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Biomedical subjects

W F Crowley

Publications and source records attributed to W F Crowley.

At least 145 records · Page 8Linked to original sources
PubMed1987

The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations.

Several lines of evidence indicate that hypothalamic-pituitary-gonadal activity varies among men with idiopathic hypogonadotropic hypogonadism (IHH). To test the hypothesis that a spectrum of abnormalities of GnRH secretion underlies the syndrome of IHH, we characterized the patterns of GnRH-induced gonadotropin secretion during periods of frequent sampling in 50 consecutive men with IHH and contrasted them with those in 20 normal men. The largest group of IHH patients (n = 42) had no detectable LH or FSH pulsations and could be categorized into 2 subsets according to the presence or absence of evidence of spontaneous puberty. The most severely affected subset (n = 32), who recalled no history of puberty, had testes with a mean volume of 3.3 +/- 0.5 (+/- SEM) ml, with a prepubertal appearance on biopsy, and often were anosmic (n = 17). The second subset of apulsatile IHH men (n = 10) had histories of partial or complete spontaneous sexual development with subsequent isolated loss of sexual function, testes with a mean volume of 13.3 +/- 1.9 ml (P less than 0.01 compared to the first subset), a pubertal or adult appearance of the testes on biopsy, and an intact sense of smell. In a second group of IHH patients (n = 3), LH was secreted predominantly in a nighttime pattern similar to that of normal children during early puberty. These men were aged 18-24 yr, had a mean testicular volume of 10.5 +/- 2.3 ml, pubertal changes on testicular biopsy, and an intact sense of smell. A third group of IHH men (n = 4) had LH pulses of abnormally low amplitude. Only one patient in this group had a history of spontaneous sexual development. The mean testicular volume of these patients was 5.6 +/- 1.9 ml, and the testes appeared prepubertal (n = 3) or pubertal (n = 1) on biopsy. In addition to these groups, another patient had apparent LH pulsations and nearly normal amplitude, but the LH was bioinactive and appeared to consist chiefly of alpha-subunit. Testing of other anterior pituitary hormone functions did not distinguish IHH men from normal men. However, those IHH patients with some evidence of endogenous GnRH secretion had higher basal and stimulated serum PRL levels than IHH men without such evidence (P less than 0.05), suggesting an influence of GnRH on PRL secretion.

Adolescent↗
PubMed1987

Luteinizing hormone-secreting pituitary tumor: biosynthetic characterization and clinical studies.

Although gonadotropin-secreting pituitary adenomas are increasingly recognized, tumors secreting only LH are rare. Since gonadotropin production by pituitary adenomas may reflect imbalanced glycoprotein biosynthesis, we studied tumor LH and subunit biosynthesis and secretion in a patient with a LH- and alpha-subunit-producing pituitary tumor. Northern blot analysis of RNA from the tumor revealed the presence of mRNAs encoding both alpha- and beta-subunits of LH with a marked excess of the mRNA encoding LH beta. Analysis of tumor extracts by gel filtration chromatography confirmed an excess of free LH beta relative to free alpha-subunit. Clinical studies demonstrated that the secretion of LH and alpha-subunit by the tumor increased in response to the acute administration of LHRH (100 micrograms, iv) and decreased during a 4-h dopamine infusion (4 micrograms/kg X min). During a 4-week course of LHRH analog (D-Trp6-Pro9-NEt-LHRH) administration, given as a daily sc dose (8 micrograms/kg X day), serum LH and alpha-subunit concentrations increased 7- and 3-fold, respectively, consistent with a chronic agonist effect. Chronic administration of bromocriptine resulted in reduction of serum LH and alpha-subunit levels to normal.

Adenoma↗
PubMed1987

Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men.

The effects of increasing the frequency of pulsatile GnRH administration on LH and FSH responsiveness were studied in five GnRH-deficient men who had achieved normal sex steroid levels during prior long term GnRH replacement. Intravenous doses of GnRH were employed that had previously been demonstrated to produce LH and FSH levels in each subject similar to those in normal men. Both acute and chronic changes in pituitary responses were studied after progressive increases in GnRH frequency (from every 120 to 60 min, from 60 to 30 min, and from 30 to 15 min) during three 12-h admissions, each separated by 7 days. During the two intervals between the studies GnRH frequency was 60 and 30 min, respectively. Pituitary responses were characterized by determining the mean serum LH and FSH levels, LH pulse amplitudes, and mean LH and FSH levels which were normalized for the frequency of GnRH administration (nLH and nFSH). As the frequency of GnRH stimulation was increased acutely, mean serum LH levels rose progressively, in contrast to both LH pulse amplitude and nLH levels which decreased, while serum testosterone (T) concentrations remained constant. No further evidence of gonadotroph desensitization occurred after chronic GnRH administration at either 60- or 30-min intervals. At higher frequencies of GnRH stimulation, discrete pulses of LH were not always apparent after injections of GnRH, and in two men, marked destabilization of the gonadotroph responses occurred. Even without detectable LH pulses, serum T levels did not decline during administration of GnRH at intervals as rapid as 15 min. In contrast, there was no change in mean FSH concentrations, although nFSH values decreased progressively as the GnRH frequency was increased. nFSH levels fell to a greater degree than nLH after each increase in GnRH frequency. Thus, pituitary gonadotroph responsiveness to a fixed dose of GnRH decreased as the frequency of GnRH stimulation increased. FSH responsiveness decreased to a greater degree than did LH. Gonadotropin secretory responses are destabilized at higher frequencies of GnRH administration. Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion.

Adult↗
PubMed1987

Osteoporosis in men with idiopathic hypogonadotropic hypogonadism.

To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarly decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.

Adult↗
PubMed1986

Sonographic monitoring of LHRH analogue therapy in idiopathic precocious puberty in young girls.

Precocious puberty in young girls is defined as the development of secondary sexual characteristics and gonadal growth before 8 years of age. Approximately 60% of isosexual precocious development in girls has no organic cause and is termed idiopathic precocious puberty. Thirteen young girls with idiopathic precocious puberty were treated with LHRH analogue under a well-established protocol. Pelvic ultrasound was added to the protocol to examine ultrasound's role in supplying a morphologic parameter of suppression of the pubertal process. Initially, 11 patients had ovarian volumes greater than normal, and ovarian cysts measuring 0.5 cm to 4 cm in diameter were identified in seven patients. All 13 patients had enlarged pretreatment uteri greater than 3 cm in length. Eleven of these patients had a pubertal or adult uterine configuration. After 1 year of therapy, 11 patients had normal prepubertal ovarian volumes, and 12 of 13 patients had a decrease in ovarian volume. No demonstrable cysts were present at 1 year. Eleven had a reduction in uterine length. Nine of the 11 patients with a pubertal uterine configuration reverted to a more prepubertal-like morphology. The sonographic morphologic changes correlated well with laboratory and clinical data indicating suppression of the hypothalamic-pituitary-gonadal axis.

Child↗
PubMed1986

Endocrine impact of pure estradiol replacement in postmenopausal women: alterations in anterior pituitary hormone release and circulating sex steroid hormone concentrations.

Thirteen healthy postmenopausal volunteers were studied under basal conditions and at intervals (days 1, 5, 10, and 30) after intravaginal placement of a polysiloxane ring impregnated with 400 mg of estradiol. Mean serum estradiol concentrations rose 26-fold with a twofold increase in serum estrone concentrations. Serum delta 4-androstenedione, dehydroepiandrosterone sulfate, and total testosterone did not change, but absolute and percent free testosterone concentrations declined significantly by day 5. Concurrently, serum concentrations of immunoactive follicle-stimulating hormone declined progressively, while serum luteinizing hormone and free alpha-subunit concentrations exhibited a biphasic pattern of suppression. Serum levels of prolactin increased monophasically and those of growth hormone, somatomedin C, and thyroid-stimulating hormone did not change.

Estradiol↗
PubMed1986

Interpulse interval sequence of LH in normal men essentially constitutes a renewal process.

Luteinizing hormone (LH) is released from the anterior pituitary gland in an episodic pattern driven by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Autocorrelation analysis of the sequence of interpulse intervals of LH secretion in normal men supports the hypothesis that the underlying mechanism driving LH secretion is a renewal process. That is, whatever "memory" the GnRH pulse generator (i.e., the hypothalamus or its antecedent neural drive) may have, it does not go back in time further than the preceding secretory pulse. Thus the hypothalamic timer starts over again each time there is a GnRH secretory episode.

Feedback↗
PubMed1986

Adrenarche and skeletal maturation during luteinizing hormone releasing hormone analogue suppression of gonadarche.

During puberty the effects of adrenal androgens upon skeletal maturation are obscured by the influence of gonadal steroids. Suppression of gonadarche with an analogue of luteinizing hormone releasing hormone (LHRHa) affords an opportunity to examine the onset and progression of adrenarche in the absence of pubertal levels of gonadal steroids in a controlled fashion and to explore the relationship between adrenal androgens and the rate of epiphyseal maturation. In 29 children with central precocious puberty, gonadarche was suppressed with LHRHa administration for 1-4 yr. During LHRHa exposure, dehydroepiandrosterone sulfate (DHAS) levels, as an index of adrenal maturation, were constant or increased in an age-expected manner. The change in bone age for change in chronologic age decreased from 1.7 +/- 0.1 to 0.49 +/- 0.05 (P = 0.00005), indicating that the LHRHa-induced return to a prepubertal gonadal steroid environment was associated with a slowing of skeletal maturation. DHAS levels were correlated with the rate of skeletal advancement before (r = 0.57, P = 0.001) and during 12 to 48 mo of exposure to LHRHa (r = 0.52, P = 0.003). A negative correlation of DHAS values with subsequent increases in predicted mature height was observed (r = -0.49, P = 0.007). Thus, in children with central precocious puberty, adrenarche progressed normally during LHRHa suppression of gonadarche. In children with the onset of progression of adrenarche during maintenance of a prepubertal gonadal steroid milieu, there was less evidence than in preadrenarchal children of a restraint upon skeletal maturation. These data suggest that adrenal androgens contribute importantly to epiphyseal advancement during childhood.

Adrenal Cortex↗
PubMed1986

Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone.

Hypogonadotropic hypogonadism (HH) is a clinical syndrome occurring in both sexes which has long puzzled clinicians due to the apparent paradox of nonfunctioning gonads in the face of normal or only slightly lowered levels of circulating gonadotropins. Using frequent sampling of gonadotropin levels as an index of hypothalamic GnRH secretion, we have examined the hypothesis that this group of disorders represents a spectrum of abnormal patterns of the pulsatile release of endogenous GnRH. After a broad, normative data base was established in both men and women for purposes of comparison, it appears that quantifiable abnormalities of GnRH secretion are discernible in both males and females with HH. These abnormalities include a total absence of GnRH secretion, defects of the amplitude and frequency of its secretion, and altered bioactivity of the gonadotropins released. In addition, physiological regimens of hypothalamic replacement therapy with exogenous GnRH, which are fashioned to mimic the normal frequency of endogenous GnRH secretion, result in complete normalization of reproductive function and fertility in hypogonadotropic subjects of both sexes. Thus, the heterogeneous nature of HH, as well as its favorable clinical and biochemical responses to GnRH, suggest that the basic defect in this family of disorders involves a partial or complete inability to synthesize and/or release GnRH from the hypothalamus in a manner compatible with physiological reproductive function. Conversely, these findings imply that maintenance of a physiological amplitude and frequency of endogenous GnRH secretion appear to be essential for normal reproductive function.

Adolescent↗
PubMed1986

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1986

Administration of low dose pulsatile gonadotropin-releasing hormone (GnRH) to GnRH-deficient men regulates free alpha-subunit secretion.

Although pharmacological doses of GnRH and TRH stimulate free alpha-subunit (alpha-subunit) secretion from the pituitary, little is known about the pattern and control of alpha-subunit release under physiological circumstances. Euthyroid men with idiopathic hypogonadotropic hypogonadism, a condition of deficient GnRH release, provide a unique opportunity to study alpha-subunit secretion before and during administration of a physiological regimen of GnRH administration. Before GnRH therapy, six euthyroid IHH men with normal endogenous TSH secretion had circulating alpha-subunit levels close to or below assay detection limits, with a mean level less than 0.5 ng/ml. During 12-42 weeks of physiological GnRH replacement, serum alpha-subunit concentrations rose to a mean value of 2.07 +/- 0.3 (+/- SEM) ng/ml (P less than 0.01). After GnRH administration, alpha-subunit was released in a pulsatile pattern following each dose of GnRH and mirrored the secretory pattern of LH. Increases in serum alpha-subunit concentrations during GnRH administration were closely correlated with increases in LH (r = 0.91; P less than 0.01), but not FSH (r = 0.24; P = NS), levels. In addition, a situation in which LH secretion was clearly predominant and FSH levels were barely detectable was created by increasing the frequency of GnRH administration to every 30 min. In this circumstance, free alpha-subunit concentrations increased in conjunction with LH levels in the face of decreased FSH levels. We conclude that replacement of GnRH regulates both the level and pattern of alpha-subunit secretion in GnRH-deficient men, and that there is tight correlation of alpha-subunit with LH, but not with FSH, secretion.

Adolescent↗
PubMed1986

Intravenous administration of pulsatile gonadotropin-releasing hormone in hypothalamic amenorrhea: effects of dosage.

Eighteen women with well characterized hypothalamic amenorrhea underwent 30 cycles of pulsatile GnRH treatment in an effort to examine the role of GnRH dosage in pituitary and ovarian responses. GnRH was administered iv at 2 doses (25 and 100 ng/kg bolus) at a physiological range of frequencies (90 and 60 min) in the follicular phase of the induced cycles. After demonstration of ovulation by ultrasound and clinical parameters, the frequency of GnRH administration was progressively slowed from every 60 min to every 90 min and then to every 240 min to mimic the slowing of endogenous LH secretion that occurs during the luteal phase in normal women. The results of these induced cycles were compared to those of 62 ovulatory cycles from normal women. Overall clinical and biochemical results revealed the following. Patients receiving doses of 25 ng/kg GnRH successfully ovulated only 80% of the time, with recruitment of a single dominant follicle. Two of 5 patients became pregnant. Peak estradiol levels were significantly lower than normal [261 +/- 33 (+/- SE) vs. 342 +/- 11 pg/ml, respectively; P less than 0.02]. Integrated luteal phase progesterone production was also significantly reduced in the 25 ng/kg group compared to normal (78 +/- 17 vs. 145 +/- 8 ng/ml/entire luteal phase, respectively; P less than 0.02). All women receiving bolus doses of 100 ng/kg GnRH ovulated; maturation of multiple follicles occurred in 5 of 20 cycles, and 6 of 7 women conceived. Peak estradiol values were significantly higher than those in either normal women or the 25 ng/kg group (478 +/- 48 pg/ml; P less than 0.02 for both), with integrated luteal phase progesterone levels significantly higher than those in patients receiving the 25 ng/kg dose (196 +/- 25 ng/ml/luteal phase; P less than 0.02). This study demonstrates that ovulation and fertility can be achieved with a physiological frequency regimen of pulsatile GnRH administration using bolus doses of both 25 and 100 ng/kg in women with hypothalamic amenorrhea; the 25 ng/kg dose of GnRH may represent a threshold of stimulation of the pituitary-ovarian axis and recreates cycles with an inadequate luteal phase; and a 100 ng/kg dose of GnRH may well cause a supraphysiological stimulation of the pituitary-gonadal axis.

Amenorrhea↗
PubMed1986

Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle.

To characterize the spectrum of pulsatile gonadotropin secretion during the course of the normal menstrual cycle, we studied normal women during 51 ovulatory cycles. Plasma gonadotropin concentrations were measured at 10-min intervals for 20-24 h during the early, mid-, and late follicular phases and the early, mid-, and late luteal phases. LH data series were analyzed using 2 different computer-assisted algorithms for pulse detection. The LH interpulse interval decreased during the follicular phase (FP) from 94 +/- 4 (+/- SEM) min in the early FP (EFP) to 71 +/- 4 min by the late FP (LFP; P less than 0.001). The estimation of LH pulse frequency in the EFP was significantly affected by slowing of episodic LH secretion during sleep. In the luteal phase (LP), the LH interpulse interval progressively increased from 103 +/- 8 min in the early LP (ELP) to 216 +/- 39 min by the late LP (LLP; P less than 0.001). Sleep-associated slowing of episodic LH secretion also occurred in the ELP. The mean LH pulse amplitude in the EFP (6.5 +/- 0.4 mIU/ml) decreased significantly by the midfollicular phase (MFP; 5.1 +/- 0.8 mIU/ml; P less than 0.05) and increased once again by the LFP (7.2 +/- 1.2 mIU/ml). LH pulse amplitude was highest in the ELP (14.9 +/- 1.7 mIU/ml), decreased by the midluteal phase (MLP) to 12.2 +/- 2.0 mIU/ml, and declined further by the LLP to 7.6 +/- 1.1 mIU/ml (P less than 0.001 vs. ELP). FSH secretion was significantly (P less than 0.05) correlated with LH secretion at time lags of 0-10 min in 82% of the studies. These results indicate the following. 1) In the EFP and ELP, the frequency of gonadotropin pulsations is reduced at night in association with sleep. 2) The frequency of LH secretion increases from the EFP to MFP and LFP. 3) LH pulse amplitude decreases in the MFP, suggesting enhanced negative feedback of estrogen on the hypothalamic-pituitary axis and/or a decrease in GnRH secretion at this stage. 4) A progressive reduction of LH pulse frequency and amplitude occurs during the LP which is correlated with the duration of exposure of the hypothalamic-pituitary axis to progesterone. 5) A close relationship exists between secretion of LH and FSH, suggesting a common stimulatory factor for both gonadotropins.

Adolescent↗
PubMed1986

Bio- and immunoactive luteinizing hormone responses to low doses of gonadotropin-releasing hormone (GnRH): dose-response curves in GnRH-deficient men.

Previous investigations of the effects of GnRH on pituitary LH responses in normal men required pharmacological doses of GnRH to avoid the confounding effects of endogenous GnRH secretion and employed nonphysiological dose intervals. To examine the role of GnRH in determining both the qualitative and quantitative nature of physiological LH responses, we studied five GnRH-deficient men in whom pituitary and gonadal function had been normalized with GnRH replacement. Both bio- and immunoactive LH responses were evaluated in these men after a wide range of GnRH doses (7.5-250 ng/kg) administered at a physiological frequency (every 2 h), while gonadal steroid levels were within the normal adult male range. In addition, the amplitude and contour of the immunoactive LH pulses were compared to those of 15 normal men to assure that these experiments achieved physiological pituitary responses. The relationship between bio- and immunoactive LH was compared between patients, between doses as the amount of GnRH was increased, and within pulses of LH. As the dose of GnRH was increased, both bio- and immunoactive LH responses increased in a log-linear fashion when assessed by both amplitude (r = 0.96 for bioactive LH and r = 0.98 for immunoactive LH) and area under the curve (r = 0.99 for bioactive LH and r = 0.97 for immunoactive LH). GnRH doses of 7.5 and 25 ng/kg produced LH responses with amplitudes similar to those in normal men. The relationship between bio- and immunoactive LH between patients and between differing doses of GnRH was analyzed by comparing the slopes of lines fit to individual bioactive vs. immunoactive LH plots after each dose of GnRH in each patient. There was a marked variation in the relationship of bio- to immunoactive LH between patients (P less than 0.005). No change was found in the biopotency of LH as the dose of GnRH was increased (P less than 0.10). Finally, no variation of the bioactivity of LH was evident within individual pulses. We conclude that a log-linear relationship exists between doses of GnRH that produce physiological LH pulses and both bio- and immunoactive LH responses; the bioactivity of secreted LH varies markedly between patients; the relative bioactivity of LH in an individual does not change as the dose of GnRH is increased; and no change in bioactivity of LH responses was demonstrated within pulses of LH.

Adolescent↗
PubMed1986

Long-term administration of gonadotropin-releasing hormone in men with idiopathic hypogonadotropic hypogonadism. A model for studies of the hormone's physiologic effects.

The effect of long-term administration of gonadotropin-releasing hormone (GnRH) for induction and maintenance of sexual maturation was characterized in 23 men with idiopathic hypogonadotropic hypogonadism. Twenty-two men achieved normal adult male serum testosterone concentrations (575 +/- 33 ng/dL; p less than 0.0001 compared with the baseline mean of 61 +/- 6 ng/dL) that were sustained in 21 men for up to 36 months with bolus doses of GnRH varying from 25 to 300 ng/kg body weight administered every 2 hours. Pulsatile luteinizing hormone (LH) secretion occurred in all 23 men, with mean levels of LH (14.7 +/- 1.3 mlU/mL) and follicle-stimulating hormone (11.3 +/- 1.3 mlU/mL) within or above the normal range for adult men. Mature sperm were observed in the ejaculates of 20 men, with counts ranging from less than 1 X 10(6) to 96 X 10(6)/mL. Increasing responsiveness of the pituitary-gonadal axis to GnRH was shown in 6 men. Men with idiopathic hypogonadotropic hypogonadism present a useful model to study the onset and maintenance of reproductive function in men.

Adolescent↗
PubMed1986

Gonadotropin-releasing hormone (GnRH) physiology in men and women.

The combined approach used in studies of GnRH secretion provided a complimentary array of techniques with which to establish the program of amplitude (dose) and frequency of GnRH secretion in the physiologic state. Normative data in men and women were useful in formulating frequency estimates, which could then be applied to the task of replacement of GnRH in deficient (IHH) individuals. Comparison of the results of therapy with these 'ablation-replacement' models then allowed to arrive closer to the true amplitude or dose of exogenous GnRH required to duplicate the physiologic ideal. In addition to providing insight into the neuroendocrine control of reproduction, these applications provided treatment of various reproductive disorders in men and women. Further expansion of the efforts into other potential defects of endogenous GnRH secretion will ultimately uncover those disorders amenable to therapy.

Adolescent↗