751 results match your criteria Gonadotropin-Releasing Hormone Deficiency in Adults

Treatment of congenital adrenal hyperplasia and Klinefelter Syndrome with central precocious puberty: a case report.

Transl Pediatr 2022 Feb;11(2):298-305

Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

The simultaneous occurrence of Klinefelter syndrome (KS) and congenital adrenal hyperplasia (CAH) is extremely rare, as the former causes androgen deficiency, while the latter results in androgen excess. In addition, central precocious puberty (CPP) will occur, which is caused by the activation of the hypothalamic-pituitary-gonadal (HPG) axis by androgens. We present the 7th reported case of simultaneous KS and CAH in a boy with CPP due to protopathy of CAH. Read More

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February 2022

Whole-Exome Sequencing Identified a Novel Mutation in RNF216 in a Family with Gordon Holmes Syndrome.

J Mol Neurosci 2022 Apr 28;72(4):691-694. Epub 2022 Jan 28.

Department of Neurology and Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Gordon Holmes syndrome (GHS) is a rare disease characterized by hypogonadotropic hypogonadism (HH), progressive cognitive decline and variable movement disorders. Mutations in RNF216 have been found to be associated with GHS. Here, we identify a novel homozygous RNF216 p. Read More

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Current concepts surrounding neonatal hormone therapy for boys with congenital hypogonadotropic hypogonadism.

Expert Rev Endocrinol Metab 2022 01 7;17(1):47-61. Epub 2022 Jan 7.

Department of Endocrinology, Diabetes & Metabolism Royal Victoria Infirmary, Newcastle-Upon-Tyne Hospitals, Newcastle-upon-Tyne, UK.

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a genetic disorder of reproduction and development, characterized by deficient gonadotropin-releasing hormone (GnRH) secretion or action, affecting 1-in-4,000-15,000 males. Micropenis and undescended testes are cardinal features of antenatal GnRH deficiency and could indicate absent minipuberty in the first postnatal months. In this review, we outline the pathophysiology and clinical consequences of absent minipuberty and its implications for optimal approaches to the endocrine management of affected boys. Read More

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January 2022

Should Skeletal Maturation Be Manipulated for Extra Height Gain?

Jan M Wit

Front Endocrinol (Lausanne) 2021 16;12:812196. Epub 2021 Dec 16.

Division of Pediatric Endocrinology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. Read More

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February 2022

Evidence for Perinatal Steroid Influence on Human Sexual Orientation and Gendered Behavior.

Cold Spring Harb Perspect Biol 2021 Dec 6. Epub 2021 Dec 6.

Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.

In laboratory animals, exposure to gonadal steroid hormones before and immediately after birth can exert permanent effects on many behaviors, particularly reproductive behaviors. The extent to which such effects occur in humans remains an open question, but several lines of evidence indicate that perinatal levels of both androgens and estrogens may affect adult human psychology and behavior, including sexual orientation and gender nonconformity. Some putative indicators of prenatal androgen exposure, including the ratio of the length of the index finger to that of the ring finger (2D:4D), have repeatedly indicated that lesbians, on average, were exposed to more prenatal androgens than straight women, suggesting that sufficient fetal androgen exposure predisposes a fetus to gynephilia (attraction to women) at maturity. Read More

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December 2021

Next-generation sequencing-based mutational analysis of idiopathic short stature and isolated growth hormone deficiency in Korean pediatric patients.

Mol Cell Endocrinol 2022 03 12;544:111489. Epub 2021 Oct 12.

Department of Pediatrics, Severance Children's Hospital, College of Medicine Yonsei University, Seoul, South Korea. Electronic address:

We investigated the distribution of short stature-associated mutations in Korean pediatric patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD) via targeted next-generation sequencing (TNGS). We employed a 96-gene TNGS panel for short stature in a total of 144 patients (5-19 years-old) previously diagnosed with ISS or IGHD and identified heterozygous pathogenic or likely pathogenic genetic variants in 14 (10%) patients. Of the mutated genes, PROKR2 (n = 3) is associated with gonadotropin-releasing hormone deficiency or hypopituitarism, while FGFR1 (n = 1) and NPR2 (n = 3) encode growth plate paracrine factors. Read More

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Case Report: A Rare Case of Coexisting of Autoimmune Polyglandular Syndrome Type 3 and Isolated Gonadotropin-Releasing Hormone Deficiency.

Front Immunol 2021 14;12:734685. Epub 2021 Sep 14.

Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison's disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. Read More

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December 2021

Treatments for seizures in catamenial (menstrual-related) epilepsy.

Cochrane Database Syst Rev 2021 09 16;9:CD013225. Epub 2021 Sep 16.

Department of Health Data Science, University of Liverpool, Liverpool, UK.

Background: This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). Read More

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September 2021

Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production.

Exp Mol Med 2021 08 27;53(8):1238-1249. Epub 2021 Aug 27.

Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Xinqiao Main Street No. 183, Shapingba, Chongqing, China.

P62 is a protein adaptor for various metabolic processes. Mice that lack p62 develop adult-onset obesity. However, investigations on p62 in reproductive dysfunction are rare. Read More

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Supplementation with human menopausal gonadotropin in the gonadotropin-releasing hormone antagonist cycles of women with high AMH: Pregnancy outcomes and serial hormone levels.

Taiwan J Obstet Gynecol 2021 Jul;60(4):739-744

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, No. 5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan. Electronic address:

Objective: To evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH.

Materials And Methods: This retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. Read More

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Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome.

Genes (Basel) 2021 06 5;12(6). Epub 2021 Jun 5.

Department of Endocrinology Metabolism and Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjects (41 males, 5 females; average age: 29 years old). Read More

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Non-GH Agents and Novel Therapeutics in the Management of Short Stature.

Indian J Pediatr 2021 Dec 1;88(12):1209-1213. Epub 2021 Jul 1.

Division of Pediatric Endocrinology, Department of Pediatrics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA.

Short stature is one of the most common reasons for referral to pediatric endocrinologists. The vast majority of short children do not have growth hormone (GH) deficiency or another pathologic process that is interfering with normal growth. While GH has been approved in the US for several etiologies of non-GH deficient short stature, its high cost and need for daily injections represent barriers for many families. Read More

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December 2021

Deficiency of arcuate nucleus kisspeptin results in postpubertal central hypogonadism.

Am J Physiol Endocrinol Metab 2021 08 28;321(2):E264-E280. Epub 2021 Jun 28.

Department of Pediatrics, Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, New Jersey.

Kisspeptin (encoded by ), a neuropeptide critically involved in neuroendocrine regulation of reproduction, is primarily synthesized in two hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). AVPV kisspeptin is thought to regulate the estrogen-induced positive feedback control of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), and the preovulatory LH surge in females. In contrast, ARC kisspeptin neurons, which largely coexpress neurokinin B and dynorphin A (collectively named KNDy neurons), are thought to mediate estrogen-induced negative feedback control of GnRH/LH and be the major regulators of pulsatile GnRH/LH release. Read More

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Gordon Holmes syndrome caused by two novel mutations in the PNPLA6 gene.

Clin Neurol Neurosurg 2021 08 17;207:106763. Epub 2021 Jun 17.

Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address:

Gordon Holmes syndrome (GHS) is an autosomal recessive disease characterized by cerebellar ataxia and hypogonadotropic hypogonadism. Among the genes associated with this syndrome, mutations in PNPLA6 have been detected and correlated with the phenotype of GHS. We report a case of a patient affected with GHS, confirmed by physical, neurological, laboratory and genetic analyses. Read More

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Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome.

Cancer Immunol Immunother 2021 Dec 11;70(12):3669-3677. Epub 2021 May 11.

Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. Read More

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December 2021

Successful Delivery in 17,20-Lyase Deficiency.

J Clin Endocrinol Metab 2021 06;106(7):1882-1886

Pediatric Endocrinology Unit, Clalit Health Services, Lady Davis Carmel Medical Center, Haifa, Israel.

Context: Pregnancy achievement in an infertile patient with 17,20-lyase deficiency.

Objective: To study and describe the achievement of successful pregnancy and delivery in a patient with 17,20-lyase deficiency.

Method: Controlled ovarian stimulation (COS) and in vitro fertilization (IVF), cryopreservation of embryos and frozen-thawed embryo transfer (ET). Read More

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Novel model to study the physiological effects of temporary or prolonged sex steroid deficiency in male mice.

Am J Physiol Endocrinol Metab 2021 03 14;320(3):E415-E424. Epub 2020 Dec 14.

Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium.

Sex steroids are critical for skeletal development and maturation during puberty as well as for skeletal maintenance during adult life. However, the exact time during puberty when sex steroids have the highest impact as well as the ability of bone to recover from transient sex steroid deficiency is unclear. Surgical castration is a common technique to study sex steroid effects in rodents, but it is irreversible, invasive, and associated with metabolic and behavioral alterations. Read More

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Somatotropic-Testicular Axis: A crosstalk between GH/IGF-I and gonadal hormones during development, transition, and adult age.

Andrology 2021 01 23;9(1):168-184. Epub 2020 Oct 23.

Department of Experimental Medicine, Sapienza University, Rome, Italy.

Background: The hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-somatotropic (HPS) axes are strongly interconnected. Interactions between these axes are complex and poorly understood. These interactions are characterized by redundancies in reciprocal influences at each level of regulation and the combination of endocrine and paracrine effects that change during development. Read More

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January 2021

A closer look at the role of insulin for the regulation of male reproductive function.

Gen Comp Endocrinol 2021 01 2;300:113643. Epub 2020 Oct 2.

Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

While insulin demonstrates to have a considerable influence on the reproductive system, there are various unanswered questions regarding its precise sites, mechanisms of action, and roles for the developing and functioning of the adult male reproductive system. Apart from its effects on glucose level, insulin has an important role in the reproductive system directly by binding on insulin and IGF receptors in the brain and testis. To date, however, the effect of insulin or its alterations on blood-testis-barrier, as an important regulator of normal spermatogenesis and fertility, has not yet been studied. Read More

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January 2021

GnRH Deficient Patients With Congenital Hypogonadotropic Hypogonadism: Novel Genetic Findings in , and Genes in a Case Series and Review of the Literature.

Front Endocrinol (Lausanne) 2020 28;11:626. Epub 2020 Aug 28.

Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease caused by Gonadotropin-Releasing Hormone (GnRH) deficiency. So far a limited number of variants in several genes have been associated with the pathogenesis of the disease. In this original research and review manuscript the retrospective analysis of known variants in (, and genes is described, along with novel variants identified in patients with CHH by the present study. Read More

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Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.

J Clin Endocrinol Metab 2021 03;106(3):e1441-e1452

National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina.

Context: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility.

Objective: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls. Read More

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Homozygous p.R31H GNRH1 mutation and normosmic congenital hypogonadotropic hypogonadism in a patient and self-limited delayed puberty in his relatives.

J Pediatr Endocrinol Metab 2020 Sep;33(9):1237-1240

Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Bruxelles, Belgium.

Objectives Congenital hypogonadotropic hypogonadism (CHH) is a rare condition resulting from GnRH deficiency. Gonadotropin Releasing Hormone 1 (GNRH1) homozygous mutations are an extremely rare cause of normosmic CHH (nCHH). Most heterozygous individuals are asymptomatic, with the notable exception of individuals heterozygous for a p. Read More

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September 2020

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Hum Mol Genet 2020 08;29(14):2435-2450

Center for Human Disease Modeling, Duke University, Durham, NC 27701, USA.

Dysfunction of the gonadotropin-releasing hormone (GnRH) axis causes a range of reproductive phenotypes resulting from defects in the specification, migration and/or function of GnRH neurons. To identify additional molecular components of this system, we initiated a systematic genetic interrogation of families with isolated GnRH deficiency (IGD). Here, we report 13 families (12 autosomal dominant and one autosomal recessive) with an anosmic form of IGD (Kallmann syndrome) with loss-of-function mutations in TCF12, a locus also known to cause syndromic and non-syndromic craniosynostosis. Read More

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Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.

Psychoneuroendocrinology 2020 09 6;119:104733. Epub 2020 Jun 6.

Department of Anthropology, Pennsylvania State University, Carpenter Building, University Park, PA, 16802, USA. Electronic address:

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Read More

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September 2020

Multiple-dose versus single-dose gonadotropin-releasing hormone agonist after first in vitro fertilization failure associated with luteal phase deficiency: A randomized controlled trial.

Danni Qu Yuan Li

J Int Med Res 2020 Jun;48(6):300060520926026

Medical Center for Human Reproduction, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Objective: To evaluate the efficacy and safety of multiple- versus single-dose gonadotropin-releasing hormone agonist (GnRH-a) addition to luteal phase support (LPS), in patients with a first in vitro fertilization (IVF) failure associated with luteal phase deficiency (LPD).

Methods: Eighty patients with a first IVF failure associated with LPD were randomly assigned into single-dose and multiple-dose GnRH-a groups. In the second IVF attempt, patients in the single-dose group were given standard LPS plus a single dose of GnRH-a 6 days after oocyte retrieval. Read More

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Hypogonadotropic hypogonadism due to variants in : expanding the phenotypic and genotypic spectrum of Martsolf syndrome.

Cold Spring Harb Mol Case Stud 2020 06 12;6(3). Epub 2020 Jun 12.

Harvard Reproductive Endocrine Sciences Center, Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Biallelic pathogenic variants in cause Warburg Micro syndrome (WARBM) and Martsolf syndrome (MS), two rare, phenotypically overlapping disorders characterized by congenital cataracts, intellectual disability, and hypogonadism. Although the initial report documented hypergonadotropic hypogonadism (implying a gonadal defect), an adolescent girl with WARBM/MS was subsequently reported to have hypogonadotropic hypogonadism (implying a central defect in either the hypothalamus or anterior pituitary). However, in adult MS, hypogonadotropism has not been convincingly demonstrated. Read More

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Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan.

Cerebellum 2020 Aug;19(4):544-549

Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.

Mutations in STUB1 have been identified to cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16), also named as Gordon Holmes syndrome, which is characterized by cerebellar ataxia, cognitive decline, and hypogonadism. Additionally, several heterozygous mutations in STUB1 have recently been described as a cause of autosomal dominant spinocerebellar ataxia type 48. STUB1 encodes C-terminus of HSC70-interacting protein (CHIP), which functions as an E3 ubiquitin ligase and co-chaperone and has been implicated in several neurodegenerative diseases. Read More

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A Novel SEMA3G Mutation in Two Siblings Affected by Syndromic GnRH Deficiency.

Neuroendocrinology 2021 4;111(5):421-441. Epub 2020 May 4.

Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy,

Introduction: Gonadotropin-releasing hormone (GnRH) deficiency causes hypogonadotropic hypogonadism (HH), a rare genetic disorder that impairs sexual reproduction. HH can be due to defective GnRH-secreting neuron development or function and may be associated with other clinical signs in overlapping genetic syndromes. With most of the cases being idiopathic, genetics underlying HH is still largely unknown. Read More

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November 2021

Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men With Pedophilic Disorder: A Randomized Clinical Trial.

JAMA Psychiatry 2020 09;77(9):897-905

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Importance: Evidence-based treatments from randomized clinical trials for pedophilic disorder are lacking.

Objective: To determine whether a gonadotropin-releasing hormone antagonist reduces dynamic risk factors for committing child sexual abuse.

Design, Setting, And Participants: This academically initiated, double-blind, placebo-controlled, parallel-group, phase 2 randomized clinical trial was conducted at the ANOVA center in Stockholm, Sweden, from March 1, 2016, to April 30, 2019. Read More

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September 2020