Long-Term Clinical Follow-Up of Adult-Onset Idiopathic Hypogonadotropic Hypogonadism

[Swifto]

Dwyer AA, Hayes FJ, Plummer L, Pitteloud N, Crowley WF, Jr.

The Long-Term Clinical Follow-Up and Natural History of Men with Adult-Onset Idiopathic Hypogonadotropic Hypogonadism.

J Clin Endocrinol Metab 2010;95(9):4235-43.

Context and Objective: Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder.

Design and Setting: Long-term follow up, including detailed clinical, biochemical, and genetic examinations, were performed and compared with those at diagnosis. Patients: Patients included 10 men with AHH [serum testosterone (T) <125 ng/dl].

Interventions: Overnight neuroendocrine studies, semen fluid analyses, and genetic screening were performed (KAL1, FGFR1, PROK2, PROKR2, NELF, TAC3, TACR3, and GNRH1) over a decade of longitudinal follow up.

Results: Follow-up evaluations were conducted 10.6 {+/-} 5.9 yr after initial studies and revealed that the clinical characteristics and seminal fluid analyses of AHH men (body mass index, 28.8 {+/-} 4.1 vs. 27.0 {+/-} 4.3 kg/m2; testicular volume, 18 {+/-} 6 vs. 19 {+/-} 6 ml) do not change over a decade with no spontaneous reversals. Several men exhibited some variability in their endogenous GnRH-induced LH secretory patterns, including emergence of endogenous pulsatility in three individuals. However, all remained hypogonadal (T [&le;]130 ng/dl). A single heterozygous DNA sequence change in PROKR2 (V317L) was identified, although this rare sequence variant did not prove to be functionally abnormal in vitro. Seven days of pulsatile GnRH therapy in this subject nearly normalized his serum T, supporting that the site of the defect is hypothalamic and not pituitary.

Conclusions: 1) AHH in men appears to be a long-lasting condition. 2) Although minor changes in the abnormal pattern of endogenous GnRH-induced LH secretion occurred in some AHH patients, all remained frankly hypogonadal.

This is what you DONT want from AAS. Your hypothalamus failing...










3 parts of the HPT-axis can fail.

Hypothalamus - Thats addressed with SERMs, directly.

Pituitary - Thats also addresses with SERMs some direct and some indirect.

- Direct stimulation by SERMs at the pituitary would be Tamoxifen /Toremifene. As it sensitizes the pituitary to GnRH (the signal from the hypothalamus)

- Indirect would be Clomid, where it has the opposite effect to Tamoxifen.

Testes - HCG stimulates them directly and SERMs do because of there capactiy to increase endogenous GnRH, LH and FSH.



Treatments for each

Hypothalamus = SERMs, AI's, Naltrexone

Pituitary = SERMs, AI's, Naltrexone

Testes = HCG/HMG



Little lesson there... Class dismissed.

[Spartans09]

Good stuff. People who can pinpoint why pct failed to recover hpta via bloodwork can then use this info to potentially treat again with the right chemicals targeting the problem.