Serum inhibin B in polycystic ovary syndrome: regulation by insulin and luteinizing hormone

Inhibin B is a product of the granulosa cells of growing preantral and antral follicles. Despite the large ovarian volume and increased follicle number typically detected in women with polycystic ovary syndrome (PCOS), previous studies demonstrate that inhibin B is not elevated as would be expected in PCOS, but is inversely correlated with body mass index (BMI). We therefore hypothesized that inhibin B levels in women with PCOS are regulated by a factor related to BMI. Thus, LH, sex steroids, and metabolic parameters were measured in 50 anovulatory PCOS subjects in pools constituted from equal aliquots of serum drawn every 10 min for 4 h and were correlated with inhibin B. Based on the results of these correlative studies, inhibin B regulation by human chorionic gonadotropin (hCG) and insulin was tested directly. In PCOS subjects, inhibin B correlated inversely with BMI (r = -0.413; P < 0.004) and fasting insulin (r = -0.409; P < 0.004). Inhibin B also correlated directly with pool LH (r = 0.419; P < 0.003), LH pulse amplitude (r = 0.512; P < 0.0001), and SHBG (r = 0.429; P < 0.003). The relationships demonstrated for inhibin B were not demonstrated for inhibin A, nor were they evident in normal subjects. To determine whether the correlations represent regulation of inhibin B, i.e. stimulation of inhibin B by LH or suppression by insulin, two interventional studies were performed. In the first study hCG (5000 U) was administered to PCOS subjects (n = 15) to mimic the effects of LH. Inhibin B was not increased, but was significantly reduced 24 h after hCG administration (223.8 +/- 21.3 vs. 152.4 +/- 15.9 pg/ml; P < 0.0005). In the second study, diazoxide (100 mg every 8 h) was administered for 3 d to PCOS subjects (n = 9). Inhibin B increased (85.4 +/- 12.4 to 136.6 +/- 18.8 pg/ml; P < 0.05) in association with a decrease in the insulin area under the curve (104 +/- 29 to 83 +/- 22 nmol/liter.min; P < 0.05) induced by diazoxide. In PCOS subjects, inhibin B demonstrated significant relationships with BMI and factors related to BMI, including LH, insulin, and SHBG. Although LH was associated with inhibin B, hCG administration suppressed inhibin B secretion after 24 h, whereas short-term insulin suppression increased inhibin B. These findings suggest that both increased LH and insulin may account for the relative suppression of inhibin B in patients with PCOS.     

Variable response to a long-acting agonist of luteinizing hormone-releasing hormone in girls with McCune-Albright syndrome

Six girls with McCune-Albright syndrome were treated for at least 2 months with the long-acting LHRH agonist D-Trp6-Pro9-NEt-LHRH, which previously was found to be an effective treatment for true precocious puberty. Nocturnal and LHRH-stimulated serum gonadotropin levels and plasma estradiol levels were measured before treatment and after 2-3 months of treatment. Five of the six girls had no decrease in serum gonadotropin or plasma estradiol levels during therapy, and their pubertal signs were unaffected by treatment. All five of these girls had serum gonadotropin levels that were within or below the normal prepubertal range. The sixth girl, who had gonadotropin levels in the normal pubertal range before treatment, had decreased serum gonadotropin and plasma estradiol levels during 1 yr of LHRH analog therapy. This was associated with cessation of menses and regression of secondary sexual changes. The failure of LHRH analog to modify the course of precocious puberty in the five patients with prepubertal serum gonadotropin concentrations is further evidence that the mechanism of precocious puberty in most girls with McCune-Albright syndrome differs from that in patients with true precocious puberty.     

Prolactin-lowering effect of luteinizing hormone-releasing hormone agonist administration in prolactinoma patients

We studied the effect of LHRH agonist administration on serum PRL levels in five women with microprolactinomas and two women and a man with intrasellar macroprolactinomas. Each patient received either D-Trp6-LHRH or buserelin for 90 days. Serum PRL levels decreased significantly in the patients with microprolactinomas by 65%, from 156 +/- 93 (+/- SD) to 54 +/- 49 micrograms/L on day 90 (P = 0.011), but it did not decrease in the macroprolactinoma patients. Mean serum LH and FSH decreased by 43% and 62.5%, respectively, in all eight patients. There was no statistically significant correlation between the serum PRL and LH or FSH levels in the microprolactinoma patients. We conclude that LHRH agonists can counteract the hyperprolactinemia produced by microprolactinomas and that the effect probably is not exerted by an action on the gonadotrophs.     

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome

CONTEXT: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. OBJECTIVE: The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. DESIGN: A prospective study was conducted to compare androgen production in response to FSH in two groups of women. SETTING: The study was conducted in a General Clinical Research Center in a tertiary academic medical center. PATIENTS: Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. INTERVENTIONS: Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). MAIN OUTCOME MEASURES: The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. RESULTS: Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. CONCLUSIONS: These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.     

Pituitary response to luteinizing hormone-releasing hormone in women with variant luteinizing hormone

OBJECTIVE: To assess the LH response of the pituitary gland to GnRH stimulation in healthy women with a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN: Clinical study. PATIENTS: We studied 40 healthy non-pregnant Japanese women of known zygosity for the LH beta-subunit gene (3 homozygotes for the mutant gene, 17 heterozygotes, and 20 homozygotes for the wild type). All women had normal ovulatory cycles. MEASUREMENTS: Serum LH status was determined by comparing LH immunoassays results using a monoclonal antibody recognizing only wild-type LH with those from a polyclonal antibody assay recognizing both variant and wild-type LH. The ratio of monoclonal to polyclonal immunoassay results determined the serum LH status. LH secretion in response to a GnRH stimulation test was measured. RESULTS: All women with the wild-type LH showed a normal response of LH to GnRH according to both assays. Over the time course of the response, the ratios in women with wild-type LH showed no remarkable changes. The response curves in women heterozygous for the mutant peaked 15-30min after GnRH injection; their response patterns included a statistically significant decrease in the rates of response at 15min after injection. CONCLUSIONS: There are the differences in circulatory kinetics between the two LH forms and in regulation of the two types of LHbeta genes. The maximal response of the variant LH to pituitary stimulation with GnRH appears to be greater than that of wild-type LH.     

多囊卵巢综合征性激素水平检测

目的：探讨血清性激素各项检测指标与不同年龄段的多囊卵巢综合征（PCOS）患者的关系及其临床意义。方法：以月经周期正常的健康妇女为对照组,采用化学发光法测定30岁以下年龄组和30岁及以上年龄组PCOS患者促黄体生成素（LH）、促卵泡生成素（FSH）、泌乳素（PRL）、雌二醇（E2）、睾酮（TESTO）、孕酮（Prog）水平,通过统计学软件进行比较分析。结果：多囊卵巢综合征患者,30岁以下年龄组和30岁及以上年龄组LH高于对照组（P〈0．01）,E2高于对照组（P〈0．05）,TESTO高于对照组（P〈0．01）。30岁以下PCOS患者组和30岁及以上PCOS患者组各检测指标之间差异无统计学意义（P〉0．05）。结论：血清中LH,E2高水平及TESTO增高可能是多囊卵巢综合征的预示因子,高LH、高E2、高雄激素血症可能是引起PCOS发生的因素之     

Serum luteinizing hormone and follicle-stimulating hormone and the response to luteinizing hormone-releasing factor in children and adolescents with isolated growth hormone deficiency

Serum concentrations of LH and FSH were measured in 95 patients (62 males and 33 females) with presumed isolated GH deficiency [chronological age range, 5-17 yr; bone age (BA) range, 2-15.5 yr] before and after the iv administration of 100 micrograms LRF. The results were compared to those of patients of similar skeletal maturity, derived from a population of 136 children (79 males and 57 females) with constitutional short stature. Mean serum LH concentrations were similar in the GH-deficient and control patients of either sex within the age ranges studied. Mean basal FSH concentrations in males with GH deficiency were similar to the controls between BA 2 to less than 10 yr and more than 12 to 15.5 yr. The mean peak, peak minus basal, and integrated responses of LH concentrations after the iv administration of LRF were not significantly different in patients with GH deficiency from the responses in normal short children of similar ages. After LRF administration, GH-deficient males of BA between 2 and less than 10 yr had diminished FSH responses. The mean peak concentration was 1.9 +/- 0.2 ng/ml in GH-deficient males (n = 34) and 2.8 +/- 0.3 ng/ml (less than 0.05) in control males (n = 45). GH-deficient males of BA between 10-12 yr had slightly elevated mean peak and total integrated FSH concentrations; in GH-deficient patients (n = 15), these values were 2.7 +/- 0.2 ng/ml and 2.1 +/- 0.2 ng X min ml-1, respectively; and in controls (n = 18), they were 1.8 +/- 0.2 ng/ml (P less than 0.05) and 1.5 +/- 0.2 ng X min ml-1 (P less than 0.05). In the BA range from 4-8 yr, the mean peak response to LRF was diminished in GH-deficient females (n = 24; 4.0 +/- 0.4 ng/ml) compared to that in control females (n = 18; 6.0 +/- 0.9 ng/ml; P less than 0.05). In the BA range from more than 8 to 13 yr, the corresponding mean peak FSH concentration in GH-deficient females (n = 9) was 3.2 +/- 0.3 ng/ml; in control females (n = 39), it was 4.9 +/- 0.4 ng/ml (P less than 0.05). This study fails to confirm previous reports that LRF-evoked LH release is diminished in patients with isolated GH deficiency compared to that in normal short children of similar skeletal maturity. Small differences in group mean FSH concentrations were noted, but these findings are of limited clinical importance because an extensive degree of overlap of individual FSH concentrations was found in all comparisons between GH-deficient patients and normal children.     

Porcine ovarian inhibin preparations sensitize cultured ovine gonadotrophs to luteinizing hormone-releasing hormone

Treatment of ovine pituitary cell cultures with an acetone powder of porcine follicular fluid (APPFF; 50 micrograms/ml) decreased FSH secretion 60%, did not alter basal LH secretion, but increased by 2- to 3-fold the effectiveness of LHRH or D-Lys6-LHRH (10(-8) M) in releasing LH. Chromatography of APPFF on Matrex Gel Red A (MGRA) yielded a protein fraction (MGRA-IV) in which both FSH-inhibiting and LHRH-enhancing activities were enriched 8-fold. Both activities were destroyed by trypsin, but both were highly resistant to heat. The apparent mol wt of the active substance(s) was greater than 10,000. The LHRH-enhancing effect of MGRA-IV was reversible and declined, with an apparent half-life of 7 h, when MGRA-IV treatment was discontinued. There was too little estrogen in either APPFF or MGRA-IV to account for any of the activities. These results demonstrate that porcine follicular fluid contains LHRH-enhancing activity along with classical inhibin activity and that both activities may be linked in one molecule. These dual activities may be important in a number of species.     

Inappropriate growth hormone response to luteinizing hormone-releasing hormone in diabetes mellitus

We randomly administered luteinizing hormone-releasing hormone (LHRH) or thyrotropin releasing hormone (TRH) (25 micrograms and 200 micrograms, respectively, as a bolus), to 16 diabetic male subjects (9 type I, 7 type II) and to 9 healthy male controls in two different mornings. While GH in the basal state was similar in type I, type II, and normal subjects, LHRH administration surprisingly evoked a significant GH release in 7 (5 type 1, 2 type II) diabetic patients. GH-responders had higher glycated hemoglobin than non-responders (11 +/- 1 nu 8.3 +/- 0.5%) but superimposable fasting and intratest average glucose levels. Only one patient among the GH-responders to LHRH showed a GH release also after TRH. These data support the hypothesis that GH secretion in diabetes, especially when poorly controlled, is abnormal.     

Long term therapy with luteinizing hormone-releasing hormone in isolated gonadotropin deficiency: failure of therapeutic response

We have evaluated the therapeutic response to exogenous LRH (1 mg, sc, either twice daily or three times daily) in six subjects with isolated gonadotropin deficiency. Four males were treated for 6 months, of whom two showed a transient rise in serum testosterone. However, testosterone levels subsequently remained at pretreatment levels in each of the four subjects during LRH therapy. One of the two female subjects displayed a transient rise in 17 beta-estradiol levels. All four males showed a notable rise in testosterone after hCG, and the one female tested responded to menotropins, while receiving LRH. We propose that the number of quanta of gonadotropins released per day with our therapeutic regimen was inadequate to generate a normal gonadal response.     

Serum irisin levels in polycystic ovary syndrome after ovarian drilling

BackgroundMany cases of Poly-Cystic Ovary Syndrome (PCOS) are overweight and presenting with insulin resistance.Main objectivewas to evaluate the effects of ovarian drilling on the serum levels of Irisin in women with polycystic ovaries.Study design and settingSerum Irisin levels were investigated in 100 cases with PCOS before ovarian drilling and 3 months after drilling, and in 80 control cases. Serum Irisin, hormonal profile and HOMA-IR were estimated in PCOS cases before and after ovarian drilling. Statistical analysis was performed by using Statistical Package for Social Scientists (SPSS).ResultsThe serum irisin levels in overweight and in normal weight PCOS cases before ovarian drilling were significantly higher as compared with the corresponding control cases. Fasting serum Irisin levels were found to be significantly elevated in PCOS patients before ovarian drilling as compared to the levels after drilling. The serum irisin levels in overweight and in normal weight PCOS cases before ovarian drilling were found to be significantly positively correlated with BMI, insulin levels, and HOMA-IR.ConclusionElevated serum Irisin levels in PCOS may contribute to the development of insulin resistance. Ovarian drilling for polycystic ovaries results in a significant decrease in the serum Irisin levels. The analysis of ROC curves may suggest that serum Irisin may be a valuable biomarker for diagnosis and for monitoring cases with PCOS during treatment.     

Serum concentration and urinary excretion of the luteinizing hormone-releasing hormone agonist buserelin in patients with endometriosis

We studied the pharmacokinetics of iv and intranasally administered buserelin, a LHRH agonist peptide, in 14 women with endometriosis. Serum and urinary buserelin concentrations were determined by specific RIA (buserelin antiserum AS-639). Intact buserelin and the metabolites in urine were separated by reverse phase high performance liquid chromatography and measured by RIA. The mean serum buserelin concentrations were 101 +/- 33 (+/- SD) ng/mL 20 min and 1.12 +/- 0.12 ng/mL 360 min after its iv injection in 6 women, and the mean elimination half-life between 20 and 360 min was 51 min. In serum, intact buserelin was the main constituent (10 min, 90%; 120 min, 74%; 360 min, 52%), and the major metabolite was the buserelin-(5-9) pentapeptide (10 min, 0.6%; 120 min, 19%; 360 min, 12%). In the urine collected 0-1 h after buserelin administration, intact buserelin was 66% and the 5-9 pentapeptide was 28% of the total excretion. In the urine collected between 6-24 h after buserelin administration, intact buserelin accounted for 67% and the 5-9 pentapeptide for 32% of the total excretion. The urinary buserelin concentration was 1345 +/- 156 micrograms/g creatinine 1 h and 25 +/- 5 micrograms/g creatinine 6-24 h after buserelin administration. Serum LH, FSH, and estradiol concentrations increased acutely up to 10-fold above basal values; the mean peak LH, FSH, and estradiol values occurred at 180-240 min, 240 min, and 24 h, respectively. In therapeutic studies with buserelin nasal spray in 5 women, serum concentrations of 0.9-1.4 ng/mL were found 15 min after a single dose of 300 micrograms, intranasally, and the urinary excretion was 2.52-3.68 micrograms/24 h during daily administration of 3 doses of 300 micrograms at intervals of 8 h. These results confirm that buserelin is slowly inactivated and remains available to pituitary receptors for a prolonged period after its iv or intranasal administration.     

Maintenance of the ratio of bioactive to immunoreactive follicle-stimulating hormone in normal men during chronic luteinizing hormone-releasing hormone agonist administration

Chronic administration of LHRH agonist analogs to humans reduces gonadal function through pituitary desensitization. Serum immunoreactive gonadotropin levels are modestly reduced, whereas serum bioactive LH levels are drastically suppressed. The effects on bioactive FSH levels, however, are not known. In this study, serum bioactive FSH was measured using an in vitro granulosa cell aromatase bioassay in four normal men given a LHRH agonist, [D-Trp6,Pro9-NEt]LHRH (LHRHA; 500 micrograms/day for 16 weeks), by sc infusion and testosterone enanthate (TE; 100 mg, im every 2 weeks) and in five men given 500 micrograms/day LHRHA by daily sc injection for 20 weeks and TE (100 mg every 2 weeks) from weeks 10 through 20. During the first study, serum immunoreactive FSH levels (IR-FSH) decreased by 56.5 +/- 4.8% (+/- SEM), and serum bioactive FSH (Bio-FSH) level decreased by 57.6 +/- 6.4%. The ratio of Bio-FSH to IR-FSH did not change. During the second study, both serum IR-FSH and Bio-FSH levels followed a triphasic pattern, decreasing slightly but not significantly immediately after initiation of LHRHA administration, progressively increasing to a peak (P less than 0.5 vs, baseline) at week 10, and then, after addition of TE to this regimen, decreasing slightly again. The Bio-FSH to IR-FSH ratio, as in the first study, did not change. When serum obtained at week 10 during the second study, just before initiation of TE, was chromatographed on a Sephadex G-100 column, IR-LH eluted in two distinct peaks, while IR-FSH eluted as a single peak. These results demonstrate that in normal men chronic LHRHA administration alone for up to 10 weeks or LHRHA plus TE for up to 16 weeks does not alter the qualitative characteristics of secreted FSH, since there was no dissociation between serum IR- and Bio-FSH levels.     

A new contributing factor to polycystic ovary syndrome: the genetic variant of luteinizing hormone.

Although the etiology of polycystic ovary syndrome (PCOS) is still unclear, LH is considered to play a central role in its pathogenesis. An immunologically anomalous form of LH, with two point mutations in the LHbeta gene, has been recently described. This genetic variant of LH (v-LH), of wide geographic distribution, is functionally different from wild-type (wt) LH. To assess the role of the v-LH in PCOS, we analyzed its frequency in groups of PCOS patients from Finland, The Netherlands, the United Kingdom, and the United States. The LH status was determined by two immunofluorometric assays from a total of 1466 subjects. The carrier frequency of the v-LH allele in the whole study population was 18.5%, being highest (28.9%) in Finland and lowest (11.2%) in The Netherlands. In the individual countries, the frequency of v-LH was similar in obese and nonobese controls, but in The Netherlands and Finland, it was 5- to 7-fold lower in obese PCOS subjects compared with that in the other groups (2-4.5% vs. 10.3-33.3%; P < 0.05). A similar tendency was found in the United States (5.7% vs. 11.1-25.0%), but not in the United Kingdom. The overall high prevalence of v-LH in healthy women and women with PCOS suggests that it is compatible with fertility. The similar frequency of v-LH in healthy nonobese and obese women indicates that obesity per se is not related to the variant. In contrast, the lower frequency of v-LH in obese PCOS patients suggests that v-LH somehow protects obese women from developing symptomatic PCOS. However, the regional differences in this finding between patients with apparently similar diagnostic criteria emphasizes the multifactorial nature of this syndrome, and that its pathogenesis may vary according to the genetic background. Although the definitive role of v-LH in PCOS remains to be proven, its determination may improve the prediction of risk of PCOS, especially in obese women.     

Inhibitory effect of bromocriptine treatment on luteinizing hormone secretion in polycystic ovary syndrome

In order to investigate a possible common role of central dopaminergic mechanisms in the release of PRL and LH in patients with the polycystic ovary syndrome (PCO), plasma LH pulsatile profiles and the response to GnRH were studied in a group of 12 PCO patients before and after 3 months of treatment with bromocriptine, 2.5 mg twice daily. They were divided into two groups of six patients according to the occurrence or not of hyperprolactinemia (plasma PRL, 30.3 +/- 2.7 (SE) ng/ml vs. 9.5 +/- 0.8 (SE) ng/ml). Integrated LH secretion significantly decreased in hyperprolactinemic [2537 +/- 371 (SE) vs. 907 +/- 102 mIU/ml X min] as well as in normoprolactinemic (2847 +/- 460 vs. 901 +/- 152 mIU/ml X min) patients, but there was no difference in the response of the two groups. The LH increment after a bolus injection of 100 micrograms GnRH was reduced (P less than 0.01) to the same extent in both groups. These results indicate a dopaminergic component in the control of LH release in PCO patients, independent of the mechanism governing PRL secretion. Since bromocriptine reduced LH secretion, it may be useful for the management of this condition.     

Serum follicle-stimulating hormone, luteinizing hormone, and prolactin during the induction of ovulation with exogenous gonadotropin

To examine the gonadotropic milieu presiding over recruitment and selection of a dominant follicle during gonadotropin induction of ovulation, four patients were studied over nine cycles of human pituitary gonadotropin (hPG) therapy. These hypogonadotropic subjects received a routine schedule of hPG injections monitored by daily urinary estrogen and pregnanediol determinations. Serum FSH, LH, and PRL profiles were measured in daily morning blood samples throughout each menstrual cycle. hPG therapy produced markedly abnormal gonadotropin patterns. Mean serum FSH levels were above the upper limit of the normal serum FSH range and no early or midfollicular FSH peaks occurred. The FSH-LH ratio was abnormally high for 8 days before ovulation. Progressive and marked elevations of serum PRL developed during hPG treatment. A bimodal luteal phase serum PRL profile appeared with peak values of 40.7 +/- 5.6 ng/ml (mean +/- SE) 1 day and 42.0 +/- 3.0 ng/ml 9 days after the LH peak. We conclude that: 1) Current gonadotropin treatment regimens to induce ovulation produce radioimmunoassayable serum FSH, LH, and PRL profiles which are qualitatively and quantitatively abnormal, and 2) Excessive FSH levels and the elevated FSH-LH ratio orchestrate aberrant folliculogenesis and result in the clinical problems of multiple ovulation and hyperstimulation.     

Changes in plasma luteinizing hormone-releasing hormone and gonadotropin concentrations during constant rate intravenous infusion of luteinizing hormone-releasing hormone in cyclic rats.

Further analysis has been made of the response of the rat pituitary gland to LHRH during the 4-day estrous cycle. LHRH was infused iv at a constant rate (50 ng/h) into phenobarbital-treated rats at different times during the estrous cycle. Infusion at this rate in proestrous rats simulates the rising and plateau phases of the spontaneous proestrous surges of LH and FSH in plasma. Plasma LH rose to similar heights during the "initial phase" of LH release (during the first 40 min of infusion) on the afternoons of estrus, diestrous day one, and proestrus and during the morning of proestrus. The increase during the afternoon of diestrous day two was significantly less than that in all the other groups. A similar response was seen in the case of FSH release. A "rapid rising" or "augmented" phase of LH release (during 40-120 min of infusion) was present in all groups and the magnitude of the response was greatest during the afternoon of proestrus. In the case of FSH, an augmented phase of release started 60 min after the start of infusion, and the response during the afternoon of proestrus was slightly greater than the responses measured at the other times tested. The responses on diestrous day one were not altered when phenobarbital was omitted or when rats were ovariectomized shortly before LHRH infusion. Other differences in the LH and FSH responses during both initial and augmented phases of release were seen in rats tested at different times during the estrous cycle with an LHRH infusion rate which caused a supraphysiological response on proestrus. The results suggest that 1) the initial rising phases in plasma LH and FSH during the spontaneous surges during proestrus are not the result of an increase in pituitary responsiveness to LHRH during the estrous cycle, 2) augmented phases of LH and FSH release can be elicited on all days of the estrous cycle, and 3) the increases in magnitude of the augmented phases of LH and FSH release on proestrus, as compared to those on other days of the cycle, are the result of an increase in pituitary responsiveness to LHRH during the estrous cycle.     

Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone

Premature thelarche is a benign condition that affects young girls. In contrast, central precocious puberty is considered a more serious disorder that causes progressive secondary sexual development, accelerated growth and skeletal maturation, early epiphyseal fusion, and short adult stature. Differentiation between these 2 conditions is important, but may be difficult on clinical grounds, since patients with both disorders may present initially as isolated breast development. To examine the potential usefulness of gonadotropin measurements in distinguishing early central precocious puberty from premature thelarche, we measured basal and LHRH-stimulated plasma gonadotropin levels in 58 girls with idiopathic premature breast development. The girls were divided into six clinically distinct groups, based on the severity of clinical presentation, ranging from isolated breast development (group A) to complete secondary sexual development and accelerated growth and skeletal maturation (group F). The mean basal plasma LH levels and the peak LH response to LHRH stimulation were significantly less in girls with isolated thelarche (group A) than in girls with complete sexual development (group F). The mean basal plasma FSH levels did not differ between these groups, but the peak FSH response to LHRH was greater in girls with isolated thelarche than in girls with complete sexual development. Thus, girls with isolated premature thelarche had a FSH-predominant response to LHRH [mean ratio of peak LH to peak FSH, 0.29 +/- 0.10 (+/- SD)], while girls with complete sexual development had a LH-predominant response (peak LH/FSH, 4.16 +/- 1.80). All girls with isolated thelarche had peak LH/FSH ratios less than 1, and all girls with complete sexual development had a ratio greater than 1. Girls with early or intermediate manifestations of central precocious puberty, who had features of puberty in addition to breast development but lacked all of the features of group F, comprised groups B-E. These girls also had intermediate peak LH/FSH ratios, ranging from 0.29 +/- 0.10 (group B) to 3.35 +/- 2.66 (group E). We conclude that girls with early central precocious puberty frequently have LH and FSH responses to LHRH that are indistinguishable from the FSH-predominant responses of girls with isolated thelarche. These data are consistent with the hypothesis that premature thelarche and central precocious puberty may represent different positions along a continuum of hypothalamic LHRH neuron activation.