Low LH Levels Research Articles

LH Levels May Be Used as an Indicator for the Time of Antagonist Administration in GnRH Antagonist Protocols-A Proof-Of-Concept Study.

Objective: To investigate whether circulating LH levels could be used as an indicator for the timing of antagonist addition in GnRH antagonist protocol.Design: Retrospective cohort study.Setting: University-based hospital.Patients: A total of 567 women stimulated with recombinant FSH monotherapy in a GnRH antagonist protocol were studied. Among them, 256 patients showed relatively low LH levels [highest LH level (LHmax) < 4 IU/L] during the entire ovarian stimulation process; 88 (Group A) and 168 patients (Group B) were stimulated without and with antagonist co-treatment, respectively. The remaining 311 patients had LHmax≥4 IU/L and were stimulated with a modified flexible antagonist protocol based on LH levels (Group C).Intervention(s): Patients in Group B and C received antagonist during ovarian stimulation, whereas patients in Group A did not.Main outcome measure: Clinical pregnancy rate and ongoing pregnancy rate.Results: The clinical and ongoing pregnancy rates were significantly higher in group A than group B (69.3 vs. 54.7%, P = 0.03 and 62.5 vs. 48.2%, P = 0.04, respectively), but the primary outcome measures did not differ between groups B and C. There were no significant differences in terms of patient demographics, LH levels, total dosage of gonadotrophin, duration of stimulation, follicular output rate between groups A and B, and between groups B and C. Also, there were no significant differences in laboratory and clinical outcomes in pairwise group comparisons. No canceled cycles due to premature ovulation was reported among the treated patients.Conclusion: LH levels may be used as an indicator for the time of antagonist addition. Patients with sustained low LH levels (LHmax<4 IU/L) during controlled ovarian stimulation (COS) might not require antagonist administration. Although further well-designed randomized controlled trials (RCTs) are needed to confirm our results, a novel treatment regimen based on LH measurements during COS might provide clinicians new insights about when to start antagonist administration in the GnRH antagonist protocol.

Follicle growth and endocrine dynamics in women with spontaneous luteinized unruptured follicles versus ovulation.

Do growth patterns and endocrine profiles differ between ovulatory follicles (OvFs) and luteinized unruptured follicles (LUFs) in women? Growth rates, diameters and associated endocrine profiles differed between OvFs and LUFs in unstimulated cycles. Two-three waves of antral follicles develop during the menstrual cycle in ovulatory women of reproductive age, with the second or third wave terminating in ovulation. In contrast, some women can develop LUFs, where a preovulatory follicle fails to rupture and there is subsequent luteinization of the follicle wall. However, no study has compared OvFs and LUFs in unstimulated cycles. This retrospective observational study was conducted in 56 healthy women of reproductive age (range: 19-41 years) and with a history of regular menstrual cycles. Participants who met inclusion criteria were enrolled, as previously reported. Daily transvaginal ultrasonography was performed for one interovulatory interval (IOI) to measure the diameters of all follicles >2 mm. Blood samples were collected every 3 days during the IOI to measure serum concentrations of FSH, LH, estradiol and progesterone. The interval from emergence to deviation (i.e. follicle selection) was shorter (P < 0.05) for LUFs compared to OvFs. However, the intervals from emergence to maximum diameter and deviation to maximum diameter were longer (P < 0.05) for LUFs compared to OvFs. Follicle deviation in LUFs occurred at a larger diameter (P < 0.05) compared to OvFs, and LUFs grew to larger (P < 0.0001) diameters compared to OvFs. Moreover, LUFs grew faster (P < 0.05) from emergence to deviation and from deviation to maximum diameter, compared to OvFs. LUFs were associated with low (P < 0.05) systemic LH levels at emergence and maximum diameter compared to OvFs. LUFs were also associated with low (P < 0.05) systemic FSH and high (P < 0.05) systemic progesterone at deviation and maximum diameter, respectively. Estradiol was higher (P < 0.05) at deviation and lower (P < 0.05) at maximum diameter for LUFs compared to OvFs. A 3-day interval of blood sampling for hormonal analyses was conducted, as a more frequent sampling interval was not considered acceptable by the study volunteers. A 3-day sampling interval did not allow characterization of acute changes in hormone production during the IOI. In addition, study visits were less frequent when LUFs persisted long after the expected day of the second ovulation of the IOI. Information about the growth and endocrine dynamics of OvFs and LUFs developing in unstimulated cycles in women may be applied to the early detection of LUF-associated anovulatory infertility and clinical management of women with this condition. No external funding sources were used for this study. The authors have no conflicts of interest in publishing this manuscript. ClinicalTrials.gov Identifier: NCT01389141.

The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in boys, but not in girls.

ObjectiveFetal anti-Müllerian hormone (AMH) is responsible for normal male sexual differentiation, and circulating AMH is used as a marker of testicular tissue in newborns with disorders of sex development. Little is known about the mechanism of action in postnatal life. A recent genome wide association study (GWAS) reported genetic variation of AMH affecting AMH levels in young men. This study investigated the effect of genetic variation of AMH and AMH type II receptor (AMHR2) (AMHrs10407022 T>G and AMHR2rs11170547 C>T) on circulating reproductive hormone levels and pubertal onset in boys and girls.Design and methodsThis study is a combined longitudinal and cross-sectional study in healthy Danish boys and girls from the general population. We included 658 boys aged 5.8–19.8 years and 320 girls aged 5.6–16.5 years. The main outcome measures were genotyping of AMH and AMHR2, pubertal staging and serum levels of reproductive hormones.ResultsAMHrs10407022T>G was associated with higher serum levels of AMH in prepubertal boys (TT: 575 pmol/L vs TG: 633 pmol/L vs GG: 837 pmol/L, P = 0.002) and adolescents (TT: 44 pmol/L vs TG: 58 pmol/L vs GG: 79 pmol/L, P < 0.001). Adolescent boys carrying the genetic variation also had lower levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L, P = 0.012). Hormone levels in girls and pubertal onset in either sex did not seem to be profoundly affected by the genotypes.ConclusionOur findings support recent GWAS results in young adults and expand our understanding of genetic variation affecting AMH levels even in boys prior to the pubertal decline of circulating AMH.

Characterization of hormonal profiles during the luteal phase in regularly menstruating women

To characterize the variability of hormonal profiles during the luteal phase in normal cycles. Observational study. Not applicable. Ninety-nine women contributing 266 menstrual cycles. The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10μg/mg Cr. Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis.

Novel FSHβ mutation in a male patient with isolated FSH deficiency and infertility

Isolated follicle stimulating hormone (FSH) deficiency due to mutations in FSHβ is an extremely rare autosomal recessive disease that has only been reported in ten patients to date. Symptoms of the disease include amenorrhoea and hypogonadism in women and azoospermia and normal testosterone levels in men. This study describes a Chinese male patient who presented with cryptorchidism and infertility. His serum hormonal profile revealed low FSH, elevated LH and normal testosterone levels. Sequence analysis identified a novel homozygous mutation in the FSHβ gene (c.343C > T) predicted to result in a premature termination codon and a truncated FSH protein (p.R115X). Both parents were heterozygous carriers of the mutation with normal pubertal development and fertility. The patient's testicular volume increased after one year of exogenous FSH replacement therapy at which point spermatocytes were detected in seminal samples, indicating potential future spermatogenesis. The expanded spectrum of FSHβ mutations and associated clinical manifestations described in this study may improve the diagnosis and treatment of this disease.

Occupational exposure to pesticides, reproductive hormone levels and sperm quality in young Brazilian men

The association of occupational exposure to current-use pesticides with reproductive hormones, semen quality, and genital measures was investigated among young men in the South of Brazil. A cross-sectional study was conducted in 99 rural and 36 urban men aged 18–23 years. Information on pesticide use was obtained through questionnaire. Serum and semen samples were analyzed for sex hormones and sperm parameters, respectively, and measurement of anogenital distance (AGD) and testis volume (TV) were performed. Associations were explored using multivariate linear regression. Rural men had poorer sperm morphology, higher sperm count, and lower LH levels relative to urban subjects. Lifetime use of pesticides, especially herbicides and fungicides, was associated with poorer morphology and reduced LH and prolactin, with evidence of a linear pattern. Maternal farming during pregnancy was associated with larger AGD and TV. Chronic occupational exposure to modern pesticides may affect reproductive outcomes in young men.

REVIEW AND RECOMMENDATIONS ON MANAGEMENT OF ADULT FEMALE THALASSEMIA PATIEΝTS WITH HYPOGONADISM BASED ON LITERATURE REVIEW AND EXPERIENCE OF ICET-A NETWORK SPECIALISTS

Background: Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists.The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed.Methods: In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development, or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network.Results: The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centres (68.7%). A wide range of COCs were used with different progestin contents. In general, the patients’ compliance to treatment was reported as good in 81.2 % of centres. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centres.Conclusions: Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming to attain a full pubertal development.Key words: Thalassemia, hypogonadism, hormone replacement therapy, benefits and disadvantages

A post menopausal female with empty sella syndrome

Empty sella syndrome is an incidental anatomical finding which can occasionally present as hypopituitarism. Here we report a post-menopausal female with emptysella syndrome and anterior pituitary hormone deficiency. She is a 69 year-old mother of four children presented with progressively worsening lethargy and constipation. Her last pregnancy at 24 years was complicated with post-partum haemorrhage. She had breastfed her last child for an year. She attained menopause at the age of 45. Investigations revealed normocytic anemia, and hyponatremia. Hormonal profile showed a normal TSH level(2.09mu/l)and low free T4 (&lt;0.07 ng/dl) suggestive of secondary hypothyroidism. She also had low level of 9am cortisol, and inappropriately low FSH and LH levels. Non-contrast computerized tomography of the brain revealed cerebrospinal fluid(CSF) within sella-turcica, suggestive of empty-sella syndrome. She was treated with replacement doses of hydrocortisone and thyroxine and with that her symptoms improved.

Prevalence and Etiology of Hypogonadism in Young Men With Chronic Spinal Cord Injury: A Cross-Sectional Analysis From Two University-Based Rehabilitation Centers

BackgroundSpinal cord injury (SCI) triggers an “accelerated aging” process that may include development of hypogonadism, even among younger men with SCI; however, few studies have investigated the prevalence or etiology of hypogonadism in men with SCI. Young men with SCI also are at increased risk for developing metabolic dysfunction after injury, which may be exacerbated by concomitant testosterone (T) deficiency, thus identifying the prevalence and risk factors for T deficiency in men with SCI is important for their long-term health. ObjectiveTo investigate the prevalence, risk factors, and etiology of T deficiency (hypogonadism) in otherwise-healthy men with chronic, motor complete SCI. DesignSecondary cross-sectional analysis. SettingRehabilitation research centers in Washington, DC, and Miami, Florida. ParticipantsMen (n = 58) aged 18-45 years with chronic (≥1 year), motor complete SCI without comorbidities or use of testosterone therapy. MethodsPlasma concentrations of hormones were measured with standardized assays. Body composition was assessed with dual-energy x-ray absorptiometry scan. Main Outcome MeasurementsSerum total T and calculated free T. ResultsT deficiency was more common in men after SCI than in a matched cohort of similarly-aged men without SCI (25%, SCI versus 6.7%, non-SCI, P < .001). The risk of hypogonadism appeared to be increased in men with more extensive injury and with higher percent body fat. The majority of men with SCI with low T had low serum LH levels, suggesting that central suppression of the hypothalamic-pituitary-gonadal axis may be the most common etiology of hypogonadism after SCI. ConclusionsHypogonadism is more common in young men with SCI than in similarly aged men without SCI, suggesting that SCI should be identified as a risk factor for T deficiency and that routine screening for hypogonadism should be performed in the SCI population. Level of EvidenceII

Delayed puberty in thalassemia major patients

Background Delayed puberty is the most common endocrine com-plication in thalassemia major. The main cause of delayed pu-berty in thalassemia major is the failure of the hypothalamic-pitu-itary axis due to iron accumulation in the pituitary.Objectives The purpose of this study was to determine the preva-lence of delayed puberty in β-thalassemia major patients in theDepartment of Child Health, Cipto Mangunkusumo Hospital,Jakarta. This study also evaluated the adequacy of chelationtherapy and determined serum gonadotropin and sex hormonelevels in these patients.Methods Seventy-two patients with β-thalassemia major aged 13-18 years old who visited the Thalassemia Outpatient Clinic of CiptoMangunkusumo Hospital during February-July 2003 were includedin the study. Each subject underwent examinations to determinethe body weight and height, pubertal status, serum iron level, totaliron binding capacity, and the levels of serum LH, FSH, estradiol(in girls) or testosterone (in boys).Results Delayed puberty occurred in 40 of 72 patients (56%). Themajority of patients with delayed puberty showed low levels of se-rum LH, estradiol, and testosterone whereas low levels of serumFSH only occurred in 6 of 21 boys and 11 of 19 girls. Most of thepatients without delayed puberty had normal levels of serum LH,FSH, and estradiol, but 8 of 16 boys showed decreased serumtestosterone levels. Only 3 patients used chelation therapy ad-equately, all of them showed normal puberty.Conclusions The prevalence of delayed puberty in β-thalassemiamajor patients in this study was still high (56%). Periodic examina-tion and recording of pubertal stage need to be done in girls whohave reached 8 years old and boys who have reached 9 years oldso that early detection and management of delayed puberty canbe done.

Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology

Context: Ovulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established.Objective: To compare pulsatile GnRH therapy versus gonadotropins for ovulation induction in “FHA-PCOM” patients and to determine if one treatment strikes as superior to the other.Methods: A 12-year retrospective study, comparing 55 “FHA-PCOM” patients, treated either with GnRH therapy (38 patients, 93 cycles) or with gonadotropins (17 patients, 53 cycles).Results: Both groups were similar, defined by low serum LH and E2 levels, low BMI, excessive follicle number per ovary and/or high serum AMH level. Ovulation rates were significantly lower with gonadotropins (56.6% versus 78.6%, p = 0.005), with more cancellation and ovarian hyper-responses (14% versus 34% per initiated cycle, p < 0.005). Pregnancy rates were significantly higher with GnRH therapy, whether per initiated cycle (26.9% versus 7.6%, p = 0.005) or per patient (65.8% versus 23.5%, p = 0.007).Conclusion: In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in “FHA-PCOM” patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM.

Prospective study of histological and endocrine parameters of gonadal function in boys with cryptorchidism

A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism. Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n=12; TFI <0.2; Ad/T=0) and low infertility risk (LIR; n=9; TFI >0.9; Ad/T>0.02). Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similarTFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B(0.66,0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia). Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings.

Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats.

In the human infundibular (arcuate) nucleus, a subpopulation of neurons coexpress kisspeptin and neurokinin B (NKB), 2 peptides required for normal reproductive function. A homologous group of neurons exists in the arcuate nucleus of rodents, termed KNDy neurons based on the coexpression of kisspeptin, NKB, and dynorphin. To study their function, we recently developed a method to selectively ablate KNDy neurons using NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (SAP). Here, we ablated KNDy neurons in female rats to determine whether these neurons are required for estrous cyclicity and the steroid induced LH surge. NK3-SAP or Blank-SAP (control) was microinjected into the arcuate nucleus using stereotaxic surgery. After monitoring vaginal smears for 3-4 weeks, rats were ovariectomized and given 17β-estradiol and progesterone in a regimen that induced an afternoon LH surge. Rats were killed at the time of peak LH levels, and brains were harvested for NKB and dual labeled GnRH/Fos immunohistochemistry. In ovary-intact rats, ablation of KNDy neurons resulted in hypogonadotropic hypogonadism, characterized by low levels of serum LH, constant diestrus, ovarian atrophy with increased follicular atresia, and uterine atrophy. Surprisingly, the 17β-estradiol and progesterone-induced LH surge was 3 times higher in KNDy-ablated rats. Despite the marked increase in the magnitude of the LH surge, the number of GnRH or anterior ventral periventricular nucleus neurons expressing Fos was not significantly different between groups. Our studies show that KNDy neurons are essential for tonic levels of serum LH and estrous cyclicity and may play a role in limiting the magnitude of the LH surge.

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes.

Coexistence of endocrinopathies in children with rheumatic diseases.

Background and objectivesTo examine the frequency of endocrinopathies in children with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).Design and settingA cross-sectional study.Patients and methodsA study was conducted in Saudi children with SLE and JIA who were seen at King Faisal Specialist Hospital and Research Centre, Riyadh, between September 2013 and April 2015. All enrolled patients completed the clinical evaluation, which included information about family history of autoimmune disease, growth parameters and tanner stage, as well as the following assessments: vitamin D profile (parathyroid hormone and 25-OH vitamin D levels), TSH, FT4 and total T3, thyroglobulin antibodies, thyroperoxidase antibodies, random blood sugar, HbA1C, IGF1, IGFBP-3, LH, and FSH.ResultsA total of 42 patients, 22 with JIA and 20 with SLE, were included in the study. The mean participant age was 12.2 ± 5.3 years with a mean disease duration of 3.2 ± 3.4 years. Female gender was predominant (17 SLE, 13 JIA) in the patient population. Fifteen patients (35.7%) presented with a family history of autoimmune disease. The most frequently detected endocrinopathies were vitamin D insufficiency (35%) and thyroid disease (31%). Eight JIA patients and 7 SLE patients exhibited low vitamin D levels; 10 patients presented with hyperparathyroidism. Thyroid dysfunction was observed in 13 patients (8 SLE, 5 JIA), and 2 patients were found to be euthyroid (normal TSH, FT4) with positive thyroid autoantibodies. Furthermore, 7 patients presented with subclinical hypothyroidism (high TSH, normal FT4), and 4 patients presented with overt hypothyroidism (high TSH, low FT4). Seven patients (4 SLE and 3 JIA) presented with short stature due to growth hormone insufficiency (low IGF1, IGFBP-3). Two patients exhibited delayed puberty accompanied by low LH levels. Diabetes mellitus was more frequently observed in patients with JIA (4 patients) than in patients with SLE (1 patient).ConclusionOur findings demonstrated that coexistence of endocrinopathies is not uncommon in children diagnosed with JIA and SLE. Abnormal thyroid function occurs frequently and at a similar rate in children diagnosed with SLE and JIA. Thus, screening for endocrinopathies, namely thyroid disease, during the assessment of childhood SLE and JIA is worth consideration.

Hypogonadotropic Hypogonadism in Infants with Congenital Hypopituitarism: A Challenge to Diagnose at an Early Stage

Background: Combined pituitary hormone deficiency (CPHD) presents a wide spectrum of pituitary gland disorders. The postnatal gonadotropic surge provides a useful period to explore the gonadotropic axis for assessing the presence of congenital hypogonadotropic hypogonadism (CHH). Aim: To explore the functioning of the hypothalamic-pituitary-gonadal axis in the postnatal gonadotropic surge for an early diagnosis of CHH in newborns or infants suspected of having CPHD. Subjects and Methods: A cohort of 27 boys under 6 months and 19 girls under 24 months of age with suspected hypopituitarism was studied. Serum concentrations of LH, FSH, testosterone, inhibin B, anti-Müllerian hormone (AMH) and estradiol were measured, and male external genitalia were characterized as normal or abnormal (micropenis, microorchidism and/or cryptorchidism). Results: CPHD was confirmed in 36 out of 46 patients. Low LH and testosterone levels were found in 66% of the hypopituitary males, in significant association with the presence of abnormal external genitalia. This abnormality had a positive predictive value of 93% for CHH. No significant association was observed between serum FSH, AMH and inhibin B and the patient's external genitalia. Conclusion: In newborn or infant boys with CPHD, LH and testosterone concentrations measured throughout the postnatal gonadotropic surge, together with a detailed evaluation of the external genital phenotype, facilitate the diagnosis of CHH at an early stage.

Frequency of low serum LH level during ovarian stimulation is associated with early pregnancy loss in IVF/ICSI cycles with a GNRH antagonist protocol

The influence of low serum LH level in the antagonist protocol for controlled ovarian stimulation (COS) remained controversial. Previous studies focused on the LH level on a certain day of COS. Our study is to evaluate the association between frequencies of low serum LH levels and pregnancy outcome in IVF/ICSI cycles with a GnRH antagonist protocol.

Development of gonadotropin-releasing hormone secretion and pituitary response.

Acquisition of a mature pattern of gonadotropin-releasing hormone (GnRH) secretion from the CNS is a hallmark of the pubertal process. Little is known about GnRH release during sexual maturation, but it is assumed to be minimal before later stages of puberty. We studied spontaneous GnRH secretion in brain slices from male mice during perinatal and postnatal development using fast-scan cyclic voltammetry (FSCV) to detect directly the oxidation of secreted GnRH. There was good correspondence between the frequency of GnRH release detected by FSCV in the median eminence of slices from adults with previous reports of in vivo luteinizing hormone (LH) pulse frequency. The frequency of GnRH release in the late embryonic stage was surprisingly high, reaching a maximum in newborns and remaining elevated in 1-week-old animals despite low LH levels. Early high-frequency GnRH release was similar in wild-type and kisspeptin knock-out mice indicating that this release is independent of kisspeptin-mediated excitation. In vivo treatment with testosterone or in vitro treatment with gonadotropin-inhibitory hormone (GnIH) reduced GnRH release frequency in slices from 1-week-old mice. RF9, a putative GnIH antagonist, restored GnRH release in slices from testosterone-treated mice, suggesting that testosterone inhibition may be GnIH-dependent. At 2-3 weeks, GnRH release is suppressed before attaining adult patterns. Reduction in early life spontaneous GnRH release frequency coincides with the onset of the ability of exogenous GnRH to induce pituitary LH secretion. These findings suggest that lack of pituitary secretory response, not lack of GnRH release, initially blocks downstream activation of the reproductive system.

Vitamin D levels and bone mineral density: are LH levels involved in the pathogenesis of bone impairment in hypogonadal men?

Osteoporosis is a major public health problem also in men and it recognizes hypogonadism as a major cause. To investigate the possible pathogenetic mechanisms on bone impairment in male hypogonadism and on its improvement in response to testosterone replacement treatment (TRT). We retrospectively investigated the hormonal profile and bone mineral density (BMD), evaluated by DXA, in 17 middle-aged hypogonadal men treated for at least 5years with TRT, compared with 21 recently diagnosed untreated hypogonadal males and 18 age- and BMI-matched healthy subjects. No significant differences in clinical, biochemical and densitometric parameters were found among the three groups, with the exception of 25-OH vitamin D levels that were significantly higher in healthy subjects compared with hypogonadal patients. Untreated patients affected by central hypogonadism, despite similar hormonal levels, displayed significantly lower BMD and decreased LH and 25-OH vitamin D levels, compared with patients with primary hypogonadism. Among the treated patients, BMD parameters were similar regardless of the formulation of TRT. A recent history of central hypogonadism, compared with primary hypogonadism, appears to adversely affect bone health independently of gonadal steroids levels. This could be due to lower LH levels and consequent reduction of vitamin D 25-hydroxylation in the testis.

Predictors of success of laparoscopic ovarian drilling in women with polycystic ovary syndrome: an evidence-based approach.

Laparoscopic ovarian drilling (LOD) is currently recommended as a successful second-line treatment for ovulation induction in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). To provide a comprehensive review of the current evidence regarding different clinical, biochemical and ultrasonographic parameters that help in predicting ovulation and or pregnancy after LOD. A PubMed search of published studies on LOD and reproductive outcome was conducted using defined keywords. Abstracts of 121 articles were screened and relevant articles were identified. Clinical studies were included with priority for level I evidence, i.e., randomized controlled trials (RCTs) followed by other levels. Based on the current evidence, LOD could be predicted to result in poor reproductive outcome in women with CC-resistant PCOS when they are obese (BMI>25kg/m(2)), long duration of infertility>3years, low basal LH levels<10IU/L, marked biochemical hyperandrogenism (testosterone levels≥4.5nmol/L, free androgen index>15) and high basal AMH≥7.7ng/mL. Setting eligibility criteria based on the existing evidence concerning predictors of success of LOD is critical not only for improving its outcome, but also to avoid unnecessary surgery with possible risk of impairment of ovarian reserve and other complications.