Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone

Spratt, Daniel; O’Dea, Louis; Schoenfeld, David; Butler, James P.; Rao, P Narasimha; Crowley, William F.

doi:10.1152/ajpendo.1988.254.5.e658

Cited by 107 publications

(106 citation statements)

References 31 publications

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“…60 We found this unlikely in our study, because 67% of our patients had two successive low testosterone values measured 2 weeks to 2 months apart before any therapeutic intervention. These low testosterone values also correlated with their presenting symptoms of libido and erectile difficulties.…”

Section: Discussionmentioning

confidence: 69%

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Guay¹,

Jacobson

Perez³

et al. 2003

Int J Impot Res

116

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Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (Po0.001) and free testosterone (Po0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (Po0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

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Section: Discussionmentioning

confidence: 69%

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Guay¹,

Jacobson

Perez³

et al. 2003

Int J Impot Res

116

View full text Add to dashboard Cite

show abstract

“…Before taking part in the clinical protocol, each GnRH-deficient man underwent an intravenous GnRH dose-response study employing four or five intravenous GnRH doses ranging from 2.5 to 250 ng/kg per bolus (3). An individual dose-response curve was then constructed and the resulting LH pulses were compared to the range of LH pulse amplitudes from 20 normal men whom we studied previously (20,23) to select a GnRH dose that would produce LH pulses with amplitudes within the midrange of those in the normal male population. On the basis of these dose-response studies, the "Iphysiologic" doses of GnRH employed in this study ranged from 11 to 50 ng/kg per bolus.…”

Section: Methodsmentioning

confidence: 99%

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

Finkelstein¹,

Badger²,

O’Dea³

et al. 1988

J. Clin. Invest.

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The effects of decreasing the frequency of pulsatile gonadotropin-releasing hormone (GnRH) stimulation on pituitary responsiveness were studied in (a) men with isolated GnRH deficiency who had achieved normal sex steroid levels during prior long-term pulsatile GnRH replacement and (b) perifused dispersed pituitary cells from male rats in the absence of sex steroids. In three groups of four GnRH-deficient men, the frequency of GnRH stimulation was decreased at weekly intervals from (a) every 2-34 h (group I), (b) every 2-8 h without testosterone replacement (group II), or (c) every 2-8 h with testosterone replacement (group III). In three groups of three columns of perifused dispersed pituitary cells, pulses of GnRH were administered every 2, 4, or 8 h.In groups I and II, mean area under the luteinizing hormone (LH) curve increased (P < 0.025) and serum testosterone levels fell (P < 0.035) as the frequency of GnRH stimulation was decreased. In group III, the area under the LH curve also increased (P < 0.01) although serum testosterone levels were constant, thereby demonstrating that the increase in pituitary responsiveness to slow frequencies of GnRH stimulation occurs independently of changes in the sex steroid hormonal milieu. The area under the LH curve also increased in the perifused dispersed rat pituitary cells when the frequency of GnRH administration was decreased to every 8 h (P < 0.05), thus demonstrating that the enhanced pituitary responsiveness to slow frequencies of GnRH stimulation is maintained even in the complete absence of gonadal steroids.Nadir LH levels fell in all three groups (P < 0.01) as the frequency of GnRH stimulation was decreased. In contrast, mean peak LH levels, the rate of LH rise, and the rate of endogenous LH decay were constant as the frequency ofGnRH stimulation was decreased. Finally, as the GnRH interpulse interval increased, mean LH levels fell, and mean follicle-stimulating hormone levels were stable or fell.

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“…A, B, and C, Baseline secretory pattern of LH in three individuals with KS (arrow) assessed at 10-min intervals; shaded area, lower limit of range of serum LH concentrations defined in normal men (35); T, serum testosterone measured in pooled samples constituted from equal aliquots of the frequent blood samples; TV, testicular volumes recorded using a Prader orchidometer; inverted triangles, LH pulses.…”

Section: Fig 2 Lh Secretion In Ksmentioning

confidence: 99%

The Importance of Autosomal Genes in Kallmann Syndrome: Genotype-Phenotype Correlations and Neuroendocrine Characteristics

Oliveira¹

2001

Journal of Clinical Endocrinology & Metabolism

121

120

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Kallmann syndrome (KS) consists of congenital, isolated, idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. The gene responsible for the X-linked form of KS, KAL, encodes a protein, anosmin, that plays a key role in the migration of GnRH neurons and olfactory nerves to the hypothalamus. In addition to X-linked pedigrees, autosomal dominant and recessive kindreds with KS have been reported. The relative importance of these autosomal vs. X-linked genes in producing KS, and the frequency of KAL mutations, are currently unknown because these are rare disorders and large series are unusual.We examined 101 individuals with IHH (Ϯ anosmia) and their families to determine their modes of inheritance, incidence of mutations in the coding sequence of KAL, genotype-phenotype correlations, and [in a subset (n ϭ 38)] their neuroendocrine phenotype.Of the 101 patients, 59 had true KS (IHH ϩ anosmia/hyposmia); whereas, in the remaining 42, no anosmia was evident in the patients or their families. Of the 59 KS patients, 21 were familial, whereas 38 were sporadic cases. Mutations in the coding sequence of KAL were identified in only 3 of 21 familial cases (14%) and 4 of 38 (11%) of the sporadic cases. Of the X-linked cases confirmed by mutational analysis, only 1 of 3 pedigrees appeared X-linked by inspection whereas the other 2 contained only affected brothers. Female members of known KAL mutation families (n ϭ 3) exhibited no reproductive phenotype and were not anosmic, whereas families with anosmic women (n ϭ 3) were not found to carry mutations in KAL. Mutations were uniformly absent in nonanosmic IHH probands (n ϭ 42), as well as in families with both anosmic and nonanosmic members (n ϭ 2). Overall, 4 novel mutations were identified (C172R, R191ϫ, R457ϫ, and delC@L600).With respect to neuroendocrine phenotype, KS men with documented KAL mutations (n ϭ 8) had completely apulsatile LH secretion, whereas those with autosomal modes of inheritance demonstrated a more variable spectrum with evidence of enfeebled (but present) GnRH-induced LH pulses.Our conclusions are: 1) Confirmed mutations in the coding sequence of the KAL gene occur in the minority of KS cases, i.e. only 14% of familial and 11% of sporadic cases; 2) The majority of familial (and presumably sporadic) cases of KS are caused by defects in at least two autosomal genes that are currently unknown; 3) Obligate female carriers in families with KAL mutations have no discernible phenotype; 4) KAL mutations are uniformly absent in patients with either normosmic IHH or in families with both anosmic and nonanosmic individuals; and 5) Patients with KAL mutations have apulsatile LH secretion consistent with a complete absence of GnRH migration of GnRH cells into the hypothalamus, whereas evidence of present (but enfeebled) GnRH-induced LH pulses may be present in autosomal KS cases. Taken together, these findings suggest that autosomal genes account for the majority of familial cases of KS, and that unique neuroendocrine phenotypes consistent with some GnRH n...

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Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone

Cited by 107 publications

References 31 publications

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

The Importance of Autosomal Genes in Kallmann Syndrome: Genotype-Phenotype Correlations and Neuroendocrine Characteristics

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