a single, tertiary center on 125 patients with DSD was also included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the healthy males (n = 3144) and females (n = 3273) aged 0-80 years, reference ranges for LH, FSH and the LH/FSH ratio were established from infancy (after minipuberty) and onwards. LH, FSH, and the LH/FSH ratio in 125 patients with DSD not undergoing treatment were compared to the reference ranges. Included DSD diagnoses were: Klinefelter syndrome including mosaic variants (males: n = 14), Turner syndrome including mosaic variants without Y-chromosome material (females: n = 48), 45,X/46,XY mosaicism (males: n = 24 and females: n = 6), partial androgen insensitivity syndrome (males: n = 11), complete androgen insensitivity syndrome (females: n = 13) and anorchia (males: n = 9). MAIN RESULTS AND THE ROLE OF CHANCE: An overlap was observed in the LH/FSH ratio reference curves between males and females. However, when comparing the sexes at specific time points, the LH/FSH ratio was significantly higher in healthy males during childhood and adulthood and significantly higher in healthy females during puberty. When compared with healthy participants, male patients with anorchia and 45,X/46,XY mosaicism had significantly lower ratios, while patients with androgen insensitivity, regardless of sex, had significantly higher ratios. LIMITATIONS, REASONS FOR CAUTION: The limitations of this study include that; (i) all healthy individuals were Caucasian, so conclusions may not apply to non-Caucasians; (ii) the calculated LH/FSH ratios were restricted to the specific analytical method used and may not be applicable to other laboratories; (iii) the samples from healthy individuals were stored for varying amounts of time up to 20 years which may affect the durability; and (iv) DSD diagnoses are heterogeneous thus making sturdy conclusions across diagnoses impossible. WIDER IMPLICATIONS OF THE FINDINGS: In this study of combined cohorts of healthy participants, the largest normative ranges of LH, FSH, and the LH/FSH ratio to date were created. These reference ranges provide the opportunity for clinical as well as research use for all three markers. However, the previously rather undescribed LH/FSH ratio was not a distinct marker of sex after infancy nor a new marker of hypogonadism. Although there were significant differences between subgroups of DSD patients compared to healthy controls, the clinical significance of the LH/FSH ratio after infancy lacked. However, it can be speculated whether there are other areas of clinical application not investigated in this article, for example as a marker of fertility in select patient groups. As gonadotropin assays are readily available and gonadotropin measurements are part of regular workups, the LH/FSH ratio can easily be explored in further research without additional costs. STUDY FUNDING/COMPETING INTEREST(S): M.L.L. was funded by the Absalon Foundation. Cohort 1 was funded by the European Commission, through the Biomed 2 Program (BMH4-CT96-0314), Environmental Reproductive Health (QLK4-CT1999-01422) and EXPORED (QLK4-2001-00269), by the Danish Council for Independent Research (9700833 and 9700909), and by the Svend Andersens Foundation. Cohort 2 was funded by the Danish Environmental Research Program (96.01.015.16.05). Cohort 3 was funded by Kirsten and Freddy Johansens Foundation. TRIAL REGISTRATION NUMBER: NA. DATE OF FIRST PATIENT'S ENROLMENT: June 1990 (the launch of the department from which this project stems).

The precise ovarian volume is significantly associated with serum concentrations of antimüllerian hormone, the luteinizing hormone/follicle-stimulating hormone ratio, and total testosterone.

OBJECTIVE: To evaluate potential associations between concentrations of antimüllerian hormone (AMH) and T as well as the LH/FSH ratio and the unbiased precise ovarian volume obtained after unilateral ovariectomy. DESIGN: Cohort study. SETTING: University hospital. PATIENT(S): A total of 765 patients having one ovary surgically removed for fertility preservation. Inclusion criteria were age >15 years and ovarian volume <25 mL; 386 women had one or more hormone parameter (AMH, LH, FSH, or total T) determined before oophorectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A precise weight of the ovary was equated with ovarian volume. Associations between ovarian volume and AMH, the LH/FSH ratio, T concentrations, and body mass index (BMI) were evaluated. Patient characteristics in relation to ovarian volume cutoff values between 8 and 12 mL were also examined. RESULT(S): Ovarian volume was significantly positively associated with concentrations of AMH, the LH/FSH ratio, and T. Ovarian volume, concentrations of AMH and LH, and the LH/FSH ratio were significantly augmented in women having ovarian volumes above a threshold of 8, 9, and 10 mL compared with those below. Average age, FSH, and T concentrations did not differ between below and above the 10 mL threshold. There was a significant association between BMI and ovarian volume and BMI and T, while other hormone parameters were nonsignificant. CONCLUSION(S): The precise ovarian volume reflected ovarian activity measured as circulating concentrations of AMH and T as well as the LH/FSH ratio. These significant associations showed continuous progression, and a 10 mL threshold offered no clear difference compared with other volume threshold values.

Basal Anti Mullerian hormone levels and endometrial thickness at midcycle can predict the outcome after clomiphene citrate stimulation in anovulatory women with PCOS, a retrospective study.

PURPOSE: Recent studies reported that in polycystic ovary syndrome (PCOS) patients, other stimulation agents are superior to the popular first-line regimen, clomiphene citrate (CC) for ovarian stimulation. Nonetheless, CC is still widely used since it is not clear which patients will not respond to it. Furthermore, the prognostic value of endometrium thickness at midcycle is controversial. We aimed to find factors predicting the response to CC and the prognostic value of endometrial thickness at midcycle. METHODS: We collected data retrospectively from 89 anovulatory PCOS patients who had the first stimulation with 50 mg CC. We analyzed the basal levels of AMH, testosterone, LH, LH:FSH ratio and the endometrial thickness at midcycle by univariate, followed by multivariate regression. The outcome measures were pregnancy, follicle maturation and endometrial thickness at midcycle. RESULTS: Stimulation with 50 mg CC resulted in follicle maturation in 50.6% of the women and in 27.0% pregnancies. In the univariate analysis, greater endometrial thickness, lower LH and AMH levels and a lower LH:FSH ratio were associated with pregnancy (p < 0.05). In the multivariate analysis, only endometrial thickness remained predictive (p = 0.045). The endometrial thickness cutoff level of ≥ 8 mm showed a sensitivity of 87.5% (96% CI 67.6-97.3) and a specificity of 66.7% (95% CI 43.0-85.4) for prediction of pregnancy. In the multivariate analysis AMH levels 5.4 (3.4; 7.0) (ng/mL) predicted pregnancy (ß = - 0.194 ± 0.092; p = 0.034) CONCLUSION: We suggest to refrain from CC as first-line regimen in patients with AMH > 7 ng/ml. Under CC treatment, the cutoff value of ≥ 8 mm endometrium thickness at midcycle is associated with a better outcome.

In early pubertal boys, testosterone and LH are associated with improved anti-oxidation during an aerobic exercise bout.

PURPOSE: To investigate the association of the hypothalamic-pituitary-testicular (HPT) axis with pro- and anti- oxidation, in relation to puberty and obesity in boys, before and after an aerobic exercise bout. METHODS: This is a cross-sectional human observational study of 92 healthy normal-weight, obese pre- and early- pubertal boys that underwent a blood sampling, before, and after an aerobic exercise bout at 70% VO2max, until exhaustion. LH, FSH, total testosterone (tT) and markers of pro- (TBARS and PCs) and anti- (GSH, GSSG, GPX, catalase, TAC) oxidation were measured. RESULTS: Baseline LH, FSH, and tT concentrations were greater in early, than in pre- pubertal boys, independently of weight status. Post-exercise, LH concentrations decreased in early pubertal boys while FSH concentrations did not change in any of the studied groups. Baseline and post-exercise tT concentrations were lower in obese than in normal-weight early pubertal boys, while baseline and post-exercise LH and FSH concentrations did not differ between these groups. Post-exercise tT concentrations increased in early pubertal obese boys. Baseline LH, FSH and tT concentrations correlated positively with baseline anti-oxidation markers concentrations in pre-pubertal boys. Baseline tT concentrations correlated positively with the increase of TAC concentrations in early pubertal normal-weight boys. In all boys, baseline LH concentrations were the best positive predictors for the exercise-associated increase of TAC concentrations. CONCLUSIONS: It appears that the HPT axis maturation during puberty (in particular its LH and testosterone components) is positively associated with the increase of anti-oxidation during a bout of aerobic exercise.

The efficacy of Tung's acupuncture for sex hormones in polycystic ovary syndrome: A randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine disorder in reproductive-age women. Tung's acupuncture, a Traditional Chinese Medicine (TCM) treatment, is widely used for PCOS in East Asia, but evidence on its efficacy is rare. The aim of this RCT study was to examine whether the Tung's acupuncture could be a complementary treatment method for PCOS. METHODS: A total of 60 PCOS patients were randomly assigned to a Tung's acupuncture group (n = 30) or a cyproterone acetate/ethinylestradiol (CPA/EE) group (n = 30). Each participant received treatments for 12 weeks to assess the short-term treatment efficacy and then followed up for another 12 weeks to assess the long-term treatment efficacy. The primary outcome examined was change in the ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH); the secondary outcomes examined were changes in body mass index (BMI), LH, FSH, total testosterone (TT), ovarian volume, polycystic ovary number and menstrual frequency. RESULTS: Both groups showed significant reductions in the LH/FSH ratio, LH and TT after 12-week treatment (p < 0.001) and 12-week follow-up (p < 0.05). No significant differences existed between the two groups (p > 0.05). Both groups showed significant improvement in BMI, menstrual frequency and polycystic ovary number after 12-week treatment (p < 0.05). CONCLUSION: Compared with CPA/EE, Tung's acupuncture showed no better improvement on LH/FSH ratio for PCOS although it could reduce the ratio. Tung's acupuncture might have some effect on long-term weight control and menstruation frequency. Further studies addressing this study's limitations are recommended.

The Effect of Sleeve Gastrectomy on the Hormonal Profile of Patients with Polycystic Ovary Syndrome.

PURPOSE: To prospectively evaluate the hormonal profile and weight loss of women with obesity and PCOS submitted to sleeve gastrectomy (SG). METHODS: A Prospective study carried out at the Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil, in 2018, where 18 patients with PCOS, whose age varied from 18 to 40 years, with an indication for bariatric surgery were evaluated. Plasma estradiol (E2), fasting insulin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured prior to bariatric surgery and 3 months after surgery. The LH/FSH ratio and BMI of the study participants were also calculated. RESULTS: Postoperative E2 levels were higher (preoperative mean of 63.4 pg/dL versus postoperative mean of 91.0 pg/dL), with no statistical significance then (p = 0.139). It was observed, at the postoperative period, statistically significant decreases in mean fasting insulin levels (24.4 mIU/mL vs. 9.0 mIU/mL; p < 0.001), LH levels (7.2 vs. 4.5; p = 0.047), and an inverted LH/FSH ratio (1.5 vs. 0.9; p = 0.008); relevant weight loss occurred (mean BMI, 40.5 kg/m2 vs. 33.4 kg/m2; p < 0.001). CONCLUSION: Relevant changes in the hormone profile and significant alterations in the gonadotropic and insulin patterns were seen. In addition to satisfactory weight loss, the observed endocrine alterations revealed an internal environment that was more homeostatic and conducive to reproduction, indicating that SG was able to produce attractive physiological outcomes for women with PCOS.

Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome.

OBJECTIVE: This study explores the role of anti-Mullerian hormone (AMH) and LH/FSH ratio in diagnosis of polycystic ovary syndrome (PCOS). METHODS: In this multicentre cross-sectional descriptive study, a total of 863 infertile women between 18 and 45 years were evaluated at three infertility centres in Vietnam and were recruited from June 2016 to June 2017. The patients were classified into two groups: Group I included 441 patients with PCOS (based on Rotterdam criteria consensus) and Group II included 422 non-PCOS women. Diagnosis of PCOS was established based on Rotterdam 2003 consensus, and exclusion criteria were ovarian disease (ovary cyst/tumour), history of ovarian surgery and ovarian failure. RESULTS: At an optimum cut-off level of 32.79 pmol/L, AMH showed sensitivity and specificity of 78.50% and 75.83%, respectively, with the AUC 0.852 (95% CI: 0.826-0.875). The LH/FSH ratio had a similar AUC at the optimum cut-off of 1.33 (AUC = 0.867, 95% CI 0.842-0.889), which demonstrated a similar diagnosis value to AMH (P = 0.340). By using multiple logistic regression analysis, 1 ng/mL increase in AMH levels was associated with an increased risk of PCOS (OR = 1.63, 95% CI: 1.506-1.764; P < 0.001). Similarly, one unit increase in LH/FSH ratio was associated with 14.433 times increased (95% CI: 9.302-22.395; P < 0.001) risk of PCOS. There were no significant differences between values of AMH and LH/FSH ratio in PCOS diagnosis, as the difference between the two AUCs was 0.013, 95% CI: -0.024 to 0.028 and P = 0.897. CONCLUSION: The value of serum AMH concentration has been found not significantly superior to LH/FSH ratio in PCOS diagnosis. Although these biomarkers separately are not adequate for PCOS diagnosis based on their own value, the combination of different endocrine factors including AMH, LH and LH/FSH ratio together with BMI and other anthropometric and clinical characteristics may offer extra value to establish the diagnosis of PCOS.

Licorice ethanol extract improves symptoms of polycytic ovary syndrome in Letrozole-induced female rats.

BACKGROUND: Licorice (Glycyrrhizae radix et rhizome, GRR) has long been used as an ingredient in Korean traditional medicinal herbal formulas for various metabolic and reproductive diseases. Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women. In the present study, we examined the effects of GRR extract on PCOS-like symptoms in female rats. METHODS: Symptoms of PCOS were induced by Letrozole treatment for 4 weeks in 6-week-old female SD rats, after which the effects of GRR extract on recovery of normal hormonal levels and polycystic ovaries were assessed. Serum levels of luteinizing hormone (LH), follicular-stimulating hormone (FSH), LH/FSH ratio, and follicular cysts were evaluated, followed by the expression levels of known follicular phase markers such as Kitl, Cyp11a1, and Ptgs2. RESULTS: The serum level of FSH was reduced only in the Lestrozole treatment group (PCOS), whereas significant recovery of FSH level was observed in the Letrozole and GRR co-treatment group (PCOS + GRR). Serum LH levels were not altered in any of the groups. Furthermore, the LH/FSH ratio (known biomarker for PCOS) was elevated only in the Letrozole treatment group (PCOS), whereas it was significantly reduced in the Letrozole and GRR co-treatment group (PCOS + GRR). For histological changes, follicular cysts, antral follicles, and increased thickness of the theca- and granulosa layers were observed in the PCOS group, whereas these alterations were remarkably reversed by GRR treatment. CONCLUSION: These results suggest that GRR extract inhibits the symptoms of PCOS by regulating imbalanced hormonal levels and irregular ovarian follicles.

LH/FSH Ratio Is Associated With Visceral Adipose Dysfunction in Chinese Women Older Than 55.

No study examined the association of luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio with both visceral obesity outside the context of polycystic ovary syndrome. Thus, we hypothesized that the LH/FSH ratio was associated with visceral adipose accumulation and dysfunction among Chinese women older than 55. From 2014 to 2015, a total of 2,525 women aged 55-89 years were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China. Anthropometric indices, biochemical parameters, sex hormones and clinical characteristics were measured. Visceral adipose accumulation and function were identified by visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI) and lipid accumulation product (LAP). Linear regression and logistic regression analyses were conducted to explore the association. A total of 1,462 (57.9%) participants had visceral obesity. In the linear regression, after full adjustment for demographic variables, metabolic factors, total testosterone (T), and estradiol (E2), LH/FSH ratio was positively associated with all indices estimating visceral obesity [B (95% CI): Log VAI 0.060 (0.030-0.090), Log CVAI 0.045 (0.029-0.061), Log LAP 0.103 (0.063-0.142), all P < 0.001]. Logistic regression analyses showed that the risk of visceral obesity increased with increasing LH/FSH ratio after controlling for age and smoking [OR (95% CI): 1.99 (1.52, 2.59), P < 0.001]. After further controlling for metabolic factors, the association was attenuated but remained significant [OR (95% CI): 1.89 (1.42, 2.53), P < 0.001]. The OR of visceral obesity in the fully adjusted model was 1.83 (95% CI 1.37, 2.45) (P < 0.001). Thus, high LH/FSH ratio was significantly associated with visceral adipose over-accumulation and dysfunction in women over 55 years old. This ratio may be an early marker for metabolic disorders in Chinese women older than 55, which warrants further investigation.