Journal of Human Reproductive Science
Home Ahead of Print Current Issue Archives
   Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size    Users online: 795

   Table of Contents     
Year : 2022  |  Volume : 15  |  Issue : 4  |  Page : 351-356

Male idiopathic hypogonadotropic hypogonadism: Serum insulin-like growth factor-1 and oestradiol levels

1 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR; Department of Biology, Science and Research Branch Islamic Azad University, Tehran, Iran
2 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
3 Department of Biology, Science and Research Branch Islamic Azad University, Tehran, Iran

Date of Submission13-Sep-2022
Date of Decision27-Nov-2022
Date of Acceptance28-Nov-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. Marjan Sabbaghian
Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jhrs.jhrs_132_22

Rights and Permissions



Background: Idiopathic hypogonadotropic hypogonadism (IHH) is a form of male infertility caused by a congenital defect in the secretion or action of gonadotropin-releasing hormone from the hypothalamus. Oestradiol emerged as the main sex steroid in the regulation of the hypothalamic–pituitary–testicular axis, reproductive function and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in men. Moreover, GH/IGF-1 axis has been suggested to play a role in IHH. Aims: This study evaluated serum IGF-1 in IHH men and controls. Furthermore, we evaluated the association between serum total oestradiol (TE2) and IGF-1 levels in patients and controls. Parameters including age, body mass index and fertility history were analysed. Settings and Design: This prospective study was conducted at the Royan institute. Materials and Methods: In 20 men with IHH and 20 controls, serum IGF-1 levels were estimated using chemiluminescence immunoassay and serum E2 levels were assessed by means of the electrochemiluminescence method. Statistical Analysis Used: Kolmogorov-Smirnov test, parametric t-test or the Mann-Whitney and the Pearson correlation coefficient were performed. SPSS version 22 was used for the analysis of data. Results: There was a significant decrease in serum IGF-1 levels in IHH patients compared with controls (145.1 ± 8.9 ng/ml vs. 229.6 ± 7.3 ng/ml P < 0.001, respectively). Furthermore, a significant decrease was observed in TE2 levels in IHH male patients (12.3 ± 2.5 pg/ml) compared with controls (31.9 ± 5.3 pg/ml P < 0.001). A positive correlation was observed between serum IGF-1 and TE2 levels in the total number of participants, suggesting that E2 deficiency in IHH cases can explain the lower levels of serum IGF-1. Conclusions: These findings suggest that the reduction in IGF-1 levels may be associated with the influence of E2 on the GH/IGF-1 axis, and may confirm the role of the GH/IGF-1 axis in IHH. Further investigations will be required to determine the exact mechanisms by which E2 and IGF-1 affect the reproductive neuroendocrine function.

Keywords: Oestradiol, hypothalamic-pituitary axis, idiopathic hypogonadotropic hypogonadism, insulin-like growth factor-1

How to cite this article:
Salehisedeh N, Parhizkar A, Yaghmaei P, Sabbaghian M. Male idiopathic hypogonadotropic hypogonadism: Serum insulin-like growth factor-1 and oestradiol levels. J Hum Reprod Sci 2022;15:351-6

How to cite this URL:
Salehisedeh N, Parhizkar A, Yaghmaei P, Sabbaghian M. Male idiopathic hypogonadotropic hypogonadism: Serum insulin-like growth factor-1 and oestradiol levels. J Hum Reprod Sci [serial online] 2022 [cited 2023 Feb 4];15:351-6. Available from:

   Introduction Top

Idiopathic hypogonadotropic hypogonadism (IHH) is defined through delayed or absent sexual development that results in low serum testosterone levels, decreased spermatogenesis and low or inappropriately normal levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH), but with normal levels of other pituitary hormones; Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH) ) and no anatomical and functional abnormalities of the hypothalamic-pituitary (HP) axis.[1],[2],[3] It is primarily defined by idiopathic gonadotropin-releasing hormone (GnRH) deficit in production, secretion and action.[4],[5],[6],[7]

Insulin-like growth factor-1 (IGF-1) stimulates GnRH promoter activity in vitro,[8],[9] and also stimulates the release of GnRH from GnRH neuronal cell lines (GT1-7 cells).[10] In addition, GH and IGF-1 affect the migration of GnRH neurons (GN11) from the olfactory placode to the hypothalamus-preoptic area in foetal life and stimulate GnRH post-natal life secretion.[11] In the human GnRH (hGnRH) promoter, it has been shown an AP-1 site that mediates IGF-1 stimulation of hGnRH promoter activity in vitro.[9]

Oestradiol is known as a critical player in male reproductive function and in controlling the HP–testicular (HPT) axis.[12],[13] E2 directly inhibited pituitary gonadotropin production to reduce sensitivity to GnRH.[14],[15]. Furthermore, E2 reduced GnRH pulse frequency through an action site in the hypothalamus and reduced responsiveness to GnRH in the pituitary, therefore, decreased LH pulse amplitude.[16] A study on male IHH has reported that the predominant negative effect of E2 on LH occurs in the hypothalamus.[17] E2 may indirectly regulate GnRH neurons through functions on oestrogen receptor α (ER) in kisspeptin, neurokinin B and dynorphin-expressing neurons in the infundibular nucleus of the hypothalamus.[18] Furthermore, ER is expressed by hGnRH neurons.[19]

The cascade of hormonal events is shown in [Figure 1].
Figure 1: Schematic illustration of the effects of GH/IGF-1 and E2 on HPT axis. GH/IGF-1 axis stimulates GnRH secretion in (GT1-7 cells) GnRH neurones. Hypothetically, this stimulatory effect may reduce due to decreased levels of IGF-1 in IHH patients. The image was created in Biorender.Com. LH = Luteinizing hormone, FSH = Follicle-stimulating hormone, GnRH = Gonadotropin-releasing hormone, GH = Growth hormone, IGF-1 = Insulin-like growth factor-1, HPT = Hypothalamic–pituitary–testicular, IHH = Idiopathic hypogonadotropic hypogonadism

Click here to view

However, only a few studies have investigated the serum levels of IGF-1 in IHH patients.[20],[21] To obtain a better understanding of the role of IGF-1 and oestradiol in IHH, the present study was conducted to investigate the relationship between serum IGF-1 and E2 as two important regulatory factors in the HPT axis.

   Materials and Methods Top

This single-centre study with ethic code: IR.ACECR.ROYAN.REC.1398.010 was approved at the research ethics committee of Royan Institute, Tehran, Iran. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 2013. All the volunteers gave their written informed consent before the start of the study. Men who used any anabolic medication were excluded from the study. General health history was obtained at the initial visit. Based on the clinical history, physical examination and routine laboratory measurements, men with diabetes, endocrine, renal, liver and cardiovascular diseases were not included in this story.

Patients with idiopathic hypogonadotropic hypogonadism

This study was conducted on 20 male IHH subjects referred to Royan institution, from November 2018 to May 2019. The mean age was 34.1 ± 3.1 (range, 30–40) years; the mean body mass index (BMI) was 23.8 ± 3.8 (range, 18.2–33.6 kg/m2). IHH patients were characterised by (1) incomplete or absent puberty by the age of 18 years, (2) decreased serum T levels below 2.5 ng/ml in the existence of low serum LH and FSH levels below 1.2 mIU/ml and 2 mIU/ml, respectively, (3) standard hypothalamus and pituitary magnetic resonance imaging findings and (4) normal sense of smell and normal karyotypes (46, XY). Detailed physical investigations were completed, including evaluation of the testis volume by Prader orchidometer. All patients had previous treatment, although there had been a washout period of 4 months before entering the study.


Twenty men were evaluated in our department because they belonged to couples presenting with infertility of female origin. The mean age was 35.3 ± 2.6 (range, 31–40) years; the mean BMI was 24.1 ± 2.5 (range, 18.4–27.7 kg/m2). They were selected for the assessment of normal semen analysis according to WHO 2010; (sperm concentration: 15 × 106 sperm/ml, Percentage motility: 40%, 1.5 Ml volume)[22], testicular volume more than 15 ml (Prader orchidometer), normal serum concentrations of LH, FSH, and T.

Sample size

G Power version 3.1 software (G power Source Company Ltd. offers alternative energy services) was used to calculate the sample size. Considering the comparison of the mean of the two independent groups of the study, an independent t-test was used. To determine the sample size, type I error 0.05 and type II error 0.2 (power 0.8) were considered.

Hormone analysis

Blood samples were collected in red plain blood collection tubes (Hebei Xinle Sci and Tech CO., Ltd), between 8 and 10, in the morning. Serum was separated from the blood samples and labelled with a code and serum samples were then stored in a freezer at –70°C. Samples were kept for not more than 4 months and were then analysed.

Levels of serum FSH and LH were estimated using the ELISA method (commercial kit, Stat Fax 3200). Total oestradiol (TE2) and thrombin time (TT) levels were measured using the electrochemiluminescence method by Roche kit and Cobas 6000 analyser. For all subjects, serum IGF-1 levels were assessed from blood samples by means of chemiluminescence immunoassay (the DiaSorin LIAISON system). Reference ranges are based on those used by some commercial and reference-laboratory ranges and vary by laboratory [Table 1].[4]
Table 1: Clinical and laboratory characteristics of patients and controls (mean±standard deviation)

Click here to view

Statistical analysis

All results are reported as individual values in the figure and as means ± standard deviation (SD) in the table and text. At the first, we used the Kolmogorov–Smirnov test to check the normality of variables. Hormonal parameters were compared using a parametric t-test or the Mann–Whitney. We used the Pearson correlation coefficient to examine the relationship between variables. SPSS version 22 (SPSS 22, Inc., Chicago, IL, USA) was used for the analysis of data. P < 0.001 was considered to denote significant differences. [Figure 2] has been made in Microsoft Office Excel.
Figure 2: Correlation between serum IGF-1 and TE2 levels in combined population of controls and patients with IHH; P < 0.001. IHH = Idiopathic hypogonadotropic hypogonadism, IGF-1 = Insulin-like growth factor-1, TE2 = Total oestradiol

Click here to view

   Results Top

Kolmogorov–Smirnov test was used to check the normality of variables, and all the variables were normal. Mean IGF-1 levels in groups are revealed in [Table 1]. The patients with IHH (145.1 ± 8.9 ng/ml) had meaningfully lower levels of IGF-1 levels than controls (229.6 ± 7.3 ng/ml; P < 0.001). Serum IGF-1 levels in patients and controls were within the normal range.[23] Mean ± SD TT, LH, FSH and TE2 in the control and patients are shown in [Table 1]. Compared with patients, controls had higher TT, LH, FSH and E2 levels. Linear Pearson's correlations were accomplished to define the trends of serum IGF-1 levels relating to the serum TE2 levels in the total number of patients and controls. The combined population of men with IHH and controls had a positive association between serum TE2 and IGF-1 levels [Figure 2].

   Discussion Top

The present study is a human study with a total number of 40 participants. This study aimed to investigate serum IGF-1 levels in 20 men with IHH and 20 controls. There is a negative correlation between circulating IGF-1 levels and age; peaking during puberty and gradually declining throughout adult life,[24],[25] hence two groups of participants with matched ages were used in this study. We observed that serum IGF-1 levels were lower in men with IHH than in the controls. GH was not measured in the present study, but this finding possibly supports the role of the GH/IGF-1 system in IHH.

IHH is caused by an isolated failure of release, action or both of the GnRH.[26] It has been indicated that in patients with IHH, variants of the IGF-1 gene have been described but it remains to be confirmed if these variants play a role in the pathogenesis of IHH.[27] Other study has also shown that GH and IGF-1 have a stimulatory effect on the migration of GnRH neurons and GnRH secretion.[11]

In men with isolated hypogonadotropic hypogonadism, GH and IGF-1 secretion have been reported to be lower before therapy with sex steroids.[21] In another study, serum IGF-1 levels have been shown to be within the normal range in men with IHH and increased after gonadotropin replacement therapy.[20] Furthermore, it has been indicated that in HH patients, the plasma concentration of IGF-1 increased after testosterone therapy,[28] because testosterone has a stimulatory influence on the GH axis.[29],[30]

We also found a significant E2 deficiency in the serum of patients with IHH than in controls, which is in accordance with the published result.[31] The substrate–product link between TE2 and TT[31] explains lower E2 levels in patients compared with controls. LH is considered to regulate E2 secretion by Leydig cells in a positive way,[31],[32],[33] therefore, lower TE2 levels in IHH patients can be correlated with circulating LH deficit.[31] ERβ expression has been documented in the somatotroph, and both subtypes of oestrogen receptors regulate the GH gene expression.[34]

We noted a positive association amongst serum E2 and IGF-1 levels, which is logical, given the significant role of E2 in the regulation of IGF-1 secretion,[35] and suggests that the lower levels of IGF-1 in IHH men are related to the circulating E2 shortage. Compared with testosterone, E2 becomes clear as the significant sex steroid in the regulation of the GH-IGF-1 axis in men.[12] An intense positive correlation has been reported between GH secretion and E2 concentration as the main determinant of GH secretion in men.[36] The results of the present study confirm that a linkage exists between levels of serum IGF-1 and sex steroids. Compared with controls, men with aromatase deficiency had GH shortage and decreased levels of IGF-1,[35] suggesting that oestrogen shortage may interfere with the normal development of the somatotropic axis in aromatase-deficient patients. HP–adrenal axis centrally regulates endocrine actions and controls the operation of the GH/IGF-1 system.[37] This regulation requires the integrity of the hypothalamus, pituitary and liver, as reviewed in.[38] Thus, there may be mechanisms for thorough maturation of the GH-IGF-1 axis and this procedure may fail in men with IHH due to the E2 reduction.

These findings could point to a link between E2 deficiency and reduction in the levels of serum IGF-1 in male IHH patients and possibly indicate the role of the GH/IGF-1 axis in IHH. However, additional work remains to be needed to enlighten the influences of E2 on HPT and the GH/IGF-1 axis in particular and the molecular mechanisms of the interactions between E2 and IGF-1.

It has been reported that serum IGF-1 levels in children with HH are lower than in those with delayed puberty.[39] In previous study, it has been demonstrated that GH and IGF-1 can directly stimulate GnRH secretion.[11] The results of the present study can provide evidence supporting the role of the GH-IGF-1 axis in IHH and possibly have therapeutic value in clinical practice. To evaluate the role of GH and IGF-1 for the treatment of IHH, animal studies should be carried out.

Limitation in our study was that follow-up visits by the patients were unlikely because the patients had been referred to the institution from other towns, and then returned to their provinces after completing detailed investigations. Therefore, we could not assess the effect of the testosterone and/or gonadotropin replacement therapies applied to patients.

   Conclusions Top

We observed a positive correlation between serum IGF-1 and E2 levels in the participants of this study. With previous basic and clinical data, these findings may explain clinical data, addressing the role of E2 on the GH/IGF-1 axis in IHH.


We appreciate all patients who cooperated in this research.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

Data availability and sharing statement

Data supporting the results are included in the published article and the authors' are willing to share the data on request.

   References Top

Bianco SD, Kaiser UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol 2009;5:569-76.  Back to cited text no. 1
Marcelli M, Mediwala SN. Male hypogonadism: A review. J Investig Med 2020;68:335-56.  Back to cited text no. 2
Richard-Eaglin A. Male and female hypogonadism. Nurs Clin North Am 2018;53:395-405.  Back to cited text no. 3
Basaria S. Male hypogonadism. Lancet 2014;383:1250-63.  Back to cited text no. 4
Stamou MI, Georgopoulos NA. Kallmann syndrome: Phenotype and genotype of hypogonadotropic hypogonadism. Metabolism 2018;86:124-34.  Back to cited text no. 5
Cho CY, Tsai WY, Lee CT, Liu SY, Huang SY, Chien YH, et al. Clinical and molecular features of idiopathic hypogonadotropic hypogonadism in Taiwan: A single center experience. J Formos Med Assoc 2022;121:218-26.  Back to cited text no. 6
Topaloğlu AK. Update on the genetics of idiopathic hypogonadotropic hypogonadism. J Clin Res Pediatr Endocrinol 2017;9:113-22.  Back to cited text no. 7
Longo KM, Sun Y, Gore AC. Insulin-like growth factor-I effects on gonadotropin-releasing hormone biosynthesis in GT1-7 cells. Endocrinology 1998;139:1125-32.  Back to cited text no. 8
Zhen S, Zakaria M, Wolfe A, Radovick S. Regulation of gonadotropin-releasing hormone (GnRH) gene expression by insulin-like growth factor I in a cultured GnRH-expressing neuronal cell line. Mol Endocrinol 1997;11:1145-55.  Back to cited text no. 9
Anderson RA, Zwain IH, Arroyo A, Mellon PL, Yen SS. The insulin-like growth factor system in the GT1-7 GnRH neuronal cell line. Neuroendocrinology 1999;70:353-9.  Back to cited text no. 10
Cannarella R, Paganoni AJ, Cicolari S, Oleari R, Condorelli RA, La Vignera S, et al. Anti-Müllerian hormone, growth hormone, and insulin-like growth factor 1 modulate the migratory and secretory patterns of GnRH neurons. Int J Mol Sci 2021;22:2445. [doi: 10.3390/ijms22052445].  Back to cited text no. 11
Russell N, Grossmann M. Mechanisms in endocrinology: Estradiol as a male hormone. Eur J Endocrinol 2019;181:R23-43.  Back to cited text no. 12
Rambhatla A, Mills JN, Rajfer J. The role of estrogen modulators in male hypogonadism and infertility. Rev Urol 2016;18:66-72.  Back to cited text no. 13
Finkelstein JS, O'Dea LS, Whitcomb RW, Crowley WF Jr. Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 1991;73:621-8.  Back to cited text no. 14
Rochira V, Zirilli L, Genazzani AD, Balestrieri A, Aranda C, Fabre B, et al. Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: Evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback. Eur J Endocrinol 2006;155:513-22.  Back to cited text no. 15
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;85:3027-35.  Back to cited text no. 16
Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF Jr., et al. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: Evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 2008;93:784-91.  Back to cited text no. 17
Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, Lai J, Ciofi P, McMullen NT, et al. Arcuate kisspeptin/neurokinin B/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology 2012;153:2800-12.  Back to cited text no. 18
Hrabovszky E, Kalló I, Szlávik N, Keller E, Merchenthaler I, Liposits Z. Gonadotropin-releasing hormone neurons express estrogen receptor-beta. J Clin Endocrinol Metab 2007;92:2827-30.  Back to cited text no. 19
Ismailogullari S, Korkmaz C, Peker Y, Bayram F, Karaca Z, Aksu M. Impact of long-term gonadotropin replacement treatment on sleep in men with idiopathic hypogonadotropic hypogonadism. J Sex Med 2011;8:2090-7.  Back to cited text no. 20
Liu L, Merriam GR, Sherins RJ. Chronic sex steroid exposure increases mean plasma growth hormone concentration and pulse amplitude in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1987;64:651-6.  Back to cited text no. 21
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010;16:231-45.  Back to cited text no. 22
Kim B, Cho Y, Ku CR, Lee SG, Lee KA, Kim JH. Establishment of reference intervals for serum insulin-like growth factor I in Korean adult population. Endocrinol Metab (Seoul) 2020;35:960-4.  Back to cited text no. 23
Brabant G, Wallaschofski H. Normal levels of serum IGF-I: Determinants and validity of current reference ranges. Pituitary 2007;10:129-33.  Back to cited text no. 24
Friedrich N, Krebs A, Nauck M, Wallaschofski H. Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the immulite 2500: Results of the study of health in pomerania (SHIP). Clin Chem Lab Med 2010;48:115-20.  Back to cited text no. 25
Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): Pathophysiological and genetic considerations. Endocr Rev 1998;19:521-39.  Back to cited text no. 26
Zhou C, Niu Y, Xu H, Li Z, Wang T, Yang W, et al. Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism. Fertil Steril 2018;110:486-95.e5.  Back to cited text no. 27
Ghanim H, Dhindsa S, Batra M, Green K, Abuaysheh S, Kuhadiya ND, et al. Effect of testosterone on FGF2, MRF4, and myostatin in hypogonadotropic hypogonadism: Relevance to muscle growth. J Clin Endocrinol Metab 2019;104:2094-102.  Back to cited text no. 28
Weissberger AJ, Ho KK. Activation of the somatotropic axis by testosterone in adult males: Evidence for the role of aromatization. J Clin Endocrinol Metab 1993;76:1407-12.  Back to cited text no. 29
Bondanelli M, Ambrosio MR, Margutti A, Franceschetti P, Zatelli MC, degli Uberti EC. Activation of the somatotropic axis by testosterone in adult men: Evidence for a role of hypothalamic growth hormone-releasing hormone. Neuroendocrinology 2003;77:380-7.  Back to cited text no. 30
Trabado S, Maione L, Salenave S, Baron S, Galland F, Bry-Gauillard H, et al. Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment. Fertil Steril 2011;95:2324-9, 2329.e1-3.  Back to cited text no. 31
Winters SJ, Troen P. Testosterone and estradiol are co-secreted episodically by the human testis. J Clin Invest 1986;78:870-3.  Back to cited text no. 32
Young J, Couzinet B, Chanson P, Brailly S, Loumaye E, Schaison G. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: Study of Sertoli and Leydig cell secretions and interactions. J Clin Endocrinol Metab 2000;85:3239-44.  Back to cited text no. 33
Avtanski D, Novaira HJ, Wu S, Romero CJ, Kineman R, Luque RM, et al. Both estrogen receptor α and β stimulate pituitary GH gene expression. Mol Endocrinol 2014;28:40-52.  Back to cited text no. 34
Rochira V, Zirilli L, Maffei L, Premrou V, Aranda C, Baldi M, et al. Tall stature without growth hormone: Four male patients with aromatase deficiency. J Clin Endocrinol Metab 2010;95:1626-33.  Back to cited text no. 35
Roelfsema F, Yang RJ, Takahashi PY, Erickson D, Bowers CY, Veldhuis JD. Aromatized estrogens amplify nocturnal growth hormone secretion in testosterone-replaced older hypogonadal men. J Clin Endocrinol Metab 2018;103:4419-27.  Back to cited text no. 36
Petrescu AD, Kain J, Liere V, Heavener T, DeMorrow S. Hypothalamus-pituitary-adrenal dysfunction in cholestatic liver disease. Front Endocrinol (Lausanne) 2018;9:660.  Back to cited text no. 37
Bleach R, Sherlock M, O'Reilly MW, McIlroy M. Growth hormone/insulin growth factor axis in sex steroid associated disorders and related cancers. Front Cell Dev Biol 2021;9:630503.  Back to cited text no. 38
Rohayem J, Nieschlag E, Kliesch S, Zitzmann M. Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. Andrology 2015;3:882-7.  Back to cited text no. 39


  [Figure 1], [Figure 2]

  [Table 1]


Print this article  Email this article


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Article in PDF (765 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

   Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded19    
    Comments [Add]    

Recommend this journal