Adult-Onset Idiopathic Hypogonadotropic Hypogonadism — A Treatable Form of Male Infertility

Nachtigall, Lisa B.; Boepple, Paul A.; Pralong, François P.; Crowley, William F.

doi:10.1056/nejm199702063360604

Cited by 187 publications

(130 citation statements)

References 35 publications

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“…The characteristics of the studies included in the meta-analysis are summarized in Table 3 (Mortimer et al, 1974;Fraioli & Dondero, 1976;Klingm€ uller & Schweikert, 1985;Spratt et al, 1986 Liu et al, 1988a;Liu et al, 1988b;Schopohl et al, 1991;Delemarre-Van de Waal & Odink, 1993;Kliesch et al, 1994;Nachtigall et al, 1997;Pitteloud et al, 2002;Sykiotis et al, 2010;Dwyer et al, 2013). Among these studies, seven considered only subjects with prepubertal onset HHG, two had a mixed pre-and post-pubertal onset HHG and two considered only subjects with post-pubertal onset HHG.…”

Section: Spermatogenesis In Hhg Subjects Upon Gnrh Therapymentioning

confidence: 99%

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

et al. 2014

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SUMMARYA meta-analysis was performed to systematically analyse the results of gonadotropin and GnRH therapy in inducing spermatogenesis in subjects with hypogonadotropic hypogonadism (HHG) and azoospermia. An extensive Medline and Embase search was performed including the following words: 'gonadotropins' or 'GnRH', 'infertility', 'hypogonadotropic', 'hypogonadism' and limited to studies in male humans. Overall, 44 and 16 studies were retrieved for gonadotropin and GnRH therapy, respectively. Of those, 43 and 16 considered the appearance of at least one spermatozoa in semen, whereas 26 and 10 considered sperm concentration upon gonadotropin and GnRH, respectively. The combination of the study results showed an overall success rate of 75% (69-81) and 75% (60-85) in achieving spermatogenesis, with a mean sperm concentration obtained of 5.92 (4.72-7.13) and 4.27 (1.80-6.74) million/ mL for gonadotropin and GnRH therapy, respectively. The results upon gonadotropin were significantly worse in studies involving only subjects with a pre-pubertal onset HHG, as compared with studies involving a mixed population of pre-and post-pubertal onset [68% (58-77) vs. 84% (76-89), p = 0.011 and 3.37 (2.25-4.49) vs. 12.94 (8.00-17.88) million/mL, p < 0.0001; for dichotomous and continuous data, respectively]. A similar effect was observed also upon GnRH. No difference in terms of successful achievement of spermatogenesis and sperm concentration was found for different FSH preparations. Previous use of testosterone replacement therapy (TRT) did not affect the results obtained with gonadotropins. Finally, a higher success rate was found for subjects with lower levels of gonadotropins at the baseline and for those using both human chorionic gonadotropin and FSH. Gonadotropin therapy, even with urinary derivatives, is a suitable option in inducing/restoring fertility in azoospermic HHG subjects. Gonadotropins appear to be more efficacious in subjects with a pure secondary nature (low gonadotropins) and a post-pubertal onset of the disorder, whereas previous TRT does not affect outcome.

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Section: Spermatogenesis In Hhg Subjects Upon Gnrh Therapymentioning

confidence: 99%

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

et al. 2014

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“…Kallmann's syndrome is considered a congenital form of hypogonadotropic hypogonadism. It is characterized by the association of an inability to smell (anosmia) with a defect in gonadal development due to GnRH deficiency (13)(14)(15)(16)(17)(18)(19). However, in humans, Kallmann's syndrome is characterized by considerable clinical and genetic heterogeneity.…”

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confidence: 99%

“…Some forms of idiopathic hypogonadotropic hypogonadism, without an identifiable cause, develop after puberty, arising in sexually mature men. This adult-onset hypogonadotropic hypogonadism represents one of the few treatable forms of male infertility (15). Our contribution to clarify this complex biological problem has been to utilize the human GnRH-secreting neuronal cell line, FNC-B4 neurons (21)(22)(23)(24).…”

mentioning

confidence: 99%

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons

Romanelli

Barni

Maggi

et al. 2004

Journal of Biological Chemistry

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Olfactory neurons and gonadotropin-releasing hormone (GnRH) neurons share a common origin during organogenesis. Kallmann's syndrome, clinically characterized by anosmia and hypogonadotropic hypogonadism, is due to an abnormality in the migration of olfactory and GnRH neurons. We recently characterized the human FNC-B4 cell line, which retains properties present in vivo in both olfactory and GnRH neurons. In this study, we found that FNC-B4 neurons expressed GnRH receptor and responded to GnRH with time-and dose-dependent increases in GnRH gene expression and protein release (up to 5-fold). In addition, GnRH and its analogs stimulated cAMP production and calcium mobilization, although at different biological thresholds (nanomolar for cAMP and micromolar concentrations for calcium). We also observed that GnRH triggered axon growth, actin cytoskeleton remodeling, and a dosedependent increase in migration (up to 3-4-fold), whereas it down-regulated nestin expression. All these effects were blocked by a specific GnRH receptor antagonist, cetrorelix. We suggest that GnRH, secreted by olfactory neuroblasts, acts in an autocrine pattern to promote differentiation and migration of those cells that diverge from the olfactory sensory lineage and are committed to becoming GnRH neurons.

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“…Adult-onset idiopathic HH caused by an unknown etiology has been reported (12). In the description given, regardless of the lack of causative factors including medical history and imaging studies for defects in GnRH release, the patient had low levels of testosterone and gonadotropins.…”

Section: Discussionmentioning

confidence: 94%

Adult-onset Idiopathic Hypogonadotropic Hypogonadism due to Isolated Pituitary Gonadotropin Deficiency

et al. 2004

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A 25-year-old Japanese man with adult-onset idiopathic hypogonadotropic hypogonadism is reported. He had been delivered normally, had normal puberty, and experienced erectile dysfunction at age 24 years. Brain MRI revealed no abnormal findings and endocrinological data supported the diagnosis of isolated gonadotropin deficiency. Although most patients with idiopathic hypogonadotropic hypogonadism have a hypothalamic dysfunction, the lesion in this case may be considered to be in the pituitary since repetitive GnRH loading failed to increase serum LH and FSH.

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Adult-Onset Idiopathic Hypogonadotropic Hypogonadism — A Treatable Form of Male Infertility

Abstract: The recognition of adult-onset hypogonadotropic hypogonadism in men as a distinct disorder expands the spectrum of GnRH deficiency and identifies a treatable form of male infertility.

Cited by 187 publications

References 35 publications

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons

Adult-onset Idiopathic Hypogonadotropic Hypogonadism due to Isolated Pituitary Gonadotropin Deficiency

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