good article on restart of hypothalamus hypogonadism...I am sure it was posted before

Discussion in 'Men's Health Forum' started by jtmoy19607, Mar 19, 2011.

  1. #1
    jtmoy19607

    jtmoy19607 Junior Member

    MMS: Error


    Although neurogenesis in humans is thought to occur primarily during embryonic and early postnatal stages, multipotential progenitor cells residing in the subcortical white matter of the adult human brain have recently been identified as having the potential to replace neuronal lineages.[ 37] Furthermore, neurons in the olfactory epithelium, the olfactory bulbs, and the dentate gyrus of the hippocampus are generated throughout life,[ 38][ 39][ 40] and their generation appears to be modulated by sex steroids.[ 41] Indeed, exposure to sex steroids, although the length of exposure was variable, seems to be a common denominator in our patients who underwent reversal. We therefore speculate that sex steroids enhance the plasticity of the neuronal network producing GnRH in the adult human brain, leading to reversal of hypogonadotropic hypogonadism.




    The criterion for sustained reversal of idiopathic hypogonadotropic hypogonadism was a normal adult endogenous serum testosterone level (at least 270 ng per deciliter [9.4 nmol per liter]) after discontinuation of hormonal therapy. On the basis of the half-life of the drug, the treatment regimen, and the route of administration, the washout periods before assessment were determined as 2 weeks or more for pulsatile GnRH, 4 weeks or more for transdermal testosterone, and 6 to 8 weeks or more for testosterone or human chorionic gonadotropin injections.

    Sustained reversal of idiopathic hypogonadotropic hypogonadism was identified either retrospectively or prospectively. Of the 10 men in whom reversal was identified retrospectively, 5 underwent successful initial treatment and had no hypogonadal symptoms after ceasing to adhere to treatment, 3 had reversals after discontinuing hormone therapy for neuroendocrine studies, and 2 had increased testicular size while receiving androgen therapy.

    To assess the frequency of sustained reversal of idiopathic hypogonadotropic hypogonadism, we conducted a 3-year prospective study that identified five men with reversal. The patients were identified from January 2003 through April 2006. Fifty men who had previously received a diagnosis of idiopathic hypogonadotropic hypogonadism agreed to come to the Reproductive Endocrine Unit of the Massachusetts General Hospital for a physical examination, biochemical profiling, neuroendocrine evaluation, and semen analysis after discontinuation of hormone-replacement therapy.



    Nine patients had some degree of spontaneous pubertal development, and puberty was absent (testicular volume, 4 ml or less) in the other six





    Figure 1] shows a timeline of hormonal treatment for each patient from diagnosis to the documentation of reversal. After diagnosis, all patients with idiopathic hypogonadotropic hypogonadism received hormonal treatment for a period ranging from 5 months to 21 years; five men were treated with testosterone alone, three men received pulsatile GnRH therapy only, and seven men received a mixed regimen that could include testosterone, gonadotropins, or GnRH. Regardless of the specific regimen, all patients were exposed to androgens while receiving therapy.

























    Episodic secretion of GnRH from the hypothalamus is a key requirement for the initiation and maintenance of a normal reproductive axis in humans. However, the genetic and environmental factors modulating the secretion of this hormone remain poorly understood.



    Our results indicate that reversal of hypogonadotropic hypogonadism occurs across a broad spectrum of GnRH deficiency and its related phenotypes. Consistent with the few case reports published to date, the present cohort of men with sustained reversal of idiopathic hypogonadotropic hypogonadism includes patients with the Kallmann syndrome and patients with normosmic idiopathic hypogonadotropic hypogonadism.[ 13][ 14][ 15][ 16][ 17][ 18] It is notable that reversal occurred in Patient 3, who had a "fertile eunuch" variant of idiopathic hypogonadotropic hypogonadism characterized by lack of virilization and hypogonadal serum testosterone levels but active spermatogenesis.[ 27] Furthermore, reversals occurred both in men with absent puberty and in men with partial puberty, suggesting that evidence of previous endogenous GnRH secretion is not predictive of future reversal of idiopathic hypogonadotropic hypogonadism. However, testicular growth, a biomarker of gonadotropin secretion over time, represents a subtle yet key factor pointing to reversal of idiopathic hypogonadotropic hypogonadism, as evidenced by testicular growth during androgen therapy in four patients with reversal of idiopathic hypogonadotropic hypogonadism

    In contrast to patients with constitutional delay of puberty, all patients in the present study received a diagnosis of idiopathic hypogonadotropic hypogonadism at or after the age of 18. Moreover, seven patients presented with characteristics not typically seen in constitutional delay of puberty, such as unilateral cryptorchidism, anosmia, and synkinesia. However, we have previously demonstrated that the rate of delayed puberty in families with idiopathic hypogonadotropic hypogonadism is 12 times as high as normal,[ 31] and some patients with delayed puberty carry the same gene defects as the probands with idiopathic hypogonadotropic hypogonadism.[ 17][ 32] Therefore, it is possible that this reversible variant form of idiopathic hypogonadotropic hypogonadism and delayed puberty both lie on the milder end of the phenotypic spectrum of GnRH deficiency.



    Although the precise mechanism of reversal of hypogonadotropic hypogonadism is unclear, the mechanism may involve plasticity of the GnRH-producing neurons in adulthood. Plasticity, defined as the ability of the nervous system to adapt in response to the environment, is a striking feature of the vertebrate brain. For example, the size and function of the nuclei that regulate singing behavior in songbirds are modulated by environmental cues and sex steroids.[ 36]

    Although neurogenesis in humans is thought to occur primarily during embryonic and early postnatal stages, multipotential progenitor cells residing in the subcortical white matter of the adult human brain have recently been identified as having the potential to replace neuronal lineages.[ 37] Furthermore, neurons in the olfactory epithelium, the olfactory bulbs, and the dentate gyrus of the hippocampus are generated throughout life,[ 38][ 39][ 40] and their generation appears to be modulated by sex steroids.[ 41] Indeed, exposure to sex steroids, although the length of exposure was variable, seems to be a common denominator in our patients who underwent reversal. We therefore speculate that sex steroids enhance the plasticity of the neuronal network producing GnRH in the adult human brain, leading to reversal of hypogonadotropic hypogonadism.
     

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    Last edited: Mar 19, 2011
  2. #2
    amar7

    amar7 Junior Member

    Re: good article on restart of hypothalamus hypogonadism...I am sure it was posted be

    jtmoy, I didnt read any thread about this subject before, thanks for posting it.
    It is never seen, that primary hypogonadism is ever treated with hcg or FSH/HMG for that matter with TRT, which has studywise lead to success.

    Primary hypogonadism has different levels, depending on the testosterone and sperm production state, which has to be tested. If there is some sperm left and testosterone, then there is the possibility to increase the healthy functioning part, especially if s.o. is hypogonadotropic, with this medical substitution.

    Still the science has a long way to go on this, until it reaches conservative treatment instead of the usual TRT. Unfortunately the price for HCG and FSH/HMG is pretty high, so that the andrologists avoid using it for treatment of hypogonadism usually
     
  3. #3
    jtmoy19607

    jtmoy19607 Junior Member

    Re: good article on restart of hypothalamus hypogonadism...I am sure it was posted be

    yeah, i thought this was a good article too
     

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