High LH Levels Research Articles

P-34 XX MALE SYNDROME DIAGNOSED AT AGE 52

Abstract Introduction XX male syndrome (de la Chapelle syndrome) is a rare disorder of sex development linked to a 46,XX karyotype. Depending on the presence of the SRY gene, two variants of this disease are distinguished: SRY-positive and SRY-negative ones. The SRY (sex-determining region Y) gene is involved in the differentiation of Sertoli cells and development of the tests. Typically, de la Chapelle syndrome is diagnosed in childhood or adolescence. We present a case where XX male syndrome was diagnosed at age 52. Clinical Case A 52-year-old man came to our clinic complaining of excess weight, decreased libido, and fatigue with little physical activity. Physical examination discovered full masculinization, microorchidism, gynecomastia, obesity. At the time of his visit, he was undergoing chemotherapy for β-cell lymphoma. It is known that due to severe pain in the spine, he had been injecting himself with dexamethasone every day for six months, which led to secondary adrenal insufficiency. When he came, we stopped dexamethasone and initiated hydrocortisone. We reduced the dosage until it was completely discontinued over 4 months. The function of the adrenal glands was completely restored, which was shown by laboratory tests. On the first visit patient said that over the past 9-10 years he had been periodically receiving testosterone therapy due to low testosterone level. The decrease in testosterone was explained by obesity. About 10 years ago, investigation was performed due to infertility. Investigation showed a low testosterone level, a high FSH and LH level, azoospermia, a small testicular volume in the ultrasound were detected. Hypergonadotropic hypogonadism was diagnosed. Karyotyping analysis revealed a chromosomal complement of 46,XX. Molecular genetic testing confirmed the SRY-positive variant of de la Chapelle syndrome. Thus, we understand the reason for patient's low testosterone, and replacement therapy with testosterone was prescribed. And we recommended assisted reproductive technologies using donor sperm. Conclusion It is important to remember that in men of any age with hypogonadism and infertility, chromosomal abnormalities must be excluded (and not only in children and adolescents).Figure 1:Karyogram of the patient, 46,XX

Effect of Oral Bisphosphonates on Vertebral Fractures in Males Living with HIV: A Seven Year Study.

Background: Osteoporosis and vertebral fractures (VFs) are frequently observed in males living with HIV (MLWH). While bisphosphonates seem effective on bone mineral density (BMD) in MLWH, data on VFs are lacking. In this real-life longitudinal study performed on 118 MLWH (median age 53) who were followed-up for a median of 7 years, we aimed to evaluate the long-term efficacy of oral bisphosphonates on VFs in MLWH. Methods: The inclusion criteria were age >18, stable HIV infection, bisphosphonate-naïve, blood samples from the same laboratory, and three densitometries and morphometries performed with the same densitometer. Results: At baseline, VFs were detected in 29/118 patients (24.6%). Patients with VFs were older (p. 0.042), had longer HIV infection duration (p. 0.046) and antiretroviral exposure (p. 0.025), and demonstrated higher luteinizing hormone levels (LH, p. 0.044). Of the 29 patients with VFs at inclusion, 11 developed new VFs, of which 8 were under oral bisphosphonates (p. 0.018). Among the 89 without basal VFs, 11 developed VFs, of which 2 were under oral bisphosphonates. Patients with a worsened bone condition (regarding BMD and/or new VFs, n. 32) had more frequently high LH levels (>9.4 mIU/mL, p. 0.046) and higher HCV co-infection compared to patients with a stable bone condition (p. 0.045). It should be noted that 38.6% of patients discontinued oral bisphosphonates due to medical indication or personal choice, and 14.0% never started them. Conclusions: In conclusion, we found that oral bisphosphonates were not completely effective in preventing VFs, especially in patients with VFs at baseline; this is probably due to the multifactorial pathogenesis of fragility fractures in this population. A poor adherence to treatment and attention to gonadal function are also important issues in this population.

Luteinizing Hormone Variability in Polycystic Ovary Syndrome: A Comparative Analysis

An endocrine with metabolic condition known as Polycystic Ovarian Syndrome (PCOS) affects women who are of reproductive age, women with PCOS are a condition often associated with dysregulation of the hypothalamic-pituitary axis. A Cross-sectional study, the study included 88 patients who visited the outpatient clinic in total. These individuals were split up into two groups. All females are assessed the status of obesity by the body mass index (BMI), [BMI= weight (kg) / height (m)²], LH, FSH, Estradiol and Testosterone levels measured by ELISA technique. There was no discernible variation in BMI between groups A and B. (P ≥ 0.456), The patients' mean FSH and LH values were 5.06 mIU/ml and 5.47 mIU/ml, compared with group B mean that equal to 6.05 mlU/ml, 18.91mlU/ml respectively. Serum testosterone was slightly elevated in group B that was (41.19 ± 5.16 ng/dL), and (39.53 ± 4.98 ng/dL) in group A. Moreover, the level of estradiol (E2) in group A was 79.45ng/dL while in group B the level was 72.65 ng/dL there are no significant difference between two groups. The study found conflicting evidence regarding the impact of high LH levels on oocyte quality, fertilization, and pregnancy outcomes in PCOS patients. According to the research, ovarian theca cells from PCOS patients may be more effective than normal theca cells at converting androgenic precursors to testosterone. While ovulatory dysfunction in PCOS is linked to reduced estradiol production, the study indicates that ovarian tissue may still contribute to circulating estradiol levels in affected women.

Study of hypothalamic-pituitary-testicular axis in Egyptian post-COVID-19 patients

ABSTRACT Background SARS-CoV-2, was identified as a global pandemic by the World Health Organization a few months after the first epidemic. It penetrates host cells through angiotensin-converting enzyme 2 receptors and spreads by respiratory droplets. Testes are among the several tissues that have high expression levels of ACE-2 receptors. The current study aimed to evaluate the hypothalamic-pituitary-testicular axis integrity among Egyptian post-COVID-19 patients. Methods This is a cross-sectional study that included patients with a history of COVID-19 infection, at least 3 months from the onset of COVID-19. A detailed clinical history was obtained, and a thorough examination was performed. Laboratory tests included FBG, total testosterone, free testosterone, bioactive testosterone, FSH, LH, prolactin, E2, albumin, and SHBG. Testicular ultrasonography was performed. The data were statistically analyzed. Results Eighty male patients were evaluated with a mean age of 35.53 ± 10.35 years. The mean serum total testosterone was 5.48 ± 1.65 ng/ml. Low testosterone was detected in 2.8% of the patients. High LH levels were detected in 17/80 patients (21.3%). High FSH levels were detected in 4/80 patients (5%). Six patients had elevated serum E2 level. The mean serum prolactin value was 10.90 ± 5.66 ng/ml. Fourteen patients had elevated prolactin levels. The mean serum T/LH ratio was 3.28 ± 1.52. The ratio of T/LH was decreased in eight COVID-19 patients (10%). In COVID-19 patients, a statistically significant negative correlation was found between age and free testosterone (FT) (r=-0.381, p < 0.001), bioavailable testosterone (Bio. T) (r=-0.375, p = 0.001), and androgen index (A. index) (r=-0.446, p < 0.001). Conclusion The data of the current study suggest that COVID-19 infection might deteriorate pituitary – gonadal axis. The prevalence of low testosterone in COVID-19 male survivors is low. The risk of hypogonadism is increased with advanced age. More studies are required to confirm the relationship between COVID-19 infection and male gonadal function.

Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome.

Do hyperactive kisspeptin neurons contribute to abnormally high LH secretion and downstream hyperandrogenemia in polycystic ovary syndrome (PCOS)-like conditions and can inhibition of kisspeptin neurons rescue such endocrine impairments? Targeted inhibition of endogenous kisspeptin neuron activity in a mouse model of PCOS reduced the abnormally hyperactive LH pulse secretion and hyperandrogenemia to healthy control levels. PCOS is a reproductive disorder characterized by hyperandrogenemia, anovulation, and/or polycystic ovaries, along with a hallmark feature of abnormal LH hyper-pulsatility, but the mechanisms underlying the endocrine impairments remain unclear. A chronic letrozole (LET; aromatase inhibitor) mouse model recapitulates PCOS phenotypes, including polycystic ovaries, anovulation, high testosterone, and hyperactive LH pulses. LET PCOS-like females also have increased hypothalamic kisspeptin neuronal activation which may drive their hyperactive LH secretion and hyperandrogenemia, but this has not been tested. Transgenic KissCRE+/hM4Di female mice or littermates Cre- controls were treated with placebo, or chronic LET (50 µg/day) to induce a PCOS-like phenotype, followed by acute (once) or chronic (2 weeks) clozapine-N-oxide (CNO) exposure to chemogenetically inhibit kisspeptin cells (n = 6 to 10 mice/group). Key endocrine measures, including in vivo LH pulse secretion patterns and circulating testosterone levels, were assessed before and after selective kisspeptin neuron inhibition and compared between PCOS groups and healthy controls. Alterations in body weights were measured and pituitary and ovarian gene expression was determined by qRT-PCR. Acute targeted inhibition of kisspeptin neurons in PCOS mice successfully lowered the abnormally hyperactive LH pulse secretion (P < 0.05). Likewise, chronic selective suppression of kisspeptin neuron activity reversed the previously high LH and testosterone levels (P < 0.05) down to healthy control levels and rescued reproductive gene expression (P < 0. 05). N/A. Ovarian morphology was not assessed in this study. Additionally, mouse models can offer mechanistic insights into neuroendocrine processes in PCOS-like conditions but may not perfectly mirror PCOS in women. These data support the hypothesis that overactive kisspeptin neurons can drive neuroendocrine PCOS-like impairments, and this may occur in PCOS women. Our findings complement recent clinical investigations using NKB receptor antagonists to lower LH in PCOS women and suggest that pharmacological dose-dependent modulation of kisspeptin neuron activity may be a valuable future therapeutic target to clinically treat hyperandrogenism and lower elevated LH in PCOS women. This research was supported by NIH grants R01 HD111650, R01 HD090161, R01 HD100580, P50 HD012303, R01 AG078185, and NIH R24 HD102061, and a pilot project award from the British Society for Neuroendocrinology. There are no competing interests.

Un association of Anti-Mullerian Hormone gene (rs4807216) polymorphism in Polycystic Ovary Syndrome (PCOS) Among Iraqi Women

The current work aimed to assess the hormonal profile of women with PCOS, including the AMH hormone and the AMH gene (rs4807216) polymorphism. The blood samples were obtained from 60 patients with PCOs who visited Reproductive Medicine Centre of General Hospital of Kirkuk and 30 healthy women. The serum level of LH, FSH, TSH, Estrogen and AMH determined by Enzyme linked immunosorbent assay (ELISA), while Polymerase chain reaction (PCR) was used to genotype the AMH gene (rs4807216). The current results showed a significant increase in LH, TSH, Estrogen, and AMH serum levels in PCOS females as compared to the control female group at P value= 0.05. In contrast, the serum level of FSH was not significantly increased at p value = 0.05. Polymorphism rs4807216was not significantly associated with serum AMH levels in the population study. In conclusion, Women with PCOS have high levels of LH, TSH, Estrogen, and AMH. Therefore, these hormones consider biomarkers for detecting PCOS in Iraqi females.

(O-05) ESTRADIOL LEVELS IN MEXICAN MEN WITH ERECTILE DYSFUNCTION

Abstract Introduction and Objective Erectile dysfunction is associated with various psychological and physiological causes, including hormone levels such as testosterone. The role of estradiol in male sexual function is controversial, and studies reporting its impact on erectile function have been inconsistent. The aim of this study was to describe the levels of testosterone and estradiol in Mexican men with erectile dysfunction, based on the severity of dysfunction. Materials and Methods Hormonal levels of TSH, T3, T4, LH, FSH, total and free testosterone, and estradiol were measured in men over 18 years of age with erectile dysfunction, attending a clinic in Mexico. Clinical variables were analyzed, estimating measures of central tendency and dispersion for numerical variables, and absolute and relative frequencies for categorical variables. The proportion of men with abnormal levels of estradiol and testosterone was calculated based on the severity of erectile dysfunction. Results A total of 70 participants were included. The average age was 53.9 years old (+/- 11.8); 18.5% had severe dysfunction, 65.7% had moderate dysfunction, 14.2% had mild to moderate dysfunction, and 1.4% had mild dysfunction. 35.7% were diabetic, and 34.2% were hypertensive. 62.8% had abnormal levels in at least one of the evaluated hormones: 5.7% had low TSH levels; 2.8% had low T3 levels; 1.4% had low T4 levels; 5.7% had low and 7.1% had high total testosterone levels; 12.8% had low and 2.8% had high free testosterone levels; 17.1% had high prolactin levels; 1.4% had low and 10% had high LH levels; 5.7% had high FSH levels. Estradiol level was high in 6 men (8.5%), 1 had mild-moderate and 5 moderate dysfunction; 8 men had low estradiol levels (11.42%), 1 had mild-moderate, 4 moderate and 3 severe dysfunction. Conclusions Alteration on the levels of Estradiol was common in the analyzed group of patients with erectile dysfunction, especially in men with moderate dysfunction, observed in 12.8% of them. Financing Boston Medical Group.

Parameters of PCOS in Tertiary Hospital in Bangladesh

Background: Polycystic ovarian syndrome (PCOS) represents a complex endocrinopathy with significant metabolic implications. The Rotterdam criteria establish the diagnosis based on the presence of two of three criteria: ultrasound-confirmed polycystic ovaries, hyperandrogenism, and persistent anovulation. Objective: Our objective was to investigate hormonal and anthropometric parameters in PCOS patients compared to controls, aiming to elucidate predictive markers and metabolic aberrations. Method: A case-control study comprising 50 PCOS subjects and 50 controls was conducted, focusing on females aged 18-40 attending an obstetrics and gynecology department, Tertiary hospital. Hormonal assays and anthropometric measurements were performed following strict inclusion and exclusion criteria. Results: Significant differences emerged between PCOS and control groups across various parameters. PCOS individuals displayed elevated levels of TSH, LH, FSH, and prolactin, coupled with increased BMI and altered waist-to-hip ratio, indicating early metabolic disruptions. Notably, the LH:FSH ratio was lower in PCOS subjects, suggesting hormonal imbalances. Conclusion: High levels of thyroid-stimulating hormone, LH, FSH, and prolactin, coupled with elevated body mass index and waist-to-hip ratio, served as indicators of PCOS and early metabolic irregularities.

Pretreatment with oral contraceptive pills in women with PCOS scheduled for IVF: a randomized clinical trial.

What is the effect of pretreatment with oral contraceptive pills (OCPs) on oocyte and embryo quality and pregnancy rates in women with polycystic ovary syndrome (PCOS) scheduled for IVF/ICSI cycles? In women with PCOS who underwent a first or second IVF/ICSI cycle with a GnRH antagonist protocol and were randomized to start ovarian stimulation immediately, the quality of cleavage-stage embryos was non-inferior to pretreatment with OCP. PCOS in Asian populations is characterized by high levels of circulating LH in the early follicular phase. Previous studies indicated that inappropriately high LH levels might affect oocyte maturation and fertilization rates, and impaired embryo quality, consequently resulting in higher rates of impaired pregnancy and miscarriage in women with PCOS. OCPs are frequently used as pretreatment to lower LH levels in PCOS patients. We performed a randomized controlled trial. After informed consent, women diagnosed with PCOS scheduled for their first or second IVF/ICSI cycle with a GnRH antagonist protocol were randomized to receive OCPs (OCP group) or start ovarian stimulation immediately, regardless of the day of the menstrual cycle (non-OCP group). Using a non-inferiority hypothesis, the sample size was calculated at 242 women. The study lasted from 7 February 2018 to 31 August 2021. A total of 242 infertility patients with PCOS undergoing the first or second cycle of IVF or ICSI were enrolled and randomized into two groups. In the OCP group, recombinant FSH was started on Day 7 of the washout period after pretreatment with OCP. In the non-OCP group, recombinant FSH was started immediately regardless of the day of the menstrual cycle. All participants received standardized GnRH antagonist ovarian stimulation. The freeze-all strategy was applied to all participants. The primary outcome was the number of good-quality embryos on Day 3 after insemination. Secondary outcomes included the rates of blastocyst formation, implantation, clinical pregnancy, and live birth from the first frozen/warmed embryo transfer cycles and cumulative live birth rates. We randomized 242 women to receive OCP (n = 121) or start immediately with ovarian stimulation (n = 121). The number of good-quality embryos on Day 3 in the OCP group was non-inferior to the non-OCP group (OCP group versus non-OCP group, 6.58 ± 4.93 versus 7.18 ± 4.39, AD -0.61, 95% CI: -1.86 to 0.65, P = 0.34). The rates of blastocyst formation (55.4% versus 52.9%, relative risk (RR) 1.11, 95% CI: 0.96 to 1.28, P = 0.17), implantation (63.0% versus 65.5%, RR 0.90, 95% CI: 0.53 to 1.53, P = 0.79), clinical pregnancy (67.9% versus 68.8%, RR 0.96, 95% CI: 0.54 to 1.71, P = 1.0), and live birth rate (52.8% versus 55.1%, RR 0.92, 95% CI: 0.53 to 1.56, P = 0.79) of the first frozen/warmed embryo transfer cycles were all comparable between the OCP and non-OCP group, respectively. Cumulative live birth rates were also similar in the OCP and non-OCP groups (78.3% versus 83.5%, respectively RR 0.71, 95% CI: 0.36 to 1.42, P = 0.39). Only patients with PCOS in Southern China were recruited. Therefore, caution is necessary when generalizing our results to all such patients with PCOS. Also, since a freeze-only strategy was used, the results of this study are only applicable when infertile women with PCOS undergo the freeze-only method. The obvious treatment difference between the two groups meant that the study was designed as an open-label study for women and doctors. The study had a randomized controlled design that minimized bias. Pretreatment with OCPs to lower LH levels in patients with PCOS before ovarian stimulation in IVF or ICSI cycles may not improve the quality of cleavage-stage embryos. This study was funded by the National Key Research and Development Program of China (No. 2023YFC2705503). This study was supported in part by the Investigator-Initiated Studies Program (grant from MSD and Organon). BWM reports consultancy, travel support, and research funding from Merck. He reports consultancy from Organon and Norgine, and also reports holding stock from ObsEva. No conflicts of interest are declared for the other authors. Chinese Clinical Trial Registry (No. chiCTR1800014822). URL: https://www.chictr.org.cn/showproj.html?proj=25280. 7 February 2018. 22 February 2018.

Low libido despite high normal testosterone levels in a male with an FSH-secreting pituitary macroadenoma.

Functioning gonadotroph adenomas with clinical manifestations are extremely rare and the majority of these are FSH-secreting macroadenomas. Clinical symptoms are due to excess gonadotrophins and sex hormones, and these may be present for a long time before the diagnosis of pituitary adenoma is made. We present the case of a 37-year-old Caucasian male with clinical manifestations of an FSH-secreting pituitary macroadenoma. He had sexual dysfunction for a year followed by bilateral testicular pain and enlargement which was initially treated as suspected recurrent epididymitis, but his symptoms did not resolve. He presented a year later with headaches and bilateral superior temporal visual field defects. Brain imaging confirmed a pituitary macroadenoma with optic chiasm compression. Pituitary profile demonstrated an unusually high FSH with high normal LH and normal testosterone level. The patient successfully underwent transsphenoidal hypophysectomy and histology confirmed gonadotroph differentiation and immunoreactivity predominantly with FSH. Gonadotrophin levels and testosterone dropped significantly after surgery, and he was started on testosterone replacement. MR imaging, 2 years post surgery, showed no recurrence of pituitary adenoma. In conclusion, testicular enlargement and hypogonadal symptoms associated with low testosterone levels are recognised features in FSH-secreting pituitary adenomas. Our patient had hypogonadal symptoms but consistently high normal testosterone levels prior to surgery. The reason for low libido despite high testosterone is unclear. Our case highlights the need to suspect such rare underlying pituitary pathology when dealing with unusual combinations of hypogonadal symptoms, testicular enlargement with low or normal testosterone levels. Functioning pituitary adenomas that secrete excess follicle-stimulating hormone (FSH) are very rare and often present with symptoms related to pituitary mass effect. Testicular enlargement alongside sexual dysfunction are commonly reported symptoms amongst male patients. Pituitary profile results demonstrate a raised FSH level with either a low, normal, or even high testosterone level which may not always correlate to clinical symptoms. Pituitary pathology should be considered in males presenting with unusual combinations of testicular enlargement and hypogonadal symptoms even with normal testosterone levels.

Relationship of vitamin D level with HOMA IR and LH in PCOS patients

Background: the most prevalent endocrine disorder in young women is polycystic ovary syndrome (PCOS). In many patients, vitamin D insufficiency aggravates the condition. Early diagnosis of insulin resistance and vitamin D insufficiency will simplify management and reduce morbidity in the future. This study analyzes the relationship between vitamin D levels and HOMA IR and LH in PCOS patients and compares the levels of LH and HOMA IR between obese and non-obese PCOS. Method: This study used a cross-sectional study on 48 women of reproductive age who were diagnosed with PCOS according to the Rotterdam criteria and who met the inclusion and exclusion criteria. Subjects were taken by consecutive sampling, measured levels of vitamin D, HOMA IR, and LH, then correlated and compared between obese and non-obese. Results: 48 samples were included in the study conducted within 3 months. A significant relationship was found between vitamin D and HOMA IR levels in PCOS patients with a p-value of 0.000. There was a significant relationship between vitamin D and LH levels in PCOS patients with a p-value of 0.000. There were significant differences in HOMA IR and LH levels in obese and non-obese PCOS patients, with higher HOMA IR in obese patients with a p-value of 0.001 and higher LH levels in non-obese PCOS patients with a p-value of 0.045. Conclusion: there was a significant relationship between vitamin D levels and HOMA IR and LH in PCOS patients and a significant difference in HOMA IR and LH in obese and non-obese PCOS patients.

Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. N/A.

Endocrine disorders after combined chemoradiotherapy in Hodgkin Lymphoma survivors

Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of toxic effects leading to dysfunction of endocrine system. Hormonal disorders in HL and their relationships with the therapy used remain to be clarified. To assess disorders of the endocrine function of thyroid, parathyroid glands and gonads in HL survivors. Screening of endocrine dysfunction of the thyroid, parathyroid glands and gonads was performed in 160 adult patients with HL, 55 men and 105 women, at remission stage induced by chemotherapy or chemoradiotherapy. Forty healthy subjects, matched by age, were acted as control. The levels of TSH, T3, free T4, PTH, FSH, LH, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone binding globulin (SHBG) were measured in blood serum by ELISA. Bone mineral density (BMD) was assessed by DEXA. Hypothyroidism (25%), hyperparathyroidism (15.6%) and hypogonadism (29% of men and 25.3% of women) were the most prevalent endocrine disorders in LH survivors. Hypothyroidism was significantly more common in patients after chemoradiotherapy than in those who received only chemotherapy (χ2=9.4, р=0.002). In patients with hyperparathyroidism, there were negative correlations between PTH levels and BMD in the lumbar spine (r=-0.74, p=0.00002) and in the femoral neck (r=-0.66, p=0.0003). Men with HL demonstrated lower free testosterone concentrations when compared to control (p=0.04); LH and FSH levels were elevated (p=0.0004 and p=0.04, respectively). In men with HL the levels of DHEA-S were reduced (p=0.0009). The increased SHBG concentrations were revealed in 13 (23.6%) men. Women of reproductive age with HL had higher levels of LH in the luteal phase (p=0.05) and FSH in the follicular phase (p=0.02) than controls. The data indicate a high prevalence of the dysfunctions of thyroid, parathyroid glands, and gonads in HL survivors. Screening for endocrine disorders in these patients is highly recommended.

Endocrine late effects in survivors of infantile acute lymphoblastic leukemia

Infantile acute lymphoblastic leukemia (ALL) is a rare disease. In survivors, endocrine late effects, such as growth disorder and hypothyroidism, have been reported, but gonadal function remains unclear. Infantile ALL frequently requires transplantation and higher doses of alkylating agents, even in the absence of transplantation. Some studies in childhood cancer survivors reported that a cyclophosphamide equivalent dose (CED) of > 20 g/m2 was associated with testosterone deficiency in boys and > 8 g/m2 with ovarian dysfunction in girls. We retrospectively reviewed the treatment and endocrine function of 6 infantile ALL survivors treated at our hospital using their medical records. The patients' age at the time of the study was between 12 and 26 yr. One patient had 0 transplant, four of them had 1 transplant, and one had 2 transplants, with CEDs of 3, 9-11, and 24 g/m2 respectively. Two patients had short stature, and two patients experienced hypothyroidism. All three girls with a CED of 9-11 g/m2 had primary hypogonadism, and the boy with a CED of 24 g/m2 had high LH and FSH levels, suggesting testosterone deficiency and spermatogenesis disorders. In conclusion, gonadal function, growth and thyroid function should be carefully monitored in infantile ALL, and CED may be useful for predicting the development of hypogonadism.

Reversal of idiopathic hypogonadotropic hypogonadism in a Chinese male cohort.

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetically heterogeneous disease and characterized by incomplete or absent puberty and infertility. It is worth noting that partial IHH patients could recover reproductive endocrine function following treatment, which is termed reversal. This study aimed to investigate clinical and genetic characteristics of IHH reversal patients. A total of 141 IHH male patients were enrolled and followed up regularly. Their clinical and genetic features were collected and analysed to discover something in common in reversal cases. These IHH patients with a median age of 21 years (interquartile range: 18-24) were divided into reversal group (n=13) and non-reversal group (n=128). IL17RD, ERBB4, DLX5, EGFR, SEMA4D, B3GNT1 and CCKAR RSVs were demonstrated in reversal cases for the first time. Pathogenic/likely pathogenic (P/LP) RSVs consisted of 3 RSVs (one each patient, including PROKR2 p.W178S, EGFR p.G630R and CCKAR p.S291del) in reversal group. Reversal of IHH could not be ignored in clinical follow-up. Patients with high levels of basal LH and T may harbour more possibility of reversal and worthy extra attention to identify whether reversal occurs or not. Relapse after reversal also needs to be monitored.

Correlation Between BMI And LH Level and LH/FSH Ratio-A Cross-Sectional Study

Background: Polycystic ovarian syndrome is the most common reproductive endocrinopathy of women during their childbearing age. Elevated LH/FSH ratio, abnormally high androgen level and relatively high endogenous estrogen production are indicative of PCOS. The diagnosis of polycystic ovarian syndrome remains controversial with some considering transvaginal sonography with the combination of clinical criteria for diagnosis. In this study, we tried to determine whether there is any impact of BMI on LH or LH/FSH ratio in PCOS for better management in the future.&#x0D; Materials and Methods: This is a cross-sectional study. Those clinically presented as obese, hirsute, and with menstrual disturbances were non-smokers and had not been on any medications for the last three months before the study. Age groups ˂20 and ˃40 years, non-PCOS with infertility, and nonobese patients were excluded from the study.&#x0D; Results: Among the total 58 patients, BMI in the range of 25-28 kg/m 2 was found in the highest frequency in 44 cases (75.9%), high LH level group in 33 cases (56.9%). LH/FSH ratio ˃2 found in 27 cases (46.66%). The correlation between BMI and LH/FSH ratio showed the highest frequency in 21 cases in the BMI group (25-28kg/m 2 ) (p ˂0.009). Random LH level amplitude was found higher in low BMI (25-28kg/m 2 ) than lower in higher BMI (28-34kg/m 2 ) (p ˂0.003).&#x0D; Conclusion:Assessments of basal LH levels and the LH/FSH ratio in hyperandrogenic anovulatory women would be clinically meaningful when BMI is taken into account.&#x0D; TAJ 2022; 35: No-1: 71-76

Slower progression of central puberty in overweight girls presenting with precocious breast development.

Overweight (OW)/obese girls tend to have an earlier pubertal onset than girls with normal weight. However, only a few studies have reported the progression of puberty in these girls. This study aimed to identify risk factors for rapid pubertal progression in OW/obese girls presenting with precocious breast development. This retrospective cohort study reviewed the medical records of 110 OW (body mass index [BMI] ≥85th percentile for age and sex) and 213 nonoverweight (NW, BMI <85th percentile for age and sex) girls who presented with breast budding before 8 years of age. OW girls were divided into 2 subgroups: girls with central puberty progression before 9 years of age (OW-RP) and those without (OW-SP). Progression to central puberty before the age of 9 was more common in NW girls than in OW girls (83.8 % vs. 65.2 % in NW vs. OW group, p<0.001), and progression-free survival for 1, 2, and 3 years was higher in the OW group (p<0.001). In a subgroup analysis of OW girls, the OW-RP subgroup had more advanced bone age (BA) at the first visit (p=0.047) and higher initial luteinizing hormone (LH, p=0.010) levels than the OW-SP subgroup. Being NW (p=0.001) and having more advanced BA (p=0.023) at the initial workup were the risk factors for pubertal progression before age 9. Pubertal progression seems to be slower in OW girls than in NW girls presenting with precocious breast development. However, it can progress rapidly in OW girls with particularly pronounced BA advancement and high LH levels at the initial workup.

Early onset obesity due to a mutation in the human leptin receptor gene.

SummaryLeptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.Learning pointsThe early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome.

Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.

An Ayurvedic Approach to Manage PCOD - A Case Study

Polycystic Ovarian Disease (PCOD) is an endocrine disorder that causes metabolic changes in women of reproductive age. PCOD has evolved into a lifestyle disorder as a result of sedentary habits, fast food consumption, and a poor lifestyle. The precise cause of PCOD is mysterious, but high levels of insulin, hyper androgen, and LH are the main causes. PCOD symptoms include irregular menstruation, oligomenorrhea, acne, hirsutism, hair loss, obesity, and constipation. PCOD is not directly stated in the Samhita, but clinically it is similar to Aartavavaha strotas dushti, Nastaartava, Granthi, Santarponnth vyadhi, and Yonivyapad. In this present case study, a 22 year old female patient came with symptoms of irregular, delayed menstruation, scanty menses, acne on the face and hair fall. The USG report reveals polycystic patterns of both ovaries with Right ovary volume 11.6cc and Left ovary volume 11cc, both ovaries are bulky in size with increased stromal echogenicity and multiple (10-12) small follicles (2-5mm) arranged in peripheral distribution. She had taken the medication so many times but she had not been completely cured. As a result she came to our hospital for Ayurvedic treatment. Result was made on the basis of Clinical symptoms relief and USG report. So in this case study, we will look at an Ayurvedic approach in the management of Polycystic Ovarian Disease.