Kallmann's syndrome: is it always for life?

Quinton,; Cheow,; Tymms,; Bouloux,; Wu, Kan; Jacobs, Jacobs

doi:10.1046/j.1365-2265.1999.00708.x

Cited by 77 publications

(37 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of note, testosterone treatment will not induce gonadal maturation or fertility in these patients. 94,177 Importantly, increased testicular volume following testosterone treatment is an indicator of reversal 6,7,[179][180][181][182][183][184][185] and requires re-assessment of the HPG axis in the absence of testosterone replacement therapy. An estimated 10-20% of patients with CHH undergo spontaneous recovery of reproductive function, 6,7 and this includes patients with mutations in known CHH genes (Table 1).…”

Section: Induction Of Male Sexual Characteristicsmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

View full text Add to dashboard Cite

| Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ~50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRHsynthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ~10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.

show abstract

Section: Induction Of Male Sexual Characteristicsmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In the subsequent two decades, additional case reports emerged documenting reversals (37) including fertility/conception (38,39,40) and two series were published demonstrating pulsatile LH secretion in a subset of CHH men following cessation of treatment (41,42). The first estimate of prevalence of reversal came from Quinton and et al (43) who depicted five cases among a retrospective cohort of 76 CHH patients revealing a prevalence of 5%. Authors went on to recommend that patients with a testicular volume of 6 ml or greater (i.e.…”

Section: Chh Reversibilitymentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Reversible hypogonadotropic hypogonadism

Dwyer

Raivio

Pitteloud

2016

European Journal of Endocrinology

View full text Add to dashboard Cite

Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of puberty and infertility. Traditionally, it has been considered a life-long condition yet cases of reversibility have been described wherein patients spontaneously recover function of the reproductive axis following treatment. Reversibility occurs in both male and female CHH cases and appears to be more common (~10-15%) than previously thought. These reversal patients span a range of GnRH deficiency from mild to severe and many reversal patients harbor mutations in genes underlying CHH. However, to date there are no clear factors for predicting reversible CHH. Importantly, recovery of reproductive axis function may not be permanent. Thus, CHH is not always life-long and the incidence of reversal warrants periodic treatment withdrawal with close monitoring and follow-up. Reversible CHH highlights the importance of environmental (epigenetic) factors such as sex steroid treatment on the reproductive axis in modifying the phenotype. This review provides an overview and an update on what is known about this phenomenon.

show abstract

“…When considering also those studies which excluded patients with previous TRT, the outcome after gonadotropins was not improved with respect to the rest of the studies; however, the number of the available investigations was small, and data of studies excluding TRT were largely derived from one single survey, with relatively low baseline gonadotropin levels (Warne et al, 2009). It must also be underlined that genetic forms of HHG after treatment with either TRT or gonadotropins or GnRH, in a variable percentage of cases, revert the condition (Quinton et al, 1999;Pitteloud et al, 2005;Raivio et al, 2007a;Ribeiro et al, 2007). In particular, it has been recently reported, in a retrospective analysis of more than 300 HHG subjects, that reversal is achieved in 20% of cases after the discontinuation of therapy lasted for a mean time of 4.4 years (Sidhoum et al, 2014).…”

mentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

Kallmann's syndrome: is it always for life?

Cited by 77 publications

References 28 publications

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

MANAGEMENT OF ENDOCRINE DISEASE: Reversible hypogonadotropic hypogonadism

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

Contact Info

Product

Resources

About